ID ADT1_HUMAN Reviewed; 298 AA. AC P12235; D3DP59; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 28-JAN-2026, entry version 253. DE RecName: Full=ADP/ATP translocase 1 {ECO:0000305}; DE AltName: Full=ADP,ATP carrier protein 1 {ECO:0000250|UniProtKB:P48962}; DE AltName: Full=ADP,ATP carrier protein, heart/skeletal muscle isoform T1 {ECO:0000303|PubMed:2541251}; DE AltName: Full=Adenine nucleotide translocator 1 {ECO:0000303|PubMed:2823266}; DE Short=ANT 1 {ECO:0000303|PubMed:2823266}; DE AltName: Full=Solute carrier family 25 member 4 {ECO:0000305}; GN Name=SLC25A4 {ECO:0000303|PubMed:25732997, ECO:0000312|HGNC:HGNC:10990}; GN Synonyms=AAC1 {ECO:0000250|UniProtKB:P48962}, GN ANT1 {ECO:0000303|PubMed:2823266}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2823266; DOI=10.1073/pnas.84.21.7580; RA Neckelmann N., Li K., Wade R.P., Shuster R., Wallace D.C.; RT "cDNA sequence of a human skeletal muscle ADP/ATP translocator: lack of a RT leader peptide, divergence from a fibroblast translocator cDNA, and RT coevolution with mitochondrial DNA genes."; RL Proc. Natl. Acad. Sci. U.S.A. 84:7580-7584(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2541251; DOI=10.1016/0022-2836(89)90477-4; RA Cozens A.L., Runswick M.J., Walker J.E.; RT "DNA sequences of two expressed nuclear genes for human mitochondrial RT ADP/ATP translocase."; RL J. Mol. Biol. 206:261-280(1989). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2547778; DOI=10.1016/s0021-9258(18)71632-3; RA Li K., Warner C.K., Hodge J.A., Minoshima S., Kudoh J., Fukuyama R., RA Maekawa M., Shimizu Y., Shimizu N., Wallace D.C.; RT "A human muscle adenine nucleotide translocator gene has four exons, is RT located on chromosome 4, and is differentially expressed."; RL J. Biol. Chem. 264:13998-14004(1989). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=20843780; DOI=10.1093/nar/gkq750; RA Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R., RA Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M., RA Speed T.P., Scharfe C.; RT "Identification of rare DNA variants in mitochondrial disorders with RT improved array-based sequencing."; RL Nucleic Acids Res. 39:44-58(2011). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Eye, Mammary gland, and PNS; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-37. RC TISSUE=Liver; RX PubMed=2829183; DOI=10.1073/pnas.85.2.377; RA Houldsworth J., Attardi G.; RT "Two distinct genes for ADP/ATP translocase are expressed at the mRNA level RT in adult human liver."; RL Proc. Natl. Acad. Sci. U.S.A. 85:377-381(1988). RN [8] RP PROTEIN SEQUENCE OF 2-31; 34-43; 64-92; 141-147; 189-199 AND 273-296, RP CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT GLY-2, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RC TISSUE=B-cell lymphoma; RA Bienvenut W.V.; RL Submitted (OCT-2004) to UniProtKB. RN [9] RP INTERACTION WITH HIV-1 VPR (MICROBIAL INFECTION). RX PubMed=16120388; DOI=10.1016/j.mito.2004.06.012; RA Deniaud A., Brenner C., Kroemer G.; RT "Mitochondrial membrane permeabilization by HIV-1 Vpr."; RL Mitochondrion 4:223-233(2004). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, RP AND CHARACTERIZATION OF VARIANTS PEOA2 PRO-114 AND MET-289. RX PubMed=21586654; DOI=10.1093/hmg/ddr200; RA Kawamata H., Tiranti V., Magrane J., Chinopoulos C., Manfredi G.; RT "adPEO mutations in ANT1 impair ADP-ATP translocation in muscle RT mitochondria."; RL Hum. Mol. Genet. 20:2964-2974(2011). RN [13] RP INVOLVEMENT IN MTDPS12B. RX PubMed=22187496; DOI=10.1136/jmedgenet-2011-100504; RA Echaniz-Laguna A., Chassagne M., Ceresuela J., Rouvet I., Padet S., RA Acquaviva C., Nataf S., Vinzio S., Bozon D., Mousson de Camaret B.; RT "Complete loss of expression of the ANT1 gene causing cardiomyopathy and RT myopathy."; RL J. Med. Genet. 49:146-150(2012). RN [14] RP FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=23173940; DOI=10.3109/09687688.2012.745175; RA Mifsud J., Ravaud S., Krammer E.M., Chipot C., Kunji E.R., RA Pebay-Peyroula E., Dehez F.; RT "The substrate specificity of the human ADP/ATP carrier AAC1."; RL Mol. Membr. Biol. 30:160-168(2013). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [16] RP FUNCTION, INVOLVEMENT IN MTDPS12A, VARIANTS MTDPS12A HIS-80 AND GLY-235, RP CHARACTERIZATION OF VARIANTS MTDPS12A HIS-80 AND GLY-235, CHARACTERIZATION RP OF VARIANTS PEOA2 ASP-90; PRO-98; GLY-104 AND PRO-114, AND CHARACTERIZATION RP OF VARIANTS MTDPS12B ASP-123 AND PRO-236. RX PubMed=27693233; DOI=10.1016/j.ajhg.2016.08.014; RA Thompson K., Majd H., Dallabona C., Reinson K., King M.S., Alston C.L., RA He L., Lodi T., Jones S.A., Fattal-Valevski A., Fraenkel N.D., Saada A., RA Haham A., Isohanni P., Vara R., Barbosa I.A., Simpson M.A., Deshpande C., RA Puusepp S., Bonnen P.E., Rodenburg R.J., Suomalainen A., Ounap K., RA Elpeleg O., Ferrero I., McFarland R., Kunji E.R., Taylor R.W.; RT "Recurrent de novo dominant mutations in SLC25A4 cause severe early-onset RT mitochondrial disease and loss of mitochondrial DNA copy number."; RL Am. J. Hum. Genet. 99:860-876(2016). RN [17] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=27641616; DOI=10.1038/srep33516; RA Marginedas-Freixa I., Hattab C., Bouyer G., Halle F., Chene A., RA Lefevre S.D., Cambot M., Cueff A., Schmitt M., Gamain B., Lacapere J.J., RA Egee S., Bihel F., Le Van Kim C., Ostuni M.A.; RT "TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to RT the inhibition of P. falciparum growth in human blood."; RL Sci. Rep. 6:33516-33516(2016). RN [18] RP FUNCTION, AND INTERACTION WITH ARHGAP11B. RX PubMed=31883789; DOI=10.1016/j.neuron.2019.11.027; RA Namba T., Doczi J., Pinson A., Xing L., Kalebic N., Wilsch-Braeuninger M., RA Long K.R., Vaid S., Lauer J., Bogdanova A., Borgonovo B., Shevchenko A., RA Keller P., Drechsel D., Kurzchalia T., Wimberger P., Chinopoulos C., RA Huttner W.B.; RT "Human-specific ARHGAP11B acts in mitochondria to expand neocortical RT progenitors by glutaminolysis."; RL Neuron 105:867-881(2020). RN [19] RP FUNCTION. RX PubMed=37278158; DOI=10.15252/embr.202357127; RA Cimadamore-Werthein C., Jaiquel Baron S., King M.S., Springett R., RA Kunji E.R.; RT "Human mitochondrial ADP/ATP carrier SLC25A4 operates with a ping-pong RT kinetic mechanism."; RL EMBO Rep. 24:e57127-e57127(2023). RN [20] RP VARIANTS PEOA2 PRO-114 AND MET-289. RX PubMed=10926541; DOI=10.1126/science.289.5480.782; RA Kaukonen J., Juselius J.K., Tiranti V., Kyttala A., Zeviani M., Comi G.P., RA Keranen J., Peltonen L., Suomalainen A.; RT "Role of adenine nucleotide translocator 1 in mtDNA maintenance."; RL Science 289:782-785(2000). RN [21] RP VARIANT PEOA2 PRO-98. RX PubMed=11756613; DOI=10.1212/wnl.57.12.2295; RA Napoli L., Bordoni A., Zeviani M., Hadjigeorgiou G.M., Sciacco M., RA Tiranti V., Terentiou A., Moggio M., Papadimitriou A., Scarlato G., RA Comi G.P.; RT "A novel missense adenine nucleotide translocator-1 gene mutation in a RT Greek adPEO family."; RL Neurology 57:2295-2298(2001). RN [22] RP VARIANT PEOA2 GLY-104. RX PubMed=12112115; DOI=10.1002/ana.10172; RA Komaki H., Fukazawa T., Houzen H., Yoshida K., Nonaka I., Goto Y.; RT "A novel D104G mutation in the adenine nucleotide translocator 1 gene in RT autosomal dominant progressive external ophthalmoplegia patients with RT mitochondrial DNA with multiple deletions."; RL Ann. Neurol. 51:645-648(2002). RN [23] RP VARIANT PEOA2 MET-289. RX PubMed=12707443; DOI=10.1212/01.wnl.0000056088.09408.3c; RA Agostino A., Valletta L., Chinnery P.F., Ferrari G., Carrara F., RA Taylor R.W., Schaefer A.M., Turnbull D.M., Tiranti V., Zeviani M.; RT "Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external RT ophthalmoplegia (PEO)."; RL Neurology 60:1354-1356(2003). RN [24] RP VARIANT MTDPS12B ASP-123. RX PubMed=16155110; DOI=10.1093/hmg/ddi341; RA Palmieri L., Alberio S., Pisano I., Lodi T., Meznaric-Petrusa M., Zidar J., RA Santoro A., Scarcia P., Fontanesi F., Lamantea E., Ferrero I., Zeviani M.; RT "Complete loss-of-function of the heart/muscle-specific adenine nucleotide RT translocator is associated with mitochondrial myopathy and RT cardiomyopathy."; RL Hum. Mol. Genet. 14:3079-3088(2005). RN [25] RP VARIANT PEOA2 ASP-90. RX PubMed=15792871; DOI=10.1016/j.nmd.2004.12.004; RA Deschauer M., Hudson G., Mueller T., Taylor R.W., Chinnery P.F., Zierz S.; RT "A novel ANT1 gene mutation with probable germline mosaicism in autosomal RT dominant progressive external ophthalmoplegia."; RL Neuromuscul. Disord. 15:311-315(2005). RN [26] RP VARIANTS PEOA2 PRO-98 AND PRO-114. RX PubMed=18575922; DOI=10.1007/s00415-008-0926-3; RA Virgilio R., Ronchi D., Hadjigeorgiou G.M., Bordoni A., Saladino F., RA Moggio M., Adobbati L., Kafetsouli D., Tsironi E., Previtali S., RA Papadimitriou A., Bresolin N., Comi G.P.; RT "Novel Twinkle (PEO1) gene mutations in Mendelian progressive external RT ophthalmoplegia."; RL J. Neurol. 255:1384-1391(2008). RN [27] RP VARIANT MTDPS12B PRO-236. RX PubMed=25732997; DOI=10.1007/8904_2015_409; RA Koerver-Keularts I.M., de Visser M., Bakker H.D., Wanders R.J., RA Vansenne F., Scholte H.R., Dorland L., Nicolaes G.A., Spaapen L.M., RA Smeets H.J., Hendrickx A.T., van den Bosch B.J.; RT "Two novel mutations in the SLC25A4 gene in a patient with mitochondrial RT myopathy."; RL JIMD Rep. 22:39-45(2015). RN [28] RP VARIANT GLN-33, CHARACTERIZATION OF VARIANT GLN-33, AND FUNCTION. RX PubMed=30046662; DOI=10.1212/nxg.0000000000000256; RA King M.S., Thompson K., Hopton S., He L., Kunji E.R.S., Taylor R.W., RA Ortiz-Gonzalez X.R.; RT "Expanding the phenotype of de novo SLC25A4-linked mitochondrial disease to RT include mild myopathy."; RL Neurol. Genet. 4:e256-e256(2018). CC -!- FUNCTION: ADP:ATP antiporter that mediates import of ADP into the CC mitochondrial matrix for ATP synthesis, and export of ATP out to fuel CC the cell (PubMed:21586654, PubMed:27693233, PubMed:23173940, CC PubMed:30046662). Cycles between the cytoplasmic-open state (c-state) CC and the matrix-open state (m-state): operates by the alternating access CC mechanism with a single substrate-binding site intermittently exposed CC to either the cytosolic (c-state) or matrix (m-state) side of the inner CC mitochondrial membrane (By similarity). Substrate exchange across the CC membrane occurs consecutively with one substrate being transported CC first, then dissociating from the substrate binding site before the CC second substrate binds for transport in the opposite direction CC (PubMed:37278158). In addition to its ADP:ATP antiporter activity, also CC involved in mitochondrial uncoupling and mitochondrial permeability CC transition pore (mPTP) activity (PubMed:31883789). Plays a role in CC mitochondrial uncoupling by acting as a proton transporter: proton CC transport uncouples the proton flows via the electron transport chain CC and ATP synthase to reduce the efficiency of ATP production and cause CC mitochondrial thermogenesis (By similarity). Proton transporter CC activity is inhibited by ADP:ATP antiporter activity, suggesting that CC SLC25A4/ANT1 acts as a master regulator of mitochondrial energy output CC by maintaining a delicate balance between ATP production (ADP:ATP CC antiporter activity) and thermogenesis (proton transporter activity) CC (By similarity). Proton transporter activity requires free fatty acids CC as cofactor, but does not transport it (By similarity). Also plays a CC key role in mPTP opening, a non-specific pore that enables free passage CC of the mitochondrial membranes to solutes of up to 1.5 kDa, and which CC contributes to cell death (PubMed:31883789). It is however unclear if CC SLC25A4/ANT1 constitutes a pore-forming component of mPTP or regulates CC it (By similarity). Acts as a regulator of mitophagy independently of CC ADP:ATP antiporter activity: promotes mitophagy via interaction with CC TIMM44, leading to inhibit the presequence translocase TIMM23, thereby CC promoting stabilization of PINK1 (By similarity). CC {ECO:0000250|UniProtKB:G2QNH0, ECO:0000250|UniProtKB:P48962, CC ECO:0000269|PubMed:21586654, ECO:0000269|PubMed:23173940, CC ECO:0000269|PubMed:27693233, ECO:0000269|PubMed:31883789, CC ECO:0000269|PubMed:37278158}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ADP(in) + ATP(out) = ADP(out) + ATP(in); Xref=Rhea:RHEA:34999, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:456216; CC Evidence={ECO:0000269|PubMed:21586654, ECO:0000269|PubMed:23173940}; CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+)(in) = H(+)(out); Xref=Rhea:RHEA:34979, ChEBI:CHEBI:15378; CC Evidence={ECO:0000250|UniProtKB:P48962}; CC -!- ACTIVITY REGULATION: The matrix-open state (m-state) is inhibited by CC the membrane-permeable bongkrekic acid (BKA) PubMed:23173940. The CC cytoplasmic-open state (c-state) is inhibited by the membrane- CC impermeable toxic inhibitor carboxyatractyloside (CATR) CC (PubMed:21586654, PubMed:23173940). Proton transporter activity is CC inhibited by ADP:ATP antiporter activity (By similarity). CC {ECO:0000250|UniProtKB:G2QNH0, ECO:0000250|UniProtKB:P48962, CC ECO:0000269|PubMed:21586654}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=23.7 uM for ATP {ECO:0000269|PubMed:23173940}; CC Vmax=14.6 nmol/min/mg enzyme for ATP uptake CC {ECO:0000269|PubMed:23173940}; CC -!- SUBUNIT: Monomer (By similarity). Found in a complex with ARL2, ARL2BP CC and SLC25A4/ANT1 (By similarity). Interacts with ARL2BP (By CC similarity). Interacts with ARHGAP11B, thereby inhibiting the CC mitochondrial permeability transition pore (mPTP) (PubMed:31883789). CC Interacts with TIMM44; leading to inhibit the presequence translocase CC TIMM23, thereby promoting stabilization of PINK1 (By similarity). CC {ECO:0000250|UniProtKB:G2QNH0, ECO:0000250|UniProtKB:P02722, CC ECO:0000250|UniProtKB:P48962, ECO:0000269|PubMed:31883789}. CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Vpr. CC {ECO:0000269|PubMed:16120388}. CC -!- INTERACTION: CC P12235; Q5S007: LRRK2; NbExp=2; IntAct=EBI-359074, EBI-5323863; CC P12235; P22736-1: NR4A1; NbExp=2; IntAct=EBI-359074, EBI-16085263; CC P12235; P12236: SLC25A6; NbExp=2; IntAct=EBI-359074, EBI-356254; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:21586654}; Multi-pass membrane protein CC {ECO:0000255}. Membrane {ECO:0000269|PubMed:27641616}; Multi-pass CC membrane protein {ECO:0000255}. Note=The complex formed with ARL2BP, CC ARL2 and SLC25A4/ANT1 is expressed in mitochondria (By similarity). May CC localize to non-mitochondrial membranes (PubMed:27641616). CC {ECO:0000250|UniProtKB:P48962, ECO:0000269|PubMed:27641616}. CC -!- TISSUE SPECIFICITY: Expressed in erythrocytes (at protein level). CC {ECO:0000269|PubMed:27641616}. CC -!- DOMAIN: The transmembrane helices are not perpendicular to the plane of CC the membrane, but cross the membrane at an angle. Odd-numbered CC transmembrane helices exhibit a sharp kink, due to the presence of a CC conserved proline residue. {ECO:0000250|UniProtKB:P02722}. CC -!- PTM: Under cell death induction, transglutaminated by TGM2. CC Transglutamination leads to formation of covalent cross-links between a CC glutamine and the epsilon-amino group of a lysine residue, forming CC polymers. {ECO:0000250|UniProtKB:P48962}. CC -!- DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA CC deletions, autosomal dominant, 2 (PEOA2) [MIM:609283]: A disorder CC characterized by progressive weakness of ocular muscles and levator CC muscle of the upper eyelid. In a minority of cases, it is associated CC with skeletal myopathy, which predominantly involves axial or proximal CC muscles and which causes abnormal fatigability and even permanent CC muscle weakness. Ragged-red fibers and atrophy are found on muscle CC biopsy. A large proportion of chronic ophthalmoplegias are associated CC with other symptoms, leading to a multisystemic pattern of this CC disease. Additional symptoms are variable, and may include cataracts, CC hearing loss, sensory axonal neuropathy, ataxia, depression, CC hypogonadism, and parkinsonism. {ECO:0000269|PubMed:10926541, CC ECO:0000269|PubMed:11756613, ECO:0000269|PubMed:12112115, CC ECO:0000269|PubMed:12707443, ECO:0000269|PubMed:15792871, CC ECO:0000269|PubMed:18575922, ECO:0000269|PubMed:21586654, CC ECO:0000269|PubMed:27693233}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Mitochondrial DNA depletion syndrome 12B, cardiomyopathic type CC (MTDPS12B) [MIM:615418]: An autosomal recessive mitochondrial disorder CC characterized by childhood onset of slowly progressive hypertrophic CC cardiomyopathy and generalized skeletal myopathy resulting in exercise CC intolerance and, in some patients, muscle weakness and atrophy. CC Skeletal muscle biopsy shows ragged red fibers, mtDNA depletion, and CC accumulation of abnormal mitochondria. {ECO:0000269|PubMed:16155110, CC ECO:0000269|PubMed:22187496, ECO:0000269|PubMed:25732997, CC ECO:0000269|PubMed:27693233}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Mitochondrial DNA depletion syndrome 12A, cardiomyopathic type CC (MTDPS12A) [MIM:617184]: An autosomal dominant mitochondrial disorder CC characterized by severe hypotonia due to mitochondrial dysfunction CC apparent at birth. Affected infants have respiratory insufficiency CC requiring mechanical ventilation and have poor or no motor development. CC Many die in infancy, and those that survive have profound hypotonia CC with significant muscle weakness and inability to walk independently. CC Some patients develop hypertrophic cardiomyopathy. Muscle samples show CC mtDNA depletion and severe combined mitochondrial respiratory chain CC deficiencies. {ECO:0000269|PubMed:27693233}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the mitochondrial carrier (TC 2.A.29) family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J02966; AAA61223.1; -; mRNA. DR EMBL; J04982; AAA51736.1; -; Genomic_DNA. DR EMBL; HQ206346; ADP92294.1; -; Genomic_DNA. DR EMBL; HQ206347; ADP92295.1; -; Genomic_DNA. DR EMBL; HQ206348; ADP92296.1; -; Genomic_DNA. DR EMBL; HQ206349; ADP92297.1; -; Genomic_DNA. DR EMBL; HQ206350; ADP92298.1; -; Genomic_DNA. DR EMBL; HQ206351; ADP92299.1; -; Genomic_DNA. DR EMBL; HQ206352; ADP92300.1; -; Genomic_DNA. DR EMBL; HQ206353; ADP92301.1; -; Genomic_DNA. DR EMBL; HQ206354; ADP92302.1; -; Genomic_DNA. DR EMBL; HQ206355; ADP92303.1; -; Genomic_DNA. DR EMBL; HQ206356; ADP92304.1; -; Genomic_DNA. DR EMBL; HQ206357; ADP92305.1; -; Genomic_DNA. DR EMBL; HQ206358; ADP92306.1; -; Genomic_DNA. DR EMBL; HQ206359; ADP92307.1; -; Genomic_DNA. DR EMBL; HQ206360; ADP92308.1; -; Genomic_DNA. DR EMBL; HQ206361; ADP92309.1; -; Genomic_DNA. DR EMBL; HQ206362; ADP92310.1; -; Genomic_DNA. DR EMBL; HQ206363; ADP92311.1; -; Genomic_DNA. DR EMBL; HQ206364; ADP92312.1; -; Genomic_DNA. DR EMBL; HQ206365; ADP92313.1; -; Genomic_DNA. DR EMBL; HQ206366; ADP92314.1; -; Genomic_DNA. DR EMBL; HQ206367; ADP92315.1; -; Genomic_DNA. DR EMBL; HQ206368; ADP92316.1; -; Genomic_DNA. DR EMBL; HQ206369; ADP92317.1; -; Genomic_DNA. DR EMBL; HQ206370; ADP92318.1; -; Genomic_DNA. DR EMBL; HQ206371; ADP92319.1; -; Genomic_DNA. DR EMBL; HQ206372; ADP92320.1; -; Genomic_DNA. DR EMBL; HQ206373; ADP92321.1; -; Genomic_DNA. DR EMBL; HQ206374; ADP92322.1; -; Genomic_DNA. DR EMBL; HQ206375; ADP92323.1; -; Genomic_DNA. DR EMBL; HQ206376; ADP92324.1; -; Genomic_DNA. DR EMBL; HQ206377; ADP92325.1; -; Genomic_DNA. DR EMBL; HQ206378; ADP92326.1; -; Genomic_DNA. DR EMBL; HQ206379; ADP92327.1; -; Genomic_DNA. DR EMBL; HQ206380; ADP92328.1; -; Genomic_DNA. DR EMBL; HQ206381; ADP92329.1; -; Genomic_DNA. DR EMBL; HQ206382; ADP92330.1; -; Genomic_DNA. DR EMBL; HQ206383; ADP92331.1; -; Genomic_DNA. DR EMBL; HQ206384; ADP92332.1; -; Genomic_DNA. DR EMBL; HQ206385; ADP92333.1; -; Genomic_DNA. DR EMBL; CH471056; EAX04655.1; -; Genomic_DNA. DR EMBL; CH471056; EAX04656.1; -; Genomic_DNA. DR EMBL; BC008664; AAH08664.1; -; mRNA. DR EMBL; BC061589; AAH61589.1; -; mRNA. DR EMBL; BC063643; AAH63643.1; -; mRNA. DR EMBL; J03593; AAA36751.1; -; mRNA. DR CCDS; CCDS34114.1; -. DR PIR; A44778; A44778. DR RefSeq; NP_001142.2; NM_001151.4. DR AlphaFoldDB; P12235; -. DR SMR; P12235; -. DR BioGRID; 106788; 352. DR DIP; DIP-33116N; -. DR FunCoup; P12235; 1978. DR IntAct; P12235; 125. DR MINT; P12235; -. DR STRING; 9606.ENSP00000281456; -. DR DrugBank; DB01736; [3-(Dodecanoylamino)Propyl](Hydroxy)Dimethylammonium. DR DrugBank; DB00171; ATP. DR DrugBank; DB02426; Carboxyatractyloside. DR DrugBank; DB00720; Clodronic acid. DR DrugBank; DB04178; Di-Stearoyl-3-Sn-Phosphatidylcholine. DR DrugBank; DB01077; Etidronic acid. DR DrugBank; DB03429; Tetrastearoyl cardiolipin. DR DrugCentral; P12235; -. DR MoonProt; P12235; -. DR TCDB; 2.A.29.1.2; the mitochondrial carrier (mc) family. DR GlyGen; P12235; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P12235; -. DR MetOSite; P12235; -. DR PhosphoSitePlus; P12235; -. DR SwissPalm; P12235; -. DR BioMuta; SLC25A4; -. DR DMDM; 113455; -. DR jPOST; P12235; -. DR MassIVE; P12235; -. DR PaxDb; 9606-ENSP00000281456; -. DR PeptideAtlas; P12235; -. DR ProteomicsDB; 52836; -. DR Pumba; P12235; -. DR TopDownProteomics; P12235; -. DR Antibodypedia; 28911; 156 antibodies from 24 providers. DR DNASU; 291; -. DR Ensembl; ENST00000281456.11; ENSP00000281456.5; ENSG00000151729.12. DR GeneID; 291; -. DR KEGG; hsa:291; -. DR MANE-Select; ENST00000281456.11; ENSP00000281456.5; NM_001151.4; NP_001142.2. DR UCSC; uc003ixd.4; human. DR AGR; HGNC:10990; -. DR ClinPGx; PA35866; -. DR CTD; 291; -. DR DisGeNET; 291; -. DR GeneCards; SLC25A4; -. DR HGNC; HGNC:10990; SLC25A4. DR HPA; ENSG00000151729; Group enriched (heart muscle, skeletal muscle, tongue). DR MalaCards; SLC25A4; -. DR MIM; 103220; gene. DR MIM; 609283; phenotype. DR MIM; 615418; phenotype. DR MIM; 617184; phenotype. DR OpenTargets; ENSG00000151729; -. DR Orphanet; 254892; Autosomal dominant progressive external ophthalmoplegia. DR Orphanet; 1369; Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome. DR VEuPathDB; HostDB:ENSG00000151729; -. DR eggNOG; KOG0749; Eukaryota. DR GeneTree; ENSGT00940000154622; -. DR InParanoid; P12235; -. DR OMA; HPAMYQR; -. DR OrthoDB; 270584at2759; -. DR PAN-GO; P12235; 4 GO annotations based on evolutionary models. DR PhylomeDB; P12235; -. DR PathwayCommons; P12235; -. DR Reactome; R-HSA-1268020; Mitochondrial protein import. DR Reactome; R-HSA-166187; Mitochondrial Uncoupling. DR Reactome; R-HSA-180897; Vpr-mediated induction of apoptosis by mitochondrial outer membrane permeabilization. DR Reactome; R-HSA-83936; Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane. DR SignaLink; P12235; -. DR SIGNOR; P12235; -. DR Agora; ENSG00000151729; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 291; 14 hits in 1168 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; SLC25A4; human. DR GeneWiki; SLC25A4; -. DR GenomeRNAi; 291; -. DR Pharos; P12235; Tbio. DR PRO; PR:P12235; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P12235; protein. DR Bgee; ENSG00000151729; Expressed in left ventricle myocardium and 209 other cell types or tissues. DR ExpressionAtlas; P12235; baseline and differential. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB. DR GO; GO:0005757; C:mitochondrial permeability transition pore complex; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc. DR GO; GO:0015207; F:adenine transmembrane transporter activity; TAS:ProtInc. DR GO; GO:0005471; F:ATP:ADP antiporter activity; IDA:UniProtKB. DR GO; GO:0017077; F:oxidative phosphorylation uncoupler activity; ISS:UniProtKB. DR GO; GO:0015078; F:proton transmembrane transporter activity; TAS:Reactome. DR GO; GO:1990845; P:adaptive thermogenesis; ISS:UniProtKB. DR GO; GO:0015866; P:ADP transport; IMP:UniProtKB. DR GO; GO:0008637; P:apoptotic mitochondrial changes; IEA:Ensembl. DR GO; GO:0006091; P:generation of precursor metabolites and energy; TAS:ProtInc. DR GO; GO:0140021; P:mitochondrial ADP transmembrane transport; IDA:UniProtKB. DR GO; GO:1990544; P:mitochondrial ATP transmembrane transport; IDA:UniProtKB. DR GO; GO:1901029; P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; IBA:GO_Central. DR GO; GO:0060546; P:negative regulation of necroptotic process; IMP:BHF-UCL. DR GO; GO:1901526; P:positive regulation of mitophagy; ISS:UniProtKB. DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISS:UniProtKB. DR FunFam; 1.50.40.10:FF:000002; Putative ADP/ATP translocase 2-like; 1. DR Gene3D; 1.50.40.10; Mitochondrial carrier domain; 1. DR InterPro; IPR002113; ADT_euk_type. DR InterPro; IPR002067; MCP. DR InterPro; IPR023395; MCP_dom_sf. DR InterPro; IPR018108; MCP_transmembrane. DR PANTHER; PTHR45635; ADP,ATP CARRIER PROTEIN 1-RELATED-RELATED; 1. DR PANTHER; PTHR45635:SF32; ADP_ATP TRANSLOCASE 1; 1. DR Pfam; PF00153; Mito_carr; 3. DR PRINTS; PR00927; ADPTRNSLCASE. DR PRINTS; PR00926; MITOCARRIER. DR SUPFAM; SSF103506; Mitochondrial carrier; 1. DR PROSITE; PS50920; SOLCAR; 3. PE 1: Evidence at protein level; KW Acetylation; Antiport; ATP-binding; Cardiomyopathy; KW Direct protein sequencing; Disease variant; Host-virus interaction; KW Membrane; Methylation; Mitochondrion; Mitochondrion inner membrane; KW Nucleotide-binding; Phosphoprotein; Primary mitochondrial disease; KW Progressive external ophthalmoplegia; Proteomics identification; KW Reference proteome; Repeat; S-nitrosylation; Transmembrane; KW Transmembrane helix; Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.8" FT CHAIN 2..298 FT /note="ADP/ATP translocase 1" FT /id="PRO_0000090574" FT TOPO_DOM 2..7 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000305" FT TRANSMEM 8..37 FT /note="Helical; Name=1" FT /evidence="ECO:0000250|UniProtKB:P02722" FT TOPO_DOM 38..74 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000305" FT TRANSMEM 75..99 FT /note="Helical; Name=2" FT /evidence="ECO:0000250|UniProtKB:P02722" FT TOPO_DOM 100..109 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000305" FT TRANSMEM 110..130 FT /note="Helical; Name=3" FT /evidence="ECO:0000250|UniProtKB:P02722" FT TOPO_DOM 131..178 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000305" FT TRANSMEM 179..199 FT /note="Helical; Name=4" FT /evidence="ECO:0000250|UniProtKB:P02722" FT TOPO_DOM 200..210 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000305" FT TRANSMEM 211..231 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:P02722" FT TOPO_DOM 232..273 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000305" FT TRANSMEM 274..291 FT /note="Helical; Name=6" FT /evidence="ECO:0000250|UniProtKB:P02722" FT TOPO_DOM 292..298 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000305" FT REPEAT 6..98 FT /note="Solcar 1" FT REPEAT 111..201 FT /note="Solcar 2" FT REPEAT 212..297 FT /note="Solcar 3" FT REGION 235..240 FT /note="Important for transport activity" FT /evidence="ECO:0000269|PubMed:27693233" FT MOTIF 235..240 FT /note="Nucleotide carrier signature motif" FT /evidence="ECO:0000250|UniProtKB:P02722" FT BINDING 80 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P02722" FT BINDING 92 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P02722" FT BINDING 235 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000250|UniProtKB:P02722" FT MOD_RES 2 FT /note="N-acetylglycine" FT /evidence="ECO:0000269|Ref.8" FT MOD_RES 7 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q05962" FT MOD_RES 52 FT /note="N6,N6,N6-trimethyllysine" FT /evidence="ECO:0000250|UniProtKB:Q05962" FT MOD_RES 147 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P48962" FT MOD_RES 160 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000250|UniProtKB:Q05962" FT MOD_RES 245 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P48962" FT MOD_RES 272 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P48962" FT VARIANT 33 FT /note="K -> Q (found in a patient with mild childhood-onset FT myopathy without evidence of other clinical features such FT as cardiomyopathy, encephalopathy or ophthalmoplegia; FT likely pathogenic; abolishes ADP transport)" FT /evidence="ECO:0000269|PubMed:30046662" FT /id="VAR_090742" FT VARIANT 80 FT /note="R -> H (in MTDPS12A; decreased function in ADP FT transport; dbSNP:rs886041081)" FT /evidence="ECO:0000269|PubMed:27693233" FT /id="VAR_078071" FT VARIANT 90 FT /note="A -> D (in PEOA2; decreased function in ADP FT transport)" FT /evidence="ECO:0000269|PubMed:15792871, FT ECO:0000269|PubMed:27693233" FT /id="VAR_038814" FT VARIANT 98 FT /note="L -> P (in PEOA2; decreased function in ADP FT transport; dbSNP:rs104893876)" FT /evidence="ECO:0000269|PubMed:11756613, FT ECO:0000269|PubMed:18575922, ECO:0000269|PubMed:27693233" FT /id="VAR_022459" FT VARIANT 104 FT /note="D -> G (in PEOA2; decreased function in ADP FT transport; dbSNP:rs28999114)" FT /evidence="ECO:0000269|PubMed:12112115, FT ECO:0000269|PubMed:27693233" FT /id="VAR_022460" FT VARIANT 114 FT /note="A -> P (in PEOA2; decreased function in ADP FT transport; inverted direction of ADP:ATP transport, with FT ATP entering the mitochondrial matrix; dbSNP:rs104893873)" FT /evidence="ECO:0000269|PubMed:10926541, FT ECO:0000269|PubMed:18575922, ECO:0000269|PubMed:21586654, FT ECO:0000269|PubMed:27693233" FT /id="VAR_012111" FT VARIANT 123 FT /note="A -> D (in MTDPS12B; loss of function in ADP FT transport; dbSNP:rs121912683)" FT /evidence="ECO:0000269|PubMed:16155110, FT ECO:0000269|PubMed:27693233" FT /id="VAR_038815" FT VARIANT 235 FT /note="R -> G (in MTDPS12A; severely decreased function in FT ADP transport; dbSNP:rs886041082)" FT /evidence="ECO:0000269|PubMed:27693233" FT /id="VAR_078072" FT VARIANT 236 FT /note="R -> P (in MTDPS12B; loss of function in ADP FT transport; dbSNP:rs770816416)" FT /evidence="ECO:0000269|PubMed:25732997, FT ECO:0000269|PubMed:27693233" FT /id="VAR_078073" FT VARIANT 289 FT /note="V -> M (in PEOA2; inverted direction of ADP:ATP FT transport, with ATP entering the mitochondrial matrix; FT dbSNP:rs104893874)" FT /evidence="ECO:0000269|PubMed:10926541, FT ECO:0000269|PubMed:12707443, ECO:0000269|PubMed:21586654" FT /id="VAR_012112" FT CONFLICT 16 FT /note="G -> A (in Ref. 1; AAA61223)" FT /evidence="ECO:0000305" FT CONFLICT 147..149 FT /note="KGA -> RR (in Ref. 1; AAA61223)" FT /evidence="ECO:0000305" FT CONFLICT 227 FT /note="V -> L (in Ref. 1; AAA61223)" FT /evidence="ECO:0000305" SQ SEQUENCE 298 AA; 33064 MW; 59F0DFAEC4E7CFBB CRC64; MGDHAWSFLK DFLAGGVAAA VSKTAVAPIE RVKLLLQVQH ASKQISAEKQ YKGIIDCVVR IPKEQGFLSF WRGNLANVIR YFPTQALNFA FKDKYKQLFL GGVDRHKQFW RYFAGNLASG GAAGATSLCF VYPLDFARTR LAADVGKGAA QREFHGLGDC IIKIFKSDGL RGLYQGFNVS VQGIIIYRAA YFGVYDTAKG MLPDPKNVHI FVSWMIAQSV TAVAGLVSYP FDTVRRRMMM QSGRKGADIM YTGTVDCWRK IAKDEGAKAF FKGAWSNVLR GMGGAFVLVL YDEIKKYV // ID CIA30_HUMAN Reviewed; 327 AA. AC Q9Y375; Q9BVZ5; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 20-JUN-2002, sequence version 2. DT 28-JAN-2026, entry version 189. DE RecName: Full=Complex I intermediate-associated protein 30, mitochondrial {ECO:0000305}; DE AltName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 1; DE Flags: Precursor; GN Name=NDUFAF1 {ECO:0000312|HGNC:HGNC:18828}; Synonyms=CIA30; GN ORFNames=CGI-65; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=10810093; DOI=10.1101/gr.10.5.703; RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.; RT "Identification of novel human genes evolutionarily conserved in RT Caenorhabditis elegans by comparative proteomics."; RL Genome Res. 10:703-713(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS HIS-9; LEU-31; RP LYS-176 AND GLY-314. RX PubMed=11935339; DOI=10.1007/s00439-001-0673-3; RA Janssen R., Smeitink J., Smeets R., van den Heuvel L.; RT "CIA30 complex I assembly factor: a candidate for human complex I RT deficiency?"; RL Hum. Genet. 110:264-270(2002). RN [4] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=16218961; DOI=10.1111/j.1742-4658.2005.04928.x; RA Vogel R.O., Janssen R.J., Ugalde C., Grovenstein M., Huijbens R.J., RA Visch H.J., van den Heuvel L.P., Willems P.H., Zeviani M., Smeitink J.A., RA Nijtmans L.G.; RT "Human mitochondrial complex I assembly is mediated by NDUFAF1."; RL FEBS J. 272:5317-5326(2005). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INVOLVEMENT IN MC1DN11, AND RP VARIANTS MC1DN11 PRO-207; 252-VAL-LYS-253 DEL AND ARG-253. RX PubMed=17557076; DOI=10.1038/sj.emboj.7601748; RA Dunning C.J., McKenzie M., Sugiana C., Lazarou M., Silke J., Connelly A., RA Fletcher J.M., Kirby D.M., Thorburn D.R., Ryan M.T.; RT "Human CIA30 is involved in the early assembly of mitochondrial complex I RT and mutations in its gene cause disease."; RL EMBO J. 26:3227-3237(2007). RN [6] RP INTERACTION WITH ECSIT. RX PubMed=17344420; DOI=10.1101/gad.408407; RA Vogel R.O., Janssen R.J.R.J., van den Brand M.A.M., Dieteren C.E.J., RA Verkaart S., Koopman W.J.H., Willems P.H.G.M., Pluk W., RA van den Heuvel L.P.W.J., Smeitink J.A.M., Nijtmans L.G.J.; RT "Cytosolic signaling protein Ecsit also localizes to mitochondria where it RT interacts with chaperone NDUFAF1 and functions in complex I assembly."; RL Genes Dev. 21:615-624(2007). RN [7] RP INTERACTION WITH ACAD9. RX PubMed=20816094; DOI=10.1016/j.cmet.2010.08.002; RA Nouws J., Nijtmans L., Houten S.M., van den Brand M., Huynen M., RA Venselaar H., Hoefs S., Gloerich J., Kronick J., Hutchin T., Willems P., RA Rodenburg R., Wanders R., van den Heuvel L., Smeitink J., Vogel R.O.; RT "Acyl-CoA dehydrogenase 9 is required for the biogenesis of oxidative RT phosphorylation complex I."; RL Cell Metab. 12:283-294(2010). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP INVOLVEMENT IN MC1DN11, AND VARIANTS MC1DN11 CYS-211 AND ARG-245. RX PubMed=21931170; DOI=10.1136/jmedgenet-2011-100340; RA Fassone E., Taanman J.W., Hargreaves I.P., Sebire N.J., Cleary M.A., RA Burch M., Rahman S.; RT "Mutations in the mitochondrial complex I assembly factor NDUFAF1 cause RT fatal infantile hypertrophic cardiomyopathy."; RL J. Med. Genet. 48:691-697(2011). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-318, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [12] RP IDENTIFICATION IN THE MCIA COMPLEX, AND FUNCTION. RX PubMed=32320651; DOI=10.1016/j.celrep.2020.107541; RA Formosa L.E., Muellner-Wong L., Reljic B., Sharpe A.J., Jackson T.D., RA Beilharz T.H., Stojanovski D., Lazarou M., Stroud D.A., Ryan M.T.; RT "Dissecting the Roles of Mitochondrial Complex I Intermediate Assembly RT Complex Factors in the Biogenesis of Complex I."; RL Cell Rep. 31:107541-107541(2020). RN [13] RP INTERACTION WITH TMEM70 AND TMEM242. RX PubMed=33753518; DOI=10.1073/pnas.2100558118; RA Carroll J., He J., Ding S., Fearnley I.M., Walker J.E.; RT "TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase RT and interact with assembly factors for complex I."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). CC -!- FUNCTION: As part of the MCIA complex, involved in the assembly of the CC mitochondrial complex I. {ECO:0000269|PubMed:16218961, CC ECO:0000269|PubMed:17557076, ECO:0000269|PubMed:32320651}. CC -!- SUBUNIT: Part of the mitochondrial complex I assembly/MCIA complex that CC comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 CC and complement subunits such as COA1 and TMEM186 (PubMed:32320651). CC Interacts with ECSIT (PubMed:17344420). Interacts with ACAD9 CC (PubMed:20816094). At early stages of complex I assembly, it is found CC in intermediate subcomplexes that contain different subunits including CC NDUFB6, NDUFA6, NDUFA9, NDUFS3, NDUFS7, ND1, ND2 and ND3 CC (PubMed:17557076). Interacts with TMEM70 and TMEM242 (PubMed:33753518). CC {ECO:0000269|PubMed:17344420, ECO:0000269|PubMed:17557076, CC ECO:0000269|PubMed:20816094, ECO:0000269|PubMed:32320651, CC ECO:0000269|PubMed:33753518}. CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16218961, CC ECO:0000269|PubMed:17557076}. Mitochondrion matrix CC {ECO:0000305|PubMed:17557076}. Note=Peripherally associated with the CC matrix face of the mitochondrial inner membrane. CC {ECO:0000305|PubMed:17557076}. CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:11935339}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 11 (MC1DN11) CC [MIM:618234]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN11 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:17557076, CC ECO:0000269|PubMed:21931170}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the CIA30 family. {ECO:0000305}. CC -!- CAUTION: There is a putative pseudogene of CIA30 on chromosome 19 CC (19p12). {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF151823; AAD34060.1; -; mRNA. DR EMBL; BC000780; AAH00780.1; -; mRNA. DR CCDS; CCDS10075.1; -. DR RefSeq; NP_001424415.1; NM_001437486.1. DR RefSeq; NP_001424416.1; NM_001437487.1. DR RefSeq; NP_057097.2; NM_016013.3. DR RefSeq; XP_047288593.1; XM_047432637.1. DR RefSeq; XP_054234114.1; XM_054378139.1. DR AlphaFoldDB; Q9Y375; -. DR SASBDB; Q9Y375; -. DR SMR; Q9Y375; -. DR BioGRID; 119292; 185. DR ComplexPortal; CPX-6322; Mitochondrial complex I intermediate assembly (MCIA) complex. DR CORUM; Q9Y375; -. DR FunCoup; Q9Y375; 1003. DR MINT; Q9Y375; -. DR STRING; 9606.ENSP00000260361; -. DR BindingDB; Q9Y375; -. DR ChEMBL; CHEMBL2363065; -. DR DrugCentral; Q9Y375; -. DR iPTMnet; Q9Y375; -. DR PhosphoSitePlus; Q9Y375; -. DR BioMuta; NDUFAF1; -. DR DMDM; 21542405; -. DR jPOST; Q9Y375; -. DR MassIVE; Q9Y375; -. DR PaxDb; 9606-ENSP00000260361; -. DR PeptideAtlas; Q9Y375; -. DR ProteomicsDB; 85980; -. DR Pumba; Q9Y375; -. DR Antibodypedia; 23296; 168 antibodies from 29 providers. DR DNASU; 51103; -. DR Ensembl; ENST00000260361.9; ENSP00000260361.4; ENSG00000137806.11. DR Ensembl; ENST00000560978.2; ENSP00000453944.2; ENSG00000137806.11. DR GeneID; 51103; -. DR KEGG; hsa:51103; -. DR MANE-Select; ENST00000260361.9; ENSP00000260361.4; NM_016013.4; NP_057097.2. DR UCSC; uc001znx.4; human. DR AGR; HGNC:18828; -. DR ClinPGx; PA134934729; -. DR CTD; 51103; -. DR DisGeNET; 51103; -. DR GeneCards; NDUFAF1; -. DR HGNC; HGNC:18828; NDUFAF1. DR HPA; ENSG00000137806; Low tissue specificity. DR MalaCards; NDUFAF1; -. DR MIM; 606934; gene. DR MIM; 618234; phenotype. DR OpenTargets; ENSG00000137806; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000137806; -. DR eggNOG; KOG2435; Eukaryota. DR GeneTree; ENSGT00390000007200; -. DR HOGENOM; CLU_059028_2_0_1; -. DR InParanoid; Q9Y375; -. DR OMA; KRTGYAN; -. DR OrthoDB; 42561at2759; -. DR PAN-GO; Q9Y375; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q9Y375; -. DR PathwayCommons; Q9Y375; -. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q9Y375; -. DR Agora; ENSG00000137806; -. DR BioGRID-ORCS; 51103; 219 hits in 1175 CRISPR screens. DR ChiTaRS; NDUFAF1; human. DR GeneWiki; NDUFAF1; -. DR GenomeRNAi; 51103; -. DR Pharos; Q9Y375; Tclin. DR PRO; PR:Q9Y375; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q9Y375; protein. DR Bgee; ENSG00000137806; Expressed in apex of heart and 197 other cell types or tissues. DR ExpressionAtlas; Q9Y375; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central. DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IDA:UniProtKB. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IBA:GO_Central. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR GO; GO:0065003; P:protein-containing complex assembly; NAS:UniProtKB. DR Gene3D; 2.60.120.430; Galactose-binding lectin; 1. DR InterPro; IPR008979; Galactose-bd-like_sf. DR InterPro; IPR013857; NADH-UbQ_OxRdtase-assoc_prot30. DR InterPro; IPR039131; NDUFAF1. DR PANTHER; PTHR13194; COMPLEX I INTERMEDIATE-ASSOCIATED PROTEIN 30; 1. DR PANTHER; PTHR13194:SF23; COMPLEX I INTERMEDIATE-ASSOCIATED PROTEIN 30, MITOCHONDRIAL; 1. DR Pfam; PF08547; CIA30; 1. DR SUPFAM; SSF49785; Galactose-binding domain-like; 1. PE 1: Evidence at protein level; KW Chaperone; Disease variant; Mitochondrion; Phosphoprotein; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Transit peptide. FT TRANSIT 1..24 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 25..327 FT /note="Complex I intermediate-associated protein 30, FT mitochondrial" FT /id="PRO_0000005464" FT REGION 42..63 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 53..63 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 318 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VARIANT 9 FT /note="R -> H (in dbSNP:rs1899)" FT /evidence="ECO:0000269|PubMed:11935339" FT /id="VAR_013559" FT VARIANT 31 FT /note="R -> L (in dbSNP:rs3204853)" FT /evidence="ECO:0000269|PubMed:11935339" FT /id="VAR_013560" FT VARIANT 176 FT /note="E -> K (in dbSNP:rs35227875)" FT /evidence="ECO:0000269|PubMed:11935339" FT /id="VAR_013561" FT VARIANT 207 FT /note="T -> P (in MC1DN11; dbSNP:rs387906956)" FT /evidence="ECO:0000269|PubMed:17557076" FT /id="VAR_081445" FT VARIANT 211 FT /note="R -> C (in MC1DN11; dbSNP:rs387906958)" FT /evidence="ECO:0000269|PubMed:21931170" FT /id="VAR_081446" FT VARIANT 245 FT /note="G -> R (in MC1DN11; dbSNP:rs376344575)" FT /evidence="ECO:0000269|PubMed:21931170" FT /id="VAR_081447" FT VARIANT 252..253 FT /note="Missing (in MC1DN11; due to a nucleotide FT substitution located in the splice site consensus sequence FT at the end of exon 3; patient cells contain transcripts FT lacking the final 6 base pairs of exon 3 but also contain FT normally spliced transcripts corresponding to protein FT variant R-253)" FT /evidence="ECO:0000269|PubMed:17557076" FT /id="VAR_081448" FT VARIANT 253 FT /note="K -> R (in MC1DN11; due to a nucleotide substitution FT located in the splice site consensus sequence at the end of FT exon 3; patient cells contain normally spliced transcripts FT corresponding to protein variant R-253 but also transcripts FT lacking the final 6 base pairs of exon 3 and corresponding FT to protein variant 252-VK-253 del; dbSNP:rs387906957)" FT /evidence="ECO:0000269|PubMed:17557076" FT /id="VAR_081449" FT VARIANT 314 FT /note="A -> G (in dbSNP:rs12900702)" FT /evidence="ECO:0000269|PubMed:11935339" FT /id="VAR_013562" FT CONFLICT 178 FT /note="T -> S (in Ref. 1; AAD34060)" FT /evidence="ECO:0000305" FT CONFLICT 195 FT /note="E -> K (in Ref. 1; AAD34060)" FT /evidence="ECO:0000305" SQ SEQUENCE 327 AA; 37764 MW; 13D76605CC50DFF7 CRC64; MALVHKLLRG TYFLRKFSKP TSALYPFLGI RFAEYSSSLQ KPVASPGKAS SQRKTEGDLQ GDHQKEVALD ITSSEEKPDV SFDKAIRDEA IYHFRLLKDE IVDHWRGPEG HPLHEVLLEQ AKVVWQFRGK EDLDKWTVTS DKTIGGRSEV FLKMGKNNQS ALLYGTLSSE APQDGESTRS GYCAMISRIP RGAFERKMSY DWSQFNTLYL RVRGDGRPWM VNIKEDTDFF QRTNQMYSYF MFTRGGPYWQ EVKIPFSKFF FSNRGRIRDV QHELPLDKIS SIGFTLADKV DGPFFLEIDF IGVFTDPAHT EEFAYENSPE LNPRLFK // ID COQ2_HUMAN Reviewed; 371 AA. AC Q96H96; A0A1D8H0A6; O95331; Q1JQ78; Q684R2; DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot. DT 12-OCT-2022, sequence version 2. DT 28-JAN-2026, entry version 174. DE RecName: Full=4-hydroxybenzoate polyprenyltransferase, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03189}; DE Short=4-HB polyprenyltransferase {ECO:0000255|HAMAP-Rule:MF_03189}; DE EC=2.5.1.39 {ECO:0000269|PubMed:15153069, ECO:0000269|PubMed:16400613, ECO:0000269|PubMed:17374725}; DE AltName: Full=4-hydroxybenzoate decaprenyltransferase {ECO:0000303|PubMed:15153069}; DE AltName: Full=COQ2 homolog; DE Short=hCOQ2 {ECO:0000303|PubMed:15153069}; DE AltName: Full=Para-hydroxybenzoate--polyprenyltransferase {ECO:0000303|PubMed:16400613}; DE Short=PHB:PPT {ECO:0000255|HAMAP-Rule:MF_03189}; DE Short=PHB:polyprenyltransferase {ECO:0000255|HAMAP-Rule:MF_03189}; DE Flags: Precursor; GN Name=COQ2 {ECO:0000255|HAMAP-Rule:MF_03189, ECO:0000303|PubMed:15153069}; GN Synonyms=CL640; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, CATALYTIC ACTIVITY, RP TISSUE SPECIFICITY, PATHWAY, AND VARIANT LEU-16. RC TISSUE=Liver, and Muscle; RX PubMed=15153069; DOI=10.1042/bj20040261; RA Forsgren M., Attersand A., Lake S., Gruenler J., Swiezewska E., Dallner G., RA Climent I.; RT "Isolation and functional expression of human COQ2, a gene encoding a RT polyprenyl transferase involved in the synthesis of CoQ2."; RL Biochem. J. 382:519-526(2004). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORMS 4; 5 RP AND 6), FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, CHARACTERIZATION OF RP VARIANTS COQ10D1 VAL-78; ASN-96; ARG-132; HIS-147; SER-178; CYS-247 AND RP VAL-252, AND CATALYTIC ACTIVITY. RX PubMed=27493029; DOI=10.1093/hmg/ddw257; RA Desbats M.A., Morbidoni V., Silic-Benussi M., Doimo M., Ciminale V., RA Cassina M., Sacconi S., Hirano M., Basso G., Pierrel F., Navas P., RA Salviati L., Trevisson E.; RT "The COQ2 genotype predicts the severity of coenzyme Q10 deficiency."; RL Hum. Mol. Genet. 25:4256-4265(2016). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-16. RC TISSUE=Lung, Melanoma, and Pancreatic carcinoma; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 104-334 (ISOFORM 3). RA Barrow I.K.-P., Boguski M.S., Touchman J.W., Spencer F.; RT "Full-insert sequence of mapped XREF EST."; RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 198-371 (ISOFORM 3). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP CHARACTERIZATION OF VARIANTS COQ10D1 CYS-247, FUNCTION, CATALYTIC ACTIVITY, RP AND PATHWAY. RX PubMed=17374725; DOI=10.1093/hmg/ddm058; RA Lopez-Martin J.M., Salviati L., Trevisson E., Montini G., DiMauro S., RA Quinzii C., Hirano M., Rodriguez-Hernandez A., Cordero M.D., RA Sanchez-Alcazar J.A., Santos-Ocana C., Navas P.; RT "Missense mutation of the COQ2 gene causes defects of bioenergetics and de RT novo pyrimidine synthesis."; RL Hum. Mol. Genet. 16:1091-1097(2007). RN [8] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=20526342; DOI=10.1038/nchembio.372; RA Forsman U., Sjoeberg M., Turunen M., Sindelar P.J.; RT "4-Nitrobenzoate inhibits coenzyme Q biosynthesis in mammalian cell RT cultures."; RL Nat. Chem. Biol. 6:515-517(2010). RN [9] RP VARIANT COQ10D1 CYS-247, CHARACTERIZATION OF VARIANT COQ10D1 CYS-247, RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=16400613; DOI=10.1086/500092; RA Quinzii C., Naini A., Salviati L., Trevisson E., Navas P., Dimauro S., RA Hirano M.; RT "A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes RT primary coenzyme Q10 deficiency."; RL Am. J. Hum. Genet. 78:345-349(2006). RN [10] RP VARIANTS COQ10D1 ASN-96; HIS-147; SER-178 AND CYS-247. RX PubMed=17855635; DOI=10.1681/asn.2006080833; RA Diomedi-Camassei F., Di Giandomenico S., Santorelli F.M., Caridi G., RA Piemonte F., Montini G., Ghiggeri G.M., Murer L., Barisoni L., Pastore A., RA Muda A.O., Valente M.L., Bertini E., Emma F.; RT "COQ2 nephropathy: a newly described inherited mitochondriopathy with RT primary renal involvement."; RL J. Am. Soc. Nephrol. 18:2773-2780(2007). RN [11] RP VARIANT COQ10D1 VAL-252. RX PubMed=23343605; DOI=10.1016/j.jns.2013.01.004; RA Jakobs B.S., van den Heuvel L.P., Smeets R.J., de Vries M.C., Hien S., RA Schaible T., Smeitink J.A., Wevers R.A., Wortmann S.B., Rodenburg R.J.; RT "A novel mutation in COQ2 leading to fatal infantile multisystem disease."; RL J. Neurol. Sci. 326:24-28(2013). RN [12] RP VARIANTS MSA1 LEU-29; HIS-49; THR-57; VAL-78; THR-97; SER-107; PHE-113; RP ALA-267; CYS-297; GLN-337 AND ALA-343, AND VARIANTS LEU-16; LEU-22; HIS-69 RP AND HIS-336. RX PubMed=23758206; DOI=10.1056/nejmoa1212115; RG Multiple-System Atrophy Research Collaboration; RT "Mutations in COQ2 in familial and sporadic multiple-system atrophy."; RL N. Engl. J. Med. 369:233-244(2013). RN [13] RP VARIANT COQ10D1 ARG-132. RX PubMed=25564041; DOI=10.1038/ejhg.2014.277; RA Desbats M.A., Vetro A., Limongelli I., Lunardi G., Casarin A., Doimo M., RA Spinazzi M., Angelini C., Cenacchi G., Burlina A., RA Rodriguez Hernandez M.A., Chiandetti L., Clementi M., Trevisson E., RA Navas P., Zuffardi O., Salviati L.; RT "Primary coenzyme Q10 deficiency presenting as fatal neonatal multiorgan RT failure."; RL Eur. J. Hum. Genet. 23:1254-1258(2015). RN [14] RP VARIANT COQ10D1 ALA-340. RX PubMed=28044327; DOI=10.1111/cge.12960; RA Gigante M., Diella S., Santangelo L., Trevisson E., Acosta M.J., RA Amatruda M., Finzi G., Caridi G., Murer L., Accetturo M., Ranieri E., RA Ghiggeri G.M., Giordano M., Grandaliano G., Salviati L., Gesualdo L.; RT "Further phenotypic heterogeneity of CoQ10 deficiency associated with RT steroid resistant nephrotic syndrome and novel COQ2 and COQ6 variants."; RL Clin. Genet. 92:224-226(2017). RN [15] RP VARIANT COQ10D1 SER-53. RX PubMed=33215859; DOI=10.1002/ajmg.a.61983; RA Hashemi S.S., Zare-Abdollahi D., Bakhshandeh M.K., Vafaee A., RA Abolhasani S., Inanloo Rahatloo K., DanaeeFard F., Farboodi N., Rohani M., RA Alavi A.; RT "Clinical spectrum in multiple families with primary COQ10 deficiency."; RL Am. J. Med. Genet. A 185:440-452(2021). CC -!- FUNCTION: Mediates the second step in the final reaction sequence of CC coenzyme Q (CoQ) biosynthesis (PubMed:15153069, PubMed:16400613, CC PubMed:17374725, PubMed:20526342). Catalyzes the prenylation of para- CC hydroxybenzoate (PHB) with an all-trans polyprenyl donor (such as all- CC trans-decaprenyl diphosphate) (PubMed:15153069, PubMed:16400613, CC PubMed:17374725, PubMed:20526342). The length of the polyprenyl side CC chain varies depending on the species, in humans, the side chain is CC comprised of 10 isoprenyls (decaprenyl) producing CoQ10 (also known as CC ubiquinone), whereas rodents predominantly generate CoQ9 CC (PubMed:15153069, PubMed:16400613). However, this specificity is not CC complete, human tissues have low amounts of CoQ9 and rodent organs CC contain some CoQ10 (PubMed:15153069). Plays a central role in the CC biosynthesis of CoQ10 (PubMed:15153069, PubMed:16400613, CC PubMed:17374725). CoQ10 is a vital molecule that transports electrons CC from mitochondrial respiratory chain complexes (PubMed:16400613, CC PubMed:17374725, PubMed:27493029). CoQs also function as cofactors for CC uncoupling protein and play a role as regulators of the CC extracellularly-induced ceramide-dependent apoptotic pathway CC (PubMed:16400613, PubMed:17374725). Regulates mitochondrial CC permeability transition pore (mPTP) opening and ROS production (pivotal CC events in cell death) in a tissue specific manner (By similarity). CC {ECO:0000250|UniProtKB:Q499N4, ECO:0000269|PubMed:15153069, CC ECO:0000269|PubMed:16400613, ECO:0000269|PubMed:17374725, CC ECO:0000269|PubMed:20526342, ECO:0000269|PubMed:27493029, CC ECO:0000303|PubMed:15153069, ECO:0000303|PubMed:16400613, CC ECO:0000303|PubMed:17374725}. CC -!- CATALYTIC ACTIVITY: CC Reaction=an all-trans-polyprenyl diphosphate + 4-hydroxybenzoate = a 4- CC hydroxy-3-(all-trans-polyprenyl)benzoate + diphosphate; CC Xref=Rhea:RHEA:44504, Rhea:RHEA-COMP:9514, Rhea:RHEA-COMP:9564, CC ChEBI:CHEBI:17879, ChEBI:CHEBI:33019, ChEBI:CHEBI:58914, CC ChEBI:CHEBI:78396; EC=2.5.1.39; CC Evidence={ECO:0000269|PubMed:15153069, ECO:0000269|PubMed:16400613, CC ECO:0000269|PubMed:17374725, ECO:0000305|PubMed:20526342, CC ECO:0000305|PubMed:27493029}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44505; CC Evidence={ECO:0000269|PubMed:15153069, ECO:0000269|PubMed:16400613, CC ECO:0000269|PubMed:17374725, ECO:0000305|PubMed:20526342, CC ECO:0000305|PubMed:27493029}; CC -!- CATALYTIC ACTIVITY: CC Reaction=all-trans-decaprenyl diphosphate + 4-hydroxybenzoate = 4- CC hydroxy-3-(all-trans-decaprenyl)benzoate + diphosphate; CC Xref=Rhea:RHEA:44564, ChEBI:CHEBI:17879, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:60721, ChEBI:CHEBI:84503; EC=2.5.1.39; CC Evidence={ECO:0000269|PubMed:15153069, ECO:0000269|PubMed:16400613, CC ECO:0000269|PubMed:17374725, ECO:0000305|PubMed:20526342}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44565; CC Evidence={ECO:0000269|PubMed:15153069, ECO:0000269|PubMed:16400613, CC ECO:0000269|PubMed:17374725, ECO:0000305|PubMed:20526342}; CC -!- CATALYTIC ACTIVITY: CC Reaction=all-trans-nonaprenyl diphosphate + 4-hydroxybenzoate = 4- CC hydroxy-3-(all-trans-nonaprenyl)benzoate + diphosphate; CC Xref=Rhea:RHEA:17709, ChEBI:CHEBI:17879, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:58391, ChEBI:CHEBI:84502; EC=2.5.1.39; CC Evidence={ECO:0000269|PubMed:15153069}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17710; CC Evidence={ECO:0000269|PubMed:15153069}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03189}; CC -!- PATHWAY: Cofactor biosynthesis; ubiquinone biosynthesis. CC {ECO:0000269|PubMed:16400613, ECO:0000269|PubMed:17374725, CC ECO:0000305|PubMed:15153069}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000255|HAMAP- CC Rule:MF_03189, ECO:0000269|PubMed:27493029}; Multi-pass membrane CC protein {ECO:0000255|HAMAP-Rule:MF_03189}; Matrix side CC {ECO:0000255|HAMAP-Rule:MF_03189}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing, Alternative initiation; Named isoforms=5; CC Name=1; CC IsoId=Q96H96-1; Sequence=Displayed; CC Name=3; CC IsoId=Q96H96-3; Sequence=VSP_017677, VSP_017678; CC Name=4; CC IsoId=Q96H96-4; Sequence=VSP_061606; CC Name=5; CC IsoId=Q96H96-5; Sequence=VSP_061607; CC Name=6; CC IsoId=Q96H96-6; Sequence=VSP_061608; CC -!- TISSUE SPECIFICITY: Widely expressed. Present in all of the tissues CC tested. Expressed at higher level in skeletal muscle, adrenal glands CC and the heart. {ECO:0000269|PubMed:15153069}. CC -!- DISEASE: Coenzyme Q10 deficiency, primary, 1 (COQ10D1) [MIM:607426]: An CC autosomal recessive disorder with variable manifestations consistent CC with 5 major phenotypes. The phenotypes include an encephalomyopathic CC form with seizures and ataxia; a multisystem infantile form with CC encephalopathy, cardiomyopathy and renal failure; a predominantly CC cerebellar form with ataxia and cerebellar atrophy; Leigh syndrome with CC growth retardation; and an isolated myopathic form. CC {ECO:0000269|PubMed:16400613, ECO:0000269|PubMed:17374725, CC ECO:0000269|PubMed:17855635, ECO:0000269|PubMed:23343605, CC ECO:0000269|PubMed:25564041, ECO:0000269|PubMed:27493029, CC ECO:0000269|PubMed:28044327, ECO:0000269|PubMed:33215859}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Multiple system atrophy 1 (MSA1) [MIM:146500]: A progressive CC neurodegenerative disorder clinically characterized by parkinsonism, CC cerebellar ataxia, and autonomic, urogenital, and pyramidal dysfunction CC in various combinations. Pathologically, it is characterized by CC degeneration of striatonigral and olivopontocerebellar structures, and CC glial cytoplasmic inclusions that consist of abnormally phosphorylated CC alpha-synuclein or tau. {ECO:0000269|PubMed:23758206}. Note=Disease CC susceptibility is associated with variants affecting the gene CC represented in this entry. CC -!- MISCELLANEOUS: [Isoform 4]: Potential minor and functional isoform CC produced by alternative initiation. {ECO:0000305|PubMed:27493029}. CC -!- MISCELLANEOUS: [Isoform 5]: Potential minor and functional isoform CC produced by alternative initiation. {ECO:0000305|PubMed:27493029}. CC -!- MISCELLANEOUS: [Isoform 6]: Potential minor and functional isoform CC produced by alternative initiation. {ECO:0000305|PubMed:27493029}. CC -!- SIMILARITY: Belongs to the UbiA prenyltransferase family. CC {ECO:0000255|HAMAP-Rule:MF_03189}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC72955.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAH20728.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ621061; CAF18241.1; -; mRNA. DR EMBL; KU877220; AOT85942.1; -; mRNA. DR EMBL; AC114781; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC008804; AAH08804.1; -; mRNA. DR EMBL; BC020728; AAH20728.2; ALT_INIT; mRNA. DR EMBL; BC116454; AAI16455.1; -; mRNA. DR EMBL; AF091086; AAC72955.1; ALT_FRAME; mRNA. DR EMBL; CR456860; CAG33141.1; -; mRNA. DR CCDS; CCDS47090.2; -. [Q96H96-4] DR CCDS; CCDS87234.1; -. [Q96H96-1] DR RefSeq; NP_001345850.1; NM_001358921.2. [Q96H96-1] DR RefSeq; NP_056512.5; NM_015697.7. [Q96H96-4] DR AlphaFoldDB; Q96H96; -. DR SMR; Q96H96; -. DR BioGRID; 118083; 94. DR FunCoup; Q96H96; 529. DR IntAct; Q96H96; 90. DR STRING; 9606.ENSP00000310873; -. DR iPTMnet; Q96H96; -. DR PhosphoSitePlus; Q96H96; -. DR BioMuta; COQ2; -. DR DMDM; 74731901; -. DR jPOST; Q96H96; -. DR MassIVE; Q96H96; -. DR PaxDb; 9606-ENSP00000310873; -. DR PeptideAtlas; Q96H96; -. DR ProteomicsDB; 76713; -. [Q96H96-1] DR ProteomicsDB; 76714; -. [Q96H96-3] DR Antibodypedia; 25200; 57 antibodies from 18 providers. DR DNASU; 27235; -. DR Ensembl; ENST00000311461.7; ENSP00000311835.7; ENSG00000173085.15. [Q96H96-3] DR Ensembl; ENST00000311469.9; ENSP00000310873.4; ENSG00000173085.15. [Q96H96-4] DR Ensembl; ENST00000647002.2; ENSP00000495761.2; ENSG00000173085.15. [Q96H96-1] DR GeneID; 27235; -. DR KEGG; hsa:27235; -. DR MANE-Select; ENST00000647002.2; ENSP00000495761.2; NM_001358921.2; NP_001345850.1. DR UCSC; uc003hog.3; human. [Q96H96-1] DR AGR; HGNC:25223; -. DR ClinPGx; PA142672084; -. DR CTD; 27235; -. DR DisGeNET; 27235; -. DR GeneCards; COQ2; -. DR GeneReviews; COQ2; -. DR HGNC; HGNC:25223; COQ2. DR HPA; ENSG00000173085; Tissue enhanced (tongue). DR MalaCards; COQ2; -. DR MIM; 146500; phenotype. DR MIM; 607426; phenotype. DR MIM; 609825; gene. DR OpenTargets; ENSG00000173085; -. DR Orphanet; 227510; Multiple system atrophy, cerebellar type. DR Orphanet; 98933; Multiple system atrophy, parkinsonian type. DR VEuPathDB; HostDB:ENSG00000173085; -. DR eggNOG; KOG1381; Eukaryota. DR GeneTree; ENSGT00940000153771; -. DR InParanoid; Q96H96; -. DR OrthoDB; 18170at2759; -. DR PAN-GO; Q96H96; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q96H96; -. DR BioCyc; MetaCyc:ENSG00000173085-MONOMER; -. DR BRENDA; 2.5.1.39; 2681. DR PathwayCommons; Q96H96; -. DR Reactome; R-HSA-1268020; Mitochondrial protein import. DR Reactome; R-HSA-2142789; Ubiquinol biosynthesis. DR SignaLink; Q96H96; -. DR UniPathway; UPA00232; -. DR Agora; ENSG00000173085; -. DR BioGRID-ORCS; 27235; 309 hits in 1157 CRISPR screens. DR ChiTaRS; COQ2; human. DR GeneWiki; COQ2; -. DR GenomeRNAi; 27235; -. DR Pharos; Q96H96; Tbio. DR PRO; PR:Q96H96; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q96H96; protein. DR Bgee; ENSG00000173085; Expressed in skeletal muscle tissue of biceps brachii and 197 other cell types or tissues. DR ExpressionAtlas; Q96H96; baseline and differential. DR GO; GO:0031314; C:extrinsic component of mitochondrial inner membrane; IEA:Ensembl. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0008412; F:4-hydroxybenzoate polyprenyltransferase activity; IMP:UniProtKB. DR GO; GO:0004659; F:prenyltransferase activity; IGI:MGI. DR GO; GO:0006071; P:glycerol metabolic process; IGI:UniProtKB. DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:UniProtKB-UniRule. DR GO; GO:0006744; P:ubiquinone biosynthetic process; IDA:UniProtKB. DR CDD; cd13959; PT_UbiA_COQ2; 1. DR FunFam; 1.10.357.140:FF:000003; 4-hydroxybenzoate polyprenyltransferase, mitochondrial; 1. DR Gene3D; 1.10.357.140; UbiA prenyltransferase; 1. DR HAMAP; MF_01635; UbiA; 1. DR InterPro; IPR006370; HB_polyprenyltransferase-like. DR InterPro; IPR039653; Prenyltransferase. DR InterPro; IPR000537; UbiA_prenyltransferase. DR InterPro; IPR030470; UbiA_prenylTrfase_CS. DR InterPro; IPR044878; UbiA_sf. DR NCBIfam; TIGR01474; ubiA_proteo; 1. DR PANTHER; PTHR11048:SF28; 4-HYDROXYBENZOATE POLYPRENYLTRANSFERASE, MITOCHONDRIAL; 1. DR PANTHER; PTHR11048; PRENYLTRANSFERASES; 1. DR Pfam; PF01040; UbiA; 1. DR PROSITE; PS00943; UBIA; 1. PE 1: Evidence at protein level; KW Alternative initiation; Alternative splicing; Disease variant; KW Isoprene biosynthesis; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Neurodegeneration; Parkinsonism; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Transferase; Transit peptide; Transmembrane; KW Transmembrane helix; Ubiquinone biosynthesis. FT TRANSIT 1..34 FT /note="Mitochondrion" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03189" FT CHAIN 35..371 FT /note="4-hydroxybenzoate polyprenyltransferase, FT mitochondrial" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03189" FT /id="PRO_0000228623" FT TOPO_DOM 35..83 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000305|PubMed:27493029" FT TRANSMEM 84..104 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03189" FT TOPO_DOM 105..108 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000305|PubMed:27493029" FT TRANSMEM 109..129 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03189" FT TOPO_DOM 130..148 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000305|PubMed:27493029" FT TRANSMEM 149..169 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03189" FT TOPO_DOM 170..172 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000305|PubMed:27493029" FT TRANSMEM 173..193 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03189" FT TOPO_DOM 194..203 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000305|PubMed:27493029" FT TRANSMEM 204..224 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03189" FT TOPO_DOM 225..231 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000305|PubMed:27493029" FT TRANSMEM 232..252 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03189" FT TOPO_DOM 253..277 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000305|PubMed:27493029" FT TRANSMEM 278..298 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03189" FT TOPO_DOM 299..300 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000305|PubMed:27493029" FT TRANSMEM 301..321 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03189" FT TOPO_DOM 322..332 FT /note="Mitochondrial matrix" FT /evidence="ECO:0000305|PubMed:27493029" FT TRANSMEM 333..353 FT /note="Helical" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03189" FT TOPO_DOM 354..371 FT /note="Mitochondrial intermembrane" FT /evidence="ECO:0000269|PubMed:27493029" FT VAR_SEQ 1 FT /note="M -> MTPISQVRMRKGSAHTAAQPGRLGLHPAGATAHACRGMTSIRARPGL FT TSAM (in isoform 4)" FT /evidence="ECO:0000305|PubMed:27493029" FT /id="VSP_061606" FT VAR_SEQ 1 FT /note="M -> MRKGSAHTAAQPGRLGLHPAGATAHACRGMTSIRARPGLTSAM (in FT isoform 5)" FT /evidence="ECO:0000305|PubMed:27493029" FT /id="VSP_061607" FT VAR_SEQ 1 FT /note="M -> MTSIRARPGLTSAM (in isoform 6)" FT /evidence="ECO:0000305|PubMed:27493029" FT /id="VSP_061608" FT VAR_SEQ 318..334 FT /note="IYTLDIHRPEDCWNKFI -> KWGLEILPRLV (in isoform 3)" FT /evidence="ECO:0000303|Ref.5, ECO:0000303|Ref.6" FT /id="VSP_017677" FT VAR_SEQ 335..371 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.5, ECO:0000303|Ref.6" FT /id="VSP_017678" FT VARIANT 16 FT /note="V -> L (in dbSNP:rs6818847)" FT /evidence="ECO:0000269|PubMed:15153069, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:23758206" FT /id="VAR_070237" FT VARIANT 22 FT /note="P -> L (in dbSNP:rs765747895)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070238" FT VARIANT 29 FT /note="F -> L (in MSA1; associated with disease FT susceptibility; dbSNP:rs863223933)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070239" FT VARIANT 49 FT /note="P -> H (in MSA1; associated with disease FT susceptibility; dbSNP:rs936872920)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070240" FT VARIANT 53 FT /note="G -> S (in COQ10D1; uncertain significance)" FT /evidence="ECO:0000269|PubMed:33215859" FT /id="VAR_089039" FT VARIANT 57 FT /note="S -> T (in MSA1; associated with disease FT susceptibility; dbSNP:rs550949678)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070241" FT VARIANT 69 FT /note="R -> H (in dbSNP:rs762399579)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070242" FT VARIANT 78 FT /note="M -> V (in MSA1; associated with disease FT susceptibility; decreased ubiquinone biosynthesis; FT dbSNP:rs778094136)" FT /evidence="ECO:0000269|PubMed:23758206, FT ECO:0000269|PubMed:27493029" FT /id="VAR_070243" FT VARIANT 96 FT /note="S -> N (in COQ10D1; decreased ubiquinone FT biosynthesis; dbSNP:rs121918233)" FT /evidence="ECO:0000269|PubMed:17855635, FT ECO:0000269|PubMed:27493029" FT /id="VAR_068161" FT VARIANT 97 FT /note="I -> T (in MSA1; associated with disease FT susceptibility; dbSNP:rs944546272)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070244" FT VARIANT 107 FT /note="P -> S (in MSA1; associated with disease FT susceptibility; dbSNP:rs1462568548)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070245" FT VARIANT 113 FT /note="S -> F (in MSA1; associated with disease FT susceptibility; dbSNP:rs1735249512)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070246" FT VARIANT 132 FT /note="M -> R (in COQ10D1; decreased ubiquinone FT biosynthesis; dbSNP:rs1057519348)" FT /evidence="ECO:0000269|PubMed:25564041, FT ECO:0000269|PubMed:27493029" FT /id="VAR_076913" FT VARIANT 147 FT /note="R -> H (in COQ10D1; loss of ubiquinone biosynthesis; FT dbSNP:rs121918231)" FT /evidence="ECO:0000269|PubMed:17855635, FT ECO:0000269|PubMed:27493029" FT /id="VAR_068162" FT VARIANT 178 FT /note="N -> S (in COQ10D1; decreased ubiquinone FT biosynthesis; dbSNP:rs121918232)" FT /evidence="ECO:0000269|PubMed:17855635, FT ECO:0000269|PubMed:27493029" FT /id="VAR_068163" FT VARIANT 247 FT /note="Y -> C (in COQ10D1; decreased 4-hydroxybenzoate FT decaprenyltransferase activity; dbSNP:rs121918230)" FT /evidence="ECO:0000269|PubMed:16400613, FT ECO:0000269|PubMed:17374725, ECO:0000269|PubMed:17855635, FT ECO:0000269|PubMed:27493029" FT /id="VAR_025701" FT VARIANT 252 FT /note="A -> V (in COQ10D1; loss of ubiquinone biosynthesis; FT dbSNP:rs762616589)" FT /evidence="ECO:0000269|PubMed:23343605, FT ECO:0000269|PubMed:27493029" FT /id="VAR_076914" FT VARIANT 267 FT /note="T -> A (in MSA1; associated with disease FT susceptibility; dbSNP:rs369627290)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070247" FT VARIANT 297 FT /note="S -> C (in MSA1; associated with disease FT susceptibility; dbSNP:rs566845170)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070248" FT VARIANT 336 FT /note="N -> H (in dbSNP:rs1734859571)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070249" FT VARIANT 337 FT /note="R -> Q (in MSA1; associated with disease FT susceptibility; dbSNP:rs763562410)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070250" FT VARIANT 340 FT /note="G -> A (in COQ10D1; uncertain significance; FT dbSNP:rs752608037)" FT /evidence="ECO:0000269|PubMed:28044327" FT /id="VAR_078121" FT VARIANT 343 FT /note="V -> A (in MSA1; associated with disease FT susceptibility; dbSNP:rs148156462)" FT /evidence="ECO:0000269|PubMed:23758206" FT /id="VAR_070251" SQ SEQUENCE 371 AA; 40475 MW; 8BCE473A1D0C60CB CRC64; MLGSRAAGFA RGLRAVALAW LPGWRGRSFA LARAAGAPHG GDLQPPACPE PRGRQLSLSA AAVVDSAPRP LQPYLRLMRL DKPIGTWLLY LPCTWSIGLA AEPGCFPDWY MLSLFGTGAI LMRGAGCTIN DMWDQDYDKK VTRTANRPIA AGDISTFQSF VFLGGQLTLA LGVLLCLNYY SIALGAGSLL LVITYPLMKR ISYWPQLALG LTFNWGALLG WSAIKGSCDP SVCLPLYFSG VMWTLIYDTI YAHQDKRDDV LIGLKSTALR FGENTKPWLS GFSVAMLGAL SLVGVNSGQT APYYAALGAV GAHLTHQIYT LDIHRPEDCW NKFISNRTLG LIVFLGIVLG NLWKEKKTDK TKKGIENKIE N // ID FMT_HUMAN Reviewed; 389 AA. AC Q96DP5; B7Z734; DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot. DT 27-JAN-2003, sequence version 2. DT 28-JAN-2026, entry version 188. DE RecName: Full=Methionyl-tRNA formyltransferase, mitochondrial; DE Short=MtFMT; DE EC=2.1.2.9 {ECO:0000269|PubMed:21907147, ECO:0000269|PubMed:25288793}; DE Flags: Precursor; GN Name=MTFMT; Synonyms=FMT, FMT1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 11-389 (ISOFORM 1). RC TISSUE=Neuroblastoma, and Synovium; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain, and Mammary gland; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP VARIANTS COXPD15 LEU-125 AND LEU-209, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=21907147; DOI=10.1016/j.cmet.2011.07.010; RA Tucker E.J., Hershman S.G., Koehrer C., Belcher-Timme C.A., Patel J., RA Goldberger O.A., Christodoulou J., Silberstein J.M., McKenzie M., RA Ryan M.T., Compton A.G., Jaffe J.D., Carr S.A., Calvo S.E., RA RajBhandary U.L., Thorburn D.R., Mootha V.K.; RT "Mutations in MTFMT underlie a human disorder of formylation causing RT impaired mitochondrial translation."; RL Cell Metab. 14:428-434(2011). RN [5] RP VARIANTS MC1DN27 LEU-209 AND 332-ARG--GLU-389 DEL. RX PubMed=22499348; DOI=10.1136/jmedgenet-2012-100846; RA Haack T.B., Haberberger B., Frisch E.M., Wieland T., Iuso A., Gorza M., RA Strecker V., Graf E., Mayr J.A., Herberg U., Hennermann J.B., Klopstock T., RA Kuhn K.A., Ahting U., Sperl W., Wilichowski E., Hoffmann G.F., Tesarova M., RA Hansikova H., Zeman J., Plecko B., Zeviani M., Wittig I., Strom T.M., RA Schuelke M., Freisinger P., Meitinger T., Prokisch H.; RT "Molecular diagnosis in mitochondrial complex I deficiency using exome RT sequencing."; RL J. Med. Genet. 49:277-283(2012). RN [6] RP CHARACTERIZATION OF VARIANTS COXPD15 LEU-125 AND LEU-209, FUNCTION, AND RP CATALYTIC ACTIVITY. RX PubMed=25288793; DOI=10.1074/jbc.m114.610626; RA Sinha A., Koehrer C., Weber M.H., Masuda I., Mootha V.K., Hou Y.M., RA RajBhandary U.L.; RT "Biochemical characterization of pathogenic mutations in human RT mitochondrial methionyl-tRNA formyltransferase."; RL J. Biol. Chem. 289:32729-32741(2014). CC -!- FUNCTION: Methionyl-tRNA formyltransferase that formylates methionyl- CC tRNA in mitochondria and is crucial for translation initiation. CC {ECO:0000269|PubMed:21907147, ECO:0000269|PubMed:25288793}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-methionyl-tRNA(fMet) + (6R)-10-formyltetrahydrofolate = N- CC formyl-L-methionyl-tRNA(fMet) + (6S)-5,6,7,8-tetrahydrofolate + H(+); CC Xref=Rhea:RHEA:24380, Rhea:RHEA-COMP:9952, Rhea:RHEA-COMP:9953, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57453, ChEBI:CHEBI:78530, CC ChEBI:CHEBI:78844, ChEBI:CHEBI:195366; EC=2.1.2.9; CC Evidence={ECO:0000269|PubMed:25288793}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24381; CC Evidence={ECO:0000269|PubMed:21907147}; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:O77480}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96DP5-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96DP5-2; Sequence=VSP_057059, VSP_057060; CC -!- DOMAIN: Composed of an N- and a C-terminal domain. The N-terminal CC domain carries the tetrahydrofolate (THF)-binding site and the C- CC terminal domain is presumably involved in positioning the Met-tRNA CC substrate for the formylation reaction. CC -!- DISEASE: Combined oxidative phosphorylation deficiency 15 (COXPD15) CC [MIM:614947]: An autosomal recessive, mitochondrial, neurologic CC disorder characterized by features of Leigh syndrome and combined CC oxidative phosphorylation deficiency. Clinical features include mild CC global developmental delay, white matter abnormalities, ataxia, CC incoordination, speech and reading difficulties, T2-weighted CC hyperintensities in the basal ganglia, corpus callosum, and brainstem. CC {ECO:0000269|PubMed:21907147, ECO:0000269|PubMed:25288793}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 27 (MC1DN27) CC [MIM:618248]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN27 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:22499348}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the Fmt family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH16630.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH33687.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB70984.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK055688; BAB70984.1; ALT_INIT; mRNA. DR EMBL; AK301390; BAH13470.1; -; mRNA. DR EMBL; AC013553; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC103691; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC016630; AAH16630.2; ALT_INIT; mRNA. DR EMBL; BC033687; AAH33687.1; ALT_INIT; mRNA. DR CCDS; CCDS45280.1; -. [Q96DP5-1] DR RefSeq; NP_640335.2; NM_139242.4. [Q96DP5-1] DR AlphaFoldDB; Q96DP5; -. DR SMR; Q96DP5; -. DR BioGRID; 125820; 98. DR FunCoup; Q96DP5; 640. DR IntAct; Q96DP5; 9. DR STRING; 9606.ENSP00000220058; -. DR DrugBank; DB00116; Tetrahydrofolic acid. DR iPTMnet; Q96DP5; -. DR PhosphoSitePlus; Q96DP5; -. DR BioMuta; MTFMT; -. DR DMDM; 27923776; -. DR jPOST; Q96DP5; -. DR MassIVE; Q96DP5; -. DR PaxDb; 9606-ENSP00000220058; -. DR PeptideAtlas; Q96DP5; -. DR ProteomicsDB; 6828; -. DR ProteomicsDB; 76304; -. [Q96DP5-1] DR Pumba; Q96DP5; -. DR Antibodypedia; 25895; 174 antibodies from 15 providers. DR DNASU; 123263; -. DR Ensembl; ENST00000220058.9; ENSP00000220058.4; ENSG00000103707.11. [Q96DP5-1] DR Ensembl; ENST00000543678.1; ENSP00000443754.1; ENSG00000103707.11. [Q96DP5-2] DR Ensembl; ENST00000558460.5; ENSP00000452646.1; ENSG00000103707.11. [Q96DP5-1] DR GeneID; 123263; -. DR KEGG; hsa:123263; -. DR MANE-Select; ENST00000220058.9; ENSP00000220058.4; NM_139242.4; NP_640335.2. DR UCSC; uc002aof.5; human. [Q96DP5-1] DR AGR; HGNC:29666; -. DR ClinPGx; PA142671304; -. DR CTD; 123263; -. DR DisGeNET; 123263; -. DR GeneCards; MTFMT; -. DR GeneReviews; MTFMT; -. DR HGNC; HGNC:29666; MTFMT. DR HPA; ENSG00000103707; Low tissue specificity. DR MalaCards; MTFMT; -. DR MIM; 611766; gene. DR MIM; 614947; phenotype. DR MIM; 618248; phenotype. DR OpenTargets; ENSG00000103707; -. DR Orphanet; 319524; Combined oxidative phosphorylation defect type 15. DR VEuPathDB; HostDB:ENSG00000103707; -. DR eggNOG; KOG3082; Eukaryota. DR GeneTree; ENSGT00390000017828; -. DR HOGENOM; CLU_033347_0_0_1; -. DR InParanoid; Q96DP5; -. DR OMA; GASPIHE; -. DR OrthoDB; 10268103at2759; -. DR PAN-GO; Q96DP5; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q96DP5; -. DR BRENDA; 2.1.2.9; 2681. DR PathwayCommons; Q96DP5; -. DR Reactome; R-HSA-5368286; Mitochondrial translation initiation. DR SignaLink; Q96DP5; -. DR Agora; ENSG00000103707; -. DR BioGRID-ORCS; 123263; 154 hits in 1156 CRISPR screens. DR ChiTaRS; MTFMT; human. DR GeneWiki; MTFMT; -. DR GenomeRNAi; 123263; -. DR Pharos; Q96DP5; Tbio. DR PRO; PR:Q96DP5; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q96DP5; protein. DR Bgee; ENSG00000103707; Expressed in left ventricle myocardium and 169 other cell types or tissues. DR ExpressionAtlas; Q96DP5; baseline and differential. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0004479; F:methionyl-tRNA formyltransferase activity; IDA:UniProtKB. DR GO; GO:0071951; P:conversion of methionyl-tRNA to N-formyl-methionyl-tRNA; IDA:UniProtKB. DR CDD; cd08646; FMT_core_Met-tRNA-FMT_N; 1. DR FunFam; 3.40.50.12230:FF:000003; methionyl-tRNA formyltransferase, mitochondrial; 1. DR Gene3D; 3.40.50.12230; -; 1. DR InterPro; IPR005794; Fmt. DR InterPro; IPR005793; Formyl_trans_C. DR InterPro; IPR002376; Formyl_transf_N. DR InterPro; IPR036477; Formyl_transf_N_sf. DR InterPro; IPR011034; Formyl_transferase-like_C_sf. DR InterPro; IPR041711; Met-tRNA-FMT_N. DR NCBIfam; TIGR00460; fmt; 1. DR PANTHER; PTHR11138; METHIONYL-TRNA FORMYLTRANSFERASE; 1. DR PANTHER; PTHR11138:SF5; METHIONYL-TRNA FORMYLTRANSFERASE, MITOCHONDRIAL; 1. DR Pfam; PF02911; Formyl_trans_C; 1. DR Pfam; PF00551; Formyl_trans_N; 1. DR SUPFAM; SSF50486; FMT C-terminal domain-like; 1. DR SUPFAM; SSF53328; Formyltransferase; 1. PE 1: Evidence at protein level; KW Alternative splicing; Disease variant; Mitochondrion; KW Primary mitochondrial disease; Protein biosynthesis; KW Proteomics identification; Reference proteome; Transferase; KW Transit peptide. FT TRANSIT 1..? FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN ?..389 FT /note="Methionyl-tRNA formyltransferase, mitochondrial" FT /id="PRO_0000010093" FT VAR_SEQ 141..144 FT /note="GILN -> SFQF (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057059" FT VAR_SEQ 145..389 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057060" FT VARIANT 5 FT /note="V -> A (in dbSNP:rs2946655)" FT /id="VAR_059289" FT VARIANT 125 FT /note="S -> L (in COXPD15; loss of methionyl-tRNA FT formyltransferase activity; dbSNP:rs397514614)" FT /evidence="ECO:0000269|PubMed:21907147, FT ECO:0000269|PubMed:25288793" FT /id="VAR_069303" FT VARIANT 209 FT /note="S -> L (in COXPD15 and MC1DN27; decreased methionyl- FT tRNA formyltransferase activity; dbSNP:rs201431517)" FT /evidence="ECO:0000269|PubMed:21907147, FT ECO:0000269|PubMed:22499348, ECO:0000269|PubMed:25288793" FT /id="VAR_069304" FT VARIANT 332..389 FT /note="Missing (in MC1DN27)" FT /evidence="ECO:0000269|PubMed:22499348" FT /id="VAR_081461" SQ SEQUENCE 389 AA; 43832 MW; EBBE92142AB954E0 CRC64; MRVLVRRCWG PPLAHGARRG RPSPQWRALA RLGWEDCRDS RVREKPPWRV LFFGTDQFAR EALRALHAAR ENKEEELIDK LEVVTMPSPS PKGLPVKQYA VQSQLPVYEW PDVGSGEYDV GVVASFGRLL NEALILKFPY GILNVHPSCL PRWRGPAPVI HTVLHGDTVT GVTIMQIRPK RFDVGPILKQ ETVPVPPKST AKELEAVLSR LGANMLISVL KNLPESLSNG RQQPMEGATY APKISAGTSC IKWEEQTSEQ IFRLYRAIGN IIPLQTLWMA NTIKLLDLVE VNSSVLADPK LTGQALIPGS VIYHKQSQIL LVYCKDGWIG VRSVMLKKSL TATDFYNGYL HPWYQKNSQA QPSQCRFQTL RLPTKKKQKK TVAMQQCIE // ID FXRD1_HUMAN Reviewed; 486 AA. AC Q96CU9; B3KN84; B4DHU2; Q71MG0; Q9BU39; Q9UKY9; DT 23-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 28-JAN-2026, entry version 169. DE RecName: Full=FAD-dependent oxidoreductase domain-containing protein 1 {ECO:0000312|HGNC:HGNC:26927}; DE EC=1.-.-.-; GN Name=FOXRED1 {ECO:0000312|HGNC:HGNC:26927}; ORFNames=FP634; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=10497265; DOI=10.1093/nar/27.20.4008; RA Oh J.J., Grosshans D.R., Wong S.G., Slamon D.J.; RT "Identification of differentially expressed genes associated with HER-2/neu RT overexpression in human breast cancer cells."; RL Nucleic Acids Res. 27:4008-4017(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Uterus; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Zhou X.M., Qin W.X., Wan D.F., Zhang P.P., Jiang H.Q., Huang Y., Zhao X.T., RA Gu J.R.; RT "Novel human cDNA clones with function of affecting cancer cell growth."; RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Caudate nucleus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-343. RC TISSUE=Lung, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, CHARACTERIZATION OF VARIANTS RP MC1DN19 TRP-352 AND SER-430, AND MUTAGENESIS OF TYR-327; TYR-349; TYR-359; RP TYR-410 AND TYR-411. RX PubMed=25678554; DOI=10.1093/hmg/ddv058; RA Formosa L.E., Mimaki M., Frazier A.E., McKenzie M., Stait T.L., RA Thorburn D.R., Stroud D.A., Ryan M.T.; RT "Characterization of mitochondrial FOXRED1 in the assembly of respiratory RT chain complex I."; RL Hum. Mol. Genet. 24:2952-2965(2015). RN [10] RP IDENTIFICATION. RX PubMed=25681241; DOI=10.1016/j.bbabio.2015.01.014; RA Lemire B.D.; RT "Evolution of FOXRED1, an FAD-dependent oxidoreductase necessary for RT NADH:ubiquinone oxidoreductase (Complex I) assembly."; RL Biochim. Biophys. Acta 1847:451-457(2015). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [12] RP VARIANT MC1DN19 TRP-352, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=20858599; DOI=10.1093/hmg/ddq414; RA Fassone E., Duncan A.J., Taanman J.W., Pagnamenta A.T., Sadowski M.I., RA Holand T., Qasim W., Rutland P., Calvo S.E., Mootha V.K., RA Bitner-Glindzicz M., Rahman S.; RT "FOXRED1, encoding an FAD-dependent oxidoreductase complex-I-specific RT molecular chaperone, is mutated in infantile-onset mitochondrial RT encephalopathy."; RL Hum. Mol. Genet. 19:4837-4847(2010). RN [13] RP VARIANTS MC1DN19 232-GLN--ILE-486 DEL AND SER-430. RX PubMed=20818383; DOI=10.1038/ng.659; RA Calvo S.E., Tucker E.J., Compton A.G., Kirby D.M., Crawford G., Burtt N.P., RA Rivas M., Guiducci C., Bruno D.L., Goldberger O.A., Redman M.C., RA Wiltshire E., Wilson C.J., Altshuler D., Gabriel S.B., Daly M.J., RA Thorburn D.R., Mootha V.K.; RT "High-throughput, pooled sequencing identifies mutations in NUBPL and RT FOXRED1 in human complex I deficiency."; RL Nat. Genet. 42:851-858(2010). CC -!- FUNCTION: Required for the assembly of the mitochondrial membrane CC respiratory chain NADH dehydrogenase (Complex I) (PubMed:20858599, CC PubMed:25678554). Involved in mid-late stages of complex I assembly CC (PubMed:25678554). {ECO:0000269|PubMed:20858599, CC ECO:0000269|PubMed:25678554}. CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250}; CC -!- SUBUNIT: Associates with components of the mitochondrial respiratory CC chain complex I. {ECO:0000269|PubMed:25678554}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:20858599, ECO:0000305|PubMed:25678554}; Single-pass CC membrane protein {ECO:0000255}. Note=According to a report, it is CC associated with the matrix face of the mitochondrial inner membrane and CC does not contain any transmembrane region. However, one transmembrane CC domain is clearly predicted by different methods (Probable). CC {ECO:0000305|PubMed:25678554}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q96CU9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96CU9-2; Sequence=VSP_022629; CC Name=3; CC IsoId=Q96CU9-3; Sequence=VSP_039003; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 19 (MC1DN19) CC [MIM:618241]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN19 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:20818383, CC ECO:0000269|PubMed:20858599, ECO:0000269|PubMed:25678554}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF103801; AAF02421.1; -; mRNA. DR EMBL; AL136923; CAB66857.1; -; mRNA. DR EMBL; AF447877; AAQ04652.1; -; mRNA. DR EMBL; AK023987; BAG51246.1; -; mRNA. DR EMBL; AK295267; BAG58254.1; -; mRNA. DR EMBL; CH471065; EAW67683.1; -; Genomic_DNA. DR EMBL; BC002910; AAH02910.2; -; mRNA. DR EMBL; BC013902; AAH13902.1; -; mRNA. DR CCDS; CCDS8471.1; -. [Q96CU9-1] DR RefSeq; NP_001412102.1; NM_001425173.1. [Q96CU9-2] DR RefSeq; NP_001412103.1; NM_001425174.1. [Q96CU9-2] DR RefSeq; NP_060017.1; NM_017547.4. [Q96CU9-1] DR RefSeq; XP_047283209.1; XM_047427253.1. [Q96CU9-2] DR RefSeq; XP_054225317.1; XM_054369342.1. [Q96CU9-2] DR AlphaFoldDB; Q96CU9; -. DR SMR; Q96CU9; -. DR BioGRID; 120725; 83. DR FunCoup; Q96CU9; 886. DR IntAct; Q96CU9; 41. DR MINT; Q96CU9; -. DR STRING; 9606.ENSP00000263578; -. DR GlyGen; Q96CU9; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96CU9; -. DR PhosphoSitePlus; Q96CU9; -. DR SwissPalm; Q96CU9; -. DR BioMuta; FOXRED1; -. DR DMDM; 124007188; -. DR jPOST; Q96CU9; -. DR MassIVE; Q96CU9; -. DR PaxDb; 9606-ENSP00000263578; -. DR PeptideAtlas; Q96CU9; -. DR ProteomicsDB; 76223; -. [Q96CU9-1] DR ProteomicsDB; 76224; -. [Q96CU9-2] DR ProteomicsDB; 76225; -. [Q96CU9-3] DR Pumba; Q96CU9; -. DR Antibodypedia; 32986; 164 antibodies from 27 providers. DR DNASU; 55572; -. DR Ensembl; ENST00000263578.10; ENSP00000263578.5; ENSG00000110074.13. [Q96CU9-1] DR GeneID; 55572; -. DR KEGG; hsa:55572; -. DR MANE-Select; ENST00000263578.10; ENSP00000263578.5; NM_017547.4; NP_060017.1. DR UCSC; uc001qdi.4; human. [Q96CU9-1] DR AGR; HGNC:26927; -. DR ClinPGx; PA143485473; -. DR CTD; 55572; -. DR DisGeNET; 55572; -. DR GeneCards; FOXRED1; -. DR HGNC; HGNC:26927; FOXRED1. DR HPA; ENSG00000110074; Low tissue specificity. DR MalaCards; FOXRED1; -. DR MIM; 613622; gene. DR MIM; 618241; phenotype. DR OpenTargets; ENSG00000110074; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000110074; -. DR eggNOG; KOG2853; Eukaryota. DR GeneTree; ENSGT00390000006114; -. DR HOGENOM; CLU_007884_4_4_1; -. DR InParanoid; Q96CU9; -. DR OMA; PDHNALI; -. DR OrthoDB; 424974at2759; -. DR PAN-GO; Q96CU9; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q96CU9; -. DR PathwayCommons; Q96CU9; -. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q96CU9; -. DR Agora; ENSG00000110074; -. DR BioGRID-ORCS; 55572; 140 hits in 1161 CRISPR screens. DR ChiTaRS; FOXRED1; human. DR GeneWiki; FOXRED1; -. DR GenomeRNAi; 55572; -. DR Pharos; Q96CU9; Tbio. DR PRO; PR:Q96CU9; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q96CU9; protein. DR Bgee; ENSG00000110074; Expressed in right hemisphere of cerebellum and 161 other cell types or tissues. DR ExpressionAtlas; Q96CU9; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR FunFam; 3.30.9.10:FF:000155; FAD-dependent oxidoreductase domain-containing 1; 1. DR Gene3D; 3.30.9.10; D-Amino Acid Oxidase, subunit A, domain 2; 1. DR Gene3D; 3.50.50.60; FAD/NAD(P)-binding domain; 1. DR InterPro; IPR006076; FAD-dep_OxRdtase. DR InterPro; IPR036188; FAD/NAD-bd_sf. DR PANTHER; PTHR13847:SF287; FAD-DEPENDENT OXIDOREDUCTASE DOMAIN-CONTAINING PROTEIN 1; 1. DR PANTHER; PTHR13847; SARCOSINE DEHYDROGENASE-RELATED; 1. DR Pfam; PF01266; DAO; 1. DR SUPFAM; SSF51905; FAD/NAD(P)-binding domain; 1. PE 1: Evidence at protein level; KW Alternative splicing; Disease variant; Electron transport; FAD; KW Flavoprotein; Membrane; Mitochondrion; Mitochondrion inner membrane; KW Oxidoreductase; Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transmembrane; Transmembrane helix; KW Transport. FT CHAIN 1..486 FT /note="FAD-dependent oxidoreductase domain-containing FT protein 1" FT /id="PRO_0000274142" FT TRANSMEM 62..82 FT /note="Helical" FT /evidence="ECO:0000255" FT VAR_SEQ 1..211 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_022629" FT VAR_SEQ 1..28 FT /note="MIRRVLPHGMGRGLLTRRPGTRRGGFSL -> MAHTGRTVGRLGEG (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_039003" FT VARIANT 145 FT /note="V -> I (in dbSNP:rs34542988)" FT /id="VAR_033856" FT VARIANT 232..486 FT /note="Missing (in MC1DN19)" FT /evidence="ECO:0000269|PubMed:20818383" FT /id="VAR_081414" FT VARIANT 343 FT /note="A -> P (in dbSNP:rs17855445)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_030192" FT VARIANT 352 FT /note="R -> W (in MC1DN19; hypomorphic variant in vitro; FT dbSNP:rs387907087)" FT /evidence="ECO:0000269|PubMed:20858599, FT ECO:0000269|PubMed:25678554" FT /id="VAR_073273" FT VARIANT 380 FT /note="H -> R (in dbSNP:rs7116126)" FT /id="VAR_051003" FT VARIANT 430 FT /note="N -> S (in MC1DN19; hypomorphic variant in vitro; FT dbSNP:rs267606830)" FT /evidence="ECO:0000269|PubMed:20818383, FT ECO:0000269|PubMed:25678554" FT /id="VAR_064571" FT MUTAGEN 327 FT /note="Y->A,F: No effect. Able to restore complex I FT assembly when expressed in cells lacking FOXRED1." FT /evidence="ECO:0000269|PubMed:25678554" FT MUTAGEN 349 FT /note="Y->A,F: No effect. Able to restore complex I FT assembly when expressed in cells lacking FOXRED1." FT /evidence="ECO:0000269|PubMed:25678554" FT MUTAGEN 359 FT /note="Y->A: Not able to restore complex I assembly when FT expressed in cells lacking FOXRED1." FT /evidence="ECO:0000269|PubMed:25678554" FT MUTAGEN 359 FT /note="Y->F: No effect. Able to restore complex I assembly FT when expressed in cells lacking FOXRED1." FT /evidence="ECO:0000269|PubMed:25678554" FT MUTAGEN 410 FT /note="Y->A,F: No effect. Able to restore complex I FT assembly when expressed in cells lacking FOXRED1." FT /evidence="ECO:0000269|PubMed:25678554" FT MUTAGEN 411 FT /note="Y->A,F: No effect. Able to restore complex I FT assembly when expressed in cells lacking FOXRED1." FT /evidence="ECO:0000269|PubMed:25678554" FT CONFLICT 425 FT /note="H -> HF (in Ref. 3; AAQ04652)" FT /evidence="ECO:0000305" SQ SEQUENCE 486 AA; 53812 MW; 34A18ABED84BE676 CRC64; MIRRVLPHGM GRGLLTRRPG TRRGGFSLDW DGKVSEIKKK IKSILPGRSC DLLQDTSHLP PEHSDVVIVG GGVLGLSVAY WLKKLESRRG AIRVLVVERD HTYSQASTGL SVGGICQQFS LPENIQLSLF SASFLRNINE YLAVVDAPPL DLRFNPSGYL LLASEKDAAA MESNVKVQRQ EGAKVSLMSP DQLRNKFPWI NTEGVALASY GMEDEGWFDP WCLLQGLRRK VQSLGVLFCQ GEVTRFVSSS QRMLTTDDKA VVLKRIHEVH VKMDRSLEYQ PVECAIVINA AGAWSAQIAA LAGVGEGPPG TLQGTKLPVE PRKRYVYVWH CPQGPGLETP LVADTSGAYF RREGLGSNYL GGRSPTEQEE PDPANLEVDH DFFQDKVWPH LALRVPAFET LKVQSAWAGY YDYNTFDQNG VVGPHPLVVN MYFATGFSGH GLQQAPGIGR AVAEMVLKGR FQTIDLSPFL FTRFYLGEKI QENNII // ID NDUA1_HUMAN Reviewed; 70 AA. AC O15239; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 28-JAN-2026, entry version 197. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1; DE AltName: Full=Complex I-MWFE; DE Short=CI-MWFE; DE AltName: Full=NADH-ubiquinone oxidoreductase MWFE subunit; GN Name=NDUFA1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8938439; DOI=10.1006/geno.1996.0561; RA Zhuchenko O., Wehnert M., Bailey J., Sun Z.S., Lee C.C.; RT "Isolation, mapping, and genomic structure of an X-linked gene for a RT subunit of human mitochondrial complex I."; RL Genomics 37:281-288(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Liver; RX PubMed=9224902; DOI=10.1016/s0378-1119(97)00108-x; RA Frattini A., Faranda S., Bagnasco L., Patrosso C., Nulli P., Zucchi I., RA Vezzoni P.; RT "Identification of a new member (ZNF183) of the Ring finger gene family in RT Xq24-25."; RL Gene 192:291-298(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Zhuchenko O.P., Wehnert M., Bailey J., Sun Z.S., Lee C.C.; RT "hMWFE gene -- component of human mitochondrial complex I."; RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [6] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [7] RP VARIANT [LARGE SCALE ANALYSIS] CYS-53. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [8] RP VARIANTS MC1DN12 ARG-8 AND SER-37. RX PubMed=17262856; DOI=10.1002/ana.21036; RA Fernandez-Moreira D., Ugalde C., Smeets R., Rodenburg R.J.T., RA Lopez-Laso E., Ruiz-Falco M.L., Briones P., Martin M.A., Smeitink J.A.M., RA Arenas J.; RT "X-linked NDUFA1 gene mutations associated with mitochondrial RT encephalomyopathy."; RL Ann. Neurol. 61:73-83(2007). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis. Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits. CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891}; Single-pass membrane protein CC {ECO:0000255}; Matrix side {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Primarily expressed in heart and skeletal muscle. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 12 (MC1DN12) CC [MIM:301020]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. {ECO:0000269|PubMed:17262856}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFA1 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X81900; CAA57489.1; -; mRNA. DR EMBL; U54993; AAD00084.1; -; mRNA. DR EMBL; BC000266; AAH00266.1; -; mRNA. DR CCDS; CCDS14590.1; -. DR RefSeq; NP_004532.1; NM_004541.4. DR PDB; 5XTC; EM; 3.70 A; S=1-70. DR PDB; 5XTD; EM; 3.70 A; S=1-70. DR PDB; 5XTH; EM; 3.90 A; S=1-70. DR PDB; 5XTI; EM; 17.40 A; BS/S=1-70. DR PDB; 9CWT; EM; 3.44 A; S=1-70. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; O15239; -. DR EMDB; EMD-45974; -. DR SMR; O15239; -. DR BioGRID; 110774; 45. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O15239; -. DR FunCoup; O15239; 444. DR IntAct; O15239; 42. DR MINT; O15239; -. DR STRING; 9606.ENSP00000360492; -. DR BindingDB; O15239; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; O15239; -. DR GlyGen; O15239; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O15239; -. DR PhosphoSitePlus; O15239; -. DR BioMuta; NDUFA1; -. DR jPOST; O15239; -. DR MassIVE; O15239; -. DR PaxDb; 9606-ENSP00000360492; -. DR PeptideAtlas; O15239; -. DR ProteomicsDB; 48530; -. DR Pumba; O15239; -. DR TopDownProteomics; O15239; -. DR Antibodypedia; 29846; 230 antibodies from 28 providers. DR DNASU; 4694; -. DR Ensembl; ENST00000371437.5; ENSP00000360492.4; ENSG00000125356.8. DR GeneID; 4694; -. DR KEGG; hsa:4694; -. DR MANE-Select; ENST00000371437.5; ENSP00000360492.4; NM_004541.4; NP_004532.1. DR AGR; HGNC:7683; -. DR ClinPGx; PA31489; -. DR CTD; 4694; -. DR DisGeNET; 4694; -. DR GeneCards; NDUFA1; -. DR GeneReviews; NDUFA1; -. DR HGNC; HGNC:7683; NDUFA1. DR HPA; ENSG00000125356; Low tissue specificity. DR MalaCards; NDUFA1; -. DR MIM; 300078; gene. DR MIM; 301020; phenotype. DR OpenTargets; ENSG00000125356; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000125356; -. DR eggNOG; ENOG502S3S5; Eukaryota. DR GeneTree; ENSGT00390000007560; -. DR HOGENOM; CLU_185502_2_0_1; -. DR InParanoid; O15239; -. DR OMA; WALMERD; -. DR OrthoDB; 1920692at2759; -. DR PAN-GO; O15239; 1 GO annotation based on evolutionary models. DR PhylomeDB; O15239; -. DR BioCyc; MetaCyc:HS04875-MONOMER; -. DR PathwayCommons; O15239; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; O15239; -. DR SIGNOR; O15239; -. DR Agora; ENSG00000125356; -. DR BioGRID-ORCS; 4694; 126 hits in 779 CRISPR screens. DR ChiTaRS; NDUFA1; human. DR GeneWiki; NADH_dehydrogenase_(ubiquinone),_alpha_1; -. DR GenomeRNAi; 4694; -. DR Pharos; O15239; Tclin. DR PRO; PR:O15239; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; O15239; protein. DR Bgee; ENSG00000125356; Expressed in left ventricle myocardium and 206 other cell types or tissues. DR ExpressionAtlas; O15239; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:MGI. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; TAS:ProtInc. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; NAS:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR InterPro; IPR017384; NADH_Ub_cplx-1_asu_su-1. DR PANTHER; PTHR17098:SF2; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX SUBUNIT 1; 1. DR PANTHER; PTHR17098; NADH-UBIQUINONE OXIDOREDUCTASE MWFE SUBUNIT; 1. DR Pfam; PF15879; MWFE; 1. DR PIRSF; PIRSF038095; NDUA1; 1. PE 1: Evidence at protein level; KW 3D-structure; Disease variant; Electron transport; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Primary mitochondrial disease; KW Proteomics identification; Reference proteome; Respiratory chain; KW Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..70 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT subunit 1" FT /id="PRO_0000118817" FT TRANSMEM 1..21 FT /note="Helical" FT /evidence="ECO:0000255" FT VARIANT 8 FT /note="G -> R (in MC1DN12; dbSNP:rs104894884)" FT /evidence="ECO:0000269|PubMed:17262856" FT /id="VAR_035099" FT VARIANT 32 FT /note="G -> R (in dbSNP:rs1801316)" FT /id="VAR_014485" FT VARIANT 37 FT /note="R -> S (in MC1DN12; dbSNP:rs104894885)" FT /evidence="ECO:0000269|PubMed:17262856" FT /id="VAR_035100" FT VARIANT 53 FT /note="R -> C (in a colorectal cancer sample; somatic FT mutation; dbSNP:rs1257734702)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036173" SQ SEQUENCE 70 AA; 8072 MW; E4004A62117BF253 CRC64; MWFEILPGLS VMGVCLLIPG LATAYIHRFT NGGKEKRVAH FGYHWSLMER DRRISGVDRY YVSKGLENID // ID NDUA2_HUMAN Reviewed; 99 AA. AC O43678; D6RJD6; Q6IAY8; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 28-JAN-2026, entry version 209. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2; DE AltName: Full=Complex I-B8; DE Short=CI-B8; DE AltName: Full=NADH-ubiquinone oxidoreductase B8 subunit; GN Name=NDUFA2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Heart; RX PubMed=9425316; DOI=10.1006/bbrc.1997.7707; RA Ton C., Hwang D.M., Dempsey A.A., Liew C.-C.; RT "Identification and primary structure of five human NADH-ubiquinone RT oxidoreductase subunits."; RL Biochem. Biophys. Res. Commun. 241:589-594(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Thymus; RA Iida A., Kondo K., Kitamoto T., Kitamura Y., Mishima C., Osawa K., RA Nakamura Y.; RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Adrenal gland; RA Peng Y., Song H., Huang Q., Huang C., Gu Y., Yang Y., Gao G., Xiao H., RA Xu X., Li N., Qian B., Liu F., Qu J., Gao X., Cheng Z., Xu Z., Zeng L., RA Xu S., Gu W., Tu Y., Jia J., Fu G., Ren S., Zhong M., Lu G., Hu R., RA Chen J., Chen Z., Han Z.; RT "ADBCGF02_ADB Homo sapiens cDNA clone ADBCGF02 5',mRNA sequence."; RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [9] RP INVOLVEMENT IN MC1DN13. RX PubMed=18513682; DOI=10.1016/j.ajhg.2008.05.007; RA Hoefs S.J., Dieteren C.E., Distelmaier F., Janssen R.J., Epplen A., RA Swarts H.G., Forkink M., Rodenburg R.J., Nijtmans L.G., Willems P.H., RA Smeitink J.A., van den Heuvel L.P.; RT "NDUFA2 complex I mutation leads to Leigh disease."; RL Am. J. Hum. Genet. 82:1306-1315(2008). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [13] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [14] RP STRUCTURE BY NMR, AND DISULFIDE BOND. RX PubMed=15341729; DOI=10.1016/j.str.2004.06.021; RA Brockmann C., Diehl A., Rehbein K., Strauss H., Schmieder P., Korn B., RA Kuhne R., Oschkinat H.; RT "The oxidized subunit B8 from human complex I adopts a thioredoxin fold."; RL Structure 12:1645-1654(2004). RN [15] RP VARIANT [LARGE SCALE ANALYSIS] ASN-50. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis. Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits. CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891}; Peripheral membrane protein CC {ECO:0000305}; Matrix side {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O43678-1; Sequence=Displayed; CC Name=2; CC IsoId=O43678-2; Sequence=VSP_045479; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 13 (MC1DN13) CC [MIM:618235]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN13 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:18513682}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFA2 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF047185; AAC04270.1; -; mRNA. DR EMBL; AB054976; BAB21453.1; -; Genomic_DNA. DR EMBL; AF077029; AAD27762.1; -; mRNA. DR EMBL; AV705564; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; CR457016; CAG33297.1; -; mRNA. DR EMBL; AC116353; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC003674; AAH03674.1; -; mRNA. DR CCDS; CCDS4234.1; -. [O43678-1] DR CCDS; CCDS54911.1; -. [O43678-2] DR PIR; JC5824; JC5824. DR RefSeq; NP_001171941.1; NM_001185012.2. [O43678-2] DR RefSeq; NP_002479.1; NM_002488.5. [O43678-1] DR PDB; 1S3A; NMR; -; A=1-99. DR PDB; 5XTB; EM; 3.40 A; F=14-96. DR PDB; 5XTD; EM; 3.70 A; F=14-96. DR PDB; 5XTH; EM; 3.90 A; F=14-96. DR PDB; 5XTI; EM; 17.40 A; BF/F=14-96. DR PDB; 9CWT; EM; 3.44 A; F=1-99. DR PDBsum; 1S3A; -. DR PDBsum; 5XTB; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; O43678; -. DR EMDB; EMD-45974; -. DR SMR; O43678; -. DR BioGRID; 110775; 233. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O43678; -. DR FunCoup; O43678; 1358. DR IntAct; O43678; 98. DR MINT; O43678; -. DR STRING; 9606.ENSP00000252102; -. DR BindingDB; O43678; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; O43678; -. DR GlyGen; O43678; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O43678; -. DR PhosphoSitePlus; O43678; -. DR SwissPalm; O43678; -. DR BioMuta; NDUFA2; -. DR jPOST; O43678; -. DR MassIVE; O43678; -. DR PaxDb; 9606-ENSP00000252102; -. DR PeptideAtlas; O43678; -. DR ProteomicsDB; 15115; -. DR ProteomicsDB; 49106; -. [O43678-1] DR Pumba; O43678; -. DR TopDownProteomics; O43678-1; -. [O43678-1] DR Antibodypedia; 15357; 128 antibodies from 25 providers. DR DNASU; 4695; -. DR Ensembl; ENST00000252102.9; ENSP00000252102.5; ENSG00000131495.9. [O43678-1] DR Ensembl; ENST00000512088.1; ENSP00000427220.1; ENSG00000131495.9. [O43678-2] DR GeneID; 4695; -. DR KEGG; hsa:4695; -. DR MANE-Select; ENST00000252102.9; ENSP00000252102.5; NM_002488.5; NP_002479.1. DR UCSC; uc003lgp.4; human. [O43678-1] DR AGR; HGNC:7685; -. DR ClinPGx; PA31491; -. DR CTD; 4695; -. DR DisGeNET; 4695; -. DR GeneCards; NDUFA2; -. DR HGNC; HGNC:7685; NDUFA2. DR HPA; ENSG00000131495; Low tissue specificity. DR MalaCards; NDUFA2; -. DR MIM; 602137; gene. DR MIM; 618235; phenotype. DR OpenTargets; ENSG00000131495; -. DR Orphanet; 85136; Cystic leukoencephalopathy without megalencephaly. DR VEuPathDB; HostDB:ENSG00000131495; -. DR eggNOG; KOG3446; Eukaryota. DR GeneTree; ENSGT00390000006178; -. DR HOGENOM; CLU_110897_0_0_1; -. DR InParanoid; O43678; -. DR OMA; RIHLCQH; -. DR OrthoDB; 10250268at2759; -. DR PAN-GO; O43678; 1 GO annotation based on evolutionary models. DR PhylomeDB; O43678; -. DR BioCyc; MetaCyc:HS05539-MONOMER; -. DR PathwayCommons; O43678; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR Reactome; R-HSA-9837999; Mitochondrial protein degradation. DR SignaLink; O43678; -. DR SIGNOR; O43678; -. DR Agora; ENSG00000131495; -. DR BioGRID-ORCS; 4695; 285 hits in 1165 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFA2; human. DR EvolutionaryTrace; O43678; -. DR GeneWiki; NDUFA2; -. DR GenomeRNAi; 4695; -. DR Pharos; O43678; Tclin. DR PRO; PR:O43678; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; O43678; protein. DR Bgee; ENSG00000131495; Expressed in biceps brachii and 213 other cell types or tissues. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0001835; P:blastocyst hatching; IEA:Ensembl. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; NAS:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR FunFam; 3.40.30.10:FF:000127; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2; 1. DR Gene3D; 3.40.30.10; Glutaredoxin; 1. DR InterPro; IPR016464; NADH_Ub_cplx-1_asu_su-2. DR InterPro; IPR007741; Ribosomal_mL43/mS25/NADH_DH. DR InterPro; IPR036249; Thioredoxin-like_sf. DR PANTHER; PTHR12878:SF6; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX SUBUNIT 2; 1. DR PANTHER; PTHR12878; NADH-UBIQUINONE OXIDOREDUCTASE B8 SUBUNIT; 1. DR Pfam; PF05047; L51_S25_CI-B8; 1. DR PIRSF; PIRSF005822; NDUA2; 1. DR SMART; SM00916; L51_S25_CI-B8; 1. DR SUPFAM; SSF52833; Thioredoxin-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Disulfide bond; KW Electron transport; Membrane; Mitochondrion; Mitochondrion inner membrane; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330" FT CHAIN 2..99 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT subunit 2" FT /id="PRO_0000118789" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330" FT MOD_RES 64 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9CQ75" FT MOD_RES 64 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9CQ75" FT DISULFID 24..58 FT /note="Redox-active" FT /evidence="ECO:0000269|PubMed:15341729" FT VAR_SEQ 71..99 FT /note="FGQETNVPLNNFSADQVTRALENVLSGKA -> SRVQNS (in isoform FT 2)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_045479" FT VARIANT 50 FT /note="D -> N (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036174" FT STRAND 19..22 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 25..27 FT /evidence="ECO:0007829|PDB:1S3A" FT HELIX 28..38 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 41..47 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 49..51 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 53..56 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 60..62 FT /evidence="ECO:0007829|PDB:1S3A" FT STRAND 64..68 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 70..72 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 74..76 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 84..93 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 99 AA; 10922 MW; EF026F193CAF1DF7 CRC64; MAAAAASRGV GAKLGLREIR IHLCQRSPGS QGVRDFIEKR YVELKKANPD LPILIRECSD VQPKLWARYA FGQETNVPLN NFSADQVTRA LENVLSGKA // ID NDUA6_HUMAN Reviewed; 128 AA. AC P56556; B2RE54; O43675; Q6FGW0; Q6IBT8; Q6IC39; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 20-JUN-2018, sequence version 4. DT 28-JAN-2026, entry version 206. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 {ECO:0000305}; DE AltName: Full=Complex I-B14; DE Short=CI-B14; DE AltName: Full=LYR motif-containing protein 6; DE AltName: Full=NADH-ubiquinone oxidoreductase B14 subunit; GN Name=NDUFA6 {ECO:0000312|HGNC:HGNC:7690}; Synonyms=LYRM6, NADHB14; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Heart; RX PubMed=9425316; DOI=10.1006/bbrc.1997.7707; RA Ton C., Hwang D.M., Dempsey A.A., Liew C.-C.; RT "Identification and primary structure of five human NADH-ubiquinone RT oxidoreductase subunits."; RL Biochem. Biophys. Res. Commun. 241:589-594(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-9. RC TISSUE=Skeletal muscle; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [12] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [13] RP FUNCTION, INVOLVEMENT IN MC1DN33, AND VARIANTS MC1DN33 PRO-64 AND RP 89-GLU--PRO-128 DEL. RX PubMed=30245030; DOI=10.1016/j.ajhg.2018.08.013; RA Alston C.L., Heidler J., Dibley M.G., Kremer L.S., Taylor L.S., Fratter C., RA French C.E., Glasgow R.I.C., Feichtinger R.G., Delon I., Pagnamenta A.T., RA Dolling H., Lemonde H., Aiton N., Bjoernstad A., Henneke L., Gaertner J., RA Thiele H., Tauchmannova K., Quaghebeur G., Houstek J., Sperl W., RA Raymond F.L., Prokisch H., Mayr J.A., McFarland R., Poulton J., Ryan M.T., RA Wittig I., Henneke M., Taylor R.W.; RT "Bi-allelic mutations in NDUFA6 establish its role in early-onset isolated RT mitochondrial complex I deficiency."; RL Am. J. Hum. Genet. 103:592-601(2018). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed to be not CC involved in catalysis. Required for proper complex I assembly CC (PubMed:30245030). Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371, CC ECO:0000269|PubMed:30245030}. CC -!- SUBUNIT: Mammalian complex I is composed of 45 different subunits. CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891}; Peripheral membrane protein CC {ECO:0000305}; Matrix side {ECO:0000305}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 33 (MC1DN33) CC [MIM:618253]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN33 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:30245030}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the complex I LYR family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAG30415.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF047182; AAC04267.1; -; mRNA. DR EMBL; CR456529; CAG30415.1; ALT_INIT; mRNA. DR EMBL; AK291874; BAF84563.1; -; mRNA. DR EMBL; AK316562; BAG38151.1; -; mRNA. DR EMBL; CR456714; CAG32995.1; -; mRNA. DR EMBL; CR541997; CAG46794.1; -; mRNA. DR EMBL; AL021878; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471095; EAW60489.1; -; Genomic_DNA. DR EMBL; BC002772; AAH02772.1; -; mRNA. DR CCDS; CCDS33656.2; -. DR PIR; JC5821; JC5821. DR RefSeq; NP_002481.3; NM_002490.6. DR PDB; 5XTB; EM; 3.40 A; E=16-128. DR PDB; 5XTD; EM; 3.70 A; E=16-128. DR PDB; 5XTH; EM; 3.90 A; E=16-128. DR PDB; 5XTI; EM; 17.40 A; BE/E=16-128. DR PDB; 9CWT; EM; 3.44 A; E=1-128. DR PDBsum; 5XTB; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; P56556; -. DR EMDB; EMD-45974; -. DR SMR; P56556; -. DR BioGRID; 110780; 170. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; P56556; -. DR FunCoup; P56556; 1241. DR IntAct; P56556; 83. DR MINT; P56556; -. DR STRING; 9606.ENSP00000482543; -. DR BindingDB; P56556; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; P56556; -. DR iPTMnet; P56556; -. DR PhosphoSitePlus; P56556; -. DR BioMuta; NDUFA6; -. DR DMDM; 298286909; -. DR jPOST; P56556; -. DR MassIVE; P56556; -. DR PaxDb; 9606-ENSP00000418842; -. DR PeptideAtlas; P56556; -. DR ProteomicsDB; 56926; -. DR Pumba; P56556; -. DR TopDownProteomics; P56556; -. DR Antibodypedia; 45919; 109 antibodies from 22 providers. DR DNASU; 4700; -. DR Ensembl; ENST00000498737.8; ENSP00000418842.3; ENSG00000184983.12. DR Ensembl; ENST00000605916.1; ENSP00000475402.1; ENSG00000272765.2. DR Ensembl; ENST00000628740.2; ENSP00000486781.1; ENSG00000277365.3. DR Ensembl; ENST00000630201.4; ENSP00000487431.2; ENSG00000281013.5. DR Ensembl; ENST00000630971.2; ENSP00000487462.1; ENSG00000273397.4. DR GeneID; 4700; -. DR KEGG; hsa:4700; -. DR MANE-Select; ENST00000498737.8; ENSP00000418842.3; NM_002490.6; NP_002481.3. DR UCSC; uc003bcb.4; human. DR AGR; HGNC:7690; -. DR ClinPGx; PA31496; -. DR CTD; 4700; -. DR DisGeNET; 4700; -. DR GeneCards; NDUFA6; -. DR HGNC; HGNC:7690; NDUFA6. DR HPA; ENSG00000184983; Low tissue specificity. DR MalaCards; NDUFA6; -. DR MIM; 602138; gene. DR MIM; 618253; phenotype. DR OpenTargets; ENSG00000184983; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000184983; -. DR eggNOG; KOG3426; Eukaryota. DR GeneTree; ENSGT00390000018898; -. DR InParanoid; P56556; -. DR OMA; FWKQTTH; -. DR OrthoDB; 14535at2759; -. DR PAN-GO; P56556; 2 GO annotations based on evolutionary models. DR PhylomeDB; P56556; -. DR BioCyc; MetaCyc:HS00037-MONOMER; -. DR PathwayCommons; P56556; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; P56556; -. DR SIGNOR; P56556; -. DR Agora; ENSG00000184983; -. DR BioGRID-ORCS; 4700; 309 hits in 1166 CRISPR screens. DR ChiTaRS; NDUFA6; human. DR GeneWiki; NDUFA6; -. DR GenomeRNAi; 4700; -. DR Pharos; P56556; Tclin. DR PRO; PR:P56556; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P56556; protein. DR Bgee; ENSG00000184983; Expressed in hindlimb stylopod muscle and 99 other cell types or tissues. DR ExpressionAtlas; P56556; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; TAS:ProtInc. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; NAS:UniProtKB. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR CDD; cd20266; Complex1_LYR_NDUFA6_LYRM6; 1. DR InterPro; IPR045299; Complex1_LYR_NDUFA6_LYRM6. DR InterPro; IPR016488; NADH_Ub_cplx-1_asu_su-6. DR PANTHER; PTHR12964:SF0; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX SUBUNIT 6; 1. DR PANTHER; PTHR12964; NADH-UBIQUINONE OXIDOREDUCTASE B14 SUBUNIT; 1. DR Pfam; PF13233; Complex1_LYR_2; 1. DR PIRSF; PIRSF006643; NDUA6; 1. PE 1: Evidence at protein level; KW 3D-structure; Disease variant; Electron transport; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Phosphoprotein; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transport. FT CHAIN 1..128 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT subunit 6" FT /id="PRO_0000174302" FT MOD_RES 11 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 9 FT /note="A -> V (in dbSNP:rs1801311)" FT /evidence="ECO:0000269|PubMed:14702039" FT /id="VAR_014483" FT VARIANT 64 FT /note="R -> P (in MC1DN33)" FT /evidence="ECO:0000269|PubMed:30245030" FT /id="VAR_081470" FT VARIANT 89..128 FT /note="Missing (in MC1DN33)" FT /evidence="ECO:0000269|PubMed:30245030" FT /id="VAR_081471" FT CONFLICT 6 FT /note="V -> F (in Ref. 4; CAG32995)" FT /evidence="ECO:0000305" FT HELIX 25..40 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 43..49 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 56..66 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 67..72 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 76..94 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 100..104 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 105..107 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 118..124 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 128 AA; 15137 MW; 5EE10C571A659D8B CRC64; MAGSGVRQAT STASTFVKPI FSRDMNEAKR RVRELYRAWY REVPNTVHQF QLDITVKMGR DKVREMFMKN AHVTDPRVVD LLVIKGKIEL EETIKVWKQR THVMRFFHET EAPRPKDFLS KFYVGHDP // ID NDUA8_HUMAN Reviewed; 172 AA. AC P51970; B1AM93; Q9Y6N0; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 28-JAN-2026, entry version 205. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8; DE AltName: Full=Complex I-19kD; DE Short=CI-19kD; DE AltName: Full=Complex I-PGIV; DE Short=CI-PGIV; DE AltName: Full=NADH-ubiquinone oxidoreductase 19 kDa subunit; GN Name=NDUFA8; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9860297; DOI=10.1007/s004390050869; RA Triepels R., van den Heuvel L., Loeffen J., Smeets R., Trijbels F., RA Smeitink J.; RT "The nuclear-encoded human NADH:ubiquinone oxidoreductase NDUFA8 subunit: RT cDNA cloning, chromosomal localization, tissue distribution, and mutation RT detection in complex-I-deficient patients."; RL Hum. Genet. 103:557-563(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thalamus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 2-14. RC TISSUE=Kidney; RX PubMed=9150947; DOI=10.1002/elps.1150180343; RA Sarto C., Marocchi A., Sanchez J.-C., Giannone B., Frutiger S., Golaz O., RA Wilkins M.R., Doro G., Cappellano F., Hughes G.J., Hochstrasser D.F., RA Mocarelli P.; RT "Renal cell carcinoma and normal kidney protein expression."; RL Electrophoresis 18:599-604(1997). RN [7] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP SUBCELLULAR LOCATION, SUBUNIT, AND PROBABLE DISULFIDE BOND. RX PubMed=21310150; DOI=10.1016/j.febslet.2011.01.046; RA Szklarczyk R., Wanschers B.F., Nabuurs S.B., Nouws J., Nijtmans L.G., RA Huynen M.A.; RT "NDUFB7 and NDUFA8 are located at the intermembrane surface of complex I."; RL FEBS Lett. 585:737-743(2011). RN [10] RP SUBCELLULAR LOCATION, AND DISULFIDE BONDS. RX PubMed=23676665; DOI=10.1091/mbc.e12-12-0862; RA Fischer M., Horn S., Belkacemi A., Kojer K., Petrungaro C., Habich M., RA Ali M., Kuettner V., Bien M., Kauff F., Dengjel J., Herrmann J.M., RA Riemer J.; RT "Protein import and oxidative folding in the mitochondrial intermembrane RT space of intact mammalian cells."; RL Mol. Biol. Cell 24:2160-2170(2013). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [12] RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [13] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [14] RP VARIANT [LARGE SCALE ANALYSIS] HIS-140. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [15] RP INVOLVEMENT IN MC1DN37, VARIANT MC1DN37 CYS-47, CHARACTERIZATION OF VARIANT RP MC1DN37 CYS-47, AND FUNCTION. RX PubMed=32385911; DOI=10.1111/cge.13773; RA Yatsuka Y., Kishita Y., Formosa L.E., Shimura M., Nozaki F., Fujii T., RA Nitta K.R., Ohtake A., Murayama K., Ryan M.T., Okazaki Y.; RT "A homozygous variant in NDUFA8 is associated with developmental delay, RT microcephaly, and epilepsy due to mitochondrial complex I deficiency."; RL Clin. Genet. 98:155-165(2020). RN [16] RP VARIANT MC1DN37 LEU-98, CHARACTERIZATION OF VARIANT MC1DN37 LEU-98, AND RP FUNCTION. RX PubMed=33153867; DOI=10.1016/j.ymgme.2020.10.005; RA Tort F., Barredo E., Parthasarathy R., Ugarteburu O., Ferrer-Cortes X., RA Garcia-Villoria J., Gort L., Gonzalez-Quintana A., Martin M.A., RA Fernandez-Vizarra E., Zeviani M., Ribes A.; RT "Biallelic mutations in NDUFA8 cause complex I deficiency in two siblings RT with favorable clinical evolution."; RL Mol. Genet. Metab. 131:349-357(2020). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis (PubMed:27626371, PubMed:32385911, CC PubMed:33153867). Complex I functions in the transfer of electrons from CC NADH to the respiratory chain (PubMed:27626371). The immediate electron CC acceptor for the enzyme is believed to be ubiquinone (PubMed:27626371). CC {ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:32385911, CC ECO:0000269|PubMed:33153867}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits. CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:21310150, CC ECO:0000269|PubMed:27626371}. CC -!- INTERACTION: CC P51970; G5E9A7: DMWD; NbExp=3; IntAct=EBI-1237250, EBI-10976677; CC P51970; O75489: NDUFS3; NbExp=5; IntAct=EBI-1237250, EBI-1224896; CC P51970; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-1237250, EBI-5235340; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:21310150}; Peripheral membrane protein CC {ECO:0000269|PubMed:21310150}. Mitochondrion intermembrane space CC {ECO:0000269|PubMed:21310150}. Mitochondrion CC {ECO:0000269|PubMed:23676665}. CC -!- DOMAIN: Contains four C-X9-C motifs that are predicted to form a helix- CC coil-helix structure, permitting the formation of intramolecular CC disulfide bonds. {ECO:0000305|PubMed:21310150}. CC -!- PTM: May contain intrachain disulfide bonds, as evidenced by its CC electrophoretic mobility under reducing vs non-reducing conditions. CC {ECO:0000269|PubMed:21310150}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 37 (MC1DN37) CC [MIM:619272]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN37 features include developmental delay, CC cerebral atrophy, epilepsy, growth retardation, congenital myopathy CC with disproportion of fibers, and severely decreased activity of CC complex I. MC1DN37 transmission pattern is consistent with autosomal CC recessive inheritance. {ECO:0000269|PubMed:32385911, CC ECO:0000269|PubMed:33153867}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFA8 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF044953; AAD42056.1; -; mRNA. DR EMBL; AK314135; BAG36825.1; -; mRNA. DR EMBL; AL162423; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471090; EAW87511.1; -; Genomic_DNA. DR EMBL; BC001016; AAH01016.1; -; mRNA. DR CCDS; CCDS6835.1; -. DR RefSeq; NP_055037.1; NM_014222.3. DR PDB; 5XTC; EM; 3.70 A; u=4-172. DR PDB; 5XTD; EM; 3.70 A; u=4-172. DR PDB; 5XTH; EM; 3.90 A; u=4-172. DR PDB; 5XTI; EM; 17.40 A; Bu/u=4-172. DR PDB; 9CWT; EM; 3.44 A; u=1-172. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; P51970; -. DR EMDB; EMD-45974; -. DR SMR; P51970; -. DR BioGRID; 110782; 203. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; P51970; -. DR FunCoup; P51970; 1524. DR IntAct; P51970; 89. DR MINT; P51970; -. DR STRING; 9606.ENSP00000362873; -. DR BindingDB; P51970; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; P51970; -. DR GlyGen; P51970; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P51970; -. DR PhosphoSitePlus; P51970; -. DR SwissPalm; P51970; -. DR BioMuta; NDUFA8; -. DR DMDM; 8039804; -. DR jPOST; P51970; -. DR MassIVE; P51970; -. DR PaxDb; 9606-ENSP00000362873; -. DR PeptideAtlas; P51970; -. DR ProteomicsDB; 56464; -. DR Pumba; P51970; -. DR TopDownProteomics; P51970; -. DR Antibodypedia; 30251; 221 antibodies from 31 providers. DR DNASU; 4702; -. DR Ensembl; ENST00000373768.4; ENSP00000362873.3; ENSG00000119421.8. DR GeneID; 4702; -. DR KEGG; hsa:4702; -. DR MANE-Select; ENST00000373768.4; ENSP00000362873.3; NM_014222.3; NP_055037.1. DR UCSC; uc004blv.4; human. DR AGR; HGNC:7692; -. DR ClinPGx; PA31498; -. DR CTD; 4702; -. DR DisGeNET; 4702; -. DR GeneCards; NDUFA8; -. DR HGNC; HGNC:7692; NDUFA8. DR HPA; ENSG00000119421; Tissue enhanced (heart). DR MalaCards; NDUFA8; -. DR MIM; 603359; gene. DR MIM; 619272; phenotype. DR OpenTargets; ENSG00000119421; -. DR VEuPathDB; HostDB:ENSG00000119421; -. DR eggNOG; KOG3458; Eukaryota. DR GeneTree; ENSGT00390000008938; -. DR HOGENOM; CLU_081931_2_1_1; -. DR InParanoid; P51970; -. DR OMA; FRTHWQC; -. DR OrthoDB; 276296at2759; -. DR PAN-GO; P51970; 1 GO annotation based on evolutionary models. DR PhylomeDB; P51970; -. DR BioCyc; MetaCyc:HS04297-MONOMER; -. DR PathwayCommons; P51970; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; P51970; -. DR SIGNOR; P51970; -. DR Agora; ENSG00000119421; -. DR BioGRID-ORCS; 4702; 299 hits in 1169 CRISPR screens. DR ChiTaRS; NDUFA8; human. DR GeneWiki; NDUFA8; -. DR GenomeRNAi; 4702; -. DR Pharos; P51970; Tclin. DR PRO; PR:P51970; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; P51970; protein. DR Bgee; ENSG00000119421; Expressed in apex of heart and 199 other cell types or tissues. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; TAS:ProtInc. DR GO; GO:0044877; F:protein-containing complex binding; IDA:MGI. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; NAS:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR InterPro; IPR010625; CHCH. DR InterPro; IPR016680; NDUFA8. DR PANTHER; PTHR13344:SF0; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX SUBUNIT 8; 1. DR PANTHER; PTHR13344; NADH-UBIQUINONE OXIDOREDUCTASE; 1. DR Pfam; PF06747; CHCH; 1. DR PIRSF; PIRSF017016; NDUA8; 1. DR PROSITE; PS51808; CHCH; 2. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Disease variant; Disulfide bond; KW Electron transport; Membrane; Mitochondrion; Mitochondrion inner membrane; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Repeat; Respiratory chain; Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:9150947, FT ECO:0007744|PubMed:25944712" FT CHAIN 2..172 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT subunit 8" FT /id="PRO_0000118734" FT DOMAIN 33..74 FT /note="CHCH 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT DOMAIN 75..118 FT /note="CHCH 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT REGION 133..164 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 36..46 FT /note="Cx9C motif 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT MOTIF 56..66 FT /note="Cx9C motif 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT MOTIF 78..88 FT /note="Cx9C motif 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT MOTIF 100..110 FT /note="Cx9C motif 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT DISULFID 36..66 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150, FT ECO:0000305|PubMed:23676665" FT DISULFID 46..56 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150, FT ECO:0000305|PubMed:23676665" FT DISULFID 78..110 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150, FT ECO:0000305|PubMed:23676665" FT DISULFID 88..100 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150, FT ECO:0000305|PubMed:23676665" FT VARIANT 47 FT /note="R -> C (in MC1DN37; reduced enzymatic activity of FT the respiratory chain complex I; reduced NDUFA8 protein FT levels; decrease in respiratory supercomplexes comprising FT complex I (CI/CIII 2/CIV and CI/CIII 2) as well as an FT increase in unintegrated complex III dimers; FT dbSNP:rs767864225)" FT /evidence="ECO:0000269|PubMed:32385911" FT /id="VAR_085554" FT VARIANT 98 FT /note="R -> L (in MC1DN37; defect in the assembly of FT respiratory chain complex I; reduced enzymatic activity of FT the respiratory chain complex I; altered fibroblast FT mitochondria morphology and reduced mitochondrial network FT branching; no significant differences in mitochondrial FT respiratory capacity; dbSNP:rs1319414797)" FT /evidence="ECO:0000269|PubMed:33153867" FT /id="VAR_085555" FT VARIANT 140 FT /note="N -> H (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036176" SQ SEQUENCE 172 AA; 20105 MW; E1647472B69E1149 CRC64; MPGIVELPTL EELKVDEVKI SSAVLKAAAH HYGAQCDKPN KEFMLCRWEE KDPRRCLEEG KLVNKCALDF FRQIKRHCAE PFTEYWTCID YTGQQLFRHC RKQQAKFDEC VLDKLGWVRP DLGELSKVTK VKTDRPLPEN PYHSRPRPDP SPEIEGDLQP ATHGSRFYFW TK // ID NDUA9_HUMAN Reviewed; 377 AA. AC Q16795; Q14076; Q2NKX0; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 28-JAN-2026, entry version 208. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial; DE AltName: Full=Complex I-39kD; DE Short=CI-39kD; DE AltName: Full=NADH-ubiquinone oxidoreductase 39 kDa subunit; DE Flags: Precursor; GN Name=NDUFA9; Synonyms=NDUFS2L; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Loeffen J.L.C.M., Smeets R.J.P., Triepels R., Ruitenbeek W., RA Smeitink J.A.M., van den Heuvel L.; RT "39 kDa subunit of NADH-ubiquinone oxidoreductase."; RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon, Muscle, and Skeletal muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-33. RC TISSUE=Blood; RX PubMed=8012384; DOI=10.1038/ng0394-236; RA Cross S.H., Charlton J.A., Nan X., Bird A.P.; RT "Purification of CpG islands using a methylated DNA binding column."; RL Nat. Genet. 6:236-244(1994). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-377. RC TISSUE=Liver; RX PubMed=8486360; DOI=10.1006/geno.1993.1161; RA Baens M., Chaffanet M., Cassiman J.-J., van den Berghe H., Marynen P.; RT "Construction and evaluation of a hncDNA library of human 12p transcribed RT sequences derived from a somatic cell hybrid."; RL Genomics 16:214-218(1993). RN [5] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [7] RP INTERACTION WITH BLOC1S1, AND ACETYLATION. RX PubMed=22309213; DOI=10.1042/bj20120118; RA Scott I., Webster B.R., Li J.H., Sack M.N.; RT "Identification of a molecular component of the mitochondrial acetyl RT transferase program; a novel role for GCN5L1."; RL Biochem. J. 443:655-661(2012). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [10] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [11] RP INVOLVEMENT IN MC1DN26, VARIANT MC1DN26 PRO-321, AND FUNCTION. RX PubMed=22114105; DOI=10.1136/jmedgenet-2011-100466; RA van den Bosch B.J., Gerards M., Sluiter W., Stegmann A.P., Jongen E.L., RA Hellebrekers D.M., Oegema R., Lambrichs E.H., Prokisch H., Danhauser K., RA Schoonderwoerd K., de Coo I.F., Smeets H.J.; RT "Defective NDUFA9 as a novel cause of neonatally fatal complex I disease."; RL J. Med. Genet. 49:10-15(2012). RN [12] RP ACETYLATION, AND INTERACTION WITH CLOCK. RX PubMed=28985504; DOI=10.1016/j.molcel.2017.09.008; RA Lin R., Mo Y., Zha H., Qu Z., Xie P., Zhu Z.J., Xu Y., Xiong Y., Guan K.L.; RT "CLOCK acetylates ASS1 to drive circadian rhythm of ureagenesis."; RL Mol. Cell 68:198-209(2017). RN [13] RP FUNCTION, INVOLVEMENT IN MC1DN26, VARIANTS MC1DN26 PRO-321 AND CYS-360, AND RP CHARACTERIZATION OF VARIANTS MC1DN26 PRO-321 AND CYS-360. RX PubMed=28671271; DOI=10.1111/cge.13089; RA Baertling F., Sanchez-Caballero L., van den Brand M.A.M., Fung C.W., RA Chan S.H., Wong V.C., Hellebrekers D.M.E., de Coo I.F.M., Smeitink J.A.M., RA Rodenburg R.J.T., Nijtmans L.G.J.; RT "NDUFA9 point mutations cause a variable mitochondrial complex I assembly RT defect."; RL Clin. Genet. 93:111-118(2018). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH RAB5IF. RX PubMed=31536960; DOI=10.1016/j.isci.2019.08.057; RA Moutaoufik M.T., Malty R., Amin S., Zhang Q., Phanse S., Gagarinova A., RA Zilocchi M., Hoell L., Minic Z., Gagarinova M., Aoki H., Stockwell J., RA Jessulat M., Goebels F., Broderick K., Scott N.E., Vlasblom J., Musso G., RA Prasad B., Lamantea E., Garavaglia B., Rajput A., Murayama K., Okazaki Y., RA Foster L.J., Bader G.D., Cayabyab F.S., Babu M.; RT "Rewiring of the Human Mitochondrial Interactome during Neuronal RT Reprogramming Reveals Regulators of the Respirasome and Neurogenesis."; RL IScience 19:1114-1132(2019). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis. Required for proper complex I assembly CC (PubMed:28671271). Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:22114105, CC ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:28671271}. CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Note=Binds 1 FAD per subunit.; CC -!- SUBUNIT: Complex I is composed of 45 different subunits. This a CC component of the hydrophobic protein fraction (PubMed:12611891, CC PubMed:27626371). Interacts with BLOC1S1 (PubMed:22309213). Interacts CC with SLC2A4 (By similarity). Interacts with CLOCK (PubMed:28985504). CC Interacts with RAB5IF (PubMed:31536960). {ECO:0000250|UniProtKB:Q5BK63, CC ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:22309213, CC ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:28985504, CC ECO:0000269|PubMed:31536960}. CC -!- INTERACTION: CC Q16795; P78537: BLOC1S1; NbExp=3; IntAct=EBI-1045087, EBI-348630; CC Q16795; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-1045087, EBI-3867333; CC Q16795; P42858: HTT; NbExp=7; IntAct=EBI-1045087, EBI-466029; CC Q16795; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-1045087, EBI-11962084; CC Q16795; P28331: NDUFS1; NbExp=4; IntAct=EBI-1045087, EBI-1043922; CC Q16795; Q8NC60: NOA1; NbExp=2; IntAct=EBI-1045087, EBI-717871; CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000305|PubMed:12611891}. CC -!- PTM: Acetylated on lysine residues. BLOC1S1 is required for acetylation CC (PubMed:22309213). Acetylated by CLOCK in a circadian manner CC (PubMed:28985504). {ECO:0000269|PubMed:22309213, CC ECO:0000269|PubMed:28985504}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 26 (MC1DN26) CC [MIM:618247]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN26 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:22114105, CC ECO:0000269|PubMed:28671271}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFA9 subunit family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA54099.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF050641; AAD42055.1; -; mRNA. DR EMBL; BC009311; AAH09311.1; -; mRNA. DR EMBL; BC015837; AAH15837.1; -; mRNA. DR EMBL; BC111546; AAI11547.1; -; mRNA. DR EMBL; X76665; CAA54099.1; ALT_FRAME; Genomic_DNA. DR EMBL; L04490; AAA36350.1; -; mRNA. DR CCDS; CCDS8532.1; -. DR PIR; I37258; I37258. DR RefSeq; NP_004993.1; NM_005002.5. DR PDB; 5XTB; EM; 3.40 A; J=40-376. DR PDB; 5XTD; EM; 3.70 A; J=40-376. DR PDB; 5XTH; EM; 3.90 A; J=40-376. DR PDB; 5XTI; EM; 17.40 A; BJ/J=40-376. DR PDB; 9CWT; EM; 3.44 A; J=1-377. DR PDBsum; 5XTB; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; Q16795; -. DR EMDB; EMD-45974; -. DR SMR; Q16795; -. DR BioGRID; 110784; 358. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; Q16795; -. DR DIP; DIP-38526N; -. DR FunCoup; Q16795; 2517. DR IntAct; Q16795; 135. DR MINT; Q16795; -. DR STRING; 9606.ENSP00000266544; -. DR BindingDB; Q16795; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB03147; Flavin adenine dinucleotide. DR DrugBank; DB00157; NADH. DR DrugCentral; Q16795; -. DR CarbonylDB; Q16795; -. DR GlyGen; Q16795; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q16795; -. DR PhosphoSitePlus; Q16795; -. DR SwissPalm; Q16795; -. DR BioMuta; NDUFA9; -. DR DMDM; 2833280; -. DR jPOST; Q16795; -. DR MassIVE; Q16795; -. DR PaxDb; 9606-ENSP00000266544; -. DR PeptideAtlas; Q16795; -. DR ProteomicsDB; 61072; -. DR Pumba; Q16795; -. DR TopDownProteomics; Q16795; -. DR Antibodypedia; 22301; 258 antibodies from 30 providers. DR DNASU; 4704; -. DR Ensembl; ENST00000266544.10; ENSP00000266544.5; ENSG00000139180.12. DR GeneID; 4704; -. DR KEGG; hsa:4704; -. DR MANE-Select; ENST00000266544.10; ENSP00000266544.5; NM_005002.5; NP_004993.1. DR UCSC; uc001qnc.4; human. DR AGR; HGNC:7693; -. DR ClinPGx; PA31499; -. DR CTD; 4704; -. DR DisGeNET; 4704; -. DR GeneCards; NDUFA9; -. DR HGNC; HGNC:7693; NDUFA9. DR HPA; ENSG00000139180; Low tissue specificity. DR MalaCards; NDUFA9; -. DR MIM; 603834; gene. DR MIM; 618247; phenotype. DR OpenTargets; ENSG00000139180; -. DR VEuPathDB; HostDB:ENSG00000139180; -. DR eggNOG; KOG2865; Eukaryota. DR GeneTree; ENSGT00390000006865; -. DR HOGENOM; CLU_007383_6_4_1; -. DR InParanoid; Q16795; -. DR OMA; PEDQFTN; -. DR OrthoDB; 275457at2759; -. DR PAN-GO; Q16795; 3 GO annotations based on evolutionary models. DR PhylomeDB; Q16795; -. DR BioCyc; MetaCyc:HS06589-MONOMER; -. DR PathwayCommons; Q16795; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q16795; -. DR SIGNOR; Q16795; -. DR Agora; ENSG00000139180; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 4704; 185 hits in 1172 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFA9; human. DR GeneWiki; NDUFA9; -. DR GenomeRNAi; 4704; -. DR Pharos; Q16795; Tclin. DR PRO; PR:Q16795; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q16795; protein. DR Bgee; ENSG00000139180; Expressed in apex of heart and 205 other cell types or tissues. DR ExpressionAtlas; Q16795; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB. DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0005634; C:nucleus; HDA:UniProtKB. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB. DR GO; GO:0003954; F:NADH dehydrogenase activity; IMP:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IDA:MGI. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0007623; P:circadian rhythm; IDA:UniProtKB. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; NAS:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR GO; GO:0006814; P:sodium ion transport; NAS:UniProtKB. DR GO; GO:0006744; P:ubiquinone biosynthetic process; IBA:GO_Central. DR CDD; cd05271; NDUFA9_like_SDR_a; 1. DR FunFam; 3.40.50.720:FF:000246; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR051207; ComplexI_NDUFA9_subunit. DR InterPro; IPR001509; Epimerase_deHydtase. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR PANTHER; PTHR12126:SF10; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX SUBUNIT 9, MITOCHONDRIAL; 1. DR PANTHER; PTHR12126; NADH-UBIQUINONE OXIDOREDUCTASE 39 KDA SUBUNIT-RELATED; 1. DR Pfam; PF01370; Epimerase; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Disease variant; Electron transport; FAD; KW Flavoprotein; Mitochondrion; Primary mitochondrial disease; KW Proteomics identification; Reference proteome; Respiratory chain; KW Transit peptide; Transport. FT TRANSIT 1..35 FT /note="Mitochondrion" FT /evidence="ECO:0000250" FT CHAIN 36..377 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT subunit 9, mitochondrial" FT /id="PRO_0000019992" FT MOD_RES 175 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9DC69" FT MOD_RES 189 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9DC69" FT MOD_RES 370 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9DC69" FT VARIANT 321 FT /note="R -> P (in MC1DN26; loss of function in complex I FT assembly; accumulation of several low and high molecular FT weight assembly intermediates is observed in patient FT fibroblasts; dbSNP:rs199592341)" FT /evidence="ECO:0000269|PubMed:22114105, FT ECO:0000269|PubMed:28671271" FT /id="VAR_078936" FT VARIANT 360 FT /note="R -> C (in MC1DN26; loss of function in complex I FT assembly; accumulation of several low and high molecular FT weight assembly intermediates is observed in patient FT fibroblasts; dbSNP:rs3210083)" FT /evidence="ECO:0000269|PubMed:28671271" FT /id="VAR_081457" FT STRAND 43..51 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 55..57 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 59..62 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 64..75 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 79..84 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 89..97 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 100..102 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 103..107 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 114..119 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 120..122 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 124..126 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 137..139 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 141..144 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 147..159 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 162..167 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 179..194 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 199..201 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 212..223 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 225..229 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 230..233 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 242..254 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 273..284 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 290..293 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 295..305 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 316..323 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 335..337 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 345..347 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 349..353 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 354..356 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 359..362 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 367..369 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 377 AA; 42510 MW; 66A1CC7FCE86DD0E CRC64; MAAAAQSRVV RVLSMSRSAI TAIATSVCHG PPCRQLHHAL MPHGKGGRSS VSGIVATVFG ATGFLGRYVV NHLGRMGSQV IIPYRCDKYD IMHLRPMGDL GQLLFLEWDA RDKDSIRRVV QHSNVVINLI GRDWETKNFD FEDVFVKIPQ AIAQLSKEAG VEKFIHVSHL NANIKSSSRY LRNKAVGEKV VRDAFPEAII VKPSDIFGRE DRFLNSFASM HRFGPIPLGS LGWKTVKQPV YVVDVSKGIV NAVKDPDANG KSFAFVGPSR YLLFHLVKYI FAVAHRLFLP FPLPLFAYRW VARVFEISPF EPWITRDKVE RMHITDMKLP HLPGLEDLGI QATPLELKAI EVLRRHRTYR WLSAEIEDVK PAKTVNI // ID NDUAA_HUMAN Reviewed; 355 AA. AC O95299; Q8WXC9; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 28-JAN-2026, entry version 200. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial; DE AltName: Full=Complex I-42kD; DE Short=CI-42kD; DE AltName: Full=NADH-ubiquinone oxidoreductase 42 kDa subunit; DE Flags: Precursor; GN Name=NDUFA10; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9878551; DOI=10.1006/bbrc.1998.9786; RA Loeffen J.L.C.M., Triepels R.H., van den Heuvel L.P., Schuelke M., RA Buskens C.A.F., Smeets R.J.P., Trijbels J.M.F., Smeitink J.A.M.; RT "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: RT human complex I cDNA characterization completed."; RL Biochem. Biophys. Res. Commun. 253:415-422(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Hu W., Tang L.-J., Shi Y.-W., Tian J.-Y., Jian Y.-S.; RT "Homo sapiens, NADH dehydrogenase (ubiquinone) 1 alpha subcomplex."; RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [7] RP INVOLVEMENT IN MC1DN22, AND VARIANT MC1DN22 ARG-142. RX PubMed=21150889; DOI=10.1038/ejhg.2010.204; RA Hoefs S.J., van Spronsen F.J., Lenssen E.W., Nijtmans L.G., Rodenburg R.J., RA Smeitink J.A., van den Heuvel L.P.; RT "NDUFA10 mutations cause complex I deficiency in a patient with Leigh RT disease."; RL Eur. J. Hum. Genet. 19:270-274(2011). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [10] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [11] RP INVOLVEMENT IN MC1DN22, AND VARIANT MC1DN22 PRO-294. RX PubMed=26741492; DOI=10.1371/journal.pgen.1005679; RA Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y., RA Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H., RA Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T., Sato-Miyata Y., RA Ohnuma K., Suzuki T., Nagao A., Maehata H., Matsuda F., Higasa K., RA Nagasaki M., Yasuda J., Yamamoto M., Fushimi T., Shimura M., RA Kaiho-Ichimoto K., Harashima H., Yamazaki T., Mori M., Murayama K., RA Ohtake A., Okazaki Y.; RT "A comprehensive genomic analysis reveals the genetic landscape of RT mitochondrial respiratory chain complex deficiencies."; RL PLoS Genet. 12:E1005679-E1005679(2016). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis. Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}. CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Note=Binds 1 FAD per subunit.; CC -!- SUBUNIT: Complex I is composed of 45 different subunits. This a CC component of the hydrophobic protein fraction. CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}. CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000305|PubMed:12611891}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O95299-1; Sequence=Displayed; CC Name=2; CC IsoId=O95299-2; Sequence=VSP_056417, VSP_056418, VSP_056419; CC -!- PTM: Phosphorylation at Ser-250 by PINK1 is required for the binding CC and/or reduction of the complex I substrate ubiquinone. CC {ECO:0000250|UniProtKB:Q99LC3}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 22 (MC1DN22) CC [MIM:618243]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN22 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:21150889, CC ECO:0000269|PubMed:26741492}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFA10 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF087661; AAD09755.1; -; mRNA. DR EMBL; AF453834; AAL50984.1; -; mRNA. DR EMBL; AC013469; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC114750; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC233275; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC003417; AAH03417.1; -; mRNA. DR CCDS; CCDS2531.1; -. [O95299-1] DR PIR; JE0385; JE0385. DR RefSeq; NP_004535.1; NM_004544.4. [O95299-1] DR PDB; 5XTC; EM; 3.70 A; w=36-355. DR PDB; 5XTD; EM; 3.70 A; w=36-355. DR PDB; 5XTH; EM; 3.90 A; w=36-355. DR PDB; 5XTI; EM; 17.40 A; Bw/w=36-355. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR AlphaFoldDB; O95299; -. DR SMR; O95299; -. DR BioGRID; 110785; 186. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O95299; -. DR FunCoup; O95299; 1823. DR IntAct; O95299; 92. DR MINT; O95299; -. DR STRING; 9606.ENSP00000252711; -. DR BindingDB; O95299; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; O95299; -. DR GlyGen; O95299; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O95299; -. DR PhosphoSitePlus; O95299; -. DR SwissPalm; O95299; -. DR BioMuta; NDUFA10; -. DR jPOST; O95299; -. DR MassIVE; O95299; -. DR PaxDb; 9606-ENSP00000252711; -. DR PeptideAtlas; O95299; -. DR PRIDE; O95299; -. DR ProteomicsDB; 50799; -. [O95299-1] DR ProteomicsDB; 75009; -. DR Pumba; O95299; -. DR Antibodypedia; 34509; 193 antibodies from 30 providers. DR DNASU; 4705; -. DR Ensembl; ENST00000252711.7; ENSP00000252711.2; ENSG00000130414.14. [O95299-1] DR Ensembl; ENST00000307300.8; ENSP00000302321.4; ENSG00000130414.14. [O95299-2] DR Ensembl; ENST00000676929.1; ENSP00000503956.1; ENSG00000130414.14. [O95299-1] DR Ensembl; ENST00000678158.1; ENSP00000504765.1; ENSG00000130414.14. [O95299-1] DR GeneID; 4705; -. DR KEGG; hsa:4705; -. DR MANE-Select; ENST00000252711.7; ENSP00000252711.2; NM_004544.4; NP_004535.1. DR UCSC; uc002vyn.3; human. [O95299-1] DR AGR; HGNC:7684; -. DR ClinPGx; PA31490; -. DR CTD; 4705; -. DR DisGeNET; 4705; -. DR GeneCards; NDUFA10; -. DR GeneReviews; NDUFA10; -. DR HGNC; HGNC:7684; NDUFA10. DR HPA; ENSG00000130414; Tissue enhanced (tongue). DR MalaCards; NDUFA10; -. DR MIM; 603835; gene. DR MIM; 618243; phenotype. DR OpenTargets; ENSG00000130414; -. DR VEuPathDB; HostDB:ENSG00000130414; -. DR eggNOG; KOG3877; Eukaryota. DR GeneTree; ENSGT00390000016151; -. DR HOGENOM; CLU_050591_0_0_1; -. DR InParanoid; O95299; -. DR OrthoDB; 17400at2759; -. DR PAN-GO; O95299; 3 GO annotations based on evolutionary models. DR PhylomeDB; O95299; -. DR BioCyc; MetaCyc:HS05385-MONOMER; -. DR PathwayCommons; O95299; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; O95299; -. DR SIGNOR; O95299; -. DR Agora; ENSG00000130414; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 4705; 181 hits in 1164 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFA10; human. DR GeneWiki; NDUFA10; -. DR GenomeRNAi; 4705; -. DR Pharos; O95299; Tclin. DR PRO; PR:O95299; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; O95299; protein. DR Bgee; ENSG00000130414; Expressed in apex of heart and 204 other cell types or tissues. DR ExpressionAtlas; O95299; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IBA:GO_Central. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR CDD; cd02030; NDUO42; 1. DR FunFam; 3.40.50.300:FF:000837; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR050566; Deoxyribonucleoside_kinase. DR InterPro; IPR031314; DNK_dom. DR InterPro; IPR015828; NDUFA10. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR10513; DEOXYNUCLEOSIDE KINASE; 1. DR PANTHER; PTHR10513:SF15; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX SUBUNIT 10, MITOCHONDRIAL; 1. DR Pfam; PF01712; dNK; 1. DR PIRSF; PIRSF000543; NADH_UQ_42KD; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Disease variant; Electron transport; KW FAD; Flavoprotein; Mitochondrion; Phosphoprotein; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transit peptide; Transport. FT TRANSIT 1..35 FT /note="Mitochondrion" FT /evidence="ECO:0000250|UniProtKB:P34942" FT CHAIN 36..355 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT subunit 10, mitochondrial" FT /id="PRO_0000019988" FT MOD_RES 250 FT /note="Phosphoserine; by PINK1" FT /evidence="ECO:0000250|UniProtKB:Q99LC3" FT MOD_RES 285 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99LC3" FT VAR_SEQ 183 FT /note="C -> CESALQTHFWTGVAGASGKLESGSSEEVLLINERGGRSKPG (in FT isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_056417" FT VAR_SEQ 214..223 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_056418" FT VAR_SEQ 334..355 FT /note="LPGRKYSPGYNTEVGDKWIWLK -> RLDWTVCFGEESTEVKHQGHLLSVQP FT GTVALTVGSWLRSCLLGLHWKLLFLFPESPMHTTAFMFLC (in isoform 2)" FT /evidence="ECO:0000303|Ref.2" FT /id="VSP_056419" FT VARIANT 2 FT /note="A -> G (in dbSNP:rs11541494)" FT /id="VAR_034149" FT VARIANT 142 FT /note="Q -> R (in MC1DN22; dbSNP:rs387906873)" FT /evidence="ECO:0000269|PubMed:21150889" FT /id="VAR_078937" FT VARIANT 294 FT /note="L -> P (in MC1DN22; uncertain significance; FT dbSNP:rs1057519414)" FT /evidence="ECO:0000269|PubMed:26741492" FT /id="VAR_081458" SQ SEQUENCE 355 AA; 40751 MW; B5C27BC150A3E691 CRC64; MALRLLKLAA TSASARVVAA GAQRVRGIHS SVQCKLRYGM WHFLLGDKAS KRLTERSRVI TVDGNICTGK GKLAKEIAEK LGFKHFPEAG IHYPDSTTGD GKPLATDYNG NCSLEKFYDD PRSNDGNSYR LQSWLYSSRL LQYSDALEHL LTTGQGVVLE RSIFSDFVFL EAMYNQGFIR KQCVDHYNEV KSVTICDYLP PHLVIYIDVP VPEVQRRIQK KGDPHEMKIT SAYLQDIENA YKKTFLPEMS EKCEVLQYSA REAQDSKKVV EDIEYLKFDK GPWLKQDNRT LYHLRLLVQD KFEVLNYTSI PIFLPEVTIG AHQTDRVLHQ FRELPGRKYS PGYNTEVGDK WIWLK // ID NDUAB_HUMAN Reviewed; 141 AA. AC Q86Y39; C9JT23; Q6ZS66; DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 28-JAN-2026, entry version 171. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11; DE AltName: Full=Complex I-B14.7; DE Short=CI-B14.7; DE AltName: Full=NADH-ubiquinone oxidoreductase subunit B14.7; GN Name=NDUFA11; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION BY MASS RP SPECTROMETRY, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE RP COMPLEX. RC TISSUE=Heart; RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP PROTEIN SEQUENCE OF 2-7. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [6] RP INVOLVEMENT IN MC1DN14. RX PubMed=18306244; DOI=10.1002/ana.21332; RA Berger I., Hershkovitz E., Shaag A., Edvardson S., Saada A., Elpeleg O.; RT "Mitochondrial complex I deficiency caused by a deleterious NDUFA11 RT mutation."; RL Ann. Neurol. 63:405-408(2008). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [9] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis. Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits. CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}. CC -!- INTERACTION: CC Q86Y39; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-1246415, EBI-16439278; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891}; Multi-pass membrane protein CC {ECO:0000255}; Matrix side {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q86Y39-1; Sequence=Displayed; CC Name=2; CC IsoId=Q86Y39-2; Sequence=VSP_033813; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 14 (MC1DN14) CC [MIM:618236]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN14 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:18306244}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFA11 subunit family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAC87088.1; Type=Miscellaneous discrepancy; Note=Erroneous CDS prediction.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ539081; CAD62165.1; -; mRNA. DR EMBL; AK127692; BAC87088.1; ALT_SEQ; mRNA. DR EMBL; AC024592; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC104532; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC069045; AAH69045.1; -; mRNA. DR CCDS; CCDS12155.1; -. [Q86Y39-1] DR CCDS; CCDS54203.1; -. [Q86Y39-2] DR RefSeq; NP_001180304.1; NM_001193375.3. [Q86Y39-2] DR RefSeq; NP_783313.1; NM_175614.5. [Q86Y39-1] DR PDB; 5XTC; EM; 3.70 A; V=2-141. DR PDB; 5XTD; EM; 3.70 A; V=2-141. DR PDB; 5XTH; EM; 3.90 A; V=2-141. DR PDB; 5XTI; EM; 17.40 A; BV/V=2-141. DR PDB; 9CWT; EM; 3.44 A; V=1-141. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; Q86Y39; -. DR EMDB; EMD-45974; -. DR SMR; Q86Y39; -. DR BioGRID; 125981; 71. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; Q86Y39; -. DR FunCoup; Q86Y39; 843. DR IntAct; Q86Y39; 47. DR MINT; Q86Y39; -. DR STRING; 9606.ENSP00000389160; -. DR BindingDB; Q86Y39; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; Q86Y39; -. DR GlyGen; Q86Y39; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q86Y39; -. DR PhosphoSitePlus; Q86Y39; -. DR SwissPalm; Q86Y39; -. DR BioMuta; NDUFA11; -. DR DMDM; 52000823; -. DR jPOST; Q86Y39; -. DR MassIVE; Q86Y39; -. DR PaxDb; 9606-ENSP00000389160; -. DR PeptideAtlas; Q86Y39; -. DR ProteomicsDB; 11546; -. DR ProteomicsDB; 70371; -. [Q86Y39-1] DR ProteomicsDB; 70372; -. [Q86Y39-2] DR Pumba; Q86Y39; -. DR TopDownProteomics; Q86Y39-1; -. [Q86Y39-1] DR Antibodypedia; 52912; 78 antibodies from 24 providers. DR DNASU; 126328; -. DR Ensembl; ENST00000308961.5; ENSP00000311740.4; ENSG00000174886.16. [Q86Y39-1] DR Ensembl; ENST00000418389.7; ENSP00000389160.1; ENSG00000174886.16. [Q86Y39-2] DR Ensembl; ENST00000709622.1; ENSP00000517806.1; ENSG00000292058.1. [Q86Y39-2] DR Ensembl; ENST00000709624.1; ENSP00000517808.1; ENSG00000292058.1. [Q86Y39-1] DR GeneID; 126328; -. DR KEGG; hsa:126328; -. DR MANE-Select; ENST00000308961.5; ENSP00000311740.4; NM_175614.5; NP_783313.1. DR UCSC; uc002mdp.3; human. [Q86Y39-1] DR AGR; HGNC:20371; -. DR ClinPGx; PA134914606; -. DR CTD; 126328; -. DR DisGeNET; 126328; -. DR GeneCards; NDUFA11; -. DR HGNC; HGNC:20371; NDUFA11. DR HPA; ENSG00000174886; Low tissue specificity. DR MalaCards; NDUFA11; -. DR MIM; 612638; gene. DR MIM; 618236; phenotype. DR OpenTargets; ENSG00000174886; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000174886; -. DR eggNOG; ENOG502S6F6; Eukaryota. DR GeneTree; ENSGT00390000012434; -. DR HOGENOM; CLU_1214425_0_0_1; -. DR InParanoid; Q86Y39; -. DR OMA; SIEQGWE; -. DR OrthoDB; 1913277at2759; -. DR PAN-GO; Q86Y39; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q86Y39; -. DR BioCyc; MetaCyc:HS16402-MONOMER; -. DR PathwayCommons; Q86Y39; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q86Y39; -. DR SIGNOR; Q86Y39; -. DR Agora; ENSG00000174886; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 126328; 400 hits in 1142 CRISPR screens. DR ChiTaRS; NDUFA11; human. DR GenomeRNAi; 126328; -. DR Pharos; Q86Y39; Tclin. DR PRO; PR:Q86Y39; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q86Y39; protein. DR Bgee; ENSG00000174886; Expressed in pancreatic ductal cell and 183 other cell types or tissues. DR ExpressionAtlas; Q86Y39; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IEA:InterPro. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR InterPro; IPR039205; NDUFA11. DR PANTHER; PTHR21382:SF1; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX SUBUNIT 11; 1. DR PANTHER; PTHR21382; NADH-UBIQUINONE OXIDOREDUCTASE SUBUNIT; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing; KW Electron transport; Membrane; Mitochondrion; Mitochondrion inner membrane; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transmembrane; Transmembrane helix; KW Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q8HXG6, FT ECO:0000269|PubMed:12665801" FT CHAIN 2..141 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT subunit 11" FT /id="PRO_0000118841" FT TRANSMEM 21..43 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 58..80 FT /note="Helical" FT /evidence="ECO:0000255" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:Q8HXG6" FT VAR_SEQ 105..141 FT /note="THNYGIGAAACVYFGIAASLVKMGRLEGWEVFAKPKV -> KTGSHCVVQAG FT LKLLASSSPHTSASQSAGIIGMSHCVQRFWVPSSSACLEVLSGESTDVHACSSTRGACN FT SSGSRPLPELGARASGSLRKGGHTHPAPRGAGALTPVQALIESLLNTLGSNPRT (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_033813" FT CONFLICT Q86Y39-2:160 FT /note="S -> G (in Ref. 2; BAC87088)" FT /evidence="ECO:0000305" FT CONFLICT Q86Y39-2:221 FT /note="T -> A (in Ref. 2; BAC87088)" FT /evidence="ECO:0000305" SQ SEQUENCE 141 AA; 14852 MW; 379D58482D7E8BDB CRC64; MAPKVFRQYW DIPDGTDCHR KAYSTTSIAS VAGLTAAAYR VTLNPPGTFL EGVAKVGQYT FTAAAVGAVF GLTTCISAHV REKPDDPLNY FLGGCAGGLT LGARTHNYGI GAAACVYFGI AASLVKMGRL EGWEVFAKPK V // ID NDUAC_HUMAN Reviewed; 145 AA. AC Q9UI09; F8VQS7; Q53XX0; Q9BRV6; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 28-JAN-2026, entry version 196. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12; DE AltName: Full=13 kDa differentiation-associated protein; DE AltName: Full=Complex I-B17.2; DE Short=CI-B17.2; DE Short=CIB17.2; DE AltName: Full=NADH-ubiquinone oxidoreductase subunit B17.2; GN Name=NDUFA12; Synonyms=DAP13; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10830904; DOI=10.1007/s004390000278; RA Triepels R., Smeitink J., Loeffen J., Smeets R., Trijbels F., RA van den Heuvel L.; RT "Characterization of the human complex I NDUFB7 and 17.2-kDa cDNAs and RT mutational analysis of 19 genes of the HP fraction in complex I-deficient- RT patients."; RL Hum. Genet. 106:385-391(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Adrenal gland; RX PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J., RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., RA Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis RT and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-104. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-104. RC TISSUE=Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [8] RP INVOLVEMENT IN MC1DN23, AND VARIANT MC1DN23 60-ARG--LYS-145 DEL. RX PubMed=21617257; DOI=10.1136/jmg.2011.088856; RA Ostergaard E., Rodenburg R.J., van den Brand M., Thomsen L.L., Duno M., RA Batbayli M., Wibrand F., Nijtmans L.; RT "Respiratory chain complex I deficiency due to NDUFA12 mutations as a new RT cause of Leigh syndrome."; RL J. Med. Genet. 48:737-740(2011). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [12] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis. Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits. CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}. CC -!- INTERACTION: CC Q9UI09; Q96JP2: MYO15B; NbExp=3; IntAct=EBI-1246332, EBI-7950783; CC Q9UI09; Q9H2B2: SYT4; NbExp=3; IntAct=EBI-1246332, EBI-751132; CC Q9UI09; Q6PL24: TMED8; NbExp=3; IntAct=EBI-1246332, EBI-11603430; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891}; Peripheral membrane protein CC {ECO:0000255}; Matrix side {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UI09-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UI09-2; Sequence=VSP_046948; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 23 (MC1DN23) CC [MIM:618244]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN23 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:21617257}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- MISCELLANEOUS: In NDUFA12-knockout cells, complex I assembly is not CC affected, probably due to substitution by the NDUFAF2 paralog. CC {ECO:0000269|PubMed:27626371}. CC -!- SIMILARITY: Belongs to the complex I NDUFA12 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF217092; AAF91224.1; -; mRNA. DR EMBL; AF112208; AAF17196.1; -; mRNA. DR EMBL; BT007220; AAP35884.1; -; mRNA. DR EMBL; AC011598; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC132009; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC005936; AAH05936.1; -; mRNA. DR CCDS; CCDS58263.1; -. [Q9UI09-2] DR CCDS; CCDS9050.1; -. [Q9UI09-1] DR RefSeq; NP_001245267.1; NM_001258338.2. [Q9UI09-2] DR RefSeq; NP_061326.1; NM_018838.5. [Q9UI09-1] DR PDB; 5XTB; EM; 3.40 A; N=2-144. DR PDB; 5XTD; EM; 3.70 A; N=2-144. DR PDB; 5XTH; EM; 3.90 A; N=2-144. DR PDB; 5XTI; EM; 17.40 A; BN/N=2-144. DR PDB; 9CWT; EM; 3.44 A; N=1-145. DR PDBsum; 5XTB; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; Q9UI09; -. DR EMDB; EMD-45974; -. DR SMR; Q9UI09; -. DR BioGRID; 121013; 226. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; Q9UI09; -. DR FunCoup; Q9UI09; 2240. DR IntAct; Q9UI09; 112. DR MINT; Q9UI09; -. DR STRING; 9606.ENSP00000330737; -. DR BindingDB; Q9UI09; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; Q9UI09; -. DR GlyGen; Q9UI09; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9UI09; -. DR PhosphoSitePlus; Q9UI09; -. DR BioMuta; NDUFA12; -. DR DMDM; 12229870; -. DR jPOST; Q9UI09; -. DR MassIVE; Q9UI09; -. DR PaxDb; 9606-ENSP00000330737; -. DR PeptideAtlas; Q9UI09; -. DR ProteomicsDB; 28348; -. DR ProteomicsDB; 84447; -. [Q9UI09-1] DR Pumba; Q9UI09; -. DR TopDownProteomics; Q9UI09-1; -. [Q9UI09-1] DR Antibodypedia; 30095; 166 antibodies from 28 providers. DR DNASU; 55967; -. DR Ensembl; ENST00000327772.7; ENSP00000330737.2; ENSG00000184752.15. [Q9UI09-1] DR Ensembl; ENST00000547986.5; ENSP00000450130.1; ENSG00000184752.15. [Q9UI09-2] DR GeneID; 55967; -. DR KEGG; hsa:55967; -. DR MANE-Select; ENST00000327772.7; ENSP00000330737.2; NM_018838.5; NP_061326.1. DR UCSC; uc001tdl.5; human. [Q9UI09-1] DR AGR; HGNC:23987; -. DR ClinPGx; PA142671269; -. DR CTD; 55967; -. DR DisGeNET; 55967; -. DR GeneCards; NDUFA12; -. DR HGNC; HGNC:23987; NDUFA12. DR HPA; ENSG00000184752; Tissue enhanced (skeletal muscle, tongue). DR MalaCards; NDUFA12; -. DR MIM; 614530; gene. DR MIM; 618244; phenotype. DR OpenTargets; ENSG00000184752; -. DR VEuPathDB; HostDB:ENSG00000184752; -. DR eggNOG; KOG3382; Eukaryota. DR GeneTree; ENSGT00390000005848; -. DR HOGENOM; CLU_110455_1_0_1; -. DR InParanoid; Q9UI09; -. DR OMA; VIYTAEM; -. DR OrthoDB; 274641at2759; -. DR PAN-GO; Q9UI09; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q9UI09; -. DR BioCyc; MetaCyc:HS03370-MONOMER; -. DR PathwayCommons; Q9UI09; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q9UI09; -. DR SIGNOR; Q9UI09; -. DR Agora; ENSG00000184752; -. DR BioGRID-ORCS; 55967; 14 hits in 1157 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFA12; human. DR GenomeRNAi; 55967; -. DR Pharos; Q9UI09; Tclin. DR PRO; PR:Q9UI09; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; Q9UI09; protein. DR Bgee; ENSG00000184752; Expressed in left ventricle myocardium and 190 other cell types or tissues. DR ExpressionAtlas; Q9UI09; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0042775; P:mitochondrial ATP synthesis coupled electron transport; IMP:CAFA. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR InterPro; IPR007763; NDUFA12. DR PANTHER; PTHR12910:SF2; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX SUBUNIT 12; 1. DR PANTHER; PTHR12910; NADH-UBIQUINONE OXIDOREDUCTASE SUBUNIT B17.2; 1. DR Pfam; PF05071; NDUFA12; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Disease variant; KW Electron transport; Membrane; Mitochondrion; Mitochondrion inner membrane; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transport. FT CHAIN 1..145 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT subunit 12" FT /id="PRO_0000118845" FT MOD_RES 1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378, FT ECO:0007744|PubMed:25944712" FT VAR_SEQ 58..145 FT /note="RHRWVVYTTEMNGKNTFWDVDGSMVPPEWHRWLHSMTDDPPTTKPLTARKFI FT WTNHKFNVTGTPEQYVPYSTTRKKIQEWIPPSTPYK -> IVGFTV (in isoform FT 2)" FT /evidence="ECO:0000305" FT /id="VSP_046948" FT VARIANT 60..145 FT /note="Missing (in MC1DN23)" FT /evidence="ECO:0000269|PubMed:21617257" FT /id="VAR_081459" FT VARIANT 104 FT /note="T -> A (in dbSNP:rs17850017)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3" FT /id="VAR_060682" FT HELIX 3..15 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 21..29 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 52..54 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 58..60 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 68..70 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 74..76 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 84..90 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 98..100 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 118..121 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 145 AA; 17114 MW; C76C7F2F5974AFF9 CRC64; MELVQVLKRG LQQITGHGGL RGYLRVFFRT NDAKVGTLVG EDKYGNKYYE DNKQFFGRHR WVVYTTEMNG KNTFWDVDGS MVPPEWHRWL HSMTDDPPTT KPLTARKFIW TNHKFNVTGT PEQYVPYSTT RKKIQEWIPP STPYK // ID NDUAD_HUMAN Reviewed; 144 AA. AC Q9P0J0; B4DF76; K7EK58; Q6PKI0; Q9H2L3; Q9Y327; DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 28-JAN-2026, entry version 216. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13; DE AltName: Full=Cell death regulatory protein GRIM-19; DE AltName: Full=Complex I-B16.6; DE Short=CI-B16.6; DE AltName: Full=Gene associated with retinoic and interferon-induced mortality 19 protein; DE Short=GRIM-19; DE Short=Gene associated with retinoic and IFN-induced mortality 19 protein; DE AltName: Full=NADH-ubiquinone oxidoreductase B16.6 subunit; GN Name=NDUFA13; Synonyms=GRIM19; ORFNames=CDA016, CGI-39; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Mammary carcinoma; RX PubMed=10924506; DOI=10.1074/jbc.m003929200; RA Angell J.E., Lindner D.J., Shapiro P.S., Hofmann E.R., Kalvakolanu D.V.; RT "Identification of GRIM-19, a novel cell death-regulatory gene induced by RT the interferon-beta and retinoic acid combination, using a genetic RT approach."; RL J. Biol. Chem. 275:33416-33426(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Adrenal gland; RX PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J., RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., RA Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis RT and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=10810093; DOI=10.1101/gr.10.5.703; RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.; RT "Identification of novel human genes evolutionarily conserved in RT Caenorhabditis elegans by comparative proteomics."; RL Genome Res. 10:703-713(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pheochromocytoma; RA Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.; RT "A novel gene expressed in human pheochromocytoma."; RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP INTERACTION WITH HHV-8 IRF1; HPV-16 E6 AND SV40 LT (MICROBIAL INFECTION). RX PubMed=12163600; DOI=10.1128/jvi.76.17.8797-8807.2002; RA Seo T., Lee D., Shim Y.S., Angell J.E., Chidambaram N.V., Kalvakolanu D.V., RA Choe J.; RT "Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated RT herpesvirus interacts with a cell death regulator, GRIM19, and inhibits RT interferon/retinoic acid-induced cell death."; RL J. Virol. 76:8797-8807(2002). RN [9] RP FUNCTION, INTERACTION WITH STAT3, AND SUBCELLULAR LOCATION. RX PubMed=12628925; DOI=10.1093/emboj/cdg135; RA Lufei C., Ma J., Huang G., Zhang T., Novotny-Diermayr V., Ong C.T., Cao X.; RT "GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via RT functional interaction."; RL EMBO J. 22:1325-1335(2003). RN [10] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [11] RP FUNCTION, AND INTERACTION WITH STAT3. RX PubMed=12867595; DOI=10.1073/pnas.1633516100; RA Zhang J., Yang J., Roy S.K., Tininini S., Hu J., Bromberg J.F., Poli V., RA Stark G.R., Kalvakolanu D.V.; RT "The cell death regulator GRIM-19 is an inhibitor of signal transducer and RT activator of transcription 3."; RL Proc. Natl. Acad. Sci. U.S.A. 100:9342-9347(2003). RN [12] RP SUBCELLULAR LOCATION. RX PubMed=15367666; DOI=10.1128/mcb.24.19.8447-8456.2004; RA Huang G., Lu H., Hao A., Ng D.C.H., Ponniah S., Guo K., Lufei C., Zeng Q., RA Cao X.; RT "GRIM-19, a cell death regulatory protein, is essential for assembly and RT function of mitochondrial complex I."; RL Mol. Cell. Biol. 24:8447-8456(2004). RN [13] RP SUBCELLULAR LOCATION, AND INTERACTION WITH OLFM4. RX PubMed=15059901; DOI=10.1158/0008-5472.can-03-3443; RA Zhang X., Huang Q., Yang Z., Li Y., Li C.-Y.; RT "GW112, a novel antiapoptotic protein that promotes tumor growth."; RL Cancer Res. 64:2474-2481(2004). RN [14] RP FUNCTION, AND INTERACTION WITH CARD15. RX PubMed=15753091; DOI=10.1074/jbc.m413776200; RA Barnich N., Hisamatsu T., Aguirre J.E., Xavier R., Reinecker H.-C., RA Podolsky D.K.; RT "GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as RT downstream effector of anti-bacterial function in intestinal epithelial RT cells."; RL J. Biol. Chem. 280:19021-19026(2005). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [17] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [18] RP VARIANTS ASN-5 AND PRO-115, AND INVOLVEMENT IN SUSCEPTIBILITY TO HURTHLE RP CELL THYROID CARCINOMA. RX PubMed=15841082; DOI=10.1038/sj.bjc.6602547; RA Maximo V., Botelho T., Capela J., Soares P., Lima J., Taveira A., Amaro T., RA Barbosa A.P., Preto A., Harach H.R., Williams D., Sobrinho-Simoes M.; RT "Somatic and germline mutation in GRIM-19, a dual function gene involved in RT mitochondrial metabolism and cell death, is linked to mitochondrion-rich RT (Hurthle cell) tumours of the thyroid."; RL Br. J. Cancer 92:1892-1898(2005). RN [19] RP VARIANT MC1DN28 HIS-57, INVOLVEMENT IN MC1DN28, AND CHARACTERIZATION OF RP VARIANT MC1DN28 HIS-57. RX PubMed=25901006; DOI=10.1093/hmg/ddv133; RA Angebault C., Charif M., Guegen N., Piro-Megy C., Mousson de Camaret B., RA Procaccio V., Guichet P.O., Hebrard M., Manes G., Leboucq N., Rivier F., RA Hamel C.P., Lenaers G., Roubertie A.; RT "Mutation in NDUFA13/GRIM19 leads to early onset hypotonia, dyskinesia and RT sensorial deficiencies, and mitochondrial complex I instability."; RL Hum. Mol. Genet. 24:3948-3955(2015). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis (PubMed:27626371). Complex I functions in the CC transfer of electrons from NADH to the respiratory chain. The immediate CC electron acceptor for the enzyme is believed to be ubiquinone CC (PubMed:27626371). Involved in the interferon/all-trans-retinoic acid CC (IFN/RA) induced cell death. This apoptotic activity is inhibited by CC interaction with viral IRF1. Prevents the transactivation of STAT3 CC target genes. May play a role in CARD15-mediated innate mucosal CC responses and serve to regulate intestinal epithelial cell responses to CC microbes (PubMed:15753091). {ECO:0000269|PubMed:12628925, CC ECO:0000269|PubMed:12867595, ECO:0000269|PubMed:15753091, CC ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits CC (PubMed:27626371). Interacts with CARD15, but not with CARD4 CC (PubMed:12611891, PubMed:15753091). Interacts with STAT3, but not with CC STAT1, STAT2 and STAT5A (PubMed:12628925, PubMed:12867595). Interacts CC with OLFM4 (PubMed:15059901). {ECO:0000269|PubMed:12163600, CC ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:12628925, CC ECO:0000269|PubMed:12867595, ECO:0000269|PubMed:15059901, CC ECO:0000269|PubMed:15753091, ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: (Microbial infection) Interacts with HHV-8 IRF1, in the CC nucleus, with HPV-16 E6 and SV40 LT (PubMed:12163600). CC {ECO:0000269|PubMed:12163600}. CC -!- INTERACTION: CC Q9P0J0; O43464: HTRA2; NbExp=8; IntAct=EBI-372742, EBI-517086; CC Q9P0J0; P42858: HTT; NbExp=4; IntAct=EBI-372742, EBI-466029; CC Q9P0J0; Q9HC29: NOD2; NbExp=6; IntAct=EBI-372742, EBI-7445625; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:12628925, ECO:0000269|PubMed:15059901, CC ECO:0000269|PubMed:15367666}; Single-pass membrane protein CC {ECO:0000255}; Matrix side. Nucleus {ECO:0000269|PubMed:12628925}. CC Note=Localizes mainly in the mitochondrion (PubMed:12628925). May be CC translocated into the nucleus upon IFN/RA treatment. CC {ECO:0000269|PubMed:12628925, ECO:0000269|PubMed:15059901}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9P0J0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9P0J0-2; Sequence=VSP_056644; CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in heart, CC skeletal muscle, liver, kidney and placenta. In intestinal mucosa, CC down-regulated in areas involved in Crohn disease and ulcerative CC colitis. {ECO:0000269|PubMed:10924506}. CC -!- DEVELOPMENTAL STAGE: Expressed in numerous fetal tissues. CC -!- INDUCTION: By IFNB1/IFN-beta combined with all-trans-retinoic acid CC (ATRA). CC -!- DISEASE: Hurthle cell thyroid carcinoma (HCTC) [MIM:607464]: A rare CC type of thyroid cancer accounting for only about 3-10% of all CC differentiated thyroid cancers. These neoplasms are considered a CC variant of follicular carcinoma of the thyroid and are referred to as CC follicular carcinoma, oxyphilic type. {ECO:0000269|PubMed:15841082}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 28 (MC1DN28) CC [MIM:618249]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN28 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:25901006}. CC Note=The disease may be caused by variants affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFA13 subunit family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD27748.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAG44670.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAH00589.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF286697; AAG28167.1; -; mRNA. DR EMBL; AF155662; AAF67481.1; -; mRNA. DR EMBL; AF132973; AAD27748.1; ALT_INIT; mRNA. DR EMBL; AF261134; AAG44670.1; ALT_INIT; mRNA. DR EMBL; AK293965; BAG57337.1; -; mRNA. DR EMBL; AC011448; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000589; AAH00589.2; ALT_INIT; mRNA. DR EMBL; BC009189; AAH09189.1; -; mRNA. DR CCDS; CCDS12404.2; -. [Q9P0J0-1] DR RefSeq; NP_057049.5; NM_015965.6. [Q9P0J0-1] DR PDB; 5XTB; EM; 3.40 A; W=7-28. DR PDB; 5XTC; EM; 3.70 A; W=29-144. DR PDB; 5XTD; EM; 3.70 A; W=7-144. DR PDB; 5XTH; EM; 3.90 A; W=7-144. DR PDB; 5XTI; EM; 17.40 A; BW/W=7-144. DR PDB; 9CWT; EM; 3.44 A; W=1-144. DR PDBsum; 5XTB; -. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; Q9P0J0; -. DR EMDB; EMD-45974; -. DR SMR; Q9P0J0; -. DR BioGRID; 119270; 182. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; Q9P0J0; -. DR DIP; DIP-31180N; -. DR FunCoup; Q9P0J0; 2355. DR IntAct; Q9P0J0; 126. DR MINT; Q9P0J0; -. DR STRING; 9606.ENSP00000423673; -. DR BindingDB; Q9P0J0; -. DR ChEMBL; CHEMBL4105781; -. DR DrugBank; DB18773; Flurpiridaz F-18. DR DrugBank; DB00157; NADH. DR DrugCentral; Q9P0J0; -. DR iPTMnet; Q9P0J0; -. DR PhosphoSitePlus; Q9P0J0; -. DR SwissPalm; Q9P0J0; -. DR BioMuta; NDUFA13; -. DR DMDM; 20139242; -. DR jPOST; Q9P0J0; -. DR MassIVE; Q9P0J0; -. DR PaxDb; 9606-ENSP00000423673; -. DR PeptideAtlas; Q9P0J0; -. DR ProteomicsDB; 83552; -. [Q9P0J0-1] DR Pumba; Q9P0J0; -. DR TopDownProteomics; Q9P0J0-1; -. [Q9P0J0-1] DR Antibodypedia; 28492; 294 antibodies from 38 providers. DR DNASU; 51079; -. DR Ensembl; ENST00000507754.9; ENSP00000423673.1; ENSG00000186010.20. [Q9P0J0-1] DR GeneID; 51079; -. DR KEGG; hsa:51079; -. DR MANE-Select; ENST00000507754.9; ENSP00000423673.1; NM_015965.7; NP_057049.5. DR UCSC; uc021uqu.2; human. [Q9P0J0-1] DR AGR; HGNC:17194; -. DR ClinPGx; PA142671270; -. DR CTD; 51079; -. DR DisGeNET; 51079; -. DR GeneCards; NDUFA13; -. DR HGNC; HGNC:17194; NDUFA13. DR HPA; ENSG00000186010; Low tissue specificity. DR MalaCards; NDUFA13; -. DR MIM; 607464; phenotype. DR MIM; 609435; gene. DR MIM; 618249; phenotype. DR OpenTargets; ENSG00000186010; -. DR Orphanet; 146; Differentiated thyroid carcinoma. DR VEuPathDB; HostDB:ENSG00000186010; -. DR eggNOG; KOG3300; Eukaryota. DR GeneTree; ENSGT00390000000719; -. DR HOGENOM; CLU_119720_0_0_1; -. DR InParanoid; Q9P0J0; -. DR OrthoDB; 3308at2759; -. DR PAN-GO; Q9P0J0; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q9P0J0; -. DR BioCyc; MetaCyc:HS05364-MONOMER; -. DR PathwayCommons; Q9P0J0; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR Reactome; R-HSA-9837999; Mitochondrial protein degradation. DR SignaLink; Q9P0J0; -. DR SIGNOR; Q9P0J0; -. DR Agora; ENSG00000186010; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 51079; 225 hits in 1162 CRISPR screens. DR ChiTaRS; NDUFA13; human. DR GeneWiki; NDUFA13; -. DR GenomeRNAi; 51079; -. DR Pharos; Q9P0J0; Tclin. DR PRO; PR:Q9P0J0; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q9P0J0; protein. DR Bgee; ENSG00000186010; Expressed in apex of heart and 99 other cell types or tissues. DR ExpressionAtlas; Q9P0J0; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0098803; C:respiratory chain complex; IDA:UniProtKB. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB. DR GO; GO:0061133; F:endopeptidase activator activity; IC:ParkinsonsUK-UCL. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:ParkinsonsUK-UCL. DR GO; GO:0071300; P:cellular response to retinoic acid; IDA:ParkinsonsUK-UCL. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IGI:ParkinsonsUK-UCL. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IGI:ParkinsonsUK-UCL. DR GO; GO:0045039; P:protein insertion into mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR InterPro; IPR009346; GRIM-19. DR PANTHER; PTHR12966:SF0; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX SUBUNIT 13; 1. DR PANTHER; PTHR12966; NADH DEHYDROGENASE UBIQUINONE 1 ALPHA SUBCOMPLEX SUBUNIT 13; 1. DR Pfam; PF06212; GRIM-19; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; KW Disease variant; Electron transport; Host-virus interaction; Membrane; KW Mitochondrion; Mitochondrion inner membrane; Nucleus; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transmembrane; Transmembrane helix; KW Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q95KV7" FT CHAIN 2..144 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT subunit 13" FT /id="PRO_0000118804" FT TRANSMEM 30..51 FT /note="Helical" FT /evidence="ECO:0000255" FT REGION 102..144 FT /note="Important for inducing cell death" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:Q95KV7" FT VAR_SEQ 143..144 FT /note="YT -> ALELQPPLADMGRAELSSNATTSLVQRRKQAWGRQSWLEQIWNAGP FT VCQRLHRGGSRPGAGAAGGLSLWAAAARGAVRSC (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056644" FT VARIANT 5 FT /note="K -> N (in a Hurthle cell variant of papillary FT carcinoma sample; dbSNP:rs137852869)" FT /evidence="ECO:0000269|PubMed:15841082" FT /id="VAR_045984" FT VARIANT 57 FT /note="R -> H (in MC1DN28; reduced NDUFA13 protein level FT resulting in complex I instability; dbSNP:rs752513525)" FT /evidence="ECO:0000269|PubMed:25901006" FT /id="VAR_078938" FT VARIANT 115 FT /note="R -> P (in a Hurthle cell variant of papillary FT carcinoma sample)" FT /evidence="ECO:0000269|PubMed:15841082" FT /id="VAR_045985" FT CONFLICT 2 FT /note="A -> P (in Ref. 3)" FT /evidence="ECO:0000305" SQ SEQUENCE 144 AA; 16698 MW; 058F608B235FF856 CRC64; MAASKVKQDM PPPGGYGPID YKRNLPRRGL SGYSMLAIGI GTLIYGHWSI MKWNRERRRL QIEDFEARIA LLPLLQAETD RRTLQMLREN LEEEAIIMKD VPDWKVGESV FHTTRWVPPL IGELYGLRTT EEALHASHGF MWYT // ID NDUB3_HUMAN Reviewed; 98 AA. AC O43676; Q6IB80; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 28-JAN-2026, entry version 193. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3; DE AltName: Full=Complex I-B12; DE Short=CI-B12; DE AltName: Full=NADH-ubiquinone oxidoreductase B12 subunit; GN Name=NDUFB3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Heart; RX PubMed=9425316; DOI=10.1006/bbrc.1997.7707; RA Ton C., Hwang D.M., Dempsey A.A., Liew C.-C.; RT "Identification and primary structure of five human NADH-ubiquinone RT oxidoreductase subunits."; RL Biochem. Biophys. Res. Commun. 241:589-594(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9878551; DOI=10.1006/bbrc.1998.9786; RA Loeffen J.L.C.M., Triepels R.H., van den Heuvel L.P., Schuelke M., RA Buskens C.A.F., Smeets R.J.P., Trijbels J.M.F., Smeitink J.A.M.; RT "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: RT human complex I cDNA characterization completed."; RL Biochem. Biophys. Res. Commun. 253:415-422(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP INVOLVEMENT IN MC1DN25, AND VARIANTS MC1DN25 ARG-22 AND 70-GLY--HIS-98 DEL. RX PubMed=22499348; DOI=10.1136/jmedgenet-2012-100846; RA Haack T.B., Haberberger B., Frisch E.M., Wieland T., Iuso A., Gorza M., RA Strecker V., Graf E., Mayr J.A., Herberg U., Hennermann J.B., Klopstock T., RA Kuhn K.A., Ahting U., Sperl W., Wilichowski E., Hoffmann G.F., Tesarova M., RA Hansikova H., Zeman J., Plecko B., Zeviani M., Wittig I., Strom T.M., RA Schuelke M., Freisinger P., Meitinger T., Prokisch H.; RT "Molecular diagnosis in mitochondrial complex I deficiency using exome RT sequencing."; RL J. Med. Genet. 49:277-283(2012). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [11] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [12] RP METHYLATION AT HIS-5; HIS-7 AND HIS-9, AND MUTAGENESIS OF 5-HIS--HIS-9. RX PubMed=33563959; DOI=10.1038/s41467-020-20670-7; RA Davydova E., Shimazu T., Schuhmacher M.K., Jakobsson M.E., RA Willemen H.L.D.M., Liu T., Moen A., Ho A.Y.Y., Malecki J., Schroer L., RA Pinto R., Suzuki T., Groensberg I.A., Sohtome Y., Akakabe M., Weirich S., RA Kikuchi M., Olsen J.V., Dohmae N., Umehara T., Sodeoka M., Siino V., RA McDonough M.A., Eijkelkamp N., Schofield C.J., Jeltsch A., Shinkai Y., RA Falnes P.O.; RT "The methyltransferase METTL9 mediates pervasive 1-methylhistidine RT modification in mammalian proteomes."; RL Nat. Commun. 12:891-891(2021). RN [13] RP VARIANT MC1DN25 ARG-22. RX PubMed=27091925; DOI=10.1136/jmedgenet-2015-103576; RA Alston C.L., Howard C., Olahova M., Hardy S.A., He L., Murray P.G., RA O'Sullivan S., Doherty G., Shield J.P., Hargreaves I.P., Monavari A.A., RA Knerr I., McCarthy P., Morris A.A., Thorburn D.R., Prokisch H., RA Clayton P.E., McFarland R., Hughes J., Crushell E., Taylor R.W.; RT "A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive RT facial appearance, short stature and a mild biochemical and clinical RT phenotype."; RL J. Med. Genet. 53:634-641(2016). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis. Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits. CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891}; Single-pass membrane protein CC {ECO:0000305}; Matrix side {ECO:0000305}. CC -!- PTM: Methylation at His residues by METTL9 enhances complex I-mediated CC mitochondrial respiration. {ECO:0000269|PubMed:33563959}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 25 (MC1DN25) CC [MIM:618246]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN25 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:22499348, CC ECO:0000269|PubMed:27091925}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFB3 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF047183; AAC04268.1; -; mRNA. DR EMBL; AF035839; AAC15590.1; -; mRNA. DR EMBL; CR456924; CAG33205.1; -; mRNA. DR EMBL; AC007272; AAX88972.1; -; Genomic_DNA. DR EMBL; CH471063; EAW70233.1; -; Genomic_DNA. DR EMBL; BC018183; AAH18183.1; -; mRNA. DR CCDS; CCDS2336.1; -. DR PIR; JC5822; JC5822. DR RefSeq; NP_001244031.1; NM_001257102.2. DR RefSeq; NP_002482.1; NM_002491.3. DR RefSeq; XP_011509532.1; XM_011511230.4. DR RefSeq; XP_047300444.1; XM_047444488.1. DR RefSeq; XP_054198228.1; XM_054342253.1. DR RefSeq; XP_054198229.1; XM_054342254.1. DR PDB; 5XTC; EM; 3.70 A; Z=10-89. DR PDB; 5XTD; EM; 3.70 A; Z=10-89. DR PDB; 5XTH; EM; 3.90 A; Z=10-89. DR PDB; 5XTI; EM; 17.40 A; BZ/Z=10-89. DR PDB; 9CWT; EM; 3.44 A; Z=1-98. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; O43676; -. DR EMDB; EMD-45974; -. DR SMR; O43676; -. DR BioGRID; 110789; 115. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O43676; -. DR FunCoup; O43676; 562. DR IntAct; O43676; 101. DR MINT; O43676; -. DR STRING; 9606.ENSP00000407336; -. DR BindingDB; O43676; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; O43676; -. DR iPTMnet; O43676; -. DR PhosphoSitePlus; O43676; -. DR BioMuta; NDUFB3; -. DR jPOST; O43676; -. DR MassIVE; O43676; -. DR PaxDb; 9606-ENSP00000237889; -. DR PeptideAtlas; O43676; -. DR ProteomicsDB; 49104; -. DR Pumba; O43676; -. DR TopDownProteomics; O43676; -. DR Antibodypedia; 34135; 135 antibodies from 27 providers. DR DNASU; 4709; -. DR Ensembl; ENST00000237889.9; ENSP00000237889.4; ENSG00000119013.11. DR Ensembl; ENST00000433898.5; ENSP00000410600.1; ENSG00000119013.11. DR Ensembl; ENST00000450023.6; ENSP00000401834.2; ENSG00000119013.11. DR Ensembl; ENST00000454214.1; ENSP00000407336.1; ENSG00000119013.11. DR Ensembl; ENST00000682325.1; ENSP00000507925.1; ENSG00000119013.11. DR Ensembl; ENST00000684175.1; ENSP00000508132.1; ENSG00000119013.11. DR Ensembl; ENST00000684420.1; ENSP00000508208.1; ENSG00000119013.11. DR GeneID; 4709; -. DR KEGG; hsa:4709; -. DR MANE-Select; ENST00000237889.9; ENSP00000237889.4; NM_002491.3; NP_002482.1. DR UCSC; uc002uwx.6; human. DR AGR; HGNC:7698; -. DR ClinPGx; PA31504; -. DR CTD; 4709; -. DR DisGeNET; 4709; -. DR GeneCards; NDUFB3; -. DR HGNC; HGNC:7698; NDUFB3. DR HPA; ENSG00000119013; Tissue enhanced (skeletal muscle, tongue). DR MalaCards; NDUFB3; -. DR MIM; 603839; gene. DR MIM; 618246; phenotype. DR OpenTargets; ENSG00000119013; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000119013; -. DR eggNOG; KOG4631; Eukaryota. DR GeneTree; ENSGT00390000010316; -. DR HOGENOM; CLU_160226_1_0_1; -. DR InParanoid; O43676; -. DR OMA; YMGGFAH; -. DR OrthoDB; 521512at2759; -. DR PAN-GO; O43676; 2 GO annotations based on evolutionary models. DR PhylomeDB; O43676; -. DR BioCyc; MetaCyc:HS04271-MONOMER; -. DR PathwayCommons; O43676; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; O43676; -. DR SIGNOR; O43676; -. DR Agora; ENSG00000119013; -. DR BioGRID-ORCS; 4709; 436 hits in 1068 CRISPR screens. DR ChiTaRS; NDUFB3; human. DR GenomeRNAi; 4709; -. DR Pharos; O43676; Tclin. DR PRO; PR:O43676; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; O43676; protein. DR Bgee; ENSG00000119013; Expressed in right atrium auricular region and 207 other cell types or tissues. DR ExpressionAtlas; O43676; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; TAS:ProtInc. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; TAS:ProtInc. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR InterPro; IPR012576; NDUFB3. DR PANTHER; PTHR15082:SF2; NADH DEHYDROGENASE [UBIQUINONE] 1 BETA SUBCOMPLEX SUBUNIT 3; 1. DR PANTHER; PTHR15082; NADH-UBIQUINONE OXIDOREDUCTASE B12 SUBUNIT; 1. DR Pfam; PF08122; NDUF_B12; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Disease variant; Electron transport; Membrane; KW Methylation; Mitochondrion; Mitochondrion inner membrane; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transmembrane; Transmembrane helix; KW Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q02365" FT CHAIN 2..98 FT /note="NADH dehydrogenase [ubiquinone] 1 beta subcomplex FT subunit 3" FT /id="PRO_0000118797" FT TRANSMEM 66..88 FT /note="Helical" FT /evidence="ECO:0000255" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:Q02365" FT MOD_RES 5 FT /note="Pros-methylhistidine" FT /evidence="ECO:0000269|PubMed:33563959" FT MOD_RES 7 FT /note="Pros-methylhistidine" FT /evidence="ECO:0000269|PubMed:33563959" FT MOD_RES 9 FT /note="Pros-methylhistidine" FT /evidence="ECO:0000269|PubMed:33563959" FT MOD_RES 23 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9CQZ6" FT MOD_RES 23 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9CQZ6" FT MOD_RES 34 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9CQZ6" FT MOD_RES 34 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q9CQZ6" FT VARIANT 22 FT /note="W -> R (in MC1DN25; dbSNP:rs142609245)" FT /evidence="ECO:0000269|PubMed:22499348, FT ECO:0000269|PubMed:27091925" FT /id="VAR_078939" FT VARIANT 70..98 FT /note="Missing (in MC1DN25)" FT /evidence="ECO:0000269|PubMed:22499348" FT /id="VAR_078940" FT MUTAGEN 5..9 FT /note="HGHEH->RGHER: Abolished histidine methylation by FT METTL9." FT /evidence="ECO:0000269|PubMed:33563959" SQ SEQUENCE 98 AA; 11402 MW; 1C77F0C7A4DC757F CRC64; MAHEHGHEHG HHKMELPDYR QWKIEGTPLE TIQKKLAAKG LRDPWGRNEA WRYMGGFAKS VSFSDVFFKG FKWGFAAFVV AVGAEYYLES LNKDKKHH // ID NDUB7_HUMAN Reviewed; 137 AA. AC P17568; Q6ICN9; Q9UI16; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 28-JAN-2026, entry version 209. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7; DE AltName: Full=Cell adhesion protein SQM1; DE AltName: Full=Complex I-B18; DE Short=CI-B18; DE AltName: Full=NADH-ubiquinone oxidoreductase B18 subunit; GN Name=NDUFB7; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2302251; DOI=10.1016/0006-291x(90)90908-6; RA Wong Y.-C., Tsao S.-W., Kakefuda M., Bernal S.D.; RT "cDNA cloning of a novel cell adhesion protein expressed in human squamous RT carcinoma cells."; RL Biochem. Biophys. Res. Commun. 166:984-992(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10830904; DOI=10.1007/s004390000278; RA Triepels R., Smeitink J., Loeffen J., Smeets R., Trijbels F., RA van den Heuvel L.; RT "Characterization of the human complex I NDUFB7 and 17.2-kDa cDNAs and RT mutational analysis of 19 genes of the HP fraction in complex I-deficient- RT patients."; RL Hum. Genet. 106:385-391(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Hypothalamus; RX PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J., RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., RA Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis RT and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP SUBCELLULAR LOCATION, DOMAIN, AND MOTIF. RX PubMed=21310150; DOI=10.1016/j.febslet.2011.01.046; RA Szklarczyk R., Wanschers B.F., Nabuurs S.B., Nouws J., Nijtmans L.G., RA Huynen M.A.; RT "NDUFB7 and NDUFA8 are located at the intermembrane surface of complex I."; RL FEBS Lett. 585:737-743(2011). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [11] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [12] RP INVOLVEMENT IN MC1DN39, AND FUNCTION. RX PubMed=33502047; DOI=10.1002/humu.24173; RA Correia S.P., Moedas M.F., Naess K., Bruhn H., Maffezzini C., RA Calvo-Garrido J., Lesko N., Wibom R., Schober F.A., Jemt A., RA Stranneheim H., Freyer C., Wedell A., Wredenberg A.; RT "Severe congenital lactic acidosis and hypertrophic cardiomyopathy caused RT by an intronic variant in NDUFB7."; RL Hum. Mutat. 42:378-384(2021). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis. Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371, CC ECO:0000269|PubMed:33502047}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits. CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}. CC -!- INTERACTION: CC P17568; Q5U5Z8-3: AGBL2; NbExp=3; IntAct=EBI-1246238, EBI-12226473; CC P17568; Q9NX04: AIRIM; NbExp=3; IntAct=EBI-1246238, EBI-8643161; CC P17568; Q8N2N9-4: ANKRD36B; NbExp=3; IntAct=EBI-1246238, EBI-12170453; CC P17568; Q7Z3C6-3: ATG9A; NbExp=3; IntAct=EBI-1246238, EBI-12006308; CC P17568; Q8N4L8: CCDC24; NbExp=3; IntAct=EBI-1246238, EBI-1104933; CC P17568; P24863: CCNC; NbExp=3; IntAct=EBI-1246238, EBI-395261; CC P17568; Q96GN5: CDCA7L; NbExp=3; IntAct=EBI-1246238, EBI-5278764; CC P17568; P55273: CDKN2D; NbExp=3; IntAct=EBI-1246238, EBI-745859; CC P17568; Q9UKJ5: CHIC2; NbExp=3; IntAct=EBI-1246238, EBI-741528; CC P17568; Q9BW66: CINP; NbExp=3; IntAct=EBI-1246238, EBI-739784; CC P17568; P51800-3: CLCNKA; NbExp=3; IntAct=EBI-1246238, EBI-11980535; CC P17568; Q9UI47-2: CTNNA3; NbExp=3; IntAct=EBI-1246238, EBI-11962928; CC P17568; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-1246238, EBI-744099; CC P17568; Q96MY7: FAM161B; NbExp=3; IntAct=EBI-1246238, EBI-7225287; CC P17568; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-1246238, EBI-6658203; CC P17568; P55040: GEM; NbExp=3; IntAct=EBI-1246238, EBI-744104; CC P17568; Q9NWQ4-1: GPATCH2L; NbExp=3; IntAct=EBI-1246238, EBI-11959863; CC P17568; P13807: GYS1; NbExp=3; IntAct=EBI-1246238, EBI-740553; CC P17568; P60014: KRTAP10-10; NbExp=3; IntAct=EBI-1246238, EBI-11955579; CC P17568; P25791-3: LMO2; NbExp=3; IntAct=EBI-1246238, EBI-11959475; CC P17568; Q96A72: MAGOHB; NbExp=3; IntAct=EBI-1246238, EBI-746778; CC P17568; O14770-4: MEIS2; NbExp=3; IntAct=EBI-1246238, EBI-8025850; CC P17568; Q13064: MKRN3; NbExp=3; IntAct=EBI-1246238, EBI-2340269; CC P17568; Q15653: NFKBIB; NbExp=3; IntAct=EBI-1246238, EBI-352889; CC P17568; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-1246238, EBI-10271199; CC P17568; Q9P2K3-2: RCOR3; NbExp=3; IntAct=EBI-1246238, EBI-1504830; CC P17568; Q6P9E2: RECK; NbExp=3; IntAct=EBI-1246238, EBI-10253121; CC P17568; Q0D2K3: RIPPLY1; NbExp=3; IntAct=EBI-1246238, EBI-10226430; CC P17568; Q5TAB7: RIPPLY2; NbExp=3; IntAct=EBI-1246238, EBI-10246897; CC P17568; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-1246238, EBI-748391; CC P17568; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-1246238, EBI-5235340; CC P17568; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-1246238, EBI-7082156; CC P17568; Q9BX79-6: STRA6; NbExp=3; IntAct=EBI-1246238, EBI-12140683; CC P17568; Q01664: TFAP4; NbExp=3; IntAct=EBI-1246238, EBI-2514218; CC P17568; Q08117-2: TLE5; NbExp=3; IntAct=EBI-1246238, EBI-11741437; CC P17568; Q9Y6T4: WUGSC:H_DJ0726N20.gs.b; NbExp=3; IntAct=EBI-1246238, EBI-12369705; CC P17568; Q9Y3S2: ZNF330; NbExp=3; IntAct=EBI-1246238, EBI-373456; CC P17568; Q8TAU3: ZNF417; NbExp=3; IntAct=EBI-1246238, EBI-740727; CC P17568; Q8TBZ8: ZNF564; NbExp=3; IntAct=EBI-1246238, EBI-10273713; CC P17568; Q96SQ5: ZNF587; NbExp=3; IntAct=EBI-1246238, EBI-6427977; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:21310150}; Peripheral membrane protein CC {ECO:0000269|PubMed:21310150}. Mitochondrion intermembrane space CC {ECO:0000269|PubMed:21310150}. CC -!- DOMAIN: Contains two C-X9-C motifs that are predicted to form a helix- CC coil-helix structure, permitting the formation of intramolecular CC disulfide bonds. {ECO:0000269|PubMed:21310150}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 39 (MC1DN39) CC [MIM:620135]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN39 is an autosomal recessive form characterized CC by intrauterine growth retardation, anemia, and postpartum hypertrophic CC cardiomyopathy, lactic acidosis, encephalopathy, and a severe complex I CC defect with a fatal outcome. {ECO:0000269|PubMed:33502047}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the complex I NDUFB7 subunit family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA35675.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M33374; AAA35675.1; ALT_FRAME; mRNA. DR EMBL; AF217091; AAF91223.1; -; mRNA. DR EMBL; AF112200; AAF17188.1; -; mRNA. DR EMBL; CR450354; CAG29350.1; -; mRNA. DR EMBL; CH471106; EAW84436.1; -; Genomic_DNA. DR EMBL; BC002595; AAH02595.1; -; mRNA. DR CCDS; CCDS12314.1; -. DR PIR; A34653; A34653. DR RefSeq; NP_004137.2; NM_004146.5. DR PDB; 5XTC; EM; 3.70 A; v=3-124. DR PDB; 5XTD; EM; 3.70 A; v=1-137. DR PDB; 5XTH; EM; 3.90 A; v=3-124. DR PDB; 5XTI; EM; 17.40 A; Bv/v=3-124. DR PDB; 9CWT; EM; 3.44 A; v=1-137. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; P17568; -. DR EMDB; EMD-45974; -. DR SMR; P17568; -. DR BioGRID; 110793; 115. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; P17568; -. DR FunCoup; P17568; 1894. DR IntAct; P17568; 91. DR MINT; P17568; -. DR STRING; 9606.ENSP00000215565; -. DR BindingDB; P17568; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; P17568; -. DR GlyGen; P17568; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P17568; -. DR PhosphoSitePlus; P17568; -. DR BioMuta; NDUFB7; -. DR DMDM; 12644140; -. DR jPOST; P17568; -. DR MassIVE; P17568; -. DR PaxDb; 9606-ENSP00000215565; -. DR PeptideAtlas; P17568; -. DR ProteomicsDB; 53493; -. DR Pumba; P17568; -. DR Antibodypedia; 1259; 151 antibodies from 30 providers. DR DNASU; 4713; -. DR Ensembl; ENST00000215565.3; ENSP00000215565.1; ENSG00000099795.8. DR GeneID; 4713; -. DR KEGG; hsa:4713; -. DR MANE-Select; ENST00000215565.3; ENSP00000215565.1; NM_004146.6; NP_004137.2. DR UCSC; uc002mzg.4; human. DR AGR; HGNC:7702; -. DR ClinPGx; PA31513; -. DR CTD; 4713; -. DR DisGeNET; 4713; -. DR GeneCards; NDUFB7; -. DR HGNC; HGNC:7702; NDUFB7. DR HPA; ENSG00000099795; Low tissue specificity. DR MalaCards; NDUFB7; -. DR MIM; 603842; gene. DR MIM; 620135; phenotype. DR OpenTargets; ENSG00000099795; -. DR VEuPathDB; HostDB:ENSG00000099795; -. DR eggNOG; KOG3468; Eukaryota. DR GeneTree; ENSGT00390000018759; -. DR HOGENOM; CLU_154847_1_0_1; -. DR InParanoid; P17568; -. DR OMA; FVYQCAH; -. DR OrthoDB; 268414at2759; -. DR PAN-GO; P17568; 1 GO annotation based on evolutionary models. DR PhylomeDB; P17568; -. DR BioCyc; MetaCyc:HS01908-MONOMER; -. DR PathwayCommons; P17568; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; P17568; -. DR SIGNOR; P17568; -. DR Agora; ENSG00000099795; -. DR BioGRID-ORCS; 4713; 347 hits in 1160 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFB7; human. DR GeneWiki; NDUFB7; -. DR GenomeRNAi; 4713; -. DR Pharos; P17568; Tclin. DR PRO; PR:P17568; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P17568; protein. DR Bgee; ENSG00000099795; Expressed in apex of heart and 201 other cell types or tissues. DR ExpressionAtlas; P17568; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; HDA:UniProtKB. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IMP:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; NAS:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR InterPro; IPR008698; NDUB7. DR PANTHER; PTHR20900:SF0; NADH DEHYDROGENASE [UBIQUINONE] 1 BETA SUBCOMPLEX SUBUNIT 7; 1. DR PANTHER; PTHR20900; NADH:UBIQUINONE OXIDOREDUCTASE B18-LIKE SUBUNIT; 1. DR Pfam; PF05676; NDUF_B7; 1. DR PROSITE; PS51808; CHCH; 1. PE 1: Evidence at protein level; KW 3D-structure; Disulfide bond; Electron transport; Lipoprotein; Membrane; KW Mitochondrion; Mitochondrion inner membrane; Myristate; Phosphoprotein; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transport. FT INIT_MET 1 FT /note="Removed" FT CHAIN 2..137 FT /note="NADH dehydrogenase [ubiquinone] 1 beta subcomplex FT subunit 7" FT /id="PRO_0000118811" FT DOMAIN 56..98 FT /note="CHCH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT REGION 113..137 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 59..69 FT /note="Cx9C motif 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT MOTIF 80..90 FT /note="Cx9C motif 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT MOD_RES 73 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9CR61" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000250" FT DISULFID 59..90 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT DISULFID 69..80 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT VARIANT 106 FT /note="R -> G (in dbSNP:rs3752220)" FT /id="VAR_050591" SQ SEQUENCE 137 AA; 16402 MW; 2743716544288776 CRC64; MGAHLVRRYL GDASVEPDPL QMPTFPPDYG FPERKEREMV ATQQEMMDAQ LRLQLRDYCA HHLIRLLKCK RDSFPNFLAC KQERHDWDYC EHRDYVMRMK EFERERRLLQ RKKRREKKAA ELAKGQGPGE VDPKVAL // ID NDUB8_HUMAN Reviewed; 186 AA. AC O95169; A8K0L4; Q5W143; Q5W144; Q5W145; Q9UG53; Q9UJR4; Q9UQF3; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 28-JAN-2026, entry version 208. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial; DE AltName: Full=Complex I-ASHI; DE Short=CI-ASHI; DE AltName: Full=NADH-ubiquinone oxidoreductase ASHI subunit; DE Flags: Precursor; GN Name=NDUFB8; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9878551; DOI=10.1006/bbrc.1998.9786; RA Loeffen J.L.C.M., Triepels R.H., van den Heuvel L.P., Schuelke M., RA Buskens C.A.F., Smeets R.J.P., Trijbels J.M.F., Smeitink J.A.M.; RT "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: RT human complex I cDNA characterization completed."; RL Biochem. Biophys. Res. Commun. 253:415-422(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Ge H.P., Yu L., Jin L., Fu Q., Wang X.K., Zhao S.Y.; RT "Cloning and sequencing of a novel human cDNA homologous to Bos taurus CI- RT ASHI mRNA."; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 29-71. RC TISSUE=Blood; RX PubMed=10570959; DOI=10.1016/s0378-1119(99)00330-3; RA Emahazion T., Jobs M., Howell W.M., Siegfried M., Wyoni P.I., Prince J.A., RA Brookes J.A.; RT "Identification of 167 polymorphisms in 88 genes from candidate RT neurodegeneration pathways."; RL Gene 238:315-324(1999). RN [11] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [14] RP INVOLVEMENT IN MC1DN32, AND VARIANTS MC1DN32 HIS-62; GLN-76; RP 105-MET--VAL-156 DEL AND TRP-144. RX PubMed=29429571; DOI=10.1016/j.ajhg.2018.01.008; RA Piekutowska-Abramczuk D., Assouline Z., Matakovic L., Feichtinger R.G., RA Konarikova E., Jurkiewicz E., Stawinski P., Gusic M., Koller A., Pollak A., RA Gasperowicz P., Trubicka J., Ciara E., Iwanicka-Pronicka K., Rokicki D., RA Hanein S., Wortmann S.B., Sperl W., Roetig A., Prokisch H., Pronicka E., RA Ploski R., Barcia G., Mayr J.A.; RT "NDUFB8 Mutations Cause Mitochondrial Complex I Deficiency in Individuals RT with Leigh-like Encephalomyopathy."; RL Am. J. Hum. Genet. 102:460-467(2018). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis. Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits. CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891}; Single-pass membrane protein CC {ECO:0000255}; Matrix side {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O95169-1; Sequence=Displayed; CC Name=2; CC IsoId=O95169-2; Sequence=VSP_054843, VSP_054844; CC Name=3; CC IsoId=O95169-3; Sequence=VSP_054842; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 32 (MC1DN32) CC [MIM:618252]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN32 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:29429571}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFB8 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF044958; AAD05422.1; -; mRNA. DR EMBL; AF115968; AAP97239.1; -; mRNA. DR EMBL; AF077028; AAD27761.1; -; mRNA. DR EMBL; AL080056; CAB45691.1; -; mRNA. DR EMBL; CR533490; CAG38521.1; -; mRNA. DR EMBL; AK289579; BAF82268.1; -; mRNA. DR EMBL; AK295867; BAG58666.1; -; mRNA. DR EMBL; AL133352; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471066; EAW49819.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49820.1; -; Genomic_DNA. DR EMBL; BC000466; AAH00466.1; -; mRNA. DR EMBL; BC019276; AAH19276.1; -; mRNA. DR EMBL; BI602529; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; Y18944; CAB46274.1; -; Genomic_DNA. DR CCDS; CCDS65916.1; -. [O95169-3] DR CCDS; CCDS65917.1; -. [O95169-2] DR CCDS; CCDS7497.1; -. [O95169-1] DR PIR; JE0382; JE0382. DR RefSeq; NP_001271296.1; NM_001284367.2. [O95169-2] DR RefSeq; NP_001271297.1; NM_001284368.1. [O95169-3] DR RefSeq; NP_004995.1; NM_005004.4. [O95169-1] DR PDB; 5XTC; EM; 3.70 A; c=34-186. DR PDB; 5XTD; EM; 3.70 A; c=34-186. DR PDB; 5XTH; EM; 3.90 A; c=34-186. DR PDB; 5XTI; EM; 17.40 A; Bc/c=34-186. DR PDB; 9CWT; EM; 3.44 A; c=1-186. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; O95169; -. DR EMDB; EMD-45974; -. DR SMR; O95169; -. DR BioGRID; 110794; 140. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O95169; -. DR FunCoup; O95169; 1316. DR IntAct; O95169; 85. DR MINT; O95169; -. DR STRING; 9606.ENSP00000299166; -. DR BindingDB; O95169; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; O95169; -. DR GlyGen; O95169; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; O95169; -. DR MetOSite; O95169; -. DR PhosphoSitePlus; O95169; -. DR SwissPalm; O95169; -. DR BioMuta; NDUFB8; -. DR jPOST; O95169; -. DR MassIVE; O95169; -. DR PaxDb; 9606-ENSP00000299166; -. DR PeptideAtlas; O95169; -. DR ProteomicsDB; 50683; -. [O95169-1] DR ProteomicsDB; 65796; -. DR ProteomicsDB; 65797; -. DR Pumba; O95169; -. DR TopDownProteomics; O95169-1; -. [O95169-1] DR Antibodypedia; 1271; 108 antibodies from 27 providers. DR DNASU; 4714; -. DR Ensembl; ENST00000299166.9; ENSP00000299166.4; ENSG00000166136.18. [O95169-1] DR Ensembl; ENST00000370320.4; ENSP00000359344.4; ENSG00000166136.18. [O95169-2] DR Ensembl; ENST00000370322.5; ENSP00000359346.1; ENSG00000166136.18. [O95169-3] DR Ensembl; ENST00000718301.1; ENSP00000520734.1; ENSG00000166136.18. [O95169-1] DR GeneID; 4714; -. DR KEGG; hsa:4714; -. DR MANE-Select; ENST00000299166.9; ENSP00000299166.4; NM_005004.4; NP_004995.1. DR UCSC; uc001kri.3; human. [O95169-1] DR AGR; HGNC:7703; -. DR ClinPGx; PA31514; -. DR CTD; 4714; -. DR DisGeNET; 4714; -. DR GeneCards; NDUFB8; -. DR HGNC; HGNC:7703; NDUFB8. DR HPA; ENSG00000166136; Low tissue specificity. DR MalaCards; NDUFB8; -. DR MIM; 602140; gene. DR MIM; 618252; phenotype. DR OpenTargets; ENSG00000166136; -. DR VEuPathDB; HostDB:ENSG00000166136; -. DR eggNOG; KOG4040; Eukaryota. DR GeneTree; ENSGT00390000000628; -. DR HOGENOM; CLU_108654_1_0_1; -. DR InParanoid; O95169; -. DR OMA; MEDYEPY; -. DR OrthoDB; 2014058at2759; -. DR PAN-GO; O95169; 1 GO annotation based on evolutionary models. DR PhylomeDB; O95169; -. DR BioCyc; MetaCyc:HS09335-MONOMER; -. DR PathwayCommons; O95169; -. DR Reactome; R-HSA-1268020; Mitochondrial protein import. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; O95169; -. DR SIGNOR; O95169; -. DR Agora; ENSG00000166136; -. DR BioGRID-ORCS; 4714; 311 hits in 1163 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFB8; human. DR GeneWiki; NDUFB8; -. DR GenomeRNAi; 4714; -. DR Pharos; O95169; Tclin. DR PRO; PR:O95169; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; O95169; protein. DR Bgee; ENSG00000166136; Expressed in endothelial cell and 217 other cell types or tissues. DR ExpressionAtlas; O95169; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; NAS:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR InterPro; IPR008699; NDUFB8. DR InterPro; IPR016551; Ndufb8_metazoa. DR PANTHER; PTHR12840:SF2; NADH DEHYDROGENASE [UBIQUINONE] 1 BETA SUBCOMPLEX SUBUNIT 8, MITOCHONDRIAL; 1. DR PANTHER; PTHR12840; NADH-UBIQUINONE OXIDOREDUCTASE ASHI SUBUNIT; 1. DR Pfam; PF05821; NDUF_B8; 1. DR PIRSF; PIRSF009288; NDUB8; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Disease variant; Electron transport; KW Membrane; Mitochondrion; Mitochondrion inner membrane; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transit peptide; Transmembrane; KW Transmembrane helix; Transport. FT TRANSIT 1..28 FT /note="Mitochondrion" FT /evidence="ECO:0000250" FT CHAIN 29..186 FT /note="NADH dehydrogenase [ubiquinone] 1 beta subcomplex FT subunit 8, mitochondrial" FT /id="PRO_0000020046" FT TRANSMEM 133..153 FT /note="Helical" FT /evidence="ECO:0000255" FT VAR_SEQ 1..31 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054842" FT VAR_SEQ 157..172 FT /note="GPKQYPYNNLYLERGG -> CRHHFSYNLGFLSALG (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054843" FT VAR_SEQ 173..186 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_054844" FT VARIANT 62 FT /note="Y -> H (in MC1DN32; dbSNP:rs1554843434)" FT /evidence="ECO:0000269|PubMed:29429571" FT /id="VAR_081466" FT VARIANT 76 FT /note="P -> Q (in MC1DN32; dbSNP:rs1239013578)" FT /evidence="ECO:0000269|PubMed:29429571" FT /id="VAR_081467" FT VARIANT 105..156 FT /note="Missing (in MC1DN32; due to a nucleotide FT substitution that results in exon 4 skipping or in missense FT variant W-144; patient cells contain both type of FT transcripts; transcript lacking exon 4 is the most FT abundant)" FT /evidence="ECO:0000269|PubMed:29429571" FT /id="VAR_081468" FT VARIANT 144 FT /note="C -> W (in MC1DN32; due to a nucleotide substitution FT that results in exon 4 skipping or missense variant W-144; FT patient cells contain both type of transcripts; transcript FT with the missense variant is the less abundant; FT dbSNP:rs1554843251)" FT /evidence="ECO:0000269|PubMed:29429571" FT /id="VAR_081469" FT CONFLICT 44 FT /note="T -> I (in Ref. 4; CAB45691 and 5; CAG38521)" FT /evidence="ECO:0000305" FT CONFLICT 171 FT /note="G -> S (in Ref. 3; AAD27761)" FT /evidence="ECO:0000305" FT CONFLICT 184 FT /note="Y -> N (in Ref. 4; CAB45691 and 5; CAG38521)" FT /evidence="ECO:0000305" SQ SEQUENCE 186 AA; 21766 MW; 518459D44965D202 CRC64; MAVARAGVLG VQWLQRASRN VMPLGARTAS HMTKDMFPGP YPRTPEERAA AAKKYNMRVE DYEPYPDDGM GYGDYPKLPD RSQHERDPWY SWDQPGLRLN WGEPMHWHLD MYNRNRVDTS PTPVSWHVMC MQLFGFLAFM IFMCWVGDVY PVYQPVGPKQ YPYNNLYLER GGDPSKEPER VVHYEI // ID NDUB9_HUMAN Reviewed; 179 AA. AC Q9Y6M9; B2R8M6; Q9UQE8; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 28-JAN-2026, entry version 203. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9; DE AltName: Full=Complex I-B22; DE Short=CI-B22; DE AltName: Full=LYR motif-containing protein 3; DE AltName: Full=NADH-ubiquinone oxidoreductase B22 subunit; GN Name=NDUFB9; Synonyms=LYRM3, UQOR22; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Triepels R., Smeets R., Loeffen J., Ruitenbeek W., van den Heuvel L., RA Smeitink J.; RT "B22 subunit of NADH:ubiquinone oxidoreductase (complex I)."; RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10077726; DOI=10.1159/000022848; RA Lin X., Wells D.E., Kimberling W.J., Kumar S.; RT "Human NDUFB9 gene: genomic organization and a possible candidate gene RT associated with deafness disorder mapped to chromosome 8q13."; RL Hum. Hered. 49:75-80(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Astrocytoma; RX PubMed=10944468; DOI=10.1006/bbrc.2000.3282; RA Ye Z., Connor J.R.; RT "cDNA cloning by amplification of circularized first strand cDNAs reveals RT non-IRE-regulated iron-responsive mRNAs."; RL Biochem. Biophys. Res. Commun. 275:223-227(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-146. RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE OF 2-15, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT RP ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Colon adenocarcinoma; RA Bienvenut W.V., Murray L., Brunton V.G., Frame M.C.; RL Submitted (JUL-2007) to UniProtKB. RN [9] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP INVOLVEMENT IN MC1DN24, AND VARIANT MC1DN24 PRO-64. RX PubMed=22200994; DOI=10.1136/jmedgenet-2011-100577; RA Haack T.B., Madignier F., Herzer M., Lamantea E., Danhauser K., RA Invernizzi F., Koch J., Freitag M., Drost R., Hillier I., Haberberger B., RA Mayr J.A., Ahting U., Tiranti V., Roetig A., Iuso A., Horvath R., RA Tesarova M., Baric I., Uziel G., Rolinski B., Sperl W., Meitinger T., RA Zeviani M., Freisinger P., Prokisch H.; RT "Mutation screening of 75 candidate genes in 152 complex I deficiency cases RT identifies pathogenic variants in 16 genes including NDUFB9."; RL J. Med. Genet. 49:83-89(2012). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [15] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed to be not CC involved in catalysis. Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: Mammalian complex I is composed of 45 different subunits. CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891}; Peripheral membrane protein CC {ECO:0000305}; Matrix side {ECO:0000305}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 24 (MC1DN24) CC [MIM:618245]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN24 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:22200994}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the complex I LYR family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF044956; AAD42057.1; -; mRNA. DR EMBL; AF261090; AAF99683.1; -; mRNA. DR EMBL; AF067168; AAD32452.1; -; mRNA. DR EMBL; AK313432; BAG36223.1; -; mRNA. DR EMBL; CH471060; EAW92068.1; -; Genomic_DNA. DR EMBL; BC007672; AAH07672.1; -; mRNA. DR CCDS; CCDS6352.1; -. DR RefSeq; NP_001298097.1; NM_001311168.1. DR RefSeq; NP_004996.1; NM_005005.3. DR PDB; 5XTC; EM; 3.70 A; p=8-179. DR PDB; 5XTD; EM; 3.70 A; p=8-179. DR PDB; 5XTH; EM; 3.90 A; p=8-179. DR PDB; 5XTI; EM; 17.40 A; Bp/p=8-179. DR PDB; 9CWT; EM; 3.44 A; p=1-179. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; Q9Y6M9; -. DR EMDB; EMD-45974; -. DR SMR; Q9Y6M9; -. DR BioGRID; 110795; 159. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; Q9Y6M9; -. DR FunCoup; Q9Y6M9; 1627. DR MINT; Q9Y6M9; -. DR STRING; 9606.ENSP00000276689; -. DR BindingDB; Q9Y6M9; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; Q9Y6M9; -. DR GlyGen; Q9Y6M9; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y6M9; -. DR PhosphoSitePlus; Q9Y6M9; -. DR SwissPalm; Q9Y6M9; -. DR BioMuta; NDUFB9; -. DR DMDM; 8134589; -. DR jPOST; Q9Y6M9; -. DR MassIVE; Q9Y6M9; -. DR PaxDb; 9606-ENSP00000276689; -. DR PeptideAtlas; Q9Y6M9; -. DR ProteomicsDB; 86739; -. DR Pumba; Q9Y6M9; -. DR TopDownProteomics; Q9Y6M9; -. DR Antibodypedia; 27088; 355 antibodies from 36 providers. DR DNASU; 4715; -. DR Ensembl; ENST00000276689.8; ENSP00000276689.3; ENSG00000147684.11. DR Ensembl; ENST00000677021.1; ENSP00000504235.1; ENSG00000147684.11. DR GeneID; 4715; -. DR KEGG; hsa:4715; -. DR MANE-Select; ENST00000276689.8; ENSP00000276689.3; NM_005005.3; NP_004996.1. DR UCSC; uc003yrg.5; human. DR AGR; HGNC:7704; -. DR ClinPGx; PA31515; -. DR CTD; 4715; -. DR DisGeNET; 4715; -. DR GeneCards; NDUFB9; -. DR HGNC; HGNC:7704; NDUFB9. DR HPA; ENSG00000147684; Tissue enhanced (skeletal muscle, tongue). DR MalaCards; NDUFB9; -. DR MIM; 601445; gene. DR MIM; 618245; phenotype. DR OpenTargets; ENSG00000147684; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000147684; -. DR eggNOG; KOG3466; Eukaryota. DR GeneTree; ENSGT00390000005809; -. DR HOGENOM; CLU_108081_0_0_1; -. DR InParanoid; Q9Y6M9; -. DR OMA; CVFRDKY; -. DR OrthoDB; 13598at2759; -. DR PAN-GO; Q9Y6M9; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q9Y6M9; -. DR BioCyc; MetaCyc:HS07466-MONOMER; -. DR PathwayCommons; Q9Y6M9; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q9Y6M9; -. DR SIGNOR; Q9Y6M9; -. DR Agora; ENSG00000147684; -. DR BioGRID-ORCS; 4715; 449 hits in 1177 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFB9; human. DR GeneWiki; NDUFB9; -. DR GenomeRNAi; 4715; -. DR Pharos; Q9Y6M9; Tclin. DR PRO; PR:Q9Y6M9; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q9Y6M9; protein. DR Bgee; ENSG00000147684; Expressed in left ventricle myocardium and 190 other cell types or tissues. DR ExpressionAtlas; Q9Y6M9; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; TAS:ProtInc. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; TAS:ProtInc. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR GO; GO:0007605; P:sensory perception of sound; TAS:ProtInc. DR CDD; cd20263; Complex1_LYR_NDUFB9_LYRM3; 1. DR InterPro; IPR008011; Complex1_LYR_dom. DR InterPro; IPR045292; Complex1_LYR_NDUFB9_LYRM3. DR InterPro; IPR033034; NDUFB9. DR PANTHER; PTHR12868:SF1; NADH DEHYDROGENASE [UBIQUINONE] 1 BETA SUBCOMPLEX SUBUNIT 9; 1. DR PANTHER; PTHR12868; NADH-UBIQUINONE OXIDOREDUCTASE B22 SUBUNIT; 1. DR Pfam; PF05347; Complex1_LYR; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Direct protein sequencing; Disease variant; KW Electron transport; Membrane; Mitochondrion; Mitochondrion inner membrane; KW Phosphoprotein; Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:25944712" FT CHAIN 2..179 FT /note="NADH dehydrogenase [ubiquinone] 1 beta subcomplex FT subunit 9" FT /id="PRO_0000174306" FT REGION 136..162 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:25944712" FT MOD_RES 85 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18691976" FT VARIANT 64 FT /note="L -> P (in MC1DN24; dbSNP:rs776388520)" FT /evidence="ECO:0000269|PubMed:22200994" FT /id="VAR_081460" FT VARIANT 146 FT /note="P -> S (in dbSNP:rs10195)" FT /evidence="ECO:0000269|PubMed:11042152" FT /id="VAR_014484" SQ SEQUENCE 179 AA; 21831 MW; 2287AE8757F85E68 CRC64; MAFLASGPYL THQQKVLRLY KRALRHLESW CVQRDKYRYF ACLMRARFEE HKNEKDMAKA TQLLKEAEEE FWYRQHPQPY IFPDSPGGTS YERYDCYKVP EWCLDDWHPS EKAMYPDYFA KREQWKKLRR ESWEREVKQL QEETPPGGPL TEALPPARKE GDLPPLWWYI VTRPRERPM // ID NDUBA_HUMAN Reviewed; 172 AA. AC O96000; Q96II6; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 28-JAN-2026, entry version 200. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10; DE AltName: Full=Complex I-PDSW; DE Short=CI-PDSW; DE AltName: Full=NADH-ubiquinone oxidoreductase PDSW subunit; GN Name=NDUFB10; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9878551; DOI=10.1006/bbrc.1998.9786; RA Loeffen J.L.C.M., Triepels R.H., van den Heuvel L.P., Schuelke M., RA Buskens C.A.F., Smeets R.J.P., Trijbels J.M.F., Smeitink J.A.M.; RT "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: RT human complex I cDNA characterization completed."; RL Biochem. Biophys. Res. Commun. 253:415-422(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Wang L., Zhang J., Smith D.I.; RT "One subunit of human NADH-ubiquinone oxidoreductase, hPDSW, located at RT 16p13.3 and down-regulated in a prostate cell line."; RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Ovary, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [12] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CHCHD4, DISULFIDE BOND, RP INVOLVEMENT IN MC1DN35, VARIANT MC1DN35 SER-107, AND CHARACTERIZATION OF RP VARIANT MC1DN35 SER-107. RX PubMed=28040730; DOI=10.1093/hmg/ddw431; RA Friederich M.W., Erdogan A.J., Coughlin C.R. II, Elos M.T., Jiang H., RA O'Rourke C.P., Lovell M.A., Wartchow E., Gowan K., Chatfield K.C., RA Chick W.S., Spector E.B., Van Hove J.L.K., Riemer J.; RT "Mutations in the accessory subunit NDUFB10 result in isolated complex I RT deficiency and illustrate the critical role of intermembrane space import RT for complex I holoenzyme assembly."; RL Hum. Mol. Genet. 26:702-716(2017). CC -!- FUNCTION: Accessory subunit that is involved in the functional assembly CC of the mitochondrial respiratory chain complex I. Complex I has an NADH CC dehydrogenase activity with ubiquinone as an immediate electron CC acceptor and mediates the transfer of electrons from NADH to the CC respiratory chain. {ECO:0000269|PubMed:27626371, CC ECO:0000269|PubMed:28040730}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits CC (PubMed:12611891, PubMed:27626371, PubMed:28040730). Interacts with CC CHCHD4; assists NDUFB10 oxidation, folding and import into CC mitochondrion (PubMed:28040730). {ECO:0000269|PubMed:12611891, CC ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:28040730}. CC -!- INTERACTION: CC O96000; Q8IZU0: FAM9B; NbExp=6; IntAct=EBI-1246371, EBI-10175124; CC O96000; O14964: HGS; NbExp=3; IntAct=EBI-1246371, EBI-740220; CC O96000; P42858: HTT; NbExp=13; IntAct=EBI-1246371, EBI-466029; CC O96000; O15160: POLR1C; NbExp=3; IntAct=EBI-1246371, EBI-1055079; CC O96000; P05455: SSB; NbExp=3; IntAct=EBI-1246371, EBI-358037; CC O96000; Q8NFB2: TMEM185A; NbExp=3; IntAct=EBI-1246371, EBI-21757569; CC O96000-2; P42858: HTT; NbExp=3; IntAct=EBI-25930682, EBI-466029; CC O96000-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-25930682, EBI-5235340; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:28040730, ECO:0000305|PubMed:12611891}; Peripheral CC membrane protein {ECO:0000305}; Matrix side {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O96000-1; Sequence=Displayed; CC Name=2; CC IsoId=O96000-2; Sequence=VSP_056555; CC -!- PTM: The formation of intramolecular disulfide bonds is assisted by CC CHCHD4 and ensures folding, import into the mitochondrion and is CC required for the function in mitochondrial respiratory chain complex I CC assembly. {ECO:0000269|PubMed:28040730}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 35 (MC1DN35) CC [MIM:619003]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN35 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:28040730}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFB10 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF044954; AAD05419.1; -; mRNA. DR EMBL; AF088995; AAD16091.1; -; Genomic_DNA. DR EMBL; AF088992; AAD16091.1; JOINED; Genomic_DNA. DR EMBL; AF088993; AAD16091.1; JOINED; Genomic_DNA. DR EMBL; AF088994; AAD16091.1; JOINED; Genomic_DNA. DR EMBL; AF088991; AAD08677.1; -; mRNA. DR EMBL; AF067169; AAD32453.1; -; mRNA. DR EMBL; AC005363; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471112; EAW85597.1; -; Genomic_DNA. DR EMBL; BC007509; AAH07509.1; -; mRNA. DR EMBL; BC005829; AAH05829.1; -; mRNA. DR CCDS; CCDS10451.1; -. [O96000-1] DR PIR; JE0381; JE0381. DR RefSeq; NP_004539.1; NM_004548.3. [O96000-1] DR PDB; 5XTC; EM; 3.70 A; d=1-171. DR PDB; 5XTD; EM; 3.70 A; d=1-171. DR PDB; 5XTH; EM; 3.90 A; d=1-171. DR PDB; 5XTI; EM; 17.40 A; Bd/d=1-171. DR PDB; 9CWT; EM; 3.44 A; d=1-172. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; O96000; -. DR EMDB; EMD-45974; -. DR SMR; O96000; -. DR BioGRID; 110796; 165. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O96000; -. DR DIP; DIP-38298N; -. DR FunCoup; O96000; 823. DR IntAct; O96000; 74. DR MINT; O96000; -. DR STRING; 9606.ENSP00000268668; -. DR BindingDB; O96000; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; O96000; -. DR GlyGen; O96000; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O96000; -. DR PhosphoSitePlus; O96000; -. DR SwissPalm; O96000; -. DR BioMuta; NDUFB10; -. DR jPOST; O96000; -. DR MassIVE; O96000; -. DR PaxDb; 9606-ENSP00000268668; -. DR PeptideAtlas; O96000; -. DR ProteomicsDB; 51179; -. [O96000-1] DR ProteomicsDB; 76829; -. DR Pumba; O96000; -. DR TopDownProteomics; O96000-1; -. [O96000-1] DR Antibodypedia; 23340; 349 antibodies from 32 providers. DR DNASU; 4716; -. DR Ensembl; ENST00000268668.11; ENSP00000268668.6; ENSG00000140990.16. [O96000-1] DR Ensembl; ENST00000543683.6; ENSP00000445086.2; ENSG00000140990.16. [O96000-2] DR Ensembl; ENST00000709233.1; ENSP00000517571.1; ENSG00000291930.1. [O96000-1] DR Ensembl; ENST00000709234.1; ENSP00000517572.1; ENSG00000291930.1. [O96000-2] DR GeneID; 4716; -. DR KEGG; hsa:4716; -. DR MANE-Select; ENST00000268668.11; ENSP00000268668.6; NM_004548.3; NP_004539.1. DR UCSC; uc002cni.3; human. [O96000-1] DR AGR; HGNC:7696; -. DR ClinPGx; PA31502; -. DR CTD; 4716; -. DR DisGeNET; 4716; -. DR GeneCards; NDUFB10; -. DR HGNC; HGNC:7696; NDUFB10. DR HPA; ENSG00000140990; Group enriched (heart muscle, skeletal muscle, tongue). DR MalaCards; NDUFB10; -. DR MIM; 603843; gene. DR MIM; 619003; phenotype. DR OpenTargets; ENSG00000140990; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000140990; -. DR eggNOG; KOG4009; Eukaryota. DR GeneTree; ENSGT00390000006348; -. DR HOGENOM; CLU_112615_1_0_1; -. DR InParanoid; O96000; -. DR OMA; CKPILEQ; -. DR OrthoDB; 6017729at2759; -. DR PAN-GO; O96000; 1 GO annotation based on evolutionary models. DR PhylomeDB; O96000; -. DR BioCyc; MetaCyc:HS06786-MONOMER; -. DR PathwayCommons; O96000; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; O96000; -. DR SIGNOR; O96000; -. DR Agora; ENSG00000140990; -. DR BioGRID-ORCS; 4716; 378 hits in 1183 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFB10; human. DR GeneWiki; NDUFB10; -. DR GenomeRNAi; 4716; -. DR Pharos; O96000; Tclin. DR PRO; PR:O96000; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; O96000; protein. DR Bgee; ENSG00000140990; Expressed in left ventricle myocardium and 181 other cell types or tissues. DR ExpressionAtlas; O96000; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; NAS:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR InterPro; IPR019377; NADH_UbQ_OxRdtase_su10. DR InterPro; IPR039993; NDUFB10. DR PANTHER; PTHR13094:SF1; NADH DEHYDROGENASE [UBIQUINONE] 1 BETA SUBCOMPLEX SUBUNIT 10; 1. DR PANTHER; PTHR13094; NADH-UBIQUINONE OXIDOREDUCTASE PDSW SUBUNIT; 1. DR Pfam; PF10249; NDUFB10; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Disease variant; Electron transport; KW Membrane; Mitochondrion; Mitochondrion inner membrane; Phosphoprotein; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transport. FT CHAIN 1..172 FT /note="NADH dehydrogenase [ubiquinone] 1 beta subcomplex FT subunit 10" FT /id="PRO_0000118830" FT MOD_RES 145 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 137..172 FT /note="YQDLGAYSSARKCLAKQRQRMLQERKAAKEAAAATS -> CACPTHPQPPTI FT LLRPGGQNHCKSSLPSLVLT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_056555" FT VARIANT 107 FT /note="C -> S (in MC1DN35; decreased protein abundance; FT decreased CHCHD4-mediated oxidation; loss of mitochondrial FT localization; retained in the cytosol; loss of function in FT mitochondrial respiratory chain complex I assembly)" FT /evidence="ECO:0000269|PubMed:28040730" FT /id="VAR_084767" SQ SEQUENCE 172 AA; 20777 MW; A5E6561402F4486A CRC64; MPDSWDKDVY PEPPRRTPVQ PNPIVYMMKA FDLIVDRPVT LVREFIERQH AKNRYYYYHR QYRRVPDITE CKEEDIMCMY EAEMQWKRDY KVDQEIINIM QDRLKACQQR EGQNYQQNCI KEVEQFTQVA KAYQDRYQDL GAYSSARKCL AKQRQRMLQE RKAAKEAAAA TS // ID NDUBB_HUMAN Reviewed; 153 AA. AC Q9NX14; Q5JRR3; Q5JRR4; Q6IAB6; Q8WZ96; Q9BXX9; DT 03-JUL-2003, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 28-JAN-2026, entry version 191. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial; DE AltName: Full=Complex I-ESSS; DE Short=CI-ESSS; DE AltName: Full=NADH-ubiquinone oxidoreductase ESSS subunit; DE AltName: Full=Neuronal protein 17.3; DE Short=Np17.3; DE Short=p17.3; DE Flags: Precursor; GN Name=NDUFB11; ORFNames=UNQ111/PRO1064; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal brain; RX PubMed=10544803; DOI=10.1023/a:1018734605214; RA Cui Y., Yu L., Gong R., Zhang M., Fan Y., Yue P., Zhao S.; RT "Cloning and tissue expressional characterization of a full-length cDNA RT encoding human neuronal protein P17.3."; RL Biochem. Genet. 37:175-185(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Mao Y., Xie Y., Zhou Z., Zhao W., Zhao S., Wang W., Huang Y., Wang S., RA Tang R., Chen X., Wu C.; RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [11] RP INVOLVEMENT IN LSDMCA3. RX PubMed=25772934; DOI=10.1016/j.ajhg.2015.02.002; RA van Rahden V.A., Fernandez-Vizarra E., Alawi M., Brand K., Fellmann F., RA Horn D., Zeviani M., Kutsche K.; RT "Mutations in NDUFB11, encoding a complex I component of the mitochondrial RT respiratory chain, cause microphthalmia with linear skin defects RT syndrome."; RL Am. J. Hum. Genet. 96:640-650(2015). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [13] RP VARIANTS 85-TRP--GLU-153 DEL AND 108-TYR--GLU-153 DEL. RX PubMed=25921236; DOI=10.1002/ajmg.a.37138; RA Shehata B.M., Cundiff C.A., Lee K., Sabharwal A., Lalwani M.K., Davis A.K., RA Agrawal V., Sivasubbu S., Iannucci G.J., Gibson G.; RT "Exome sequencing of patients with histiocytoid cardiomyopathy reveals a de RT novo NDUFB11 mutation that plays a role in the pathogenesis of histiocytoid RT cardiomyopathy."; RL Am. J. Med. Genet. A 167A:2114-2121(2015). RN [14] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [15] RP INTERACTION WITH BCAP31, AND SUBCELLULAR LOCATION. RX PubMed=31206022; DOI=10.1126/sciadv.aaw1386; RA Namba T.; RT "BAP31 regulates mitochondrial function via interaction with Tom40 within RT ER-mitochondria contact sites."; RL Sci. Adv. 5:eaaw1386-eaaw1386(2019). RN [16] RP INVOLVEMENT IN MC1DN30, AND VARIANT MC1DN30 LYS-121. RX PubMed=26741492; DOI=10.1371/journal.pgen.1005679; RA Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y., RA Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H., RA Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T., Sato-Miyata Y., RA Ohnuma K., Suzuki T., Nagao A., Maehata H., Matsuda F., Higasa K., RA Nagasaki M., Yasuda J., Yamamoto M., Fushimi T., Shimura M., RA Kaiho-Ichimoto K., Harashima H., Yamazaki T., Mori M., Murayama K., RA Ohtake A., Okazaki Y.; RT "A comprehensive genomic analysis reveals the genetic landscape of RT mitochondrial respiratory chain complex deficiencies."; RL PLoS Genet. 12:E1005679-E1005679(2016). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis. Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits CC (PubMed:12611891, PubMed:27626371). Interacts with BCAP31 CC (PubMed:31206022). {ECO:0000269|PubMed:12611891, CC ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:31206022}. CC -!- INTERACTION: CC Q9NX14; O95471: CLDN7; NbExp=3; IntAct=EBI-1246182, EBI-740744; CC Q9NX14; Q15125: EBP; NbExp=3; IntAct=EBI-1246182, EBI-3915253; CC Q9NX14; Q969F0: FATE1; NbExp=6; IntAct=EBI-1246182, EBI-743099; CC Q9NX14; P08034: GJB1; NbExp=3; IntAct=EBI-1246182, EBI-17565645; CC Q9NX14; Q96P66: GPR101; NbExp=3; IntAct=EBI-1246182, EBI-17935713; CC Q9NX14; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-1246182, EBI-13345167; CC Q9NX14; O15529: GPR42; NbExp=3; IntAct=EBI-1246182, EBI-18076404; CC Q9NX14; P31937: HIBADH; NbExp=3; IntAct=EBI-1246182, EBI-11427100; CC Q9NX14; Q9NPL8: TIMMDC1; NbExp=4; IntAct=EBI-1246182, EBI-6268651; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:31206022, ECO:0000305|PubMed:12611891}; Single-pass CC membrane protein {ECO:0000305}. Note=The interaction with BCAP31 CC mediates mitochondria localization. {ECO:0000269|PubMed:31206022}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9NX14-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NX14-2; Sequence=VSP_018251; CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- DISEASE: Linear skin defects with multiple congenital anomalies 3 CC (LSDMCA3) [MIM:300952]: A disorder characterized by dermal, ocular, CC neurological and cardiac abnormalities. LSDMCA3 clinical features CC include linear skin defects on face and neck at birth, lacrimal duct CC atresia, myopia, nystagmus, strabismus, cardiomyopathy, axial CC hypotonia, seizures, corpus callosum agenesis, and dilation of lateral CC ventricles. {ECO:0000269|PubMed:25772934}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 30 (MC1DN30) CC [MIM:301021]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. {ECO:0000269|PubMed:26741492}. Note=The disease may CC be caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFB11 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF044213; AAL32064.1; -; mRNA. DR EMBL; AF251063; AAK34953.1; -; mRNA. DR EMBL; AK000501; BAA91208.1; -; mRNA. DR EMBL; AY359056; AAQ89415.1; -; mRNA. DR EMBL; CR457239; CAG33520.1; -; mRNA. DR EMBL; AL513366; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC010665; AAH10665.1; -; mRNA. DR EMBL; BC107805; AAI07806.1; -; mRNA. DR CCDS; CCDS14273.1; -. [Q9NX14-2] DR CCDS; CCDS48100.1; -. [Q9NX14-1] DR RefSeq; NP_001129470.1; NM_001135998.3. [Q9NX14-1] DR RefSeq; NP_061929.2; NM_019056.6. [Q9NX14-2] DR PDB; 5XTC; EM; 3.70 A; e=54-150. DR PDB; 5XTD; EM; 3.70 A; e=54-150. DR PDB; 5XTH; EM; 3.90 A; e=54-150. DR PDB; 5XTI; EM; 17.40 A; Be/e=54-150. DR PDB; 9CWT; EM; 3.44 A; e=1-153. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; Q9NX14; -. DR EMDB; EMD-45974; -. DR SMR; Q9NX14; -. DR BioGRID; 120026; 117. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; Q9NX14; -. DR FunCoup; Q9NX14; 1018. DR IntAct; Q9NX14; 88. DR MINT; Q9NX14; -. DR STRING; 9606.ENSP00000276062; -. DR BindingDB; Q9NX14; -. DR ChEMBL; CHEMBL2363065; -. DR DrugCentral; Q9NX14; -. DR CarbonylDB; Q9NX14; -. DR GlyGen; Q9NX14; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9NX14; -. DR PhosphoSitePlus; Q9NX14; -. DR SwissPalm; Q9NX14; -. DR BioMuta; NDUFB11; -. DR DMDM; 32469787; -. DR jPOST; Q9NX14; -. DR MassIVE; Q9NX14; -. DR PaxDb; 9606-ENSP00000276062; -. DR PeptideAtlas; Q9NX14; -. DR ProteomicsDB; 83021; -. [Q9NX14-1] DR ProteomicsDB; 83022; -. [Q9NX14-2] DR Pumba; Q9NX14; -. DR TopDownProteomics; Q9NX14-1; -. [Q9NX14-1] DR TopDownProteomics; Q9NX14-2; -. [Q9NX14-2] DR Antibodypedia; 25274; 185 antibodies from 25 providers. DR DNASU; 54539; -. DR Ensembl; ENST00000377811.4; ENSP00000367042.3; ENSG00000147123.13. [Q9NX14-1] DR Ensembl; ENST00000687244.1; ENSP00000509334.1; ENSG00000147123.13. [Q9NX14-2] DR GeneID; 54539; -. DR KEGG; hsa:54539; -. DR MANE-Select; ENST00000377811.4; ENSP00000367042.3; NM_001135998.3; NP_001129470.1. DR UCSC; uc004dhc.4; human. [Q9NX14-1] DR AGR; HGNC:20372; -. DR ClinPGx; PA134924203; -. DR CTD; 54539; -. DR DisGeNET; 54539; -. DR GeneCards; NDUFB11; -. DR GeneReviews; NDUFB11; -. DR HGNC; HGNC:20372; NDUFB11. DR HPA; ENSG00000147123; Tissue enhanced (skeletal). DR MalaCards; NDUFB11; -. DR MIM; 300403; gene. DR MIM; 300952; phenotype. DR MIM; 301021; phenotype. DR OpenTargets; ENSG00000147123; -. DR Orphanet; 2609; Isolated complex I deficiency. DR Orphanet; 2556; Microphthalmia with linear skin defects syndrome. DR VEuPathDB; HostDB:ENSG00000147123; -. DR eggNOG; KOG4808; Eukaryota. DR GeneTree; ENSGT00390000003022; -. DR HOGENOM; CLU_109862_0_0_1; -. DR InParanoid; Q9NX14; -. DR OMA; DYRMKEW; -. DR OrthoDB; 5917019at2759; -. DR PAN-GO; Q9NX14; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q9NX14; -. DR BioCyc; MetaCyc:HS14193-MONOMER; -. DR PathwayCommons; Q9NX14; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q9NX14; -. DR SIGNOR; Q9NX14; -. DR Agora; ENSG00000147123; -. DR BioGRID-ORCS; 54539; 92 hits in 787 CRISPR screens. DR ChiTaRS; NDUFB11; human. DR GeneWiki; NDUFB11; -. DR GenomeRNAi; 54539; -. DR Pharos; Q9NX14; Tclin. DR PRO; PR:Q9NX14; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q9NX14; protein. DR Bgee; ENSG00000147123; Expressed in apex of heart and 203 other cell types or tissues. DR GO; GO:0001669; C:acrosomal vesicle; IDA:HPA. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0097229; C:sperm end piece; IDA:HPA. DR GO; GO:0120212; C:sperm head-tail coupling apparatus; IDA:HPA. DR GO; GO:0097225; C:sperm midpiece; IDA:HPA. DR GO; GO:0097228; C:sperm principal piece; IDA:HPA. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR InterPro; IPR019329; NADH_UbQ_OxRdtase_ESSS_su. DR PANTHER; PTHR13327:SF0; NADH DEHYDROGENASE [UBIQUINONE] 1 BETA SUBCOMPLEX SUBUNIT 11, MITOCHONDRIAL; 1. DR PANTHER; PTHR13327; NADH-UBIQUINONE OXIDOREDUCTASE ESSS SUBUNIT, MITOCHONDRIAL PRECURSOR; 1. DR Pfam; PF10183; ESSS; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cardiomyopathy; Disease variant; KW Electron transport; Membrane; Mitochondrion; Mitochondrion inner membrane; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transit peptide; Transmembrane; KW Transmembrane helix; Transport. FT TRANSIT 1..29 FT /note="Mitochondrion" FT /evidence="ECO:0000250" FT CHAIN 30..153 FT /note="NADH dehydrogenase [ubiquinone] 1 beta subcomplex FT subunit 11, mitochondrial" FT /id="PRO_0000020057" FT TRANSMEM 89..109 FT /note="Helical" FT /evidence="ECO:0000255" FT REGION 40..76 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 66..76 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 113 FT /note="R -> RCTGCPRAWDG (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2" FT /id="VSP_018251" FT VARIANT 85..153 FT /note="Missing (found in a patient with histiocytoid FT cardiomyopathy; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25921236" FT /id="VAR_078941" FT VARIANT 108..153 FT /note="Missing (found in a patient with histiocytoid FT cardiomyopathy; uncertain significance)" FT /evidence="ECO:0000269|PubMed:25921236" FT /id="VAR_078942" FT VARIANT 121 FT /note="E -> K (in MC1DN30; dbSNP:rs1057519073)" FT /evidence="ECO:0000269|PubMed:26741492" FT /id="VAR_076277" FT CONFLICT 13 FT /note="L -> P (in Ref. 1; AAL32064)" FT /evidence="ECO:0000305" FT CONFLICT 153 FT /note="E -> D (in Ref. 5; CAG33520)" FT /evidence="ECO:0000305" SQ SEQUENCE 153 AA; 17317 MW; 2AF8FDD248A86C41 CRC64; MAAGLFGLSA RRLLAAAATR GLPAARVRWE SSFSRTVVAP SAVAGKRPPE PTTPWQEDPE PEDENLYEKN PDSHGYDKDP VLDVWNMRLV FFFGVSIILV LGSTFVAYLP DYRMKEWSRR EAERLVKYRE ANGLPIMESN CFDPSKIQLP EDE // ID NDUC2_HUMAN Reviewed; 119 AA. AC O95298; E9PNU8; E9PRB2; Q549M5; Q6FIH8; Q9UBJ9; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 28-JAN-2026, entry version 186. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 subunit C2 {ECO:0000305}; DE AltName: Full=Complex I-B14.5b; DE Short=CI-B14.5b; DE AltName: Full=Human lung cancer oncogene 1 protein; DE Short=HLC-1; DE AltName: Full=NADH-ubiquinone oxidoreductase subunit B14.5b; GN Name=NDUFC2 {ECO:0000312|HGNC:HGNC:7706}; ORFNames=HLC1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9878551; DOI=10.1006/bbrc.1998.9786; RA Loeffen J.L.C.M., Triepels R.H., van den Heuvel L.P., Schuelke M., RA Buskens C.A.F., Smeets R.J.P., Trijbels J.M.F., Smeitink J.A.M.; RT "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: RT human complex I cDNA characterization completed."; RL Biochem. Biophys. Res. Commun. 253:415-422(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Dai F.Y., Yu L., Yang J., Huang H.B., Wang X.K., Zhao S.Y.; RT "Cloning and expression of a new human cDNA homology to B.taurus NADH RT dehydrogenase (ubiquinone) mRNA."; RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-46. RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-46. RC TISSUE=Kidney; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-46. RA Kim J.W.; RT "Identification of a new oncogene in human cancer."; RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-46. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [13] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [14] RP INTERACTION WITH TMEM242. RX PubMed=33753518; DOI=10.1073/pnas.2100558118; RA Carroll J., He J., Ding S., Fearnley I.M., Walker J.E.; RT "TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase RT and interact with assembly factors for complex I."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). RN [15] RP VARIANT MC1DN36 TYR-58, CHARACTERIZATION OF VARIANT MC1DN36 TYR-58, AND RP FUNCTION. RX PubMed=32969598; DOI=10.15252/emmm.202012619; RA Alahmad A., Nasca A., Heidler J., Thompson K., Olahova M., Legati A., RA Lamantea E., Meisterknecht J., Spagnolo M., He L., Alameer S., Hakami F., RA Almehdar A., Ardissone A., Alston C.L., McFarland R., Wittig I., Ghezzi D., RA Taylor R.W.; RT "Bi-allelic pathogenic variants in NDUFC2 cause early-onset Leigh syndrome RT and stalled biogenesis of complex I."; RL EMBO Mol. Med. 12:e12619-e12619(2020). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis but required for the complex assembly. Complex I CC functions in the transfer of electrons from NADH to the respiratory CC chain. The immediate electron acceptor for the enzyme is believed to be CC ubiquinone. {ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:32969598}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits. Interacts with CC TMEM242 (PubMed:33753518). {ECO:0000269|PubMed:12611891, CC ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:33753518}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891}; Single-pass membrane protein CC {ECO:0000255}; Matrix side {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=3; CC IsoId=O95298-1; Sequence=Displayed; CC Name=4; CC IsoId=O95298-2; Sequence=VSP_047317; CC Name=5; CC IsoId=O95298-3; Sequence=VSP_047318; CC Name=2; Synonyms=NDUFC2-KCTD14; CC IsoId=E9PQ53-1; Sequence=External; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 36 (MC1DN36) CC [MIM:619170]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN36 is characterized by global developmental CC delay, hypotonia, and failure to thrive apparent from infancy or early CC childhood. Affected individuals usually do not acquire ambulation, show CC progressive spasticity, and have impaired intellectual development with CC absent speech. MC1DN36 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:32969598}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFC2 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF087659; AAD09754.1; -; mRNA. DR EMBL; AF087899; AAP97198.1; -; mRNA. DR EMBL; AF070652; AAD20958.1; -; mRNA. DR EMBL; AL050278; CAB43379.1; -; mRNA. DR EMBL; AF369951; AAM21294.1; -; mRNA. DR EMBL; CR533448; CAG38479.1; -; mRNA. DR EMBL; AP003032; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471076; EAW75046.1; -; Genomic_DNA. DR EMBL; BC007323; AAH07323.1; -; mRNA. DR CCDS; CCDS55779.1; -. [O95298-2] DR CCDS; CCDS55781.1; -. [O95298-3] DR CCDS; CCDS8257.1; -. [O95298-1] DR PIR; T08728; T08728. DR RefSeq; NP_001190983.1; NM_001204054.3. [O95298-3] DR RefSeq; NP_001190984.1; NM_001204055.2. [O95298-2] DR RefSeq; NP_004540.1; NM_004549.6. [O95298-1] DR PDB; 5XTC; EM; 3.70 A; g=1-119. DR PDB; 5XTD; EM; 3.70 A; g=1-119. DR PDB; 5XTH; EM; 3.90 A; g=1-119. DR PDB; 5XTI; EM; 17.40 A; Bg/g=1-119. DR PDB; 9CWT; EM; 3.44 A; g=1-119. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; O95298; -. DR EMDB; EMD-45974; -. DR SMR; O95298; -. DR BioGRID; 110798; 88. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O95298; -. DR FunCoup; O95298; 1515. DR IntAct; O95298; 94. DR MINT; O95298; -. DR STRING; 9606.ENSP00000281031; -. DR BindingDB; O95298; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB01136; Carvedilol. DR DrugBank; DB00157; NADH. DR DrugCentral; O95298; -. DR iPTMnet; O95298; -. DR PhosphoSitePlus; O95298; -. DR BioMuta; NDUFC2; -. DR jPOST; O95298; -. DR MassIVE; O95298; -. DR PaxDb; 9606-ENSP00000281031; -. DR PeptideAtlas; O95298; -. DR ProteomicsDB; 22525; -. DR ProteomicsDB; 23265; -. DR ProteomicsDB; 50798; -. [O95298-1] DR Pumba; O95298; -. DR TopDownProteomics; O95298-1; -. [O95298-1] DR Antibodypedia; 31293; 187 antibodies from 31 providers. DR DNASU; 4718; -. DR Ensembl; ENST00000281031.5; ENSP00000281031.4; ENSG00000151366.14. [O95298-1] DR Ensembl; ENST00000525085.1; ENSP00000434262.1; ENSG00000151366.14. [O95298-2] DR Ensembl; ENST00000527806.1; ENSP00000432739.1; ENSG00000151366.14. [O95298-3] DR GeneID; 4718; -. DR KEGG; hsa:4718; -. DR MANE-Select; ENST00000281031.5; ENSP00000281031.4; NM_004549.6; NP_004540.1. DR UCSC; uc009yuw.4; human. [O95298-1] DR AGR; HGNC:7706; -. DR ClinPGx; PA31517; -. DR CTD; 4718; -. DR DisGeNET; 4718; -. DR GeneCards; NDUFC2; -. DR HGNC; HGNC:7706; NDUFC2. DR HPA; ENSG00000151366; Low tissue specificity. DR MalaCards; NDUFC2; -. DR MIM; 603845; gene. DR MIM; 619170; phenotype. DR OpenTargets; ENSG00000151366; -. DR VEuPathDB; HostDB:ENSG00000151366; -. DR eggNOG; KOG4516; Eukaryota. DR GeneTree; ENSGT00390000010352; -. DR HOGENOM; CLU_156652_0_0_1; -. DR InParanoid; O95298; -. DR OMA; WFIGYHI; -. DR OrthoDB; 6329847at2759; -. DR PAN-GO; O95298; 1 GO annotation based on evolutionary models. DR PhylomeDB; O95298; -. DR BioCyc; MetaCyc:HS07729-MONOMER; -. DR PathwayCommons; O95298; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; O95298; -. DR SIGNOR; O95298; -. DR Agora; ENSG00000151366; -. DR BioGRID-ORCS; 4718; 243 hits in 1108 CRISPR screens. DR GeneWiki; NDUFC2; -. DR GenomeRNAi; 4718; -. DR Pharos; O95298; Tclin. DR PRO; PR:O95298; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; O95298; protein. DR Bgee; ENSG00000151366; Expressed in right adrenal gland and 183 other cell types or tissues. DR ExpressionAtlas; O95298; baseline and differential. DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome. DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; NAS:UniProtKB. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR GO; GO:1901223; P:negative regulation of non-canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IEA:Ensembl. DR GO; GO:2001171; P:positive regulation of ATP biosynthetic process; IEA:Ensembl. DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; IEA:Ensembl. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR InterPro; IPR009423; NDUC2. DR PANTHER; PTHR13099:SF0; NADH DEHYDROGENASE [UBIQUINONE] 1 SUBUNIT C2-RELATED; 1. DR PANTHER; PTHR13099; NADH-UBIQUINONE OXIDOREDUCTASE SUBUNIT B14.5B; 1. DR Pfam; PF06374; NDUF_C2; 1. DR PIRSF; PIRSF017834; NADH-UbQ_OxRdtase_b14.5b; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Disease variant; Electron transport; KW Membrane; Mitochondrion; Mitochondrion inner membrane; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transmembrane; Transmembrane helix; KW Transport. FT CHAIN 1..119 FT /note="NADH dehydrogenase [ubiquinone] 1 subunit C2" FT /id="PRO_0000118837" FT TRANSMEM 56..75 FT /note="Helical" FT /evidence="ECO:0000255" FT VAR_SEQ 56..78 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_047317" FT VAR_SEQ 77..119 FT /note="REDYLYAVRDREMFGYMKLHPEDFPEEDKKTYGEIFEKFHPIR -> LEAYA FT NLYVDTL (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_047318" FT VARIANT 46 FT /note="L -> V (in dbSNP:rs8875)" FT /evidence="ECO:0000269|PubMed:11042152, FT ECO:0000269|PubMed:11230166, ECO:0000269|Ref.5, FT ECO:0000269|Ref.6" FT /id="VAR_014486" FT VARIANT 58 FT /note="H -> Y (in MC1DN36; highly decreased mitochondrial FT membrane respiratory chain NADH dehydrogenase complex I FT activity; decreased complex I assembly and protein levels; FT dbSNP:rs1306743145)" FT /evidence="ECO:0000269|PubMed:32969598" FT /id="VAR_085236" SQ SEQUENCE 119 AA; 14188 MW; 9A47DEE33DC9244D CRC64; MIARRNPEPL RFLPDEARSL PPPKLTDPRL LYIGFLGYCS GLIDNLIRRR PIATAGLHRQ LLYITAFFFA GYYLVKREDY LYAVRDREMF GYMKLHPEDF PEEDKKTYGE IFEKFHPIR // ID NDUF2_HUMAN Reviewed; 169 AA. AC Q8N183; A8K5I1; DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 28-JAN-2026, entry version 171. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 2; DE AltName: Full=B17.2-like; DE Short=B17.2L; DE AltName: Full=Mimitin {ECO:0000303|PubMed:15774466}; DE AltName: Full=Myc-induced mitochondrial protein {ECO:0000303|PubMed:15774466}; DE Short=MMTN {ECO:0000303|PubMed:15774466}; DE AltName: Full=NDUFA12-like protein; DE Flags: Precursor; GN Name=NDUFAF2; Synonyms=NDUFA12L; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP INDUCTION. RX PubMed=15774466; DOI=10.1074/jbc.m501231200; RA Tsuneoka M., Teye K., Arima N., Soejima M., Otera H., Ohashi K., Koga Y., RA Fujita H., Shirouzu K., Kimura H., Koda Y.; RT "A novel Myc-target gene, mimitin, that is involved in cell proliferation RT of esophageal squamous cell carcinoma."; RL J. Biol. Chem. 280:19977-19985(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Eye, and Hypothalamus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION AS A CHAPERONE, TISSUE SPECIFICITY, INVOLVEMENT IN MC1DN10, AND RP VARIANT MC1DN10 47-ARG--GLN-169 DEL. RX PubMed=16200211; DOI=10.1172/jci26020; RA Ogilvie I., Kennaway N.G., Shoubridge E.A.; RT "A molecular chaperone for mitochondrial complex I assembly is mutated in a RT progressive encephalopathy."; RL J. Clin. Invest. 115:2784-2792(2005). RN [6] RP INVOLVEMENT IN MC1DN10. RX PubMed=18180188; DOI=10.1016/j.ymgme.2007.11.013; RA Barghuti F., Elian K., Gomori J.M., Shaag A., Edvardson S., Saada A., RA Elpeleg O.; RT "The unique neuroradiology of complex I deficiency due to NDUFA12L RT defect."; RL Mol. Genet. Metab. 94:78-82(2008). RN [7] RP FUNCTION, INVOLVEMENT IN MC1DN10, VARIANT MC1DN10 38-TYR--GLN-169 DEL, AND RP CHARACTERIZATION OF VARIANT MC1DN10 38-TYR--GLN-169 DEL. RX PubMed=19384974; DOI=10.1002/humu.21037; RA Hoefs S.J., Dieteren C.E., Rodenburg R.J., Naess K., Bruhn H., Wibom R., RA Wagena E., Willems P.H., Smeitink J.A., Nijtmans L.G., van den Heuvel L.P.; RT "Baculovirus complementation restores a novel NDUFAF2 mutation causing RT complex I deficiency."; RL Hum. Mutat. 30:E728-E736(2009). RN [8] RP INVOLVEMENT IN MC1DN10, AND VARIANT MC1DN10 3-TRP--GLN-169 DEL. RX PubMed=20571988; DOI=10.1055/s-0030-1255062; RA Herzer M., Koch J., Prokisch H., Rodenburg R., Rauscher C., Radauer W., RA Forstner R., Pilz P., Rolinski B., Freisinger P., Mayr J.A., Sperl W.; RT "Leigh disease with brainstem involvement in complex I deficiency due to RT assembly factor NDUFAF2 defect."; RL Neuropediatrics 41:30-34(2010). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [12] RP FUNCTION. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [13] RP FUNCTION, AND INTERACTION WITH ARMC9. RX PubMed=38949024; DOI=10.1172/jci175560; RA Lo C.H., Liu Z., Chen S., Lin F., Berneshawi A.R., Yu C.Q., Koo E.B., RA Kowal T.J., Ning K., Hu Y., Wang W.J., Liao Y.J., Sun Y.; RT "Primary cilia formation requires the Leigh syndrome-associated RT mitochondrial protein NDUFAF2."; RL J. Clin. Invest. 134:0-0(2024). CC -!- FUNCTION: Acts as a molecular chaperone for mitochondrial complex I CC assembly (PubMed:16200211, PubMed:19384974). Complex I functions in the CC transfer of electrons from NADH to the respiratory chain. The immediate CC electron acceptor for the enzyme is believed to be ubiquinone CC (PubMed:16200211, PubMed:27626371). Is involved in the initial steps of CC cilia formation, including removal of CP110 from the mother centrioles, CC docking of membrane vesicles to the mother centrioles, and CC establishment of the transition zone (PubMed:38949024). CC {ECO:0000269|PubMed:16200211, ECO:0000269|PubMed:19384974, CC ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:38949024}. CC -!- SUBUNIT: Interacts with ARMC9. {ECO:0000269|PubMed:38949024}. CC -!- INTERACTION: CC Q8N183; Q7Z3E5: ARMC9; NbExp=3; IntAct=EBI-2682365, EBI-10750859; CC Q8N183; O43169: CYB5B; NbExp=3; IntAct=EBI-2682365, EBI-1058710; CC Q8N183; O43561-2: LAT; NbExp=3; IntAct=EBI-2682365, EBI-8070286; CC Q8N183; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-2682365, EBI-12033434; CC Q8N183; O95182: NDUFA7; NbExp=3; IntAct=EBI-2682365, EBI-721471; CC Q8N183; O75396: SEC22B; NbExp=3; IntAct=EBI-2682365, EBI-1058865; CC Q8N183; B2RUZ4: SMIM1; NbExp=3; IntAct=EBI-2682365, EBI-12188413; CC Q8N183; Q9NZD8: SPG21; NbExp=3; IntAct=EBI-2682365, EBI-742688; CC Q8N183; Q9UNK0: STX8; NbExp=3; IntAct=EBI-2682365, EBI-727240; CC Q8N183; Q5SNT2-2: TMEM201; NbExp=3; IntAct=EBI-2682365, EBI-11994282; CC Q8N183; Q5BJF2: TMEM97; NbExp=3; IntAct=EBI-2682365, EBI-12111910; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:15774466}. CC -!- TISSUE SPECIFICITY: Highly expressed in ESCC cells. Also expressed in CC heart, skeletal muscle, liver, and in fibroblasts. CC {ECO:0000269|PubMed:15774466, ECO:0000269|PubMed:16200211}. CC -!- INDUCTION: By MYC. Direct transcriptional target of MYC. CC {ECO:0000269|PubMed:15774466}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 10 (MC1DN10) CC [MIM:618233]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN10 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:16200211, CC ECO:0000269|PubMed:18180188, ECO:0000269|PubMed:19384974, CC ECO:0000269|PubMed:20571988}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFA12 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB183433; BAD91205.1; -; mRNA. DR EMBL; AK291296; BAF83985.1; -; mRNA. DR EMBL; CH471123; EAW55008.1; -; Genomic_DNA. DR EMBL; BC001753; AAH01753.2; -; mRNA. DR EMBL; BC033965; AAH33965.1; -; mRNA. DR CCDS; CCDS3979.1; -. DR RefSeq; NP_777549.1; NM_174889.5. DR AlphaFoldDB; Q8N183; -. DR SMR; Q8N183; -. DR BioGRID; 124893; 139. DR FunCoup; Q8N183; 1026. DR IntAct; Q8N183; 57. DR MINT; Q8N183; -. DR STRING; 9606.ENSP00000296597; -. DR BindingDB; Q8N183; -. DR ChEMBL; CHEMBL2363065; -. DR DrugCentral; Q8N183; -. DR GlyGen; Q8N183; 5 sites, 1 O-linked glycan (5 sites). DR iPTMnet; Q8N183; -. DR MetOSite; Q8N183; -. DR PhosphoSitePlus; Q8N183; -. DR SwissPalm; Q8N183; -. DR BioMuta; NDUFAF2; -. DR DMDM; 67461055; -. DR jPOST; Q8N183; -. DR MassIVE; Q8N183; -. DR PaxDb; 9606-ENSP00000296597; -. DR PeptideAtlas; Q8N183; -. DR ProteomicsDB; 71569; -. DR Pumba; Q8N183; -. DR TopDownProteomics; Q8N183; -. DR Antibodypedia; 23660; 199 antibodies from 30 providers. DR DNASU; 91942; -. DR Ensembl; ENST00000296597.10; ENSP00000296597.5; ENSG00000164182.13. DR GeneID; 91942; -. DR KEGG; hsa:91942; -. DR MANE-Select; ENST00000296597.10; ENSP00000296597.5; NM_174889.5; NP_777549.1. DR UCSC; uc003jsp.4; human. DR AGR; HGNC:28086; -. DR ClinPGx; PA162397398; -. DR CTD; 91942; -. DR DisGeNET; 91942; -. DR GeneCards; NDUFAF2; -. DR GeneReviews; NDUFAF2; -. DR HGNC; HGNC:28086; NDUFAF2. DR HPA; ENSG00000164182; Low tissue specificity. DR MalaCards; NDUFAF2; -. DR MIM; 609653; gene. DR MIM; 618233; phenotype. DR OpenTargets; ENSG00000164182; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000164182; -. DR eggNOG; ENOG502S21I; Eukaryota. DR GeneTree; ENSGT00390000002743; -. DR HOGENOM; CLU_138027_0_0_1; -. DR InParanoid; Q8N183; -. DR OMA; HKTWAGQ; -. DR OrthoDB; 10255576at2759; -. DR PAN-GO; Q8N183; 0 GO annotations based on evolutionary models. DR PhylomeDB; Q8N183; -. DR PathwayCommons; Q8N183; -. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q8N183; -. DR SIGNOR; Q8N183; -. DR Agora; ENSG00000164182; -. DR BioGRID-ORCS; 91942; 60 hits in 1137 CRISPR screens. DR ChiTaRS; NDUFAF2; human. DR GenomeRNAi; 91942; -. DR Pharos; Q8N183; Tclin. DR PRO; PR:Q8N183; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q8N183; protein. DR Bgee; ENSG00000164182; Expressed in calcaneal tendon and 98 other cell types or tissues. DR ExpressionAtlas; Q8N183; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:FlyBase. DR GO; GO:0045271; C:respiratory chain complex I; IEA:InterPro. DR GO; GO:0044877; F:protein-containing complex binding; IDA:FlyBase. DR GO; GO:0060271; P:cilium assembly; IMP:UniProtKB. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:FlyBase. DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl. DR InterPro; IPR052618; ComplexI_NDUFA12. DR InterPro; IPR007763; NDUFA12. DR PANTHER; PTHR32470; ADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX ASSEMBLY FACTOR 2; 1. DR PANTHER; PTHR32470:SF2; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX ASSEMBLY FACTOR 2; 1. DR Pfam; PF05071; NDUFA12; 1. PE 1: Evidence at protein level; KW Chaperone; Cilium biogenesis/degradation; Disease variant; Mitochondrion; KW Phosphoprotein; Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Transit peptide. FT TRANSIT 1..? FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN ?..169 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT assembly factor 2" FT /id="PRO_0000020054" FT REGION 116..169 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 146..156 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 134 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 3..169 FT /note="Missing (in MC1DN10)" FT /evidence="ECO:0000269|PubMed:20571988" FT /id="VAR_081422" FT VARIANT 38..169 FT /note="Missing (in MC1DN10; patient cells homozygous for FT the variant do not express detectable amounts of protein; FT complex I assembly is altered and activity is severely FT reduced in patient cells compared to control)" FT /evidence="ECO:0000269|PubMed:19384974" FT /id="VAR_081423" FT VARIANT 47..169 FT /note="Missing (in MC1DN10)" FT /evidence="ECO:0000269|PubMed:16200211" FT /id="VAR_081424" SQ SEQUENCE 169 AA; 19856 MW; 3D72AE8B5942E0FA CRC64; MGWSQDLFRA LWRSLSREVK EHVGTDQFGN KYYYIPQYKN WRGQTIREKR IVEAANKKEV DYEAGDIPTE WEAWIRRTRK TPPTMEEILK NEKHREEIKI KSQDFYEKEK LLSKETSEEL LPPPVQTQIK GHASAPYFGK EEPSVAPSST GKTFQPGSWM PRDGKSHNQ // ID NDUF3_HUMAN Reviewed; 184 AA. AC Q9BU61; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 28-JAN-2026, entry version 178. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3; GN Name=NDUFAF3; Synonyms=C3orf60; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B). RC TISSUE=Lung, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [2] RP FUNCTION, INTERACTION WITH NDUFAF4; NDUFS2 AND NDUFS3, SUBCELLULAR RP LOCATION, INVOLVEMENT IN MC1DN18, AND VARIANTS MC1DN18 ARG-77 AND PRO-122. RX PubMed=19463981; DOI=10.1016/j.ajhg.2009.04.020; RA Saada A., Vogel R.O., Hoefs S.J., van den Brand M.A., Wessels H.J., RA Willems P.H., Venselaar H., Shaag A., Barghuti F., Reish O., Shohat M., RA Huynen M.A., Smeitink J.A.M., van den Heuvel L.P., Nijtmans L.G.; RT "Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting RT complex I assembly protein, cause fatal neonatal mitochondrial disease."; RL Am. J. Hum. Genet. 84:718-727(2009). RN [3] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [6] RP INVOLVEMENT IN MC1DN18, AND VARIANT MC1DN18 VAL-165. RX PubMed=27986404; DOI=10.1016/j.ymgme.2016.12.005; RA Baertling F., Sanchez-Caballero L., Timal S., van den Brand M.A., Ngu L.H., RA Distelmaier F., Rodenburg R.J., Nijtmans L.G.; RT "Mutations in mitochondrial complex I assembly factor NDUFAF3 cause Leigh RT syndrome."; RL Mol. Genet. Metab. 120:243-246(2017). CC -!- FUNCTION: Essential factor for the assembly of mitochondrial CC NADH:ubiquinone oxidoreductase complex (complex I). CC {ECO:0000269|PubMed:19463981}. CC -!- SUBUNIT: Interacts with NDUFAF4, NDUFS2 and NDUFS3. CC {ECO:0000269|PubMed:19463981}. CC -!- INTERACTION: CC Q9BU61; Q6RW13-2: AGTRAP; NbExp=3; IntAct=EBI-2114801, EBI-11522760; CC Q9BU61; Q9NPB3: CABP2; NbExp=3; IntAct=EBI-2114801, EBI-12011224; CC Q9BU61; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-2114801, EBI-3867333; CC Q9BU61; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-2114801, EBI-5916454; CC Q9BU61; Q0VD86: INCA1; NbExp=3; IntAct=EBI-2114801, EBI-6509505; CC Q9BU61; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-2114801, EBI-3044087; CC Q9BU61; Q8WWY6: MBD3L1; NbExp=3; IntAct=EBI-2114801, EBI-12516603; CC Q9BU61; Q9P032: NDUFAF4; NbExp=13; IntAct=EBI-2114801, EBI-2606839; CC Q9BU61; Q16633: POU2AF1; NbExp=3; IntAct=EBI-2114801, EBI-943588; CC Q9BU61; Q9BYM8: RBCK1; NbExp=3; IntAct=EBI-2114801, EBI-2340624; CC Q9BU61; Q9NTX7-2: RNF146; NbExp=3; IntAct=EBI-2114801, EBI-11750630; CC Q9BU61; P09012: SNRPA; NbExp=6; IntAct=EBI-2114801, EBI-607085; CC Q9BU61; Q8TAS1-2: UHMK1; NbExp=3; IntAct=EBI-2114801, EBI-12157345; CC Q9BU61-2; Q9P032: NDUFAF4; NbExp=8; IntAct=EBI-10298649, EBI-2606839; CC Q9BU61-2; Q9BYM8: RBCK1; NbExp=3; IntAct=EBI-10298649, EBI-2340624; CC Q9BU61-2; Q04864: REL; NbExp=3; IntAct=EBI-10298649, EBI-307352; CC Q9BU61-2; P09012: SNRPA; NbExp=3; IntAct=EBI-10298649, EBI-607085; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Mitochondrion inner CC membrane {ECO:0000269|PubMed:19463981}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=a; CC IsoId=Q9BU61-1; Sequence=Displayed; CC Name=b; CC IsoId=Q9BU61-2; Sequence=VSP_041086; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 18 (MC1DN18) CC [MIM:618240]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN18 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:19463981, CC ECO:0000269|PubMed:27986404}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the NDUFAF3 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BC002873; AAH02873.1; -; mRNA. DR EMBL; BQ652614; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS2784.1; -. [Q9BU61-1] DR CCDS; CCDS2785.1; -. [Q9BU61-2] DR RefSeq; NP_951032.1; NM_199069.2. [Q9BU61-1] DR RefSeq; NP_951033.1; NM_199070.2. [Q9BU61-2] DR RefSeq; NP_951047.1; NM_199073.2. [Q9BU61-2] DR RefSeq; NP_951056.1; NM_199074.2. [Q9BU61-2] DR AlphaFoldDB; Q9BU61; -. DR SMR; Q9BU61; -. DR BioGRID; 117419; 131. DR FunCoup; Q9BU61; 1594. DR IntAct; Q9BU61; 50. DR MINT; Q9BU61; -. DR STRING; 9606.ENSP00000323076; -. DR BindingDB; Q9BU61; -. DR ChEMBL; CHEMBL2363065; -. DR DrugCentral; Q9BU61; -. DR iPTMnet; Q9BU61; -. DR PhosphoSitePlus; Q9BU61; -. DR SwissPalm; Q9BU61; -. DR BioMuta; NDUFAF3; -. DR DMDM; 74733183; -. DR jPOST; Q9BU61; -. DR MassIVE; Q9BU61; -. DR PaxDb; 9606-ENSP00000323076; -. DR PeptideAtlas; Q9BU61; -. DR ProteomicsDB; 79053; -. [Q9BU61-1] DR ProteomicsDB; 79054; -. [Q9BU61-2] DR Pumba; Q9BU61; -. DR Antibodypedia; 48697; 69 antibodies from 15 providers. DR DNASU; 25915; -. DR Ensembl; ENST00000326912.8; ENSP00000323003.4; ENSG00000178057.16. [Q9BU61-2] DR Ensembl; ENST00000326925.11; ENSP00000323076.5; ENSG00000178057.16. [Q9BU61-1] DR Ensembl; ENST00000395458.6; ENSP00000378843.2; ENSG00000178057.16. [Q9BU61-2] DR Ensembl; ENST00000451378.2; ENSP00000402465.2; ENSG00000178057.16. [Q9BU61-2] DR GeneID; 25915; -. DR KEGG; hsa:25915; -. DR MANE-Select; ENST00000326925.11; ENSP00000323076.5; NM_199069.2; NP_951032.1. DR UCSC; uc003cvn.4; human. [Q9BU61-1] DR AGR; HGNC:29918; -. DR ClinPGx; PA164723795; -. DR CTD; 25915; -. DR DisGeNET; 25915; -. DR GeneCards; NDUFAF3; -. DR HGNC; HGNC:29918; NDUFAF3. DR HPA; ENSG00000178057; Tissue enhanced (testis). DR MalaCards; NDUFAF3; -. DR MIM; 612911; gene. DR MIM; 618240; phenotype. DR OpenTargets; ENSG00000178057; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000178057; -. DR eggNOG; KOG3363; Eukaryota. DR GeneTree; ENSGT00390000018312; -. DR HOGENOM; CLU_074390_3_4_1; -. DR InParanoid; Q9BU61; -. DR OMA; FSKAYDH; -. DR OrthoDB; 20681at2759; -. DR PAN-GO; Q9BU61; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q9BU61; -. DR PathwayCommons; Q9BU61; -. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q9BU61; -. DR Agora; ENSG00000178057; -. DR BioGRID-ORCS; 25915; 320 hits in 1156 CRISPR screens. DR ChiTaRS; NDUFAF3; human. DR GeneWiki; C3orf60; -. DR GenomeRNAi; 25915; -. DR Pharos; Q9BU61; Tclin. DR PRO; PR:Q9BU61; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9BU61; protein. DR Bgee; ENSG00000178057; Expressed in left testis and 198 other cell types or tissues. DR ExpressionAtlas; Q9BU61; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0005634; C:nucleus; IDA:LIFEdb. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR CDD; cd05125; Mth938_2P1-like; 1. DR FunFam; 3.40.1230.10:FF:000002; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 3; 1. DR Gene3D; 3.40.1230.10; MTH938-like; 1. DR InterPro; IPR036748; MTH938-like_sf. DR InterPro; IPR034095; NDUF3. DR InterPro; IPR007523; NDUFAF3/AAMDC. DR PANTHER; PTHR21192:SF2; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX ASSEMBLY FACTOR 3; 1. DR PANTHER; PTHR21192; NUCLEAR PROTEIN E3-3; 1. DR Pfam; PF04430; DUF498; 1. DR SUPFAM; SSF64076; MTH938-like; 1. PE 1: Evidence at protein level; KW Alternative splicing; Disease variant; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Nucleus; Primary mitochondrial disease; KW Proteomics identification; Reference proteome. FT CHAIN 1..184 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT assembly factor 3" FT /id="PRO_0000281154" FT VAR_SEQ 1..57 FT /note="Missing (in isoform b)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_041086" FT VARIANT 77 FT /note="G -> R (in MC1DN18; dbSNP:rs121918134)" FT /evidence="ECO:0000269|PubMed:19463981" FT /id="VAR_058491" FT VARIANT 122 FT /note="R -> P (in MC1DN18; dbSNP:rs121918135)" FT /evidence="ECO:0000269|PubMed:19463981" FT /id="VAR_058492" FT VARIANT 165 FT /note="A -> V (in MC1DN18; dbSNP:rs138275059)" FT /evidence="ECO:0000269|PubMed:27986404" FT /id="VAR_081425" SQ SEQUENCE 184 AA; 20350 MW; FCFF7B0CB6ADBCD8 CRC64; MATALALRSL YRARPSLRCP PVELPWAPRR GHRLSPADDE LYQRTRISLL QREAAQAMYI DSYNSRGFMI NGNRVLGPCA LLPHSVVQWN VGSHQDITED SFSLFWLLEP RIEIVVVGTG DRTERLQSQV LQAMRQRGIA VEVQDTPNAC ATFNFLCHEG RVTGAALIPP PGGTSLTSLG QAAQ // ID NDUF4_HUMAN Reviewed; 175 AA. AC Q9P032; B2R4J5; DT 16-MAY-2003, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 28-JAN-2026, entry version 170. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 4; DE AltName: Full=Hormone-regulated proliferation-associated protein of 20 kDa {ECO:0000303|PubMed:17001319}; GN Name=NDUFAF4 {ECO:0000312|HGNC:HGNC:21034}; GN Synonyms=C6orf66 {ECO:0000303|PubMed:18179882}, GN HRPAP20 {ECO:0000303|PubMed:17001319}; ORFNames=HSPC125, My013; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Fetal brain; RA Mao Y.M., Xie Y., Lin Q., Li Y., Dai J.L., Ying K.; RL Submitted (APR-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Bone; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION, AND INDUCTION. RX PubMed=14871833; DOI=10.1158/0008-5472.can-03-0023; RA Karp C.M., Pan H., Zhang M., Buckley D.J., Schuler L.A., Buckley A.R.; RT "Identification of HRPAP20: a novel phosphoprotein that enhances growth and RT survival in hormone-responsive tumor cells."; RL Cancer Res. 64:1016-1025(2004). RN [8] RP FUNCTION, INTERACTION WITH CALMODULIN, AND MUTAGENESIS OF LYS-73. RX PubMed=17001319; DOI=10.1038/sj.onc.1209980; RA Karp C.M., Shukla M.N., Buckley D.J., Buckley A.R.; RT "HRPAP20: a novel calmodulin-binding protein that increases breast cancer RT cell invasion."; RL Oncogene 26:1780-1788(2007). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN MC1DN15, AND VARIANT MC1DN15 RP PRO-65. RX PubMed=18179882; DOI=10.1016/j.ajhg.2007.08.003; RA Saada A., Edvardson S., Rapoport M., Shaag A., Amry K., Miller C., RA Lorberboum-Galski H., Elpeleg O.; RT "C6ORF66 is an assembly factor of mitochondrial complex I."; RL Am. J. Hum. Genet. 82:32-38(2008). RN [10] RP INTERACTION WITH NDUFAF3. RX PubMed=19463981; DOI=10.1016/j.ajhg.2009.04.020; RA Saada A., Vogel R.O., Hoefs S.J., van den Brand M.A., Wessels H.J., RA Willems P.H., Venselaar H., Shaag A., Barghuti F., Reish O., Shohat M., RA Huynen M.A., Smeitink J.A.M., van den Heuvel L.P., Nijtmans L.G.; RT "Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting RT complex I assembly protein, cause fatal neonatal mitochondrial disease."; RL Am. J. Hum. Genet. 84:718-727(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [13] RP MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=25255805; DOI=10.1038/ncomms5919; RA Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H., RA Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.; RT "Global profiling of co- and post-translationally N-myristoylated proteomes RT in human cells."; RL Nat. Commun. 5:4919-4919(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [15] RP INTERACTION WITH VSIV PROTEIN M (MICROBIAL INFECTION). RX PubMed=33635491; DOI=10.1007/s11262-021-01833-0; RA Pan W., Shen Z., Wang H., He H.; RT "The host cellular protein Ndufaf4 interacts with the vesicular stomatitis RT virus M protein and affects viral propagation."; RL Virus Genes 57:250-257(2021). RN [16] RP FUNCTION, INVOLVEMENT IN MC1DN15, VARIANT MC1DN15 PRO-3, AND RP CHARACTERIZATION OF VARIANT MC1DN15 PRO-3. RX PubMed=28853723; DOI=10.1038/ejhg.2017.133; RA Baertling F., Sanchez-Caballero L., van den Brand M.A.M., Wintjes L.T., RA Brink M., van den Brandt F.A., Wilson C., Rodenburg R.J.T., RA Nijtmans L.G.J.; RT "NDUFAF4 variants are associated with Leigh syndrome and cause a specific RT mitochondrial complex I assembly defect."; RL Eur. J. Hum. Genet. 25:1273-1277(2017). CC -!- FUNCTION: Involved in the assembly of mitochondrial NADH:ubiquinone CC oxidoreductase complex (complex I) (PubMed:18179882, PubMed:28853723). CC May be involved in cell proliferation and survival of hormone-dependent CC tumor cells. May be a regulator of breast tumor cell invasion. CC {ECO:0000269|PubMed:14871833, ECO:0000269|PubMed:17001319, CC ECO:0000269|PubMed:18179882, ECO:0000269|PubMed:28853723}. CC -!- SUBUNIT: Binds calmodulin. Interacts with NDUFAF3. CC {ECO:0000269|PubMed:17001319, ECO:0000269|PubMed:19463981}. CC -!- SUBUNIT: (Microbial infection) Interacts with the vesicular stomatitis CC virus matrix protein/M; the interaction inhibits viral propagation. CC {ECO:0000269|PubMed:33635491}. CC -!- INTERACTION: CC Q9P032; P28799: GRN; NbExp=3; IntAct=EBI-2606839, EBI-747754; CC Q9P032; Q9BU61: NDUFAF3; NbExp=13; IntAct=EBI-2606839, EBI-2114801; CC Q9P032; Q9BU61-2: NDUFAF3; NbExp=8; IntAct=EBI-2606839, EBI-10298649; CC Q9P032; O76024: WFS1; NbExp=3; IntAct=EBI-2606839, EBI-720609; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:18179882}. CC Membrane {ECO:0000305}; Lipid-anchor {ECO:0000305}. CC -!- INDUCTION: Expression is low in quiescent cells and is induced in CC exponentially proliferating cultures. Expression is also induced when CC prolactin is added to stationary cells. Induced by dietary CC differentiating agents such as butyrate and retinoic acid. CC {ECO:0000269|PubMed:14871833}. CC -!- PTM: Phosphorylated on serine. Prolactin stimulate serine CC phosphorylation (By similarity). {ECO:0000250}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 15 (MC1DN15) CC [MIM:618237]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN15 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:18179882, CC ECO:0000269|PubMed:28853723}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the NDUFAF4 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF161474; AAF29089.1; -; mRNA. DR EMBL; AF060508; AAG43126.1; -; mRNA. DR EMBL; AK311850; BAG34792.1; -; mRNA. DR EMBL; AL159985; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW48501.1; -; Genomic_DNA. DR EMBL; BC039464; AAH39464.1; -; mRNA. DR CCDS; CCDS5037.1; -. DR RefSeq; NP_054884.1; NM_014165.4. DR AlphaFoldDB; Q9P032; -. DR SMR; Q9P032; -. DR BioGRID; 118848; 201. DR FunCoup; Q9P032; 1074. DR IntAct; Q9P032; 91. DR MINT; Q9P032; -. DR STRING; 9606.ENSP00000358272; -. DR BindingDB; Q9P032; -. DR ChEMBL; CHEMBL2363065; -. DR DrugCentral; Q9P032; -. DR GlyGen; Q9P032; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9P032; -. DR PhosphoSitePlus; Q9P032; -. DR SwissPalm; Q9P032; -. DR BioMuta; NDUFAF4; -. DR DMDM; 30912745; -. DR jPOST; Q9P032; -. DR MassIVE; Q9P032; -. DR PaxDb; 9606-ENSP00000358272; -. DR PeptideAtlas; Q9P032; -. DR ProteomicsDB; 83539; -. DR Pumba; Q9P032; -. DR TopDownProteomics; Q9P032; -. DR Antibodypedia; 48392; 124 antibodies from 28 providers. DR DNASU; 29078; -. DR Ensembl; ENST00000316149.8; ENSP00000358272.4; ENSG00000123545.7. DR GeneID; 29078; -. DR KEGG; hsa:29078; -. DR MANE-Select; ENST00000316149.8; ENSP00000358272.4; NM_014165.4; NP_054884.1. DR UCSC; uc003pow.4; human. DR AGR; HGNC:21034; -. DR ClinPGx; PA164723808; -. DR CTD; 29078; -. DR DisGeNET; 29078; -. DR GeneCards; NDUFAF4; -. DR HGNC; HGNC:21034; NDUFAF4. DR HPA; ENSG00000123545; Low tissue specificity. DR MalaCards; NDUFAF4; -. DR MIM; 611776; gene. DR MIM; 618237; phenotype. DR OpenTargets; ENSG00000123545; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000123545; -. DR eggNOG; KOG4481; Eukaryota. DR GeneTree; ENSGT00390000001627; -. DR HOGENOM; CLU_054693_2_0_1; -. DR InParanoid; Q9P032; -. DR OMA; IPDQKYK; -. DR OrthoDB; 2434756at2759; -. DR PAN-GO; Q9P032; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q9P032; -. DR PathwayCommons; Q9P032; -. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q9P032; -. DR Agora; ENSG00000123545; -. DR BioGRID-ORCS; 29078; 121 hits in 1157 CRISPR screens. DR ChiTaRS; NDUFAF4; human. DR GenomeRNAi; 29078; -. DR Pharos; Q9P032; Tclin. DR PRO; PR:Q9P032; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q9P032; protein. DR Bgee; ENSG00000123545; Expressed in pons and 200 other cell types or tissues. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome. DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR InterPro; IPR009622; NDUFAF4. DR PANTHER; PTHR13338:SF6; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX ASSEMBLY FACTOR 4; 1. DR PANTHER; PTHR13338; UPF0240 PROTEIN; 1. DR Pfam; PF06784; UPF0240; 1. PE 1: Evidence at protein level; KW Calmodulin-binding; Disease variant; Host-virus interaction; Lipoprotein; KW Membrane; Mitochondrion; Myristate; Phosphoprotein; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:25255805" FT CHAIN 2..175 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT assembly factor 4" FT /id="PRO_0000220988" FT MOD_RES 35 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000269|PubMed:25255805" FT VARIANT 3 FT /note="A -> P (in MC1DN15; results in altered complex I FT assembly; dbSNP:rs1554197721)" FT /evidence="ECO:0000269|PubMed:28853723" FT /id="VAR_081426" FT VARIANT 65 FT /note="L -> P (in MC1DN15; dbSNP:rs63751061)" FT /evidence="ECO:0000269|PubMed:18179882" FT /id="VAR_044329" FT MUTAGEN 73 FT /note="K->A: Reduces interaction with calmodulin. Does not FT promote MMP-9 secretion." FT /evidence="ECO:0000269|PubMed:17001319" SQ SEQUENCE 175 AA; 20266 MW; B6445B0B4AA905D0 CRC64; MGALVIRGIR NFNLENRAER EISKMKPSVA PRHPSTNSLL REQISLYPEV KGEIARKDEK LLSFLKDVYV DSKDPVSSLQ VKAAETCQEP KEFRLPKDHH FDMINIKSIP KGKISIVEAL TLLNNHKLFP ETWTAEKIMQ EYQLEQKDVN SLLKYFVTFE VEIFPPEDKK AIRSK // ID NDUF5_HUMAN Reviewed; 345 AA. AC Q5TEU4; A8K166; Q6GPH3; Q9H6F4; DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 28-JAN-2026, entry version 161. DE RecName: Full=Arginine-hydroxylase NDUFAF5, mitochondrial {ECO:0000305}; DE EC=1.-.-.- {ECO:0000305|PubMed:27226634}; DE AltName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 5 {ECO:0000312|HGNC:HGNC:15899}; DE AltName: Full=Putative methyltransferase NDUFAF5; DE EC=2.1.1.- {ECO:0000305}; DE Flags: Precursor; GN Name=NDUFAF5 {ECO:0000312|HGNC:HGNC:15899}; GN Synonyms=C20orf7 {ECO:0000312|HGNC:HGNC:15899}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 50-345 (ISOFORM 1). RC TISSUE=Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN MC1DN16, AND VARIANT MC1DN16 RP PRO-229. RX PubMed=18940309; DOI=10.1016/j.ajhg.2008.09.009; RA Sugiana C., Pagliarini D.J., McKenzie M., Kirby D.M., Salemi R., RA Abu-Amero K.K., Dahl H.-H.M., Hutchison W.M., Vascotto K.A., Smith S.M., RA Newbold R.F., Christodoulou J., Calvo S., Mootha V.K., Ryan M.T., RA Thorburn D.R.; RT "Mutation of C20orf7 disrupts complex I assembly and causes lethal neonatal RT mitochondrial disease."; RL Am. J. Hum. Genet. 83:468-478(2008). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NDUFS7. RX PubMed=27226634; DOI=10.1074/jbc.m116.734970; RA Rhein V.F., Carroll J., Ding S., Fearnley I.M., Walker J.E.; RT "NDUFAF5 hydroxylates NDUFS7 at an early stage in the assembly of human RT complex I."; RL J. Biol. Chem. 291:14851-14860(2016). RN [7] RP INTERACTION WITH NDUFAF8. RX PubMed=27499296; DOI=10.1016/j.molcel.2016.06.033; RA Floyd B.J., Wilkerson E.M., Veling M.T., Minogue C.E., Xia C., Beebe E.T., RA Wrobel R.L., Cho H., Kremer L.S., Alston C.L., Gromek K.A., Dolan B.K., RA Ulbrich A., Stefely J.A., Bohl S.L., Werner K.M., Jochem A., RA Westphall M.S., Rensvold J.W., Taylor R.W., Prokisch H., Kim J.J., RA Coon J.J., Pagliarini D.J.; RT "Mitochondrial protein interaction mapping identifies regulators of RT respiratory chain function."; RL Mol. Cell 63:621-632(2016). RN [8] RP SUBCELLULAR LOCATION, AND INTERACTION WITH PYURF. RX PubMed=35614220; DOI=10.1038/s41586-022-04765-3; RA Rensvold J.W., Shishkova E., Sverchkov Y., Miller I.J., Cetinkaya A., RA Pyle A., Manicki M., Brademan D.R., Alanay Y., Raiman J., Jochem A., RA Hutchins P.D., Peters S.R., Linke V., Overmyer K.A., Salome A.Z., RA Hebert A.S., Vincent C.E., Kwiecien N.W., Rush M.J.P., Westphall M.S., RA Craven M., Akarsu N.A., Taylor R.W., Coon J.J., Pagliarini D.J.; RT "Defining mitochondrial protein functions through deep multiomic RT profiling."; RL Nature 606:382-388(2022). RN [9] RP INVOLVEMENT IN MC1DN16, AND VARIANT MC1DN16 PHE-159. RX PubMed=19542079; DOI=10.1136/jmg.2009.067553; RA Gerards M., Sluiter W., van den Bosch B.J., de Wit L.E., Calis C.M., RA Frentzen M., Akbari H., Schoonderwoerd K., Scholte H.R., Jongbloed R.J., RA Hendrickx A.T., de Coo I.F., Smeets H.J.; RT "Defective complex I assembly due to C20orf7 mutations as a new cause of RT Leigh syndrome."; RL J. Med. Genet. 47:507-512(2010). RN [10] RP INVOLVEMENT IN MC1DN16, AND VARIANT MC1DN16 VAL-250. RX PubMed=21607760; DOI=10.1007/s10545-011-9348-y; RA Saada A., Edvardson S., Shaag A., Chung W.K., Segel R., Miller C., RA Jalas C., Elpeleg O.; RT "Combined OXPHOS complex I and IV defect, due to mutated complex I assembly RT factor C20ORF7."; RL J. Inherit. Metab. Dis. 35:125-131(2012). CC -!- FUNCTION: Arginine hydroxylase that mediates hydroxylation of 'Arg-111' CC of NDUFS7 and is involved in the assembly of mitochondrial CC NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) at early CC stages (PubMed:18940309, PubMed:27226634). May also have CC methyltransferase activity (Probable). {ECO:0000269|PubMed:18940309, CC ECO:0000269|PubMed:27226634, ECO:0000305}. CC -!- SUBUNIT: Interacts with NDUFAF8, leading to stabilize NDUFAF5 CC (PubMed:27499296). Interacts with NDUFS7 (PubMed:27226634). Interacts CC with PYURF (via TRM112 domain); the interaction is direct and CC stabilizes NDUFAF5 protein (PubMed:35614220). CC {ECO:0000269|PubMed:27226634, ECO:0000269|PubMed:27499296, CC ECO:0000269|PubMed:35614220}. CC -!- INTERACTION: CC Q5TEU4; A1L188: NDUFAF8; NbExp=11; IntAct=EBI-10762958, EBI-20593474; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:18940309, ECO:0000269|PubMed:27226634, CC ECO:0000269|PubMed:35614220}. Note=Peripherally localized on the matrix CC face of the mitochondrial inner membrane. CC {ECO:0000269|PubMed:18940309}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q5TEU4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5TEU4-2; Sequence=VSP_028637; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 16 (MC1DN16) CC [MIM:618238]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN16 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:18940309, CC ECO:0000269|PubMed:19542079, ECO:0000269|PubMed:21607760}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK025977; BAB15305.1; -; mRNA. DR EMBL; AK289781; BAF82470.1; -; mRNA. DR EMBL; AL161659; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL109657; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471133; EAX10311.1; -; Genomic_DNA. DR EMBL; BC005984; AAH05984.1; -; mRNA. DR EMBL; BC073158; AAH73158.1; -; mRNA. DR CCDS; CCDS13118.1; -. [Q5TEU4-1] DR CCDS; CCDS33441.1; -. [Q5TEU4-2] DR RefSeq; NP_001034464.1; NM_001039375.3. [Q5TEU4-2] DR RefSeq; NP_077025.2; NM_024120.4. [Q5TEU4-1] DR AlphaFoldDB; Q5TEU4; -. DR SMR; Q5TEU4; -. DR BioGRID; 122554; 110. DR FunCoup; Q5TEU4; 1012. DR IntAct; Q5TEU4; 57. DR MINT; Q5TEU4; -. DR STRING; 9606.ENSP00000367346; -. DR iPTMnet; Q5TEU4; -. DR PhosphoSitePlus; Q5TEU4; -. DR SwissPalm; Q5TEU4; -. DR BioMuta; NDUFAF5; -. DR DMDM; 74762247; -. DR jPOST; Q5TEU4; -. DR MassIVE; Q5TEU4; -. DR PaxDb; 9606-ENSP00000367346; -. DR PeptideAtlas; Q5TEU4; -. DR ProteomicsDB; 65062; -. [Q5TEU4-1] DR ProteomicsDB; 65063; -. [Q5TEU4-2] DR Pumba; Q5TEU4; -. DR Antibodypedia; 24277; 130 antibodies from 22 providers. DR DNASU; 79133; -. DR Ensembl; ENST00000378106.10; ENSP00000367346.5; ENSG00000101247.19. [Q5TEU4-1] DR Ensembl; ENST00000463598.1; ENSP00000420497.1; ENSG00000101247.19. [Q5TEU4-2] DR GeneID; 79133; -. DR KEGG; hsa:79133; -. DR MANE-Select; ENST00000378106.10; ENSP00000367346.5; NM_024120.5; NP_077025.2. DR UCSC; uc002wom.4; human. [Q5TEU4-1] DR AGR; HGNC:15899; -. DR ClinPGx; PA25780; -. DR CTD; 79133; -. DR DisGeNET; 79133; -. DR GeneCards; NDUFAF5; -. DR HGNC; HGNC:15899; NDUFAF5. DR HPA; ENSG00000101247; Tissue enhanced (skeletal). DR MalaCards; NDUFAF5; -. DR MIM; 612360; gene. DR MIM; 618238; phenotype. DR OpenTargets; ENSG00000101247; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000101247; -. DR eggNOG; KOG2940; Eukaryota. DR GeneTree; ENSGT00390000014687; -. DR HOGENOM; CLU_046586_0_2_1; -. DR InParanoid; Q5TEU4; -. DR OMA; YEVVYGH; -. DR OrthoDB; 16816at2759; -. DR PAN-GO; Q5TEU4; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q5TEU4; -. DR PathwayCommons; Q5TEU4; -. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q5TEU4; -. DR Agora; ENSG00000101247; -. DR BioGRID-ORCS; 79133; 134 hits in 1168 CRISPR screens. DR ChiTaRS; NDUFAF5; human. DR GenomeRNAi; 79133; -. DR Pharos; Q5TEU4; Tbio. DR PRO; PR:Q5TEU4; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q5TEU4; protein. DR Bgee; ENSG00000101247; Expressed in apex of heart and 180 other cell types or tissues. DR ExpressionAtlas; Q5TEU4; baseline and differential. DR GO; GO:0099617; C:matrix side of mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0004497; F:monooxygenase activity; ISS:UniProtKB. DR GO; GO:0008757; F:S-adenosylmethionine-dependent methyltransferase activity; IEA:InterPro. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR CDD; cd02440; AdoMet_MTases; 1. DR FunFam; 3.40.50.150:FF:000199; arginine-hydroxylase NDUFAF5, mitochondrial isoform X1; 1. DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1. DR InterPro; IPR050602; Malonyl-ACP_OMT. DR InterPro; IPR013216; Methyltransf_11. DR InterPro; IPR029063; SAM-dependent_MTases_sf. DR PANTHER; PTHR13090; ARGININE-HYDROXYLASE NDUFAF5, MITOCHONDRIAL; 1. DR PANTHER; PTHR13090:SF1; ARGININE-HYDROXYLASE NDUFAF5, MITOCHONDRIAL; 1. DR Pfam; PF08241; Methyltransf_11; 1. DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1. PE 1: Evidence at protein level; KW Alternative splicing; Disease variant; Leigh syndrome; Membrane; KW Methyltransferase; Mitochondrion; Mitochondrion inner membrane; KW Oxidoreductase; Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Transferase; Transit peptide. FT TRANSIT 1..36 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 37..345 FT /note="Arginine-hydroxylase NDUFAF5, mitochondrial" FT /id="PRO_0000307213" FT VAR_SEQ 110..160 FT /note="ETIGKFFQADIAENALKNSSETEIPTVSVLADEEFLPFKENTFDLVVSSLS FT -> LQLFHCRKLLESFSKLTLQKMLC (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_028637" FT VARIANT 159 FT /note="L -> F (in MC1DN16; dbSNP:rs267606689)" FT /evidence="ECO:0000269|PubMed:19542079" FT /id="VAR_067956" FT VARIANT 229 FT /note="L -> P (in MC1DN16; dbSNP:rs118203929)" FT /evidence="ECO:0000269|PubMed:18940309" FT /id="VAR_054119" FT VARIANT 250 FT /note="G -> V (in MC1DN16; dbSNP:rs757043077)" FT /evidence="ECO:0000269|PubMed:21607760" FT /id="VAR_076864" FT VARIANT 337 FT /note="L -> F (in dbSNP:rs6042368)" FT /id="VAR_035376" SQ SEQUENCE 345 AA; 38918 MW; 96E1D29B91980026 CRC64; MLRPAGLWRL CRRPWAARVP AENLGRREVT SGVSPRGSTS PRTLNIFDRD LKRKQKNWAA RQPEPTKFDY LKEEVGSRIA DRVYDIPRNF PLALDLGCGR GYIAQYLNKE TIGKFFQADI AENALKNSSE TEIPTVSVLA DEEFLPFKEN TFDLVVSSLS LHWVNDLPRA LEQIHYILKP DGVFIGAMFG GDTLYELRCS LQLAETEREG GFSPHISPFT AVNDLGHLLG RAGFNTLTVD TDEIQVNYPG MFELMEDLQG MGESNCAWNR KALLHRDTML AAAAVYREMY RNEDGSVPAT YQIYYMIGWK YHESQARPAE RGSATVSFGE LGKINNLMPP GKKSQ // ID NDUF6_HUMAN Reviewed; 333 AA. AC Q330K2; A8MT28; A8MWF0; B4DQ45; Q8N6U6; DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot. DT 08-APR-2008, sequence version 2. DT 28-JAN-2026, entry version 140. DE RecName: Full=NADH dehydrogenase (ubiquinone) complex I, assembly factor 6; DE AltName: Full=Putative phytoene synthase; DE Flags: Precursor; GN Name=NDUFAF6; Synonyms=C8orf38; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RA Zheng H., Xie Y., Mao Y.; RT "Cloning of a novel putative phytoene synthase."; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-322 (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP FUNCTION, AND VARIANT MC1DN17 ARG-99. RX PubMed=18614015; DOI=10.1016/j.cell.2008.06.016; RA Pagliarini D.J., Calvo S.E., Chang B., Sheth S.A., Vafai S.B., Ong S.E., RA Walford G.A., Sugiana C., Boneh A., Chen W.K., Hill D.E., Vidal M., RA Evans J.G., Thorburn D.R., Carr S.A., Mootha V.K.; RT "A mitochondrial protein compendium elucidates complex I disease biology."; RL Cell 134:112-123(2008). RN [7] RP SUBCELLULAR LOCATION, FUNCTION, AND CHARACTERIZATION OF VARIANT MC1DN17 RP ARG-99. RX PubMed=22019594; DOI=10.1016/j.jmb.2011.10.012; RA McKenzie M., Tucker E.J., Compton A.G., Lazarou M., George C., RA Thorburn D.R., Ryan M.T.; RT "Mutations in the gene encoding C8orf38 block complex I assembly by RT inhibiting production of the mitochondria-encoded subunit ND1."; RL J. Mol. Biol. 414:413-426(2011). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [9] RP TISSUE SPECIFICITY, INVOLVEMENT IN FRTS5, AND ALTERNATIVE SPLICING. RX PubMed=27466185; DOI=10.1093/hmg/ddw245; RA Hartmannova H., Piherova L., Tauchmannova K., Kidd K., Acott P.D., RA Crocker J.F., Oussedik Y., Mallet M., Hodanova K., Stranecky V., RA Pristoupilova A., Baresova V., Jedlickova I., Zivna M., Sovova J., RA Hulkova H., Robins V., Vrbacky M., Pecina P., Kaplanova V., Houstek J., RA Mracek T., Thibeault Y., Bleyer A.J., Kmoch S.; RT "Acadian variant of Fanconi syndrome is caused by mitochondrial respiratory RT chain complex I deficiency due to a non-coding mutation in complex I RT assembly factor NDUFAF6."; RL Hum. Mol. Genet. 25:4062-4079(2016). RN [10] RP INVOLVEMENT IN MC1DN17, AND VARIANTS MC1DN17 VAL-69; PRO-76; THR-124; RP ASP-269 AND GLY-274. RX PubMed=26741492; DOI=10.1371/journal.pgen.1005679; RA Kohda M., Tokuzawa Y., Kishita Y., Nyuzuki H., Moriyama Y., Mizuno Y., RA Hirata T., Yatsuka Y., Yamashita-Sugahara Y., Nakachi Y., Kato H., RA Okuda A., Tamaru S., Borna N.N., Banshoya K., Aigaki T., Sato-Miyata Y., RA Ohnuma K., Suzuki T., Nagao A., Maehata H., Matsuda F., Higasa K., RA Nagasaki M., Yasuda J., Yamamoto M., Fushimi T., Shimura M., RA Kaiho-Ichimoto K., Harashima H., Yamazaki T., Mori M., Murayama K., RA Ohtake A., Okazaki Y.; RT "A comprehensive genomic analysis reveals the genetic landscape of RT mitochondrial respiratory chain complex deficiencies."; RL PLoS Genet. 12:E1005679-E1005679(2016). RN [11] RP VARIANT MC1DN17 PRO-178. RX PubMed=27623250; DOI=10.1016/j.ymgme.2016.09.001; RA Bianciardi L., Imperatore V., Fernandez-Vizarra E., Lopomo A., RA Falabella M., Furini S., Galluzzi P., Grosso S., Zeviani M., Renieri A., RA Mari F., Frullanti E.; RT "Exome sequencing coupled with mRNA analysis identifies NDUFAF6 as a Leigh RT gene."; RL Mol. Genet. Metab. 119:214-222(2016). RN [12] RP VARIANT MC1DN17 PRO-178. RX PubMed=29531337; DOI=10.1038/s10038-018-0423-1; RA Catania A., Ardissone A., Verrigni D., Legati A., Reyes A., Lamantea E., RA Diodato D., Tonduti D., Imperatore V., Pinto A.M., Moroni I., Bertini E., RA Robinson A., Carrozzo R., Zeviani M., Ghezzi D.; RT "Compound heterozygous missense and deep intronic variants in NDUFAF6 RT unraveled by exome sequencing and mRNA analysis."; RL J. Hum. Genet. 63:563-568(2018). RN [13] RP VARIANT MC1DN17 THR-124. RX PubMed=30642748; DOI=10.1016/j.ymgme.2019.01.001; RA Baide-Mairena H., Gaudo P., Marti-Sanchez L., Emperador S., RA Sanchez-Montanez A., Alonso-Luengo O., Correa M., Grau A.M., RA Ortigoza-Escobar J.D., Artuch R., Vazquez E., Del Toro M., RA Garrido-Perez N., Ruiz-Pesini E., Montoya J., Bayona-Bafaluy M.P., RA Perez-Duenas B.; RT "Mutations in the mitochondrial complex I assembly factor NDUFAF6 cause RT isolated bilateral striatal necrosis and progressive dystonia in RT childhood."; RL Mol. Genet. Metab. 126:250-258(2019). CC -!- FUNCTION: Involved in the assembly of mitochondrial NADH:ubiquinone CC oxidoreductase complex (complex I) at early stages. May play a role in CC the biogenesis of complex I subunit MT-ND1. CC {ECO:0000269|PubMed:18614015, ECO:0000269|PubMed:22019594}. CC -!- INTERACTION: CC Q330K2-3; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-12957691, EBI-11978177; CC Q330K2-3; P32242: OTX1; NbExp=3; IntAct=EBI-12957691, EBI-740446; CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Mitochondrion inner membrane. CC Note=Peripherally localized on the matrix face of the mitochondrial CC inner membrane. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Additional isoforms seem to exist. CC {ECO:0000269|PubMed:27466185}; CC Name=1; CC IsoId=Q330K2-1; Sequence=Displayed; CC Name=2; CC IsoId=Q330K2-2; Sequence=VSP_026230; CC Name=3; CC IsoId=Q330K2-3; Sequence=VSP_026231, VSP_026232; CC -!- TISSUE SPECIFICITY: Widely expressed. A lower expression is observed in CC lung and kidney compared to heart, muscle and liver (PubMed:27466185). CC In the kidney, expression is high in the basal zone of the proximal CC tubular cells (PubMed:27466185). {ECO:0000269|PubMed:27466185}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 17 (MC1DN17) CC [MIM:618239]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN17 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:18614015, CC ECO:0000269|PubMed:22019594, ECO:0000269|PubMed:26741492, CC ECO:0000269|PubMed:27623250, ECO:0000269|PubMed:29531337, CC ECO:0000269|PubMed:30642748}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Fanconi renotubular syndrome 5 (FRTS5) [MIM:618913]: A form of CC Fanconi renotubular syndrome, a disease due to a generalized CC dysfunction of the proximal kidney tubule resulting in decreased solute CC and water reabsorption. Patients have polydipsia and polyuria with CC phosphaturia, glycosuria and aminoaciduria. They may develop CC hypophosphatemic rickets or osteomalacia, acidosis and a tendency CC toward dehydration. Some eventually develop renal insufficiency. FRTS5 CC is an autosomal recessive mitochondrial disorder characterized by CC proximal renotubular dysfunction from birth, followed by progressive CC kidney disease and pulmonary fibrosis. {ECO:0000269|PubMed:27466185}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. A homozygous disease-causing variant located in intron 2 CC leads to aberrant splicing and altered isoform synthesis. Kidney and CC lung tissues from affected individuals show specific loss of CC mitochondrial isoform 1. Patient cells show defects in mitochondrial CC complex I assembly and altered mitochondrial respiration. CC {ECO:0000269|PubMed:27466185}. CC -!- SIMILARITY: Belongs to the NDUFAF6 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG60807.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=EAW91734.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY444560; AAS68536.1; -; mRNA. DR EMBL; AC087752; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471060; EAW91734.1; ALT_SEQ; Genomic_DNA. DR EMBL; BC028166; AAH28166.1; -; mRNA. DR EMBL; AK298631; BAG60807.1; ALT_INIT; mRNA. DR CCDS; CCDS6266.2; -. [Q330K2-1] DR RefSeq; NP_001317511.1; NM_001330582.1. DR RefSeq; NP_001341445.1; NM_001354516.2. [Q330K2-2] DR RefSeq; NP_689629.2; NM_152416.4. [Q330K2-1] DR AlphaFoldDB; Q330K2; -. DR SMR; Q330K2; -. DR BioGRID; 126481; 8. DR FunCoup; Q330K2; 1917. DR IntAct; Q330K2; 5. DR STRING; 9606.ENSP00000379430; -. DR iPTMnet; Q330K2; -. DR PhosphoSitePlus; Q330K2; -. DR BioMuta; NDUFAF6; -. DR DMDM; 182676420; -. DR jPOST; Q330K2; -. DR MassIVE; Q330K2; -. DR PaxDb; 9606-ENSP00000379430; -. DR PeptideAtlas; Q330K2; -. DR ProteomicsDB; 61636; -. [Q330K2-1] DR ProteomicsDB; 61637; -. [Q330K2-2] DR ProteomicsDB; 61638; -. [Q330K2-3] DR Pumba; Q330K2; -. DR Antibodypedia; 63909; 13 antibodies from 6 providers. DR DNASU; 137682; -. DR Ensembl; ENST00000396124.9; ENSP00000379430.4; ENSG00000156170.15. [Q330K2-1] DR Ensembl; ENST00000518258.5; ENSP00000428788.1; ENSG00000156170.15. [Q330K2-3] DR Ensembl; ENST00000523337.5; ENSP00000429038.1; ENSG00000156170.15. [Q330K2-3] DR GeneID; 137682; -. DR KEGG; hsa:137682; -. DR MANE-Select; ENST00000396124.9; ENSP00000379430.4; NM_152416.4; NP_689629.2. DR UCSC; uc003yhj.4; human. [Q330K2-1] DR AGR; HGNC:28625; -. DR ClinPGx; PA142672357; -. DR CTD; 137682; -. DR DisGeNET; 137682; -. DR GeneCards; NDUFAF6; -. DR HGNC; HGNC:28625; NDUFAF6. DR HPA; ENSG00000156170; Low tissue specificity. DR MalaCards; NDUFAF6; -. DR MIM; 612392; gene. DR MIM; 618239; phenotype. DR MIM; 618913; phenotype. DR OpenTargets; ENSG00000156170; -. DR Orphanet; 3337; Primary Fanconi renotubular syndrome. DR VEuPathDB; HostDB:ENSG00000156170; -. DR eggNOG; KOG4411; Eukaryota. DR GeneTree; ENSGT00510000048688; -. DR HOGENOM; CLU_037269_6_0_1; -. DR InParanoid; Q330K2; -. DR OMA; MINAREQ; -. DR OrthoDB; 270318at2759; -. DR PAN-GO; Q330K2; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q330K2; -. DR PathwayCommons; Q330K2; -. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q330K2; -. DR Agora; ENSG00000156170; -. DR BioGRID-ORCS; 137682; 79 hits in 1165 CRISPR screens. DR ChiTaRS; NDUFAF6; human. DR GenomeRNAi; 137682; -. DR Pharos; Q330K2; Tbio. DR PRO; PR:Q330K2; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q330K2; protein. DR Bgee; ENSG00000156170; Expressed in right uterine tube and 169 other cell types or tissues. DR ExpressionAtlas; Q330K2; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR FunFam; 1.10.600.10:FF:000013; NADH dehydrogenase (ubiquinone) complex I, assembly factor 6; 1. DR Gene3D; 1.10.600.10; Farnesyl Diphosphate Synthase; 1. DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf. DR InterPro; IPR002060; Squ/phyt_synthse. DR PANTHER; PTHR21181; -; 1. DR PANTHER; PTHR21181:SF13; NADH DEHYDROGENASE (UBIQUINONE) COMPLEX I, ASSEMBLY FACTOR 6; 1. DR Pfam; PF00494; SQS_PSY; 1. DR SUPFAM; SSF48576; Terpenoid synthases; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cytoplasm; Disease variant; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Nucleus; Primary mitochondrial disease; KW Proteomics identification; Reference proteome; Transit peptide. FT TRANSIT 1..44 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 45..333 FT /note="NADH dehydrogenase (ubiquinone) complex I, assembly FT factor 6" FT /id="PRO_0000291772" FT VAR_SEQ 1..65 FT /note="MAASAHGSVWGPLRLGIPGLCCRRPPLGLYARMRRLPGPEVSGRSVAAASGP FT GAWGTDHYCLELL -> MPISISHSSWLVQ (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_026230" FT VAR_SEQ 100..120 FT /note="VKDSVSEKTIGLMRMQFWKKT -> AGLLLLLSCCTVCHWDLNTKHC (in FT isoform 3)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_026231" FT VAR_SEQ 121..333 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_026232" FT VARIANT 69 FT /note="D -> V (in MC1DN17; dbSNP:rs1057519085)" FT /evidence="ECO:0000269|PubMed:26741492" FT /id="VAR_076272" FT VARIANT 76 FT /note="S -> P (in MC1DN17; dbSNP:rs1057519084)" FT /evidence="ECO:0000269|PubMed:26741492" FT /id="VAR_076273" FT VARIANT 99 FT /note="Q -> R (in MC1DN17; dbSNP:rs137853184)" FT /evidence="ECO:0000269|PubMed:18614015, FT ECO:0000269|PubMed:22019594" FT /id="VAR_047770" FT VARIANT 124 FT /note="I -> T (in MC1DN17; dbSNP:rs201732170)" FT /evidence="ECO:0000269|PubMed:26741492, FT ECO:0000269|PubMed:30642748" FT /id="VAR_076274" FT VARIANT 178 FT /note="A -> P (in MC1DN17; dbSNP:rs201088736)" FT /evidence="ECO:0000269|PubMed:27623250, FT ECO:0000269|PubMed:29531337" FT /id="VAR_084382" FT VARIANT 269 FT /note="H -> D (in MC1DN17; dbSNP:rs768273248)" FT /evidence="ECO:0000269|PubMed:26741492" FT /id="VAR_076275" FT VARIANT 274 FT /note="R -> G (in MC1DN17; dbSNP:rs1057519086)" FT /evidence="ECO:0000269|PubMed:26741492" FT /id="VAR_076276" SQ SEQUENCE 333 AA; 38176 MW; 1D3521A817F4B4BB CRC64; MAASAHGSVW GPLRLGIPGL CCRRPPLGLY ARMRRLPGPE VSGRSVAAAS GPGAWGTDHY CLELLRKRDY EGYLCSLLLP AESRSSVFAL RAFNVELAQV KDSVSEKTIG LMRMQFWKKT VEDIYCDNPP HQPVAIELWK AVKRHNLTKR WLMKIVDERE KNLDDKAYRN IKELENYAEN TQSSLLYLTL EILGIKDLHA DHAASHIGKA QGIVTCLRAT PYHGSRRKVF LPMDICMLHG VSQEDFLRRN QDKNVRDVIY DIASQAHLHL KHARSFHKTV PVKAFPAFLQ TVSLEDFLKK IQRVDFDIFH PSLQQKNTLL PLYLYIQSWR KTY // ID NDUF8_HUMAN Reviewed; 74 AA. AC A1L188; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 20-FEB-2007, sequence version 1. DT 28-JAN-2026, entry version 107. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex assembly factor 8 {ECO:0000312|HGNC:HGNC:33551}; GN Name=NDUFAF8 {ECO:0000312|HGNC:HGNC:33551}; GN Synonyms=C17orf89 {ECO:0000312|HGNC:HGNC:33551}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NDUFAF5. RX PubMed=27499296; DOI=10.1016/j.molcel.2016.06.033; RA Floyd B.J., Wilkerson E.M., Veling M.T., Minogue C.E., Xia C., Beebe E.T., RA Wrobel R.L., Cho H., Kremer L.S., Alston C.L., Gromek K.A., Dolan B.K., RA Ulbrich A., Stefely J.A., Bohl S.L., Werner K.M., Jochem A., RA Westphall M.S., Rensvold J.W., Taylor R.W., Prokisch H., Kim J.J., RA Coon J.J., Pagliarini D.J.; RT "Mitochondrial protein interaction mapping identifies regulators of RT respiratory chain function."; RL Mol. Cell 63:621-632(2016). RN [4] RP INVOLVEMENT IN MC1DN34, AND VARIANT MC1DN34 LEU-55. RX PubMed=31866046; DOI=10.1016/j.ajhg.2019.12.001; RA Alston C.L., Veling M.T., Heidler J., Taylor L.S., Alaimo J.T., Sung A.Y., RA He L., Hopton S., Broomfield A., Pavaine J., Diaz J., Leon E., Wolf P., RA McFarland R., Prokisch H., Wortmann S.B., Bonnen P.E., Wittig I., RA Pagliarini D.J., Taylor R.W.; RT "Pathogenic bi-allelic mutations in NDUFAF8 cause Leigh syndrome with an RT isolated complex I deficiency."; RL Am. J. Hum. Genet. 106:92-101(2020). CC -!- FUNCTION: Involved in the assembly of mitochondrial NADH:ubiquinone CC oxidoreductase complex (complex I, MT-ND1) (PubMed:27499296). Required CC to stabilize NDUFAF5 (PubMed:27499296). {ECO:0000269|PubMed:27499296}. CC -!- SUBUNIT: Interacts with NDUFAF5. {ECO:0000269|PubMed:27499296}. CC -!- INTERACTION: CC A1L188; Q5TEU4: NDUFAF5; NbExp=11; IntAct=EBI-20593474, EBI-10762958; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:27499296}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 34 (MC1DN34) CC [MIM:618776]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN34 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:31866046}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CH471099; EAW89640.1; -; Genomic_DNA. DR EMBL; BC127837; AAI27838.1; -; mRNA. DR CCDS; CCDS45809.1; -. DR RefSeq; NP_001079990.1; NM_001086521.2. DR AlphaFoldDB; A1L188; -. DR SMR; A1L188; -. DR BioGRID; 129780; 40. DR FunCoup; A1L188; 357. DR IntAct; A1L188; 26. DR MINT; A1L188; -. DR STRING; 9606.ENSP00000400184; -. DR GlyGen; A1L188; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; A1L188; -. DR PhosphoSitePlus; A1L188; -. DR BioMuta; NDUFAF8; -. DR jPOST; A1L188; -. DR MassIVE; A1L188; -. DR PaxDb; 9606-ENSP00000400184; -. DR PeptideAtlas; A1L188; -. DR ProteomicsDB; 136; -. DR Pumba; A1L188; -. DR Antibodypedia; 66310; 10 antibodies from 6 providers. DR DNASU; 284184; -. DR Ensembl; ENST00000431388.3; ENSP00000400184.2; ENSG00000224877.4. DR GeneID; 284184; -. DR KEGG; hsa:284184; -. DR MANE-Select; ENST00000431388.3; ENSP00000400184.2; NM_001086521.2; NP_001079990.1. DR UCSC; uc002jzx.3; human. DR AGR; HGNC:33551; -. DR ClinPGx; PA162378532; -. DR CTD; 284184; -. DR DisGeNET; 284184; -. DR GeneCards; NDUFAF8; -. DR HGNC; HGNC:33551; NDUFAF8. DR HPA; ENSG00000224877; Low tissue specificity. DR MalaCards; NDUFAF8; -. DR MIM; 618461; gene. DR MIM; 618776; phenotype. DR OpenTargets; ENSG00000224877; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000224877; -. DR eggNOG; ENOG502SBX9; Eukaryota. DR GeneTree; ENSGT00520000061927; -. DR HOGENOM; CLU_188562_0_0_1; -. DR InParanoid; A1L188; -. DR OMA; KKDLCAQ; -. DR OrthoDB; 3821113at2759; -. DR PAN-GO; A1L188; 2 GO annotations based on evolutionary models. DR PhylomeDB; A1L188; -. DR PathwayCommons; A1L188; -. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; A1L188; -. DR Agora; ENSG00000224877; -. DR BioGRID-ORCS; 284184; 300 hits in 1141 CRISPR screens. DR ChiTaRS; NDUFAF8; human. DR GenomeRNAi; 284184; -. DR Pharos; A1L188; Tbio. DR PRO; PR:A1L188; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; A1L188; protein. DR Bgee; ENSG00000224877; Expressed in medial globus pallidus and 181 other cell types or tissues. DR ExpressionAtlas; A1L188; baseline and differential. DR GO; GO:0005759; C:mitochondrial matrix; IDA:FlyBase. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR InterPro; IPR034595; NDUFAF8. DR PANTHER; PTHR34561; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX ASSEMBLY FACTOR 8; 1. DR PANTHER; PTHR34561:SF1; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX ASSEMBLY FACTOR 8; 1. DR PROSITE; PS51808; CHCH; 1. PE 1: Evidence at protein level; KW Disease variant; Disulfide bond; Mitochondrion; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome. FT CHAIN 1..74 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT assembly factor 8" FT /id="PRO_0000299480" FT DOMAIN 22..69 FT /note="CHCH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT MOTIF 25..35 FT /note="Cx9C motif 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT MOTIF 51..61 FT /note="Cx9C motif 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT DISULFID 25..61 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT DISULFID 35..51 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01150" FT VARIANT 55 FT /note="F -> L (in MC1DN34; uncertain significance; FT dbSNP:rs1598368033)" FT /evidence="ECO:0000269|PubMed:31866046" FT /id="VAR_083800" SQ SEQUENCE 74 AA; 7756 MW; F3FCE21C67A3979F CRC64; MSANGAVWGR VRSRLRAFPE RLAACGAEAA AYGRCVQAST APGGRLSKDF CAREFEALRS CFAAAAKKTL EGGC // ID NDUS1_HUMAN Reviewed; 727 AA. AC P28331; B4DIN9; B4DJA0; B4DPG1; B4DUC1; E7ENF3; Q53TR8; Q8N1C4; Q8TCC9; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 07-MAR-2006, sequence version 3. DT 28-JAN-2026, entry version 244. DE RecName: Full=NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial; DE EC=7.1.1.2 {ECO:0000269|PubMed:30879903, ECO:0000269|PubMed:31557978}; DE AltName: Full=Complex I-75kD; DE Short=CI-75kD; DE Flags: Precursor; GN Name=NDUFS1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT PHE-649. RX PubMed=1935949; DOI=10.1111/j.1432-1033.1991.tb16313.x; RA Chow W., Ragan I., Robinson B.H.; RT "Determination of the cDNA sequence for the human mitochondrial 75-kDa Fe-S RT protein of NADH-coenzyme Q reductase."; RL Eur. J. Biochem. 201:547-550(1991). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3; 4 AND 5). RC TISSUE=Hippocampus, Kidney, and Substantia nigra; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-241. RC TISSUE=Brain, and Liver; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 185-200; 247-266; 277-289; 312-325; 361-382; 451-467; RP 471-499; 519-538; 544-557 AND 625-655, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex; RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.; RL Submitted (DEC-2008) to UniProtKB. RN [7] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [10] RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER THR-23, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, SUBCELLULAR LOCATION, AND RP INTERACTION WITH MDM2. RX PubMed=30879903; DOI=10.1016/j.molcel.2019.02.012; RA Elkholi R., Abraham-Enachescu I., Trotta A.P., Rubio-Patino C., RA Mohammed J.N., Luna-Vargas M.P.A., Gelles J.D., Kaminetsky J.R., RA Serasinghe M.N., Zou C., Ali S., McStay G.P., Pfleger C.M., Chipuk J.E.; RT "MDM2 Integrates Cellular Respiration and Apoptotic Signaling through RT NDUFS1 and the Mitochondrial Network."; RL Mol. Cell 74:452-465(2019). RN [12] RP INVOLVEMENT IN MC1DN5, AND VARIANTS MC1DN5 TRP-241 AND GLY-252. RX PubMed=11349233; DOI=10.1086/320603; RA Benit P., Chretien D., Kadhom N., de Lonlay-Debeney P., Cormier-Daire V., RA Cabral A., Peudenier S., Rustin P., Munnich A., Roetig A.; RT "Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 RT genes in mitochondrial complex I deficiency."; RL Am. J. Hum. Genet. 68:1344-1352(2001). RN [13] RP VARIANT GLY-253. RX PubMed=22499341; DOI=10.1136/jmedgenet-2012-100836; RA Shamseldin H.E., Alshammari M., Al-Sheddi T., Salih M.A., Alkhalidi H., RA Kentab A., Repetto G.M., Hashem M., Alkuraya F.S.; RT "Genomic analysis of mitochondrial diseases in a consanguineous population RT reveals novel candidate disease genes."; RL J. Med. Genet. 49:234-241(2012). RN [14] RP VARIANTS MC1DN5 ALA-228 AND GLY-252, CHARACTERIZATION OF VARIANTS MC1DN5 RP ALA-228 AND GLY-252, FUNCTION, SUBUNIT, AND CATALYTIC ACTIVITY. RX PubMed=31557978; DOI=10.3390/cells8101149; RA Ni Y., Hagras M.A., Konstantopoulou V., Mayr J.A., Stuchebrukhov A.A., RA Meierhofer D.; RT "Mutations in NDUFS1 Cause Metabolic Reprogramming and Disruption of the RT Electron Transfer."; RL Cells 8:0-0(2019). CC -!- FUNCTION: Core subunit of the mitochondrial membrane respiratory chain CC NADH dehydrogenase (Complex I) which catalyzes electron transfer from CC NADH through the respiratory chain, using ubiquinone as an electron CC acceptor (PubMed:30879903, PubMed:31557978). Essential for catalysing CC the entry and efficient transfer of electrons within complex I CC (PubMed:31557978). Plays a key role in the assembly and stability of CC complex I and participates in the association of complex I with CC ubiquinol-cytochrome reductase complex (Complex III) to form CC supercomplexes (PubMed:30879903, PubMed:31557978). CC {ECO:0000269|PubMed:30879903, ECO:0000269|PubMed:31557978}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ubiquinone + NADH + 5 H(+)(in) = a ubiquinol + NAD(+) + 4 CC H(+)(out); Xref=Rhea:RHEA:29091, Rhea:RHEA-COMP:9565, Rhea:RHEA- CC COMP:9566, ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=7.1.1.2; CC Evidence={ECO:0000269|PubMed:30879903, ECO:0000269|PubMed:31557978}; CC -!- COFACTOR: CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135; CC Evidence={ECO:0000250|UniProtKB:Q56223}; CC Note=Binds 1 [2Fe-2S] cluster per subunit. CC {ECO:0000250|UniProtKB:Q56223}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Evidence={ECO:0000250|UniProtKB:Q56223}; CC Note=Binds 2 [4Fe-4S] clusters per subunit. CC {ECO:0000250|UniProtKB:Q56223}; CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex CC I) which is composed of 45 different subunits (PubMed:12611891). This CC is the largest subunit of complex I and it is a component of the iron- CC sulfur (IP) fragment of the enzyme (By similarity). Complex I CC associates with ubiquinol-cytochrome reductase complex (Complex III) to CC form supercomplexes (PubMed:30879903, PubMed:31557978). Interacts with CC MDM2 (PubMed:30879903). Interacts with AKAP1 (By similarity). CC {ECO:0000250|UniProtKB:P15690, ECO:0000250|UniProtKB:Q91VD9, CC ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:30879903, CC ECO:0000269|PubMed:31557978}. CC -!- INTERACTION: CC P28331; Q16795: NDUFA9; NbExp=4; IntAct=EBI-1043922, EBI-1045087; CC P28331; Q99650: OSMR; NbExp=4; IntAct=EBI-1043922, EBI-2804080; CC P28331; P35610: SOAT1; NbExp=3; IntAct=EBI-1043922, EBI-6621955; CC P28331-2; Q0VDD7: BRME1; NbExp=3; IntAct=EBI-6190702, EBI-741210; CC P28331-2; Q96MW5: COG8; NbExp=3; IntAct=EBI-6190702, EBI-720875; CC P28331-2; P24310: COX7A1; NbExp=3; IntAct=EBI-6190702, EBI-25876196; CC P28331-2; Q14154: DELE1; NbExp=3; IntAct=EBI-6190702, EBI-2805660; CC P28331-2; Q9BPU6: DPYSL5; NbExp=3; IntAct=EBI-6190702, EBI-724653; CC P28331-2; Q49AJ0-4: FAM135B; NbExp=3; IntAct=EBI-6190702, EBI-25835236; CC P28331-2; Q99871: HAUS7; NbExp=3; IntAct=EBI-6190702, EBI-395719; CC P28331-2; Q6ZU52: KIAA0408; NbExp=3; IntAct=EBI-6190702, EBI-739493; CC P28331-2; Q13887: KLF5; NbExp=3; IntAct=EBI-6190702, EBI-2696013; CC P28331-2; Q92615: LARP4B; NbExp=3; IntAct=EBI-6190702, EBI-1052558; CC P28331-2; Q9BV99: LRRC61; NbExp=3; IntAct=EBI-6190702, EBI-2350424; CC P28331-2; Q8N6F8: METTL27; NbExp=3; IntAct=EBI-6190702, EBI-8487781; CC P28331-2; Q13562: NEUROD1; NbExp=3; IntAct=EBI-6190702, EBI-3908303; CC P28331-2; P22061-2: PCMT1; NbExp=3; IntAct=EBI-6190702, EBI-12386584; CC P28331-2; Q8WTV1: THAP3; NbExp=3; IntAct=EBI-6190702, EBI-17438286; CC P28331-5; Q96IK1-2: BOD1; NbExp=3; IntAct=EBI-25876328, EBI-18924329; CC P28331-5; P42858: HTT; NbExp=6; IntAct=EBI-25876328, EBI-466029; CC P28331-5; O60333-2: KIF1B; NbExp=3; IntAct=EBI-25876328, EBI-10975473; CC P28331-5; O76024: WFS1; NbExp=3; IntAct=EBI-25876328, EBI-720609; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891, ECO:0000305|PubMed:30879903}; Peripheral CC membrane protein {ECO:0000250|UniProtKB:P15690}; Matrix side CC {ECO:0000250|UniProtKB:P15690}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=P28331-1; Sequence=Displayed; CC Name=2; CC IsoId=P28331-2; Sequence=VSP_042682; CC Name=3; CC IsoId=P28331-3; Sequence=VSP_043728, VSP_043729; CC Name=4; CC IsoId=P28331-4; Sequence=VSP_043727; CC Name=5; CC IsoId=P28331-5; Sequence=VSP_045864; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 5 (MC1DN5) CC [MIM:618226]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN5 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:11349233, CC ECO:0000269|PubMed:31557978}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I 75 kDa subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X61100; CAA43412.1; -; mRNA. DR EMBL; AK295705; BAG58551.1; -; mRNA. DR EMBL; AK295987; BAG58762.1; -; mRNA. DR EMBL; AK298320; BAG60573.1; -; mRNA. DR EMBL; AK300585; BAG62283.1; -; mRNA. DR EMBL; AC007383; AAY15061.1; -; Genomic_DNA. DR EMBL; CH471063; EAW70379.1; -; Genomic_DNA. DR EMBL; BC022368; AAH22368.1; -; mRNA. DR EMBL; BC030833; AAH30833.1; -; mRNA. DR CCDS; CCDS2366.1; -. [P28331-1] DR CCDS; CCDS56162.1; -. [P28331-4] DR CCDS; CCDS56163.1; -. [P28331-3] DR CCDS; CCDS56164.1; -. [P28331-5] DR CCDS; CCDS56165.1; -. [P28331-2] DR PIR; S17854; S17854. DR RefSeq; NP_001186910.1; NM_001199981.2. [P28331-5] DR RefSeq; NP_001186911.1; NM_001199982.2. [P28331-3] DR RefSeq; NP_001186912.1; NM_001199983.2. [P28331-4] DR RefSeq; NP_001186913.1; NM_001199984.2. [P28331-2] DR RefSeq; NP_004997.4; NM_005006.6. [P28331-1] DR PDB; 5XTB; EM; 3.40 A; M=30-716. DR PDB; 5XTD; EM; 3.70 A; M=30-716. DR PDB; 5XTH; EM; 3.90 A; M=30-716. DR PDB; 5XTI; EM; 17.40 A; BM/M=30-716. DR PDB; 9CWT; EM; 3.44 A; M=1-727. DR PDBsum; 5XTB; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; P28331; -. DR EMDB; EMD-45974; -. DR SMR; P28331; -. DR BioGRID; 110799; 402. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; P28331; -. DR FunCoup; P28331; 1581. DR IntAct; P28331; 154. DR MINT; P28331; -. DR STRING; 9606.ENSP00000392709; -. DR BindingDB; P28331; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; P28331; -. DR CarbonylDB; P28331; -. DR GlyGen; P28331; 6 sites, 1 O-linked glycan (4 sites). DR iPTMnet; P28331; -. DR MetOSite; P28331; -. DR PhosphoSitePlus; P28331; -. DR SwissPalm; P28331; -. DR BioMuta; NDUFS1; -. DR DMDM; 92090799; -. DR REPRODUCTION-2DPAGE; IPI00604664; -. DR REPRODUCTION-2DPAGE; P28331; -. DR CPTAC; CPTAC-413; -. DR CPTAC; CPTAC-414; -. DR jPOST; P28331; -. DR MassIVE; P28331; -. DR PaxDb; 9606-ENSP00000392709; -. DR PeptideAtlas; P28331; -. DR ProteomicsDB; 17145; -. DR ProteomicsDB; 54470; -. [P28331-1] DR ProteomicsDB; 54471; -. [P28331-2] DR ProteomicsDB; 54472; -. [P28331-3] DR ProteomicsDB; 54473; -. [P28331-4] DR Pumba; P28331; -. DR Antibodypedia; 34175; 311 antibodies from 37 providers. DR DNASU; 4719; -. DR Ensembl; ENST00000233190.11; ENSP00000233190.5; ENSG00000023228.16. [P28331-1] DR Ensembl; ENST00000423725.5; ENSP00000397760.1; ENSG00000023228.16. [P28331-4] DR Ensembl; ENST00000432169.5; ENSP00000409689.1; ENSG00000023228.16. [P28331-3] DR Ensembl; ENST00000440274.5; ENSP00000409766.1; ENSG00000023228.16. [P28331-5] DR Ensembl; ENST00000449699.5; ENSP00000399912.1; ENSG00000023228.16. [P28331-1] DR Ensembl; ENST00000635748.2; ENSP00000489640.1; ENSG00000283447.3. [P28331-1] DR Ensembl; ENST00000636505.1; ENSP00000490898.1; ENSG00000283447.3. [P28331-1] DR Ensembl; ENST00000637298.1; ENSP00000490583.1; ENSG00000283447.3. [P28331-4] DR Ensembl; ENST00000637631.1; ENSP00000489705.1; ENSG00000283447.3. [P28331-3] DR Ensembl; ENST00000637990.1; ENSP00000490766.1; ENSG00000283447.3. [P28331-5] DR GeneID; 4719; -. DR KEGG; hsa:4719; -. DR MANE-Select; ENST00000233190.11; ENSP00000233190.5; NM_005006.7; NP_004997.4. DR UCSC; uc002vbe.4; human. [P28331-1] DR AGR; HGNC:7707; -. DR ClinPGx; PA31518; -. DR CTD; 4719; -. DR DisGeNET; 4719; -. DR GeneCards; NDUFS1; -. DR GeneReviews; NDUFS1; -. DR HGNC; HGNC:7707; NDUFS1. DR HPA; ENSG00000023228; Tissue enhanced (heart muscle, skeletal muscle, tongue). DR MalaCards; NDUFS1; -. DR MIM; 157655; gene. DR MIM; 618226; phenotype. DR OpenTargets; ENSG00000023228; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000023228; -. DR eggNOG; KOG2282; Eukaryota. DR GeneTree; ENSGT00940000153514; -. DR HOGENOM; CLU_000422_11_2_1; -. DR InParanoid; P28331; -. DR OMA; QAMAYGV; -. DR OrthoDB; 10249365at2759; -. DR PAN-GO; P28331; 1 GO annotation based on evolutionary models. DR PhylomeDB; P28331; -. DR BioCyc; MetaCyc:HS00422-MONOMER; -. DR PathwayCommons; P28331; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR Reactome; R-HSA-9837999; Mitochondrial protein degradation. DR SignaLink; P28331; -. DR SIGNOR; P28331; -. DR Agora; ENSG00000023228; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 4719; 296 hits in 1171 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFS1; human. DR GeneWiki; NDUFS1; -. DR GenomeRNAi; 4719; -. DR Pharos; P28331; Tclin. DR PRO; PR:P28331; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P28331; protein. DR Bgee; ENSG00000023228; Expressed in corpus callosum and 109 other cell types or tissues. DR ExpressionAtlas; P28331; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0009055; F:electron transfer activity; NAS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IMP:UniProtKB. DR GO; GO:0016651; F:oxidoreductase activity, acting on NAD(P)H; IEA:InterPro. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0045333; P:cellular respiration; IMP:UniProtKB. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IMP:UniProtKB. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR CDD; cd00207; fer2; 1. DR CDD; cd02773; MopB_Res-Cmplx1_Nad11; 1. DR FunFam; 3.10.20.740:FF:000001; NADH-quinone oxidoreductase subunit G; 1. DR FunFam; 3.30.200.210:FF:000002; NADH-ubiquinone oxidoreductase 75 kDa subunit; 1. DR FunFam; 3.30.70.20:FF:000002; NADH-ubiquinone oxidoreductase 75 kDa subunit; 1. DR FunFam; 3.40.50.740:FF:000002; NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial; 1. DR Gene3D; 3.10.20.740; -; 1. DR Gene3D; 3.30.200.210; -; 1. DR Gene3D; 3.30.70.20; -; 1. DR Gene3D; 3.40.50.740; -; 1. DR InterPro; IPR036010; 2Fe-2S_ferredoxin-like_sf. DR InterPro; IPR001041; 2Fe-2S_ferredoxin-type. DR InterPro; IPR006656; Mopterin_OxRdtase. DR InterPro; IPR006963; Mopterin_OxRdtase_4Fe-4S_dom. DR InterPro; IPR000283; NADH_UbQ_OxRdtase_75kDa_su_CS. DR InterPro; IPR054351; NADH_UbQ_OxRdtase_ferredoxin. DR InterPro; IPR010228; NADH_UbQ_OxRdtase_Gsu. DR InterPro; IPR019574; NADH_UbQ_OxRdtase_Gsu_4Fe4S-bd. DR InterPro; IPR015405; NDUFS1-like_C. DR InterPro; IPR050123; Prok_molybdopt-oxidoreductase. DR NCBIfam; TIGR01973; NuoG; 1. DR PANTHER; PTHR43105:SF13; NADH-UBIQUINONE OXIDOREDUCTASE 75 KDA SUBUNIT, MITOCHONDRIAL; 1. DR PANTHER; PTHR43105; RESPIRATORY NITRATE REDUCTASE; 1. DR Pfam; PF13510; Fer2_4; 1. DR Pfam; PF22151; Fer4_NDSU1; 1. DR Pfam; PF22117; Fer4_Nqo3; 1. DR Pfam; PF00384; Molybdopterin; 1. DR Pfam; PF10588; NADH-G_4Fe-4S_3; 1. DR Pfam; PF09326; NADH_dhqG_C; 1. DR SMART; SM00929; NADH-G_4Fe-4S_3; 1. DR SUPFAM; SSF54292; 2Fe-2S ferredoxin-like; 1. DR SUPFAM; SSF54862; 4Fe-4S ferredoxins; 1. DR SUPFAM; SSF53706; Formate dehydrogenase/DMSO reductase, domains 1-3; 1. DR PROSITE; PS51085; 2FE2S_FER_2; 1. DR PROSITE; PS51839; 4FE4S_HC3; 1. DR PROSITE; PS51669; 4FE4S_MOW_BIS_MGD; 1. DR PROSITE; PS00641; COMPLEX1_75K_1; 1. DR PROSITE; PS00642; COMPLEX1_75K_2; 1. DR PROSITE; PS00643; COMPLEX1_75K_3; 1. PE 1: Evidence at protein level; KW 2Fe-2S; 3D-structure; 4Fe-4S; Acetylation; Alternative splicing; KW Direct protein sequencing; Disease variant; Electron transport; Iron; KW Iron-sulfur; Membrane; Metal-binding; Mitochondrion; KW Mitochondrion inner membrane; NAD; Oxidoreductase; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transit peptide; Translocase; KW Transport; Ubiquinone. FT TRANSIT 1..23 FT /note="Mitochondrion" FT /evidence="ECO:0007744|PubMed:25944712" FT CHAIN 24..727 FT /note="NADH-ubiquinone oxidoreductase 75 kDa subunit, FT mitochondrial" FT /id="PRO_0000019968" FT DOMAIN 30..108 FT /note="2Fe-2S ferredoxin-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465" FT DOMAIN 108..147 FT /note="4Fe-4S His(Cys)3-ligated-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184" FT DOMAIN 245..301 FT /note="4Fe-4S Mo/W bis-MGD-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01004" FT BINDING 64 FT /ligand="[2Fe-2S] cluster" FT /ligand_id="ChEBI:CHEBI:190135" FT /evidence="ECO:0000250" FT BINDING 75 FT /ligand="[2Fe-2S] cluster" FT /ligand_id="ChEBI:CHEBI:190135" FT /evidence="ECO:0000250" FT BINDING 78 FT /ligand="[2Fe-2S] cluster" FT /ligand_id="ChEBI:CHEBI:190135" FT /evidence="ECO:0000250" FT BINDING 92 FT /ligand="[2Fe-2S] cluster" FT /ligand_id="ChEBI:CHEBI:190135" FT /evidence="ECO:0000250" FT BINDING 124 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184" FT BINDING 128 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184" FT BINDING 131 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184" FT BINDING 137 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01184" FT BINDING 176 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 179 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 182 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 226 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /evidence="ECO:0000250" FT MOD_RES 84 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q91VD9" FT MOD_RES 467 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q91VD9" FT MOD_RES 499 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q91VD9" FT MOD_RES 709 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q91VD9" FT VAR_SEQ 1..57 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043727" FT VAR_SEQ 1..2 FT /note="ML -> MW (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043728" FT VAR_SEQ 1 FT /note="M -> MRIRGSSGTLSRINM (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_042682" FT VAR_SEQ 3..113 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043729" FT VAR_SEQ 52..87 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045864" FT VARIANT 228 FT /note="V -> A (in MC1DN5; loss of catalytic activity)" FT /evidence="ECO:0000269|PubMed:31557978" FT /id="VAR_084177" FT VARIANT 241 FT /note="R -> Q (in dbSNP:rs17856901)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_025511" FT VARIANT 241 FT /note="R -> W (in MC1DN5; uncertain significance; FT dbSNP:rs199422225)" FT /evidence="ECO:0000269|PubMed:11349233" FT /id="VAR_019532" FT VARIANT 252 FT /note="D -> G (in MC1DN5; also found in a patient with FT muscular hypotonia; loss of catalytic activity; FT dbSNP:rs199422224)" FT /evidence="ECO:0000269|PubMed:11349233, FT ECO:0000269|PubMed:31557978" FT /id="VAR_019533" FT VARIANT 253 FT /note="V -> G (in dbSNP:rs786205666)" FT /evidence="ECO:0000269|PubMed:22499341" FT /id="VAR_069506" FT VARIANT 649 FT /note="V -> F (in dbSNP:rs1044049)" FT /evidence="ECO:0000269|PubMed:1935949" FT /id="VAR_018463" FT CONFLICT 8 FT /note="K -> R (in Ref. 1; CAA43412)" FT /evidence="ECO:0000305" FT CONFLICT 417 FT /note="R -> W (in Ref. 1; CAA43412)" FT /evidence="ECO:0000305" FT CONFLICT 572 FT /note="H -> L (in Ref. 2; BAG58551)" FT /evidence="ECO:0000305" FT CONFLICT 691 FT /note="I -> L (in Ref. 1; CAA43412)" FT /evidence="ECO:0000305" FT STRAND 32..43 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 49..56 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 91..93 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 107..120 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 134..136 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 138..145 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 181..186 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 187..190 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 209..211 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 221..225 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 227..229 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 235..238 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 242..244 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 246..251 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 260..266 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 269..275 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 279..282 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 288..291 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 293..298 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 306..308 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 314..316 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 319..330 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 335..337 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 340..342 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 348..360 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 368..370 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 380..382 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 383..385 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 391..393 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 394..396 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 407..409 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 412..423 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 448..457 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 461..468 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 469..471 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 478..481 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 482..485 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 486..503 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 522..527 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 535..537 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 545..548 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 552..554 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 576..579 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 581..583 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 589..591 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 595..597 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 603..605 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 613..615 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 619..629 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 639..647 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 652..654 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 666..673 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 674..676 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 691..695 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 699..703 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 705..715 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 727 AA; 79468 MW; 9C35F4B8294771FB CRC64; MLRIPVRKAL VGLSKSPKGC VRTTATAASN LIEVFVDGQS VMVEPGTTVL QACEKVGMQI PRFCYHERLS VAGNCRMCLV EIEKAPKVVA ACAMPVMKGW NILTNSEKSK KAREGVMEFL LANHPLDCPI CDQGGECDLQ DQSMMFGNDR SRFLEGKRAV EDKNIGPLVK TIMTRCIQCT RCIRFASEIA GVDDLGTTGR GNDMQVGTYI EKMFMSELSG NIIDICPVGA LTSKPYAFTA RPWETRKTES IDVMDAVGSN IVVSTRTGEV MRILPRMHED INEEWISDKT RFAYDGLKRQ RLTEPMVRNE KGLLTYTSWE DALSRVAGML QSFQGKDVAA IAGGLVDAEA LVALKDLLNR VDSDTLCTEE VFPTAGAGTD LRSNYLLNTT IAGVEEADVV LLVGTNPRFE APLFNARIRK SWLHNDLKVA LIGSPVDLTY TYDHLGDSPK ILQDIASGSH PFSQVLKEAK KPMVVLGSSA LQRNDGAAIL AAVSSIAQKI RMTSGVTGDW KVMNILHRIA SQVAALDLGY KPGVEAIRKN PPKVLFLLGA DGGCITRQDL PKDCFIIYQG HHGDVGAPIA DVILPGAAYT EKSATYVNTE GRAQQTKVAV TPPGLAREDW KIIRALSEIA GMTLPYDTLD QVRNRLEEVS PNLVRYDDIE GANYFQQANE LSKLVNQQLL ADPLVPPQLT IKDFYMTDSI SRASQTMAKC VKAVTEGAQA VEEPSIC // ID NDUS2_HUMAN Reviewed; 463 AA. AC O75306; D3DVG7; J3KPM7; Q5VTW0; Q969P3; Q9UEV3; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2002, sequence version 2. DT 28-JAN-2026, entry version 230. DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial; DE EC=7.1.1.2 {ECO:0000269|PubMed:22036843, ECO:0000269|PubMed:30922174}; DE AltName: Full=Complex I-49kD; DE Short=CI-49kD; DE AltName: Full=NADH-ubiquinone oxidoreductase 49 kDa subunit; DE Flags: Precursor; GN Name=NDUFS2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9647766; DOI=10.1006/bbrc.1998.8882; RA Loeffen J., van den Heuvel L., Smeets R., Triepels R., Sengers R., RA Trijbels F., Smeitink J.; RT "cDNA sequence and chromosomal localization of the remaining three human RT nuclear encoded iron sulphur protein (IP) subunits of complex I: the human RT IP fraction is completed."; RL Biochem. Biophys. Res. Commun. 247:751-758(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION. RX PubMed=9585441; DOI=10.1007/s003359900803; RA Procaccio V., de Sury R., Martinez P., Depetris D., Rabilloud T., RA Soularue P., Lunardi J., Issartel J.-P.; RT "Mapping to 1q23 of the human gene (NDUFS2) encoding the 49-kDa subunit of RT the mitochondrial respiratory complex I and immunodetection of the mature RT protein in mitochondria."; RL Mamm. Genome 9:482-484(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Muscle, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [8] RP INTERACTION WITH NDUFAF3. RX PubMed=19463981; DOI=10.1016/j.ajhg.2009.04.020; RA Saada A., Vogel R.O., Hoefs S.J., van den Brand M.A., Wessels H.J., RA Willems P.H., Venselaar H., Shaag A., Barghuti F., Reish O., Shohat M., RA Huynen M.A., Smeitink J.A.M., van den Heuvel L.P., Nijtmans L.G.; RT "Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting RT complex I assembly protein, cause fatal neonatal mitochondrial disease."; RL Am. J. Hum. Genet. 84:718-727(2009). RN [9] RP INTERACTION WITH NDUFAF7. RX PubMed=20406883; DOI=10.1242/jcs.066076; RA Carilla-Latorre S., Gallardo M.E., Annesley S.J., Calvo-Garrido J., RA Grana O., Accari S.L., Smith P.K., Valencia A., Garesse R., Fisher P.R., RA Escalante R.; RT "MidA is a putative methyltransferase that is required for mitochondrial RT complex I function."; RL J. Cell Sci. 123:1674-1683(2010). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP METHYLATION AT ARG-118, AND INTERACTION WITH NDUFAF7. RX PubMed=24089531; DOI=10.1074/jbc.m113.518803; RA Rhein V.F., Carroll J., Ding S., Fearnley I.M., Walker J.E.; RT "NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex I."; RL J. Biol. Chem. 288:33016-33026(2013). RN [12] RP METHYLATION AT ARG-118. RX PubMed=24838397; DOI=10.1093/hmg/ddu239; RA Zurita Rendon O., Silva Neiva L., Sasarman F., Shoubridge E.A.; RT "The arginine methyltransferase NDUFAF7 is essential for complex I assembly RT and early vertebrate embryogenesis."; RL Hum. Mol. Genet. 23:5159-5170(2014). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [15] RP INVOLVEMENT IN LHONAR2, VARIANTS LHONAR2 CYS-53 AND CYS-308, RP CHARACTERIZATION OF VARIANTS LHONAR2 CYS-53 AND CYS-308, AND FUNCTION. RX PubMed=28031252; DOI=10.1136/jmedgenet-2016-104212; RA Gerber S., Ding M.G., Gerard X., Zwicker K., Zanlonghi X., Rio M., RA Serre V., Hanein S., Munnich A., Rotig A., Bianchi L., Amati-Bonneau P., RA Elpeleg O., Kaplan J., Brandt U., Rozet J.M.; RT "Compound heterozygosity for severe and hypomorphic NDUFS2 mutations cause RT non-syndromic LHON-like optic neuropathy."; RL J. Med. Genet. 54:346-356(2017). RN [16] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=30922174; DOI=10.1161/circresaha.118.314284; RA Dunham-Snary K.J., Wu D., Potus F., Sykes E.A., Mewburn J.D., Charles R.L., RA Eaton P., Sultanian R.A., Archer S.L.; RT "Ndufs2, a Core Subunit of Mitochondrial Complex I, Is Essential for Acute RT Oxygen-Sensing and Hypoxic Pulmonary Vasoconstriction."; RL Circ. Res. 124:1727-1746(2019). RN [17] RP INVOLVEMENT IN MC1DN6, AND VARIANTS MC1DN6 GLN-228; GLN-229 AND PRO-413. RX PubMed=11220739; RX DOI=10.1002/1531-8249(20010201)49:2<195::aid-ana39>3.0.co;2-m; RA Loeffen J., Elpeleg O., Smeitink J., Smeets R., Stoeckler-Ipsiroglu S., RA Mandel H., Sengers R., Trijbels F., van den Heuvel L.; RT "Mutations in the complex I NDUFS2 gene of patients with cardiomyopathy and RT encephalomyopathy."; RL Ann. Neurol. 49:195-201(2001). RN [18] RP VARIANT VAL-224. RX PubMed=21057504; DOI=10.1038/ng.706; RA Haack T.B., Danhauser K., Haberberger B., Hoser J., Strecker V., Boehm D., RA Uziel G., Lamantea E., Invernizzi F., Poulton J., Rolinski B., Iuso A., RA Biskup S., Schmidt T., Mewes H.W., Wittig I., Meitinger T., Zeviani M., RA Prokisch H.; RT "Exome sequencing identifies ACAD9 mutations as a cause of complex I RT deficiency."; RL Nat. Genet. 42:1131-1134(2010). RN [19] RP VARIANT MC1DN6 ASN-446, CHARACTERIZATION OF VARIANT MC1DN6 ASN-446, RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=22036843; DOI=10.1016/j.bbadis.2011.10.012; RA Ngu L.H., Nijtmans L.G., Distelmaier F., Venselaar H., RA van Emst-de Vries S.E., van den Brand M.A., Stoltenborg B.J., Wintjes L.T., RA Willems P.H., van den Heuvel L.P., Smeitink J.A., Rodenburg R.J.; RT "A catalytic defect in mitochondrial respiratory chain complex I due to a RT mutation in NDUFS2 in a patient with Leigh syndrome."; RL Biochim. Biophys. Acta 1822:168-175(2012). CC -!- FUNCTION: Core subunit of the mitochondrial membrane respiratory chain CC NADH dehydrogenase (Complex I) which catalyzes electron transfer from CC NADH through the respiratory chain, using ubiquinone as an electron CC acceptor (PubMed:22036843, PubMed:28031252, PubMed:30922174). Essential CC for the catalytic activity of complex I (PubMed:22036843, CC PubMed:30922174). Essential for the assembly of complex I (By CC similarity). Redox-sensitive, critical component of the oxygen-sensing CC pathway in the pulmonary vasculature which plays a key role in acute CC pulmonary oxygen-sensing and hypoxic pulmonary vasoconstriction CC (PubMed:30922174). Plays an important role in carotid body sensing of CC hypoxia (By similarity). Essential for glia-like neural stem and CC progenitor cell proliferation, differentiation and subsequent CC oligodendrocyte or neuronal maturation (By similarity). CC {ECO:0000250|UniProtKB:Q91WD5, ECO:0000269|PubMed:22036843, CC ECO:0000269|PubMed:28031252, ECO:0000269|PubMed:30922174}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ubiquinone + NADH + 5 H(+)(in) = a ubiquinol + NAD(+) + 4 CC H(+)(out); Xref=Rhea:RHEA:29091, Rhea:RHEA-COMP:9565, Rhea:RHEA- CC COMP:9566, ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=7.1.1.2; CC Evidence={ECO:0000269|PubMed:22036843, ECO:0000269|PubMed:30922174}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Note=Binds 1 [4Fe-4S] cluster.; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=10.2 uM for decylubiquinone {ECO:0000269|PubMed:22036843}; CC KM=55 uM for ubiquinone-1 {ECO:0000269|PubMed:22036843}; CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex CC I) which is composed of 45 different subunits. Component of the iron- CC sulfur (IP) fragment of the enzyme (PubMed:12611891). Interacts with CC NDUFAF3 (PubMed:19463981). Interacts with NDUFAF7 (PubMed:20406883, CC PubMed:24089531). Interacts with CERS2 (By similarity). CC {ECO:0000250|UniProtKB:Q91WD5, ECO:0000269|PubMed:12611891, CC ECO:0000269|PubMed:19463981, ECO:0000269|PubMed:20406883, CC ECO:0000269|PubMed:24089531}. CC -!- INTERACTION: CC O75306; O75489: NDUFS3; NbExp=12; IntAct=EBI-1224806, EBI-1224896; CC O75306; Q99650: OSMR; NbExp=4; IntAct=EBI-1224806, EBI-2804080; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891, ECO:0000305|PubMed:9585441}; Peripheral CC membrane protein {ECO:0000250|UniProtKB:Q641Y2}; Matrix side CC {ECO:0000250|UniProtKB:Q641Y2}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O75306-1; Sequence=Displayed; CC Name=2; CC IsoId=O75306-2; Sequence=VSP_046466; CC -!- PTM: Dimethylation at Arg-118 by NDUFAF7 takes place after NDUFS2 CC assembles into the complex I, leading to stabilize the early CC intermediate complex (PubMed:24089531, PubMed:24838397). CC {ECO:0000269|PubMed:24089531, ECO:0000269|PubMed:24838397}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 6 (MC1DN6) CC [MIM:618228]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN6 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:11220739, CC ECO:0000269|PubMed:22036843}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Leber-like hereditary optic neuropathy, autosomal recessive 2 CC (LHONAR2) [MIM:620569]: An autosomal recessive form of Leber hereditary CC optic neuropathy, a mitochondrial disease resulting in bilateral CC painless loss of central vision due to selective degeneration of the CC retinal ganglion cells and their axons. LHONAR2 is characterized by CC subacute bilateral or asymmetrical visual loss, optic nerve pseudoedema CC and peripapillary telangiectasia in the early phase of the disease, and CC eventual partial recovery in some patients. CC {ECO:0000269|PubMed:28031252}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I 49 kDa subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF050640; AAC27453.1; -; mRNA. DR EMBL; AF013160; AAC34362.1; -; mRNA. DR EMBL; AK314807; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AL590714; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471121; EAW52625.1; -; Genomic_DNA. DR EMBL; CH471121; EAW52626.1; -; Genomic_DNA. DR EMBL; BC000170; AAH00170.1; -; mRNA. DR EMBL; BC001456; AAH01456.1; -; mRNA. DR EMBL; BC008868; AAH08868.1; -; mRNA. DR CCDS; CCDS1224.1; -. [O75306-1] DR CCDS; CCDS53404.1; -. [O75306-2] DR PIR; JE0193; JE0193. DR RefSeq; NP_001159631.1; NM_001166159.2. [O75306-2] DR RefSeq; NP_001364227.1; NM_001377298.1. [O75306-1] DR RefSeq; NP_001364228.1; NM_001377299.1. [O75306-1] DR RefSeq; NP_001364229.1; NM_001377300.1. [O75306-2] DR RefSeq; NP_001364230.1; NM_001377301.1. [O75306-2] DR RefSeq; NP_001364231.1; NM_001377302.1. [O75306-2] DR RefSeq; NP_004541.1; NM_004550.5. [O75306-1] DR PDB; 5XTB; EM; 3.40 A; Q=79-463. DR PDB; 5XTC; EM; 3.70 A; Q=34-79. DR PDB; 5XTD; EM; 3.70 A; Q=34-463. DR PDB; 5XTH; EM; 3.90 A; Q=34-463. DR PDB; 5XTI; EM; 17.40 A; BQ/Q=34-463. DR PDB; 9CWT; EM; 3.44 A; Q=1-463. DR PDBsum; 5XTB; -. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; O75306; -. DR EMDB; EMD-45974; -. DR SMR; O75306; -. DR BioGRID; 110800; 320. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O75306; -. DR FunCoup; O75306; 1810. DR IntAct; O75306; 112. DR MINT; O75306; -. DR STRING; 9606.ENSP00000356972; -. DR BindingDB; O75306; -. DR ChEMBL; CHEMBL3039; -. DR DrugBank; DB00997; Doxorubicin. DR DrugBank; DB00157; NADH. DR DrugCentral; O75306; -. DR GlyGen; O75306; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O75306; -. DR PhosphoSitePlus; O75306; -. DR SwissPalm; O75306; -. DR BioMuta; NDUFS2; -. DR jPOST; O75306; -. DR MassIVE; O75306; -. DR PaxDb; 9606-ENSP00000356972; -. DR PeptideAtlas; O75306; -. DR ProteomicsDB; 49883; -. [O75306-1] DR Pumba; O75306; -. DR TopDownProteomics; O75306-1; -. [O75306-1] DR Antibodypedia; 34301; 317 antibodies from 33 providers. DR DNASU; 4720; -. DR Ensembl; ENST00000367993.7; ENSP00000356972.3; ENSG00000158864.14. [O75306-1] DR Ensembl; ENST00000392179.5; ENSP00000376018.4; ENSG00000158864.14. [O75306-2] DR Ensembl; ENST00000676600.1; ENSP00000503989.1; ENSG00000158864.14. [O75306-1] DR Ensembl; ENST00000676972.1; ENSP00000503117.1; ENSG00000158864.14. [O75306-1] DR Ensembl; ENST00000677457.1; ENSP00000503294.1; ENSG00000158864.14. [O75306-2] DR Ensembl; ENST00000677550.1; ENSP00000503353.1; ENSG00000158864.14. [O75306-2] DR Ensembl; ENST00000678507.1; ENSP00000504199.1; ENSG00000158864.14. [O75306-1] DR Ensembl; ENST00000678511.1; ENSP00000504846.1; ENSG00000158864.14. [O75306-1] DR Ensembl; ENST00000678605.1; ENSP00000503969.1; ENSG00000158864.14. [O75306-2] DR Ensembl; ENST00000679176.1; ENSP00000504170.1; ENSG00000158864.14. [O75306-2] DR GeneID; 4720; -. DR KEGG; hsa:4720; -. DR MANE-Select; ENST00000676972.1; ENSP00000503117.1; NM_001377299.1; NP_001364228.1. DR UCSC; uc001fyv.4; human. [O75306-1] DR AGR; HGNC:7708; -. DR ClinPGx; PA31519; -. DR CTD; 4720; -. DR DisGeNET; 4720; -. DR GeneCards; NDUFS2; -. DR HGNC; HGNC:7708; NDUFS2. DR HPA; ENSG00000158864; Tissue enhanced (skeletal muscle, tongue). DR MalaCards; NDUFS2; -. DR MIM; 602985; gene. DR MIM; 618228; phenotype. DR MIM; 620569; phenotype. DR OpenTargets; ENSG00000158864; -. DR Orphanet; 2609; Isolated complex I deficiency. DR Orphanet; 104; Leber hereditary optic neuropathy. DR VEuPathDB; HostDB:ENSG00000158864; -. DR eggNOG; KOG2870; Eukaryota. DR GeneTree; ENSGT00390000009529; -. DR HOGENOM; CLU_015134_1_1_1; -. DR InParanoid; O75306; -. DR OMA; TRMDYLT; -. DR OrthoDB; 1009at2759; -. DR PAN-GO; O75306; 2 GO annotations based on evolutionary models. DR PhylomeDB; O75306; -. DR BioCyc; MetaCyc:HS08339-MONOMER; -. DR PathwayCommons; O75306; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; O75306; -. DR SIGNOR; O75306; -. DR Agora; ENSG00000158864; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 4720; 352 hits in 1168 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFS2; human. DR GeneWiki; NDUFS2; -. DR GenomeRNAi; 4720; -. DR Pharos; O75306; Tclin. DR PRO; PR:O75306; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O75306; protein. DR Bgee; ENSG00000158864; Expressed in apex of heart and 204 other cell types or tissues. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0009055; F:electron transfer activity; NAS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0051287; F:NAD binding; IEA:InterPro. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IMP:UniProtKB. DR GO; GO:0016651; F:oxidoreductase activity, acting on NAD(P)H; IEA:InterPro. DR GO; GO:0019826; F:oxygen sensor activity; IMP:UniProtKB. DR GO; GO:0048038; F:quinone binding; IEA:InterPro. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0071453; P:cellular response to oxygen levels; IMP:UniProtKB. DR GO; GO:0042063; P:gliogenesis; ISS:UniProtKB. DR GO; GO:0042775; P:mitochondrial ATP synthesis coupled electron transport; IMP:CAFA. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IMP:UniProtKB. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; ISS:UniProtKB. DR GO; GO:0061351; P:neural precursor cell proliferation; ISS:UniProtKB. DR GO; GO:0022008; P:neurogenesis; ISS:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR FunFam; 1.10.645.10:FF:000005; NADH-quinone oxidoreductase subunit D; 1. DR Gene3D; 1.10.645.10; Cytochrome-c3 Hydrogenase, chain B; 1. DR HAMAP; MF_01358; NDH1_NuoD; 1. DR InterPro; IPR001135; NADH_Q_OxRdtase_suD. DR InterPro; IPR014029; NADH_UbQ_OxRdtase_49kDa_CS. DR InterPro; IPR022885; NDH1_su_D/H. DR InterPro; IPR029014; NiFe-Hase_large. DR NCBIfam; TIGR01962; NuoD; 1. DR NCBIfam; NF004739; PRK06075.1; 1. DR PANTHER; PTHR11993:SF10; NADH DEHYDROGENASE [UBIQUINONE] IRON-SULFUR PROTEIN 2, MITOCHONDRIAL; 1. DR PANTHER; PTHR11993; NADH-UBIQUINONE OXIDOREDUCTASE 49 KDA SUBUNIT; 1. DR Pfam; PF00346; Complex1_49kDa; 1. DR SUPFAM; SSF56762; HydB/Nqo4-like; 1. DR PROSITE; PS00535; COMPLEX1_49K; 1. PE 1: Evidence at protein level; KW 3D-structure; 4Fe-4S; Acetylation; Alternative splicing; Disease variant; KW Electron transport; Iron; Iron-sulfur; Leber hereditary optic neuropathy; KW Membrane; Metal-binding; Methylation; Mitochondrion; KW Mitochondrion inner membrane; NAD; Oxidoreductase; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transit peptide; Translocase; KW Transport; Ubiquinone. FT TRANSIT 1..33 FT /note="Mitochondrion" FT /evidence="ECO:0000250|UniProtKB:P17694" FT CHAIN 34..463 FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein FT 2, mitochondrial" FT /id="PRO_0000019981" FT BINDING 326 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255" FT BINDING 332 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255" FT BINDING 347 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255" FT MOD_RES 62 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q91WD5" FT MOD_RES 118 FT /note="Symmetric dimethylarginine" FT /evidence="ECO:0000269|PubMed:24089531, FT ECO:0000269|PubMed:24838397" FT VAR_SEQ 454..463 FT /note="QDIVFGEVDR -> RPIV (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_046466" FT VARIANT 20 FT /note="P -> T (in dbSNP:rs11538340)" FT /id="VAR_034150" FT VARIANT 53 FT /note="Y -> C (in LHONAR2; likely pathogenic; functional FT testing in a yeast model shows decreased NADH dehydrogenase FT (ubiquinone) activity)" FT /evidence="ECO:0000269|PubMed:28031252" FT /id="VAR_089158" FT VARIANT 224 FT /note="A -> V" FT /evidence="ECO:0000269|PubMed:21057504" FT /id="VAR_071891" FT VARIANT 228 FT /note="R -> Q (in MC1DN6; dbSNP:rs121434427)" FT /evidence="ECO:0000269|PubMed:11220739" FT /id="VAR_019535" FT VARIANT 229 FT /note="P -> A (in dbSNP:rs16827493)" FT /id="VAR_034151" FT VARIANT 229 FT /note="P -> Q (in MC1DN6; dbSNP:rs121434428)" FT /evidence="ECO:0000269|PubMed:11220739" FT /id="VAR_019536" FT VARIANT 308 FT /note="Y -> C (in LHONAR2; likely pathogenic; functional FT testing in a yeast model shows decreased NADH dehydrogenase FT (ubiquinone) activity)" FT /evidence="ECO:0000269|PubMed:28031252" FT /id="VAR_089159" FT VARIANT 352 FT /note="P -> A (in dbSNP:rs11576415)" FT /id="VAR_034152" FT VARIANT 413 FT /note="S -> P (in MC1DN6; dbSNP:rs121434429)" FT /evidence="ECO:0000269|PubMed:11220739" FT /id="VAR_019537" FT VARIANT 446 FT /note="D -> N (in MC1DN6; loss of catalytic activity; no FT change in Km value for ubiquinone-1)" FT /evidence="ECO:0000269|PubMed:22036843" FT /id="VAR_084193" FT CONFLICT 24 FT /note="V -> G (in Ref. 2; AAC34362)" FT /evidence="ECO:0000305" FT STRAND 80..82 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 89..94 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 96..105 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 107..112 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 120..125 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 129..132 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 134..137 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 140..142 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 145..158 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 165..193 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 198..218 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 219..223 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 231..234 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 240..249 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 251..259 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 260..264 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 266..272 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 280..286 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 291..294 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 295..297 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 310..312 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 318..320 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 326..349 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 361..363 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 368..371 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 375..384 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 385..387 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 393..402 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 405..413 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 415..423 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 427..439 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 444..453 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 458..461 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 463 AA; 52546 MW; A2BF56F008B6312C CRC64; MAALRALCGF RGVAAQVLRP GAGVRLPIQP SRGVRQWQPD VEWAQQFGGA VMYPSKETAH WKPPPWNDVD PPKDTIVKNI TLNFGPQHPA AHGVLRLVME LSGEMVRKCD PHIGLLHRGT EKLIEYKTYL QALPYFDRLD YVSMMCNEQA YSLAVEKLLN IRPPPRAQWI RVLFGEITRL LNHIMAVTTH ALDLGAMTPF FWLFEEREKM FEFYERVSGA RMHAAYIRPG GVHQDLPLGL MDDIYQFSKN FSLRLDELEE LLTNNRIWRN RTIDIGVVTA EEALNYGFSG VMLRGSGIQW DLRKTQPYDV YDQVEFDVPV GSRGDCYDRY LCRVEEMRQS LRIIAQCLNK MPPGEIKVDD AKVSPPKRAE MKTSMESLIH HFKLYTEGYQ VPPGATYTAI EAPKGEFGVY LVSDGSSRPY RCKIKAPGFA HLAGLDKMSK GHMLADVVAI IGTQDIVFGE VDR // ID NDUS3_HUMAN Reviewed; 264 AA. AC O75489; B2R9J1; B4DFM8; Q9UNQ8; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 28-JAN-2026, entry version 226. DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial; DE EC=7.1.1.2 {ECO:0000269|PubMed:14729820, ECO:0000269|PubMed:30140060}; DE AltName: Full=Complex I-30kD; DE Short=CI-30kD; DE AltName: Full=NADH-ubiquinone oxidoreductase 30 kDa subunit; DE Flags: Precursor; GN Name=NDUFS3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9647766; DOI=10.1006/bbrc.1998.8882; RA Loeffen J., van den Heuvel L., Smeets R., Triepels R., Sengers R., RA Trijbels F., Smeitink J.; RT "cDNA sequence and chromosomal localization of the remaining three human RT nuclear encoded iron sulphur protein (IP) subunits of complex I: the human RT IP fraction is completed."; RL Biochem. Biophys. Res. Commun. 247:751-758(1998). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10967146; DOI=10.1007/s003350010160; RA Procaccio V., Lescuyer P., Bourges I., Beugnot R., Duborjal H., RA Depetris D., Mousson B., Montfort M.F., Smeets H., De Coo R., RA Issartel J.P.; RT "Human NDUFS3 gene coding for the 30-kDa subunit of mitochondrial Complex RT I: genomic organization and expression."; RL Mamm. Genome 11:808-810(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pituitary; RX PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J., RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., RA Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis RT and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Amygdala, and Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 37-51. RC TISSUE=Leukemic T-cell; RX PubMed=19892738; DOI=10.1073/pnas.0908958106; RA Xu G., Shin S.B., Jaffrey S.R.; RT "Global profiling of protease cleavage sites by chemoselective labeling of RT protein N-termini."; RL Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009). RN [9] RP PROTEIN SEQUENCE OF 126-136 AND 187-199, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Brain, and Cajal-Retzius cell; RA Lubec G., Vishwanath V.; RL Submitted (MAR-2007) to UniProtKB. RN [10] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [11] RP SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=17209039; DOI=10.1074/jbc.m609410200; RA Vogel R.O., Dieteren C.E., van den Heuvel L.P., Willems P.H., RA Smeitink J.A., Koopman W.J., Nijtmans L.G.; RT "Identification of mitochondrial complex I assembly intermediates by RT tracing tagged NDUFS3 demonstrates the entry point of mitochondrial RT subunits."; RL J. Biol. Chem. 282:7582-7590(2007). RN [12] RP SUBUNIT, SUBCELLULAR LOCATION, AND TOPOLOGY. RX PubMed=18826940; DOI=10.1074/jbc.m807323200; RA Dieteren C.E., Willems P.H., Vogel R.O., Swarts H.G., Fransen J., RA Roepman R., Crienen G., Smeitink J.A., Nijtmans L.G., Koopman W.J.; RT "Subunits of mitochondrial complex I exist as part of matrix- and membrane- RT associated subcomplexes in living cells."; RL J. Biol. Chem. 283:34753-34761(2008). RN [13] RP INTERACTION WITH NDUFAF3. RX PubMed=19463981; DOI=10.1016/j.ajhg.2009.04.020; RA Saada A., Vogel R.O., Hoefs S.J., van den Brand M.A., Wessels H.J., RA Willems P.H., Venselaar H., Shaag A., Barghuti F., Reish O., Shohat M., RA Huynen M.A., Smeitink J.A.M., van den Heuvel L.P., Nijtmans L.G.; RT "Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting RT complex I assembly protein, cause fatal neonatal mitochondrial disease."; RL Am. J. Hum. Genet. 84:718-727(2009). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH RAB5IF. RX PubMed=31536960; DOI=10.1016/j.isci.2019.08.057; RA Moutaoufik M.T., Malty R., Amin S., Zhang Q., Phanse S., Gagarinova A., RA Zilocchi M., Hoell L., Minic Z., Gagarinova M., Aoki H., Stockwell J., RA Jessulat M., Goebels F., Broderick K., Scott N.E., Vlasblom J., Musso G., RA Prasad B., Lamantea E., Garavaglia B., Rajput A., Murayama K., Okazaki Y., RA Foster L.J., Bader G.D., Cayabyab F.S., Babu M.; RT "Rewiring of the Human Mitochondrial Interactome during Neuronal RT Reprogramming Reveals Regulators of the Respirasome and Neurogenesis."; RL IScience 19:1114-1132(2019). RN [18] RP INVOLVEMENT IN MC1DN8, VARIANTS MC1DN8 ILE-145 AND TRP-199, RP CHARACTERIZATION OF VARIANTS MC1DN8 ILE-145 AND TRP-199, FUNCTION, AND RP CATALYTIC ACTIVITY. RX PubMed=14729820; DOI=10.1136/jmg.2003.014316; RA Benit P., Slama A., Cartault F., Giurgea I., Chretien D., Lebon S., RA Marsac C., Munnich A., Roetig A., Rustin P.; RT "Mutant NDUFS3 subunit of mitochondrial complex I causes Leigh syndrome."; RL J. Med. Genet. 41:14-17(2004). RN [19] RP INVOLVEMENT IN MC1DN8, AND VARIANT MC1DN8 TRP-199. RX PubMed=22499348; DOI=10.1136/jmedgenet-2012-100846; RA Haack T.B., Haberberger B., Frisch E.M., Wieland T., Iuso A., Gorza M., RA Strecker V., Graf E., Mayr J.A., Herberg U., Hennermann J.B., Klopstock T., RA Kuhn K.A., Ahting U., Sperl W., Wilichowski E., Hoffmann G.F., Tesarova M., RA Hansikova H., Zeman J., Plecko B., Zeviani M., Wittig I., Strom T.M., RA Schuelke M., Freisinger P., Meitinger T., Prokisch H.; RT "Molecular diagnosis in mitochondrial complex I deficiency using exome RT sequencing."; RL J. Med. Genet. 49:277-283(2012). RN [20] RP CHARACTERIZATION OF VARIANTS MC1DN8 ILE-145 AND TRP-199, AND FUNCTION. RX PubMed=24028823; DOI=10.1016/j.biochi.2013.08.032; RA Jaokar T.M., Patil D.P., Shouche Y.S., Gaikwad S.M., Suresh C.G.; RT "Human mitochondrial NDUFS3 protein bearing Leigh syndrome mutation is more RT prone to aggregation than its wild-type."; RL Biochimie 95:2392-2403(2013). RN [21] RP VARIANTS MC1DN8 TRP-140 AND TRP-199, CHARACTERIZATION OF VARIANTS MC1DN8 RP TRP-140 AND TRP-199, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=30140060; DOI=10.1038/s10038-018-0505-0; RA Lou X., Shi H., Wen S., Li Y., Wei X., Xie J., Ma L., Yang Y., Fang H., RA Lyu J.; RT "A Novel NDUFS3 mutation in a Chinese patient with severe Leigh syndrome."; RL J. Hum. Genet. 63:1269-1272(2018). CC -!- FUNCTION: Core subunit of the mitochondrial membrane respiratory chain CC NADH dehydrogenase (Complex I) which catalyzes electron transfer from CC NADH through the respiratory chain, using ubiquinone as an electron CC acceptor (PubMed:14729820, PubMed:30140060). Essential for the CC catalytic activity and assembly of complex I (PubMed:14729820, CC PubMed:24028823, PubMed:30140060). {ECO:0000269|PubMed:14729820, CC ECO:0000269|PubMed:24028823, ECO:0000269|PubMed:30140060}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ubiquinone + NADH + 5 H(+)(in) = a ubiquinol + NAD(+) + 4 CC H(+)(out); Xref=Rhea:RHEA:29091, Rhea:RHEA-COMP:9565, Rhea:RHEA- CC COMP:9566, ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=7.1.1.2; CC Evidence={ECO:0000269|PubMed:14729820, ECO:0000269|PubMed:30140060}; CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex CC I) which is composed of 45 different subunits (PubMed:12611891). CC Interacts with NDUFAF3 (PubMed:19463981). Interacts with RAB5IF CC (PubMed:31536960). Found in subcomplexes containing subunits NDUFS2, CC MT-ND1 and NDUFA13 (PubMed:17209039, PubMed:18826940). CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:17209039, CC ECO:0000269|PubMed:18826940, ECO:0000269|PubMed:19463981, CC ECO:0000269|PubMed:31536960}. CC -!- INTERACTION: CC O75489; Q66PJ3-4: ARL6IP4; NbExp=3; IntAct=EBI-1224896, EBI-5280499; CC O75489; Q5JUW0-3: KRBOX4; NbExp=3; IntAct=EBI-1224896, EBI-12893625; CC O75489; Q16718: NDUFA5; NbExp=13; IntAct=EBI-1224896, EBI-746417; CC O75489; P51970: NDUFA8; NbExp=5; IntAct=EBI-1224896, EBI-1237250; CC O75489; O75306: NDUFS2; NbExp=12; IntAct=EBI-1224896, EBI-1224806; CC O75489; P17152: TMEM11; NbExp=3; IntAct=EBI-1224896, EBI-723946; CC O75489; Q9H8H3: TMT1A; NbExp=3; IntAct=EBI-1224896, EBI-1390168; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:18826940, ECO:0000305|PubMed:12611891, CC ECO:0000305|PubMed:17209039}; Peripheral membrane protein CC {ECO:0000305|PubMed:18826940}; Matrix side CC {ECO:0000269|PubMed:18826940}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O75489-1; Sequence=Displayed; CC Name=2; CC IsoId=O75489-2; Sequence=VSP_057065, VSP_057066; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 8 (MC1DN8) CC [MIM:618230]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN8 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:14729820, CC ECO:0000269|PubMed:22499348, ECO:0000269|PubMed:24028823, CC ECO:0000269|PubMed:30140060}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I 30 kDa subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF067139; AAC27451.1; -; mRNA. DR EMBL; AF200954; AAG17541.1; -; Genomic_DNA. DR EMBL; AF100743; AAD40386.1; -; mRNA. DR EMBL; AK294167; BAG57489.1; -; mRNA. DR EMBL; AK313802; BAG36538.1; -; mRNA. DR EMBL; AC090559; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC104942; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471064; EAW67895.1; -; Genomic_DNA. DR EMBL; BC000617; AAH00617.1; -; mRNA. DR CCDS; CCDS7941.1; -. [O75489-1] DR PIR; JE0195; JE0195. DR RefSeq; NP_004542.1; NM_004551.3. [O75489-1] DR PDB; 5XTB; EM; 3.40 A; P=43-250. DR PDB; 5XTD; EM; 3.70 A; P=43-250. DR PDB; 5XTH; EM; 3.90 A; P=43-250. DR PDB; 5XTI; EM; 17.40 A; BP/P=43-250. DR PDB; 9CWT; EM; 3.44 A; P=1-264. DR PDBsum; 5XTB; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; O75489; -. DR EMDB; EMD-45974; -. DR SMR; O75489; -. DR BioGRID; 110801; 404. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O75489; -. DR FunCoup; O75489; 1630. DR IntAct; O75489; 215. DR MINT; O75489; -. DR STRING; 9606.ENSP00000263774; -. DR BindingDB; O75489; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00997; Doxorubicin. DR DrugBank; DB00157; NADH. DR DrugCentral; O75489; -. DR CarbonylDB; O75489; -. DR GlyCosmos; O75489; 1 site, 1 glycan. DR GlyGen; O75489; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O75489; -. DR PhosphoSitePlus; O75489; -. DR SwissPalm; O75489; -. DR BioMuta; NDUFS3; -. DR REPRODUCTION-2DPAGE; IPI00025796; -. DR REPRODUCTION-2DPAGE; O75489; -. DR CPTAC; CPTAC-100; -. DR CPTAC; CPTAC-99; -. DR jPOST; O75489; -. DR MassIVE; O75489; -. DR PaxDb; 9606-ENSP00000263774; -. DR PeptideAtlas; O75489; -. DR ProteomicsDB; 4061; -. DR ProteomicsDB; 50046; -. [O75489-1] DR Pumba; O75489; -. DR TopDownProteomics; O75489-1; -. [O75489-1] DR Antibodypedia; 1262; 314 antibodies from 35 providers. DR DNASU; 4722; -. DR Ensembl; ENST00000263774.9; ENSP00000263774.4; ENSG00000213619.12. [O75489-1] DR GeneID; 4722; -. DR KEGG; hsa:4722; -. DR MANE-Select; ENST00000263774.9; ENSP00000263774.4; NM_004551.3; NP_004542.1. DR UCSC; uc001nga.3; human. [O75489-1] DR AGR; HGNC:7710; -. DR ClinPGx; PA31520; -. DR CTD; 4722; -. DR DisGeNET; 4722; -. DR GeneCards; NDUFS3; -. DR GeneReviews; NDUFS3; -. DR HGNC; HGNC:7710; NDUFS3. DR HPA; ENSG00000213619; Tissue enhanced (skeletal). DR MalaCards; NDUFS3; -. DR MIM; 603846; gene. DR MIM; 618230; phenotype. DR OpenTargets; ENSG00000213619; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000213619; -. DR eggNOG; KOG1713; Eukaryota. DR GeneTree; ENSGT00390000017480; -. DR HOGENOM; CLU_042628_0_1_1; -. DR InParanoid; O75489; -. DR OMA; PCRKNRF; -. DR OrthoDB; 37721at2759; -. DR PAN-GO; O75489; 1 GO annotation based on evolutionary models. DR PhylomeDB; O75489; -. DR BioCyc; MetaCyc:G66-32694-MONOMER; -. DR PathwayCommons; O75489; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR Reactome; R-HSA-9013408; RHOG GTPase cycle. DR Reactome; R-HSA-9837999; Mitochondrial protein degradation. DR SignaLink; O75489; -. DR SIGNOR; O75489; -. DR Agora; ENSG00000213619; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 4722; 223 hits in 1164 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFS3; human. DR GeneWiki; NDUFS3; -. DR GenomeRNAi; 4722; -. DR Pharos; O75489; Tclin. DR PRO; PR:O75489; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; O75489; protein. DR Bgee; ENSG00000213619; Expressed in putamen and 100 other cell types or tissues. DR ExpressionAtlas; O75489; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0097228; C:sperm principal piece; IDA:HPA. DR GO; GO:0009055; F:electron transfer activity; NAS:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IMP:UniProtKB. DR GO; GO:0003954; F:NADH dehydrogenase activity; IMP:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IMP:UniProtKB. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:UniProtKB. DR GO; GO:0021762; P:substantia nigra development; HEP:UniProtKB. DR FunFam; 3.30.460.80:FF:000002; NADH dehydrogenase iron-sulfur protein 3, mitochondrial; 1. DR Gene3D; 3.30.460.80; NADH:ubiquinone oxidoreductase, 30kDa subunit; 1. DR HAMAP; MF_01357; NDH1_NuoC; 1. DR InterPro; IPR010218; NADH_DH_suC. DR InterPro; IPR037232; NADH_quin_OxRdtase_su_C/D-like. DR InterPro; IPR001268; NADH_UbQ_OxRdtase_30kDa_su. DR InterPro; IPR020396; NADH_UbQ_OxRdtase_CS. DR NCBIfam; TIGR01961; NuoC_fam; 1. DR NCBIfam; NF004733; PRK06074.1-5; 1. DR PANTHER; PTHR10884:SF14; NADH DEHYDROGENASE [UBIQUINONE] IRON-SULFUR PROTEIN 3, MITOCHONDRIAL; 1. DR PANTHER; PTHR10884; NADH DEHYDROGENASE UBIQUINONE IRON-SULFUR PROTEIN 3; 1. DR Pfam; PF00329; Complex1_30kDa; 1. DR SUPFAM; SSF143243; Nqo5-like; 1. DR PROSITE; PS00542; COMPLEX1_30K; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Direct protein sequencing; KW Disease variant; Electron transport; Membrane; Mitochondrion; KW Mitochondrion inner membrane; NAD; Oxidoreductase; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transit peptide; Translocase; KW Transport; Ubiquinone. FT TRANSIT 1..36 FT /note="Mitochondrion" FT /evidence="ECO:0000269|PubMed:19892738" FT CHAIN 37..264 FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein FT 3, mitochondrial" FT /id="PRO_0000019998" FT VAR_SEQ 128..132 FT /note="IVYNL -> VSWEI (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057065" FT VAR_SEQ 133..264 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057066" FT VARIANT 140 FT /note="R -> W (in MC1DN8; uncertain significance; decrease FT in enzyme activity; impaired assembly of complex I; FT dbSNP:rs142248674)" FT /evidence="ECO:0000269|PubMed:30140060" FT /id="VAR_081411" FT VARIANT 145 FT /note="T -> I (in MC1DN8; decrease in enzyme activity; FT increased protein instability and aggregation; compound FT heterozygous with W-199; dbSNP:rs28939714)" FT /evidence="ECO:0000269|PubMed:14729820, FT ECO:0000269|PubMed:24028823" FT /id="VAR_081412" FT VARIANT 199 FT /note="R -> W (in MC1DN8; decrease in enzyme activity; FT impaired assembly of complex I; increased protein FT instability and aggregation; compound heterozygous with I- FT 145; dbSNP:rs104894270)" FT /evidence="ECO:0000269|PubMed:14729820, FT ECO:0000269|PubMed:22499348, ECO:0000269|PubMed:24028823, FT ECO:0000269|PubMed:30140060" FT /id="VAR_081413" FT VARIANT 249 FT /note="P -> Q (in dbSNP:rs9600)" FT /id="VAR_012036" FT CONFLICT 1..7 FT /note="MAAAAVA -> MAAGRY (in Ref. 3)" FT /evidence="ECO:0000305" FT STRAND 45..47 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 52..68 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 70..72 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 76..78 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 84..87 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 90..92 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 93..101 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 113..115 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 120..124 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 129..134 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 135..138 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 139..144 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 156..160 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 162..164 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 165..172 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 178..180 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 187..189 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 207..213 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 214..217 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 218..223 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 264 AA; 30242 MW; C058D62779BEF17B CRC64; MAAAAVARLW WRGILGASAL TRGTGRPSVL LLPVRRESAG ADTRPTVRPR NDVAHKQLSA FGEYVAEILP KYVQQVQVSC FNELEVCIHP DGVIPVLTFL RDHTNAQFKS LVDLTAVDVP TRQNRFEIVY NLLSLRFNSR IRVKTYTDEL TPIESAVSVF KAANWYEREI WDMFGVFFAN HPDLRRILTD YGFEGHPFRK DFPLSGYVEL RYDDEVKRVV AEPVELAQEF RKFDLNSPWE AFPVYRQPPE SLKLEAGDKK PDAK // ID NDUS4_HUMAN Reviewed; 175 AA. AC O43181; Q9BS69; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 28-JAN-2026, entry version 203. DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial; DE AltName: Full=Complex I-18 kDa; DE Short=CI-18 kDa; DE AltName: Full=Complex I-AQDQ; DE Short=CI-AQDQ; DE AltName: Full=NADH-ubiquinone oxidoreductase 18 kDa subunit; DE Flags: Precursor; GN Name=NDUFS4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INVOLVEMENT IN MC1DN1. RX PubMed=9463323; DOI=10.1086/301716; RA van den Heuvel L., Ruitenbeek W., Smeets R., Gelman-Kohan Z., Elpeleg O., RA Loeffen J., Trijbels F., Mariman E., de Bruijn D., Smeitink J.; RT "Demonstration of a new pathogenic mutation in human complex I deficiency: RT a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit."; RL Am. J. Hum. Genet. 62:262-268(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Urinary bladder; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP FUNCTION, SUBCELLULAR LOCATION, AND VARIANT MC1DN1 15-TRP--LYS-175 DEL. RX PubMed=11181577; DOI=10.1093/hmg/10.5.529; RA Petruzzella V., Vergari R., Puzziferri I., Boffoli D., Lamantea E., RA Zeviani M., Papa S.; RT "A nonsense mutation in the NDUFS4 gene encoding the 18 kDa (AQDQ) subunit RT of complex I abolishes assembly and activity of the complex in a patient RT with Leigh-like syndrome."; RL Hum. Mol. Genet. 10:529-535(2001). RN [4] RP INVOLVEMENT IN MC1DN1. RX PubMed=12616398; DOI=10.1007/s00439-002-0884-2; RA Benit P., Steffann J., Lebon S., Chretien D., Kadhom N., de Lonlay P., RA Goldenberg A., Dumez Y., Dommergues M., Rustin P., Munnich A., Roetig A.; RT "Genotyping microsatellite DNA markers at putative disease loci in RT inbred/multiplex families with respiratory chain complex I deficiency RT allows rapid identification of a novel nonsense mutation (IVS1nt -1) in the RT NDUFS4 gene in Leigh syndrome."; RL Hum. Genet. 112:563-566(2003). RN [5] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, FUNCTION, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [6] RP INVOLVEMENT IN MC1DN1. RX PubMed=19107570; DOI=10.1007/s10545-008-1049-9; RA Anderson S.L., Chung W.K., Frezzo J., Papp J.C., Ekstein J., DiMauro S., RA Rubin B.Y.; RT "A novel mutation in NDUFS4 causes Leigh syndrome in an Ashkenazi Jewish RT family."; RL J. Inherit. Metab. Dis. 31:S461-S467(2008). RN [7] RP PHOSPHORYLATION AT SER-173, AND MUTAGENESIS OF SER-173. RX PubMed=20433953; DOI=10.1016/j.mito.2010.04.005; RA De Rasmo D., Palmisano G., Scacco S., Technikova-Dobrova Z., Panelli D., RA Cocco T., Sardanelli A.M., Gnoni A., Micelli L., Trani A., Di Luccia A., RA Papa S.; RT "Phosphorylation pattern of the NDUFS4 subunit of complex I of the RT mammalian respiratory chain."; RL Mitochondrion 10:464-471(2010). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [10] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [11] RP INTERACTION WITH TOMM40 AND BCAP31, AND SUBCELLULAR LOCATION. RX PubMed=31206022; DOI=10.1126/sciadv.aaw1386; RA Namba T.; RT "BAP31 regulates mitochondrial function via interaction with Tom40 within RT ER-mitochondria contact sites."; RL Sci. Adv. 5:eaaw1386-eaaw1386(2019). RN [12] RP VARIANTS MC1DN1 97-TRP--LYS-175 DEL AND 106-ARG--LYS-175 DEL. RX PubMed=10944442; DOI=10.1006/bbrc.2000.3257; RA Budde S.M., van den Heuvel L.P., Janssen A.J., Smeets R.J., Buskens C.A., RA DeMeirleir L., Van Coster R., Baethmann M., Voit T., Trijbels J.M., RA Smeitink J.A.; RT "Combined enzymatic complex I and III deficiency associated with mutations RT in the nuclear encoded NDUFS4 gene."; RL Biochem. Biophys. Res. Commun. 275:63-68(2000). RN [13] RP VARIANT MC1DN1 15-TRP--LYS-175 DEL. RX PubMed=15975579; DOI=10.1016/j.febslet.2005.05.035; RA Petruzzella V., Panelli D., Torraco A., Stella A., Papa S.; RT "Mutations in the NDUFS4 gene of mitochondrial complex I alter stability of RT the splice variants."; RL FEBS Lett. 579:3770-3776(2005). RN [14] RP VARIANT MC1DN1 HIS-119. RX PubMed=19364667; DOI=10.1016/j.ymgme.2009.03.002; RA Leshinsky-Silver E., Lebre A.S., Minai L., Saada A., Steffann J., Cohen S., RA Roetig A., Munnich A., Lev D., Lerman-Sagie T.; RT "NDUFS4 mutations cause Leigh syndrome with predominant brainstem RT involvement."; RL Mol. Genet. Metab. 97:185-189(2009). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis. Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:11181577, CC ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:9463323}. CC -!- SUBUNIT: Mammalian complex I is composed of 45 different subunits. This CC is a component of the iron-sulfur (IP) fragment of the enzyme. CC Interacts with BCAP31 and TOMM40; the interaction mediates its CC translocation to the mitochondria; the interaction with BCAP31 is CC direct (PubMed:31206022). {ECO:0000269|PubMed:12611891, CC ECO:0000269|PubMed:27626371, ECO:0000269|PubMed:31206022}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:11181577, ECO:0000269|PubMed:12611891, CC ECO:0000269|PubMed:31206022}; Peripheral membrane protein CC {ECO:0000269|PubMed:12611891}; Matrix side CC {ECO:0000269|PubMed:12611891}. Note=The interaction with BCAP31 CC mediates mitochondria localization. {ECO:0000269|PubMed:31206022}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 1 (MC1DN1) CC [MIM:252010]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. {ECO:0000269|PubMed:10944442, CC ECO:0000269|PubMed:11181577, ECO:0000269|PubMed:12616398, CC ECO:0000269|PubMed:15975579, ECO:0000269|PubMed:19107570, CC ECO:0000269|PubMed:19364667, ECO:0000269|PubMed:9463323}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the complex I NDUFS4 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF020351; AAB87865.1; -; mRNA. DR EMBL; BC005270; AAH05270.1; -; mRNA. DR CCDS; CCDS3960.1; -. DR RefSeq; NP_002486.1; NM_002495.4. DR PDB; 5XTB; EM; 3.40 A; L=58-175. DR PDB; 5XTD; EM; 3.70 A; L=58-175. DR PDB; 5XTH; EM; 3.90 A; L=58-175. DR PDB; 5XTI; EM; 17.40 A; BL/L=58-175. DR PDB; 9CWT; EM; 3.44 A; L=1-175. DR PDBsum; 5XTB; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; O43181; -. DR EMDB; EMD-45974; -. DR SMR; O43181; -. DR BioGRID; 110803; 206. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O43181; -. DR FunCoup; O43181; 1631. DR IntAct; O43181; 83. DR MINT; O43181; -. DR STRING; 9606.ENSP00000296684; -. DR BindingDB; O43181; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; O43181; -. DR CarbonylDB; O43181; -. DR GlyGen; O43181; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O43181; -. DR PhosphoSitePlus; O43181; -. DR BioMuta; NDUFS4; -. DR jPOST; O43181; -. DR MassIVE; O43181; -. DR PaxDb; 9606-ENSP00000296684; -. DR PeptideAtlas; O43181; -. DR ProteomicsDB; 48793; -. DR Pumba; O43181; -. DR TopDownProteomics; O43181; -. DR Antibodypedia; 1269; 307 antibodies from 35 providers. DR DNASU; 4724; -. DR Ensembl; ENST00000296684.10; ENSP00000296684.5; ENSG00000164258.13. DR GeneID; 4724; -. DR KEGG; hsa:4724; -. DR MANE-Select; ENST00000296684.10; ENSP00000296684.5; NM_002495.4; NP_002486.1. DR UCSC; uc003jpe.3; human. DR AGR; HGNC:7711; -. DR ClinPGx; PA31521; -. DR CTD; 4724; -. DR DisGeNET; 4724; -. DR GeneCards; NDUFS4; -. DR GeneReviews; NDUFS4; -. DR HGNC; HGNC:7711; NDUFS4. DR HPA; ENSG00000164258; Low tissue specificity. DR MalaCards; NDUFS4; -. DR MIM; 252010; phenotype. DR MIM; 602694; gene. DR OpenTargets; ENSG00000164258; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000164258; -. DR eggNOG; KOG3389; Eukaryota. DR GeneTree; ENSGT00390000013835; -. DR HOGENOM; CLU_077196_3_0_1; -. DR InParanoid; O43181; -. DR OMA; GTIMKFD; -. DR OrthoDB; 3089at2759; -. DR PAN-GO; O43181; 1 GO annotation based on evolutionary models. DR PhylomeDB; O43181; -. DR BioCyc; MetaCyc:ENSG00000164258-MONOMER; -. DR PathwayCommons; O43181; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; O43181; -. DR SIGNOR; O43181; -. DR Agora; ENSG00000164258; -. DR BioGRID-ORCS; 4724; 14 hits in 1158 CRISPR screens. DR ChiTaRS; NDUFS4; human. DR GeneWiki; NDUFS4; -. DR GenomeRNAi; 4724; -. DR Pharos; O43181; Tclin. DR PRO; PR:O43181; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; O43181; protein. DR Bgee; ENSG00000164258; Expressed in calcaneal tendon and 215 other cell types or tissues. DR ExpressionAtlas; O43181; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0033011; C:perinuclear theca; IDA:HPA. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0120238; C:sperm glycocalyx; IDA:HPA. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IMP:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0007420; P:brain development; IMP:UniProtKB. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; NAS:UniProtKB. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:UniProtKB. DR GO; GO:0001932; P:regulation of protein phosphorylation; IMP:MGI. DR GO; GO:0051591; P:response to cAMP; IMP:UniProtKB. DR FunFam; 3.30.160.190:FF:000001; NADH-ubiquinone oxidoreductase 21 kDa subunit mitochondrial; 1. DR Gene3D; 3.30.160.190; atu1810 like domain; 1. DR InterPro; IPR006885; NADH_UbQ_FeS_4_mit-like. DR InterPro; IPR038532; NDUFS4-like_sf. DR PANTHER; PTHR12219:SF28; NADH DEHYDROGENASE [UBIQUINONE] IRON-SULFUR PROTEIN 4, MITOCHONDRIAL; 1. DR PANTHER; PTHR12219; NADH-UBIQUINONE OXIDOREDUCTASE; 1. DR Pfam; PF04800; NDUS4; 1. PE 1: Evidence at protein level; KW 3D-structure; Disease variant; Electron transport; Membrane; Mitochondrion; KW Mitochondrion inner membrane; Phosphoprotein; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transit peptide; Transport. FT TRANSIT 1..42 FT /note="Mitochondrion" FT /evidence="ECO:0000250" FT CHAIN 43..175 FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein FT 4, mitochondrial" FT /id="PRO_0000020038" FT REGION 151..175 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 173 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:20433953" FT VARIANT 15..175 FT /note="Missing (in MC1DN1; loss of mitochondrial FT respiratory complex I; altered nonsense mediated mRNA FT decay)" FT /evidence="ECO:0000269|PubMed:11181577, FT ECO:0000269|PubMed:15975579" FT /id="VAR_078943" FT VARIANT 97..175 FT /note="Missing (in MC1DN1)" FT /evidence="ECO:0000269|PubMed:10944442" FT /id="VAR_078944" FT VARIANT 106..175 FT /note="Missing (in MC1DN1)" FT /evidence="ECO:0000269|PubMed:10944442" FT /id="VAR_078945" FT VARIANT 119 FT /note="D -> H (in MC1DN1; dbSNP:rs747359752)" FT /evidence="ECO:0000269|PubMed:19364667" FT /id="VAR_078946" FT VARIANT 174 FT /note="T -> P (in dbSNP:rs1044692)" FT /id="VAR_012037" FT MUTAGEN 173 FT /note="S->A: Loss of phosphorylation." FT /evidence="ECO:0000269|PubMed:20433953" FT CONFLICT 39 FT /note="T -> S (in Ref. 2; AAH05270)" FT /evidence="ECO:0000305" FT TURN 62..64 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 69..74 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 76..80 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 92..94 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 95..101 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 106..108 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 110..113 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 115..118 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 120..123 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 125..130 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 131..141 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 161..163 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 166..169 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 175 AA; 20108 MW; DE5B51DBDD76231E CRC64; MAAVSMSVVL RQTLWRRRAV AVAALSVSRV PTRSLRTSTW RLAQDQTQDT QLITVDEKLD ITTLTGVPEE HIKTRKVRIF VPARNNMQSG VNNTKKWKME FDTRERWENP LMGWASTADP LSNMVLTFST KEDAVSFAEK NGWSYDIEER KVPKPKSKSY GANFSWNKRT RVSTK // ID NDUS6_HUMAN Reviewed; 124 AA. AC O75380; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 28-JAN-2026, entry version 187. DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial; DE AltName: Full=Complex I-13kD-A; DE Short=CI-13kD-A; DE AltName: Full=NADH-ubiquinone oxidoreductase 13 kDa-A subunit; DE Flags: Precursor; GN Name=NDUFS6; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9647766; DOI=10.1006/bbrc.1998.8882; RA Loeffen J., van den Heuvel L., Smeets R., Triepels R., Sengers R., RA Trijbels F., Smeitink J.; RT "cDNA sequence and chromosomal localization of the remaining three human RT nuclear encoded iron sulphur protein (IP) subunits of complex I: the human RT IP fraction is completed."; RL Biochem. Biophys. Res. Commun. 247:751-758(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [4] RP INVOLVEMENT IN MC1DN9. RX PubMed=15372108; DOI=10.1172/jci20683; RA Kirby D.M., Salemi R., Sugiana C., Ohtake A., Parry L., Bell K.M., RA Kirk E.P., Boneh A., Taylor R.W., Dahl H.H., Ryan M.T., Thorburn D.R.; RT "NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial RT complex I deficiency."; RL J. Clin. Invest. 114:837-845(2004). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [8] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [9] RP VARIANT MC1DN9 TYR-115. RX PubMed=19259137; DOI=10.1038/ejhg.2009.24; RA Spiegel R., Shaag A., Mandel H., Reich D., Penyakov M., Hujeirat Y., RA Saada A., Elpeleg O., Shalev S.A.; RT "Mutated NDUFS6 is the cause of fatal neonatal lactic acidemia in Caucasus RT Jews."; RL Eur. J. Hum. Genet. 17:1200-1203(2009). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis. Complex I functions in the transfer of electrons CC from NADH to the respiratory chain. The immediate electron acceptor for CC the enzyme is believed to be ubiquinone. {ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: Mammalian complex I is composed of 45 different subunits CC (PubMed:12611891, PubMed:27626371). This is a component of the iron- CC sulfur (IP) fragment of the enzyme (PubMed:12611891). CC {ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:27626371}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891}; Peripheral membrane protein CC {ECO:0000305}; Matrix side {ECO:0000305}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 9 (MC1DN9) CC [MIM:618232]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN9 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:15372108, CC ECO:0000269|PubMed:19259137}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFS6 subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF044959; AAC27799.1; -; mRNA. DR EMBL; BC038664; AAH38664.1; -; mRNA. DR EMBL; BC046155; AAH46155.1; -; mRNA. DR CCDS; CCDS3866.1; -. DR PIR; JE0194; JE0194. DR RefSeq; NP_004544.1; NM_004553.6. DR PDB; 5XTB; EM; 3.40 A; T=29-123. DR PDB; 5XTD; EM; 3.70 A; T=29-123. DR PDB; 5XTH; EM; 3.90 A; T=29-123. DR PDB; 5XTI; EM; 17.40 A; BT/T=29-123. DR PDB; 9CWT; EM; 3.44 A; T=1-124. DR PDBsum; 5XTB; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; O75380; -. DR EMDB; EMD-45974; -. DR SMR; O75380; -. DR BioGRID; 110805; 252. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O75380; -. DR FunCoup; O75380; 1080. DR IntAct; O75380; 139. DR MINT; O75380; -. DR STRING; 9606.ENSP00000274137; -. DR BindingDB; O75380; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; O75380; -. DR GlyGen; O75380; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O75380; -. DR PhosphoSitePlus; O75380; -. DR SwissPalm; O75380; -. DR BioMuta; NDUFS6; -. DR jPOST; O75380; -. DR MassIVE; O75380; -. DR PaxDb; 9606-ENSP00000274137; -. DR PeptideAtlas; O75380; -. DR ProteomicsDB; 49952; -. DR Pumba; O75380; -. DR TopDownProteomics; O75380; -. DR Antibodypedia; 22354; 215 antibodies from 32 providers. DR DNASU; 4726; -. DR Ensembl; ENST00000274137.10; ENSP00000274137.6; ENSG00000145494.13. DR GeneID; 4726; -. DR KEGG; hsa:4726; -. DR MANE-Select; ENST00000274137.10; ENSP00000274137.6; NM_004553.6; NP_004544.1. DR AGR; HGNC:7713; -. DR ClinPGx; PA31523; -. DR CTD; 4726; -. DR DisGeNET; 4726; -. DR GeneCards; NDUFS6; -. DR HGNC; HGNC:7713; NDUFS6. DR HPA; ENSG00000145494; Tissue enhanced (skeletal). DR MalaCards; NDUFS6; -. DR MIM; 603848; gene. DR MIM; 618232; phenotype. DR OpenTargets; ENSG00000145494; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000145494; -. DR eggNOG; KOG3456; Eukaryota. DR GeneTree; ENSGT00390000015775; -. DR HOGENOM; CLU_083053_3_2_1; -. DR InParanoid; O75380; -. DR OMA; TACCDGG; -. DR OrthoDB; 307899at2759; -. DR PAN-GO; O75380; 2 GO annotations based on evolutionary models. DR PhylomeDB; O75380; -. DR BioCyc; MetaCyc:ENSG00000145494-MONOMER; -. DR PathwayCommons; O75380; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; O75380; -. DR SIGNOR; O75380; -. DR Agora; ENSG00000145494; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 4726; 15 hits in 1160 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFS6; human. DR GeneWiki; NDUFS6; -. DR GenomeRNAi; 4726; -. DR Pharos; O75380; Tclin. DR PRO; PR:O75380; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; O75380; protein. DR Bgee; ENSG00000145494; Expressed in tendon of biceps brachii and 203 other cell types or tissues. DR ExpressionAtlas; O75380; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0009055; F:electron transfer activity; NAS:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; NAS:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0090398; P:cellular senescence; IEA:Ensembl. DR GO; GO:0072359; P:circulatory system development; IEA:Ensembl. DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IEA:Ensembl. DR GO; GO:0006631; P:fatty acid metabolic process; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; IEA:Ensembl. DR GO; GO:0001822; P:kidney development; IEA:Ensembl. DR GO; GO:0072497; P:mesenchymal stem cell differentiation; IEA:Ensembl. DR GO; GO:0097168; P:mesenchymal stem cell proliferation; IEA:Ensembl. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IBA:GO_Central. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IEA:Ensembl. DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl. DR GO; GO:0006936; P:muscle contraction; IEA:Ensembl. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR GO; GO:0072593; P:reactive oxygen species metabolic process; IEA:Ensembl. DR GO; GO:0051881; P:regulation of mitochondrial membrane potential; IEA:Ensembl. DR GO; GO:0061458; P:reproductive system development; IEA:Ensembl. DR GO; GO:0017145; P:stem cell division; IEA:Ensembl. DR FunFam; 2.60.260.40:FF:000002; NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial; 1. DR Gene3D; 2.60.260.40; q5lls5 like domains; 1. DR InterPro; IPR016668; NDUFS6. DR InterPro; IPR019401; Znf_CHCC. DR PANTHER; PTHR13156:SF0; NADH DEHYDROGENASE [UBIQUINONE] IRON-SULFUR PROTEIN 6, MITOCHONDRIAL; 1. DR PANTHER; PTHR13156; NADH-UBIQUINONE OXIDOREDUCTASE 13 KD-A SUBUNIT; 1. DR Pfam; PF10276; zf-CHCC; 1. DR PIRSF; PIRSF016564; CI-13KD-A; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Disease variant; Electron transport; Membrane; KW Mitochondrion; Mitochondrion inner membrane; Primary mitochondrial disease; KW Proteomics identification; Reference proteome; Respiratory chain; KW Transit peptide; Transport. FT TRANSIT 1..28 FT /note="Mitochondrion" FT /evidence="ECO:0000250" FT CHAIN 29..124 FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein FT 6, mitochondrial" FT /id="PRO_0000020020" FT MOD_RES 98 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P52503" FT VARIANT 115 FT /note="C -> Y (in MC1DN9; dbSNP:rs267606913)" FT /evidence="ECO:0000269|PubMed:19259137" FT /id="VAR_078947" FT STRAND 36..38 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 51..56 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 68..74 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 81..83 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 85..87 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 94..96 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 99..101 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 113..115 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 124 AA; 13712 MW; 0A1465160BCA772D CRC64; MAAAMTFCRL LNRCGEAARS LPLGARCFGV RVSPTGEKVT HTGQVYDDKD YRRIRFVGRQ KEVNENFAID LIAEQPVSEV ETRVIACDGG GGALGHPKVY INLDKETKTG TCGYCGLQFR QHHH // ID NDUS7_HUMAN Reviewed; 213 AA. AC O75251; B3KRI2; Q2T9H7; Q9BV17; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 21-MAR-2006, sequence version 3. DT 28-JAN-2026, entry version 224. DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial; DE EC=7.1.1.2 {ECO:0000269|PubMed:17275378}; DE AltName: Full=Complex I-20kD; DE Short=CI-20kD; DE AltName: Full=NADH-ubiquinone oxidoreductase 20 kDa subunit; DE AltName: Full=PSST subunit {ECO:0000303|PubMed:8938450}; DE Flags: Precursor; GN Name=NDUFS7; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8938450; DOI=10.1006/geno.1996.0572; RA Hyslop S.J., Duncan A.M.V., Pitkanen S., Robinson B.H.; RT "Assignment of the PSST subunit gene of human mitochondrial complex I to RT chromosome 19p13."; RL Genomics 37:375-380(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-23. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [8] RP HYDROXYLATION AT ARG-111, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=27226634; DOI=10.1074/jbc.m116.734970; RA Rhein V.F., Carroll J., Ding S., Fearnley I.M., Walker J.E.; RT "NDUFAF5 hydroxylates NDUFS7 at an early stage in the assembly of human RT complex I."; RL J. Biol. Chem. 291:14851-14860(2016). RN [9] RP INVOLVEMENT IN MC1DN3, AND VARIANT MC1DN3 MET-122. RX PubMed=10360771; RX DOI=10.1002/1531-8249(199906)45:6<787::aid-ana13>3.0.co;2-6; RA Triepels R.H., van den Heuvel L., Loeffen J.L.C.M., Buskens C.A.F., RA Smeets R.J.P., Rubio Gozalbo M.E., Budde S.M., Mariman E.C.M., RA Wijburg F.A., Barth P.G., Trijbels J.M.F., Smeitink J.A.M.; RT "Leigh syndrome associated with a mutation in the NDUFS7 (PSST) nuclear RT encoded subunit of complex I."; RL Ann. Neurol. 45:787-790(1999). RN [10] RP INVOLVEMENT IN MC1DN3, AND VARIANT MC1DN3 MET-122. RX PubMed=10330338; DOI=10.1086/302432; RA Smeitink J., van den Heuvel L.; RT "Human mitochondrial complex I in health and disease."; RL Am. J. Hum. Genet. 64:1505-1510(1999). RN [11] RP VARIANT HIS-145, CHARACTERIZATION OF VARIANT HIS-145, FUNCTION, AND RP CATALYTIC ACTIVITY. RX PubMed=17275378; DOI=10.1016/j.ymgme.2006.12.007; RA Lebon S., Rodriguez D., Bridoux D., Zerrad A., Roetig A., Munnich A., RA Legrand A., Slama A.; RT "A novel mutation in the human complex I NDUFS7 subunit associated with RT Leigh syndrome."; RL Mol. Genet. Metab. 90:379-382(2007). CC -!- FUNCTION: Core subunit of the mitochondrial membrane respiratory chain CC NADH dehydrogenase (Complex I) which catalyzes electron transfer from CC NADH through the respiratory chain, using ubiquinone as an electron CC acceptor (PubMed:17275378). Essential for the catalytic activity of CC complex I (PubMed:17275378). {ECO:0000269|PubMed:17275378}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ubiquinone + NADH + 5 H(+)(in) = a ubiquinol + NAD(+) + 4 CC H(+)(out); Xref=Rhea:RHEA:29091, Rhea:RHEA-COMP:9565, Rhea:RHEA- CC COMP:9566, ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=7.1.1.2; CC Evidence={ECO:0000269|PubMed:17275378}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000305}; CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000305}; CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex CC I) which is composed of 45 different subunits (PubMed:12611891). This CC is a component of the iron-sulfur (IP) fragment of the enzyme (By CC similarity). {ECO:0000250|UniProtKB:P42026, CC ECO:0000269|PubMed:12611891}. CC -!- INTERACTION: CC O75251; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-719652, EBI-1055254; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P42026}; Matrix side CC {ECO:0000250|UniProtKB:P42026}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O75251-1; Sequence=Displayed; CC Name=2; CC IsoId=O75251-2; Sequence=VSP_057067; CC -!- PTM: Hydroxylated at Arg-111 by NDUFAF5 early in the pathway of CC assembly of complex I, before the formation of the juncture between CC peripheral and membrane arms. {ECO:0000269|PubMed:27226634}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 3 (MC1DN3) CC [MIM:618224]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN3 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:10330338, CC ECO:0000269|PubMed:10360771}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I 20 kDa subunit family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC27669.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK091623; BAG52394.1; -; mRNA. DR EMBL; AC005329; AAC27669.1; ALT_SEQ; Genomic_DNA. DR EMBL; BC001715; AAH01715.2; -; mRNA. DR EMBL; BC005954; AAH05954.1; -; mRNA. DR EMBL; BC111517; AAI11518.1; -; mRNA. DR CCDS; CCDS12063.1; -. [O75251-1] DR RefSeq; NP_077718.3; NM_024407.4. [O75251-1] DR PDB; 5XTB; EM; 3.40 A; C=58-213. DR PDB; 5XTD; EM; 3.70 A; C=58-213. DR PDB; 5XTH; EM; 3.90 A; C=58-213. DR PDB; 5XTI; EM; 17.40 A; BC/C=58-213. DR PDB; 9CWT; EM; 3.44 A; C=1-213. DR PDBsum; 5XTB; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; O75251; -. DR EMDB; EMD-45974; -. DR SMR; O75251; -. DR BioGRID; 131889; 326. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O75251; -. DR FunCoup; O75251; 968. DR IntAct; O75251; 142. DR MINT; O75251; -. DR STRING; 9606.ENSP00000233627; -. DR BindingDB; O75251; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00997; Doxorubicin. DR DrugBank; DB00157; NADH. DR DrugCentral; O75251; -. DR GlyGen; O75251; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O75251; -. DR MetOSite; O75251; -. DR PhosphoSitePlus; O75251; -. DR SwissPalm; O75251; -. DR BioMuta; NDUFS7; -. DR jPOST; O75251; -. DR MassIVE; O75251; -. DR PaxDb; 9606-ENSP00000233627; -. DR PeptideAtlas; O75251; -. DR ProteomicsDB; 3604; -. DR ProteomicsDB; 49873; -. [O75251-1] DR Pumba; O75251; -. DR TopDownProteomics; O75251-1; -. [O75251-1] DR Antibodypedia; 22663; 157 antibodies from 30 providers. DR DNASU; 374291; -. DR Ensembl; ENST00000233627.14; ENSP00000233627.9; ENSG00000115286.22. [O75251-1] DR Ensembl; ENST00000313408.11; ENSP00000364262.5; ENSG00000115286.22. [O75251-2] DR Ensembl; ENST00000546283.5; ENSP00000440348.1; ENSG00000115286.22. [O75251-2] DR GeneID; 374291; -. DR KEGG; hsa:374291; -. DR MANE-Select; ENST00000233627.14; ENSP00000233627.9; NM_024407.5; NP_077718.3. DR UCSC; uc060qzv.1; human. [O75251-1] DR AGR; HGNC:7714; -. DR ClinPGx; PA31524; -. DR CTD; 374291; -. DR DisGeNET; 374291; -. DR GeneCards; NDUFS7; -. DR GeneReviews; NDUFS7; -. DR HGNC; HGNC:7714; NDUFS7. DR HPA; ENSG00000115286; Tissue enhanced (skeletal). DR MalaCards; NDUFS7; -. DR MIM; 601825; gene. DR MIM; 618224; phenotype. DR OpenTargets; ENSG00000115286; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000115286; -. DR eggNOG; KOG1687; Eukaryota. DR GeneTree; ENSGT00390000006565; -. DR HOGENOM; CLU_055737_1_2_1; -. DR InParanoid; O75251; -. DR OMA; GCGGIEM; -. DR OrthoDB; 268400at2759; -. DR PAN-GO; O75251; 6 GO annotations based on evolutionary models. DR PhylomeDB; O75251; -. DR BioCyc; MetaCyc:HS03864-MONOMER; -. DR PathwayCommons; O75251; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; O75251; -. DR SIGNOR; O75251; -. DR Agora; ENSG00000115286; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 374291; 174 hits in 1162 CRISPR screens. DR ChiTaRS; NDUFS7; human. DR GeneWiki; NDUFS7; -. DR GenomeRNAi; 374291; -. DR Pharos; O75251; Tclin. DR PRO; PR:O75251; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; O75251; protein. DR Bgee; ENSG00000115286; Expressed in hindlimb stylopod muscle and 192 other cell types or tissues. DR ExpressionAtlas; O75251; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0097060; C:synaptic membrane; IEA:Ensembl. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004497; F:monooxygenase activity; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IMP:UniProtKB. DR GO; GO:0016655; F:oxidoreductase activity, acting on NAD(P)H, quinone or similar compound as acceptor; NAS:UniProtKB. DR GO; GO:0002020; F:protease binding; IEA:Ensembl. DR GO; GO:0048038; F:quinone binding; IEA:InterPro. DR GO; GO:0009060; P:aerobic respiration; IBA:GO_Central. DR GO; GO:0015990; P:electron transport coupled proton transport; IBA:GO_Central. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IMP:UniProtKB. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR FunFam; 3.40.50.12280:FF:000001; NADH-quinone oxidoreductase subunit B 2; 1. DR Gene3D; 3.40.50.12280; -; 1. DR HAMAP; MF_01356; NDH1_NuoB; 1. DR InterPro; IPR006137; NADH_UbQ_OxRdtase-like_20kDa. DR InterPro; IPR006138; NADH_UQ_OxRdtase_20Kd_su. DR NCBIfam; TIGR01957; nuoB_fam; 1. DR NCBIfam; NF005012; PRK06411.1; 1. DR PANTHER; PTHR11995; NADH DEHYDROGENASE; 1. DR PANTHER; PTHR11995:SF22; NADH DEHYDROGENASE [UBIQUINONE] IRON-SULFUR PROTEIN 7, MITOCHONDRIAL; 1. DR Pfam; PF01058; Oxidored_q6; 1. DR SUPFAM; SSF56770; HydA/Nqo6-like; 1. DR PROSITE; PS01150; COMPLEX1_20K; 1. PE 1: Evidence at protein level; KW 3D-structure; 4Fe-4S; Alternative splicing; Disease variant; KW Electron transport; Hydroxylation; Iron; Iron-sulfur; Leigh syndrome; KW Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane; NAD; KW Oxidoreductase; Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transit peptide; Translocase; KW Transport; Ubiquinone. FT TRANSIT 1..38 FT /note="Mitochondrion" FT /evidence="ECO:0000250|UniProtKB:P42026" FT CHAIN 39..213 FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein FT 7, mitochondrial" FT /id="PRO_0000020027" FT REGION 31..53 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 33..44 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 88 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255" FT BINDING 89 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255" FT BINDING 153 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255" FT BINDING 183 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255" FT MOD_RES 111 FT /note="Hydroxyarginine" FT /evidence="ECO:0000269|PubMed:27226634" FT VAR_SEQ 183..213 FT /note="CPPTAEALLYGILQLQRKIKRERRLQIWYRR -> RAGTAPPTRELETGPAP FT HGARRPL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057067" FT VARIANT 23 FT /note="P -> L (in dbSNP:rs1142530)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_014482" FT VARIANT 122 FT /note="V -> M (in MC1DN3; dbSNP:rs104894705)" FT /evidence="ECO:0000269|PubMed:10330338, FT ECO:0000269|PubMed:10360771" FT /id="VAR_008848" FT VARIANT 145 FT /note="R -> H (found in a patient with Leigh syndrome; FT uncertain significance; decrease in enzyme activity; FT dbSNP:rs121434479)" FT /evidence="ECO:0000269|PubMed:17275378" FT /id="VAR_084360" FT HELIX 60..76 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 90..96 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 99..101 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 103..106 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 114..116 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 119..121 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 128..130 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 131..140 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 151..156 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 158..160 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 162..166 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 170..172 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 187..202 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 206..211 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 213 AA; 23564 MW; B3547EA24643C1B0 CRC64; MAVLSAPGLR GFRILGLRSS VGPAVQARGV HQSVATDGPS STQPALPKAR AVAPKPSSRG EYVVAKLDDL VNWARRSSLW PMTFGLACCA VEMMHMAAPR YDMDRFGVVF RASPRQSDVM IVAGTLTNKM APALRKVYDQ MPEPRYVVSM GSCANGGGYY HYSYSVVRGC DRIVPVDIYI PGCPPTAEAL LYGILQLQRK IKRERRLQIW YRR // ID NDUS8_HUMAN Reviewed; 210 AA. AC O00217; B2RB86; Q0VDA8; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1997, sequence version 1. DT 28-JAN-2026, entry version 220. DE RecName: Full=NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial; DE EC=7.1.1.2 {ECO:0000269|PubMed:22499348}; DE AltName: Full=Complex I-23kD; DE Short=CI-23kD; DE AltName: Full=NADH-ubiquinone oxidoreductase 23 kDa subunit; DE AltName: Full=TYKY subunit; DE Flags: Precursor; GN Name=NDUFS8; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=9116042; DOI=10.1016/s0167-4781(97)00020-1; RA Procaccio V., Depetris D., Soularue P., Mattei M.-G., Lunardi J., RA Issartel J.-P.; RT "cDNA sequence and chromosomal localization of the NDUFS8 human gene coding RT for the 23 kDa subunit of the mitochondrial complex I."; RL Biochim. Biophys. Acta 1351:37-41(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=9666055; DOI=10.1016/s0378-1119(98)00275-3; RA de Sury R., Martinez P., Procaccio V., Lunardi J., Issartel J.-P.; RT "Genomic structure of the human NDUFS8 gene coding for the iron-sulfur TYKY RT subunit of the mitochondrial NADH:ubiquinone oxidoreductase."; RL Gene 215:1-10(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE NADH-UBIQUINONE RP OXIDOREDUCTASE COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH RAB5IF. RX PubMed=31536960; DOI=10.1016/j.isci.2019.08.057; RA Moutaoufik M.T., Malty R., Amin S., Zhang Q., Phanse S., Gagarinova A., RA Zilocchi M., Hoell L., Minic Z., Gagarinova M., Aoki H., Stockwell J., RA Jessulat M., Goebels F., Broderick K., Scott N.E., Vlasblom J., Musso G., RA Prasad B., Lamantea E., Garavaglia B., Rajput A., Murayama K., Okazaki Y., RA Foster L.J., Bader G.D., Cayabyab F.S., Babu M.; RT "Rewiring of the Human Mitochondrial Interactome during Neuronal RT Reprogramming Reveals Regulators of the Respirasome and Neurogenesis."; RL IScience 19:1114-1132(2019). RN [10] RP INVOLVEMENT IN MC1DN2, AND VARIANTS MC1DN2 LEU-79 AND HIS-102. RX PubMed=9837812; DOI=10.1086/302154; RA Loeffen J., Smeitink J., Triepels R., Smeets R., Schuelke M., Sengers R., RA Trijbels F., Hamel B.C.J., Mullaart R., van den Heuvel L.; RT "The first nuclear-encoded complex I mutation in a patient with Leigh RT syndrome."; RL Am. J. Hum. Genet. 63:1598-1608(1998). RN [11] RP VARIANTS MC1DN2 LEU-85 AND HIS-138. RX PubMed=15159508; DOI=10.1212/01.wnl.0000125251.56131.65; RA Procaccio V., Wallace D.C.; RT "Late-onset Leigh syndrome in a patient with mitochondrial complex I NDUFS8 RT mutations."; RL Neurology 62:1899-1901(2004). RN [12] RP VARIANT MC1DN2 CYS-18. RX PubMed=16142472; DOI=10.1007/s00109-005-0712-y; RA Hinttala R., Uusimaa J., Remes A.M., Rantala H., Hassinen I.E., Majamaa K.; RT "Sequence analysis of nuclear genes encoding functionally important complex RT I subunits in children with encephalomyopathy."; RL J. Mol. Med. 83:786-794(2005). RN [13] RP VARIANTS MC1DN2 GLN-63; TRP-77 AND ASP-159, CHARACTERIZATION OF VARIANTS RP MC1DN2 GLN-63; TRP-77 AND ASP-159, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=22499348; DOI=10.1136/jmedgenet-2012-100846; RA Haack T.B., Haberberger B., Frisch E.M., Wieland T., Iuso A., Gorza M., RA Strecker V., Graf E., Mayr J.A., Herberg U., Hennermann J.B., Klopstock T., RA Kuhn K.A., Ahting U., Sperl W., Wilichowski E., Hoffmann G.F., Tesarova M., RA Hansikova H., Zeman J., Plecko B., Zeviani M., Wittig I., Strom T.M., RA Schuelke M., Freisinger P., Meitinger T., Prokisch H.; RT "Molecular diagnosis in mitochondrial complex I deficiency using exome RT sequencing."; RL J. Med. Genet. 49:277-283(2012). CC -!- FUNCTION: Core subunit of the mitochondrial membrane respiratory chain CC NADH dehydrogenase (Complex I) which catalyzes electron transfer from CC NADH through the respiratory chain, using ubiquinone as an electron CC acceptor (PubMed:22499348). Essential for the catalytic activity and CC assembly of complex I (PubMed:22499348). {ECO:0000269|PubMed:22499348}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ubiquinone + NADH + 5 H(+)(in) = a ubiquinol + NAD(+) + 4 CC H(+)(out); Xref=Rhea:RHEA:29091, Rhea:RHEA-COMP:9565, Rhea:RHEA- CC COMP:9566, ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=7.1.1.2; CC Evidence={ECO:0000269|PubMed:22499348}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Evidence={ECO:0000250|UniProtKB:Q56224}; CC Note=Binds 2 [4Fe-4S] cluster. {ECO:0000250|UniProtKB:Q56224}; CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex CC I) which is composed of 45 different subunits (PubMed:12611891). This CC is a component of the iron-sulfur (IP) fragment of the enzyme (By CC similarity). Interacts with RAB5IF (PubMed:31536960). CC {ECO:0000250|UniProtKB:P42028, ECO:0000269|PubMed:12611891, CC ECO:0000269|PubMed:31536960}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000305|PubMed:12611891, ECO:0000305|PubMed:9666055}; Peripheral CC membrane protein {ECO:0000250|UniProtKB:P42028}; Matrix side CC {ECO:0000250|UniProtKB:P42028}. CC -!- TISSUE SPECIFICITY: Expressed in all tissues with the highest level in CC heart and skeletal muscle and the lowest level in lung. CC {ECO:0000269|PubMed:9666055}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 2 (MC1DN2) CC [MIM:618222]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN2 inheritance is autosomal recessive. CC {ECO:0000269|PubMed:15159508, ECO:0000269|PubMed:16142472, CC ECO:0000269|PubMed:22499348, ECO:0000269|PubMed:9837812}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the complex I 23 kDa subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U65579; AAB51776.1; -; mRNA. DR EMBL; AF038406; AAC34273.1; -; Genomic_DNA. DR EMBL; AK314546; BAG37133.1; -; mRNA. DR EMBL; BC119754; AAI19755.1; -; mRNA. DR CCDS; CCDS8176.1; -. DR RefSeq; NP_002487.1; NM_002496.4. DR PDB; 5XTB; EM; 3.40 A; B=35-210. DR PDB; 5XTD; EM; 3.70 A; B=35-210. DR PDB; 5XTH; EM; 3.90 A; B=35-210. DR PDB; 5XTI; EM; 17.40 A; B/BB=35-210. DR PDB; 9CWT; EM; 3.44 A; B=1-210. DR PDBsum; 5XTB; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; O00217; -. DR EMDB; EMD-45974; -. DR SMR; O00217; -. DR BioGRID; 110806; 283. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; O00217; -. DR FunCoup; O00217; 1785. DR IntAct; O00217; 78. DR MINT; O00217; -. DR STRING; 9606.ENSP00000315774; -. DR BindingDB; O00217; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; O00217; -. DR CarbonylDB; O00217; -. DR GlyGen; O00217; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O00217; -. DR PhosphoSitePlus; O00217; -. DR SwissPalm; O00217; -. DR BioMuta; NDUFS8; -. DR OGP; O00217; -. DR jPOST; O00217; -. DR MassIVE; O00217; -. DR PaxDb; 9606-ENSP00000315774; -. DR PeptideAtlas; O00217; -. DR ProteomicsDB; 47787; -. DR Pumba; O00217; -. DR TopDownProteomics; O00217; -. DR Antibodypedia; 1263; 262 antibodies from 34 providers. DR DNASU; 4728; -. DR Ensembl; ENST00000313468.10; ENSP00000315774.5; ENSG00000110717.14. DR GeneID; 4728; -. DR KEGG; hsa:4728; -. DR MANE-Select; ENST00000313468.10; ENSP00000315774.5; NM_002496.4; NP_002487.1. DR UCSC; uc001onc.4; human. DR AGR; HGNC:7715; -. DR ClinPGx; PA31525; -. DR CTD; 4728; -. DR DisGeNET; 4728; -. DR GeneCards; NDUFS8; -. DR GeneReviews; NDUFS8; -. DR HGNC; HGNC:7715; NDUFS8. DR HPA; ENSG00000110717; Low tissue specificity. DR MalaCards; NDUFS8; -. DR MIM; 602141; gene. DR MIM; 618222; phenotype. DR OpenTargets; ENSG00000110717; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000110717; -. DR eggNOG; KOG3256; Eukaryota. DR GeneTree; ENSGT00390000003049; -. DR HOGENOM; CLU_067218_5_1_1; -. DR InParanoid; O00217; -. DR OMA; WYPDFFR; -. DR OrthoDB; 204405at2759; -. DR PAN-GO; O00217; 5 GO annotations based on evolutionary models. DR PhylomeDB; O00217; -. DR BioCyc; MetaCyc:HS03332-MONOMER; -. DR PathwayCommons; O00217; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; O00217; -. DR SIGNOR; O00217; -. DR Agora; ENSG00000110717; -. DR BioGRID-ORCS; 4728; 296 hits in 1173 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR ChiTaRS; NDUFS8; human. DR GeneWiki; NDUFS8; -. DR GenomeRNAi; 4728; -. DR Pharos; O00217; Tclin. DR PRO; PR:O00217; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; O00217; protein. DR Bgee; ENSG00000110717; Expressed in apex of heart and 208 other cell types or tissues. DR ExpressionAtlas; O00217; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IMP:UniProtKB. DR GO; GO:0016651; F:oxidoreductase activity, acting on NAD(P)H; IEA:InterPro. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IMP:UniProtKB. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR FunFam; 3.30.70.3270:FF:000001; NADH-quinone oxidoreductase subunit I 1; 1. DR Gene3D; 3.30.70.3270; -; 1. DR HAMAP; MF_01351; NDH1_NuoI; 1. DR InterPro; IPR017896; 4Fe4S_Fe-S-bd. DR InterPro; IPR017900; 4Fe4S_Fe_S_CS. DR InterPro; IPR010226; NADH_quinone_OxRdtase_chainI. DR NCBIfam; TIGR01971; NuoI; 1. DR NCBIfam; NF004538; PRK05888.1-4; 1. DR NCBIfam; NF004539; PRK05888.1-5; 1. DR PANTHER; PTHR10849:SF20; NADH DEHYDROGENASE [UBIQUINONE] IRON-SULFUR PROTEIN 8, MITOCHONDRIAL; 1. DR PANTHER; PTHR10849; NADH DEHYDROGENASE UBIQUINONE IRON-SULFUR PROTEIN 8, MITOCHONDRIAL; 1. DR Pfam; PF12838; Fer4_7; 1. DR SUPFAM; SSF54862; 4Fe-4S ferredoxins; 1. DR PROSITE; PS00198; 4FE4S_FER_1; 2. DR PROSITE; PS51379; 4FE4S_FER_2; 2. PE 1: Evidence at protein level; KW 3D-structure; 4Fe-4S; Disease variant; Electron transport; Iron; KW Iron-sulfur; Membrane; Metal-binding; Mitochondrion; KW Mitochondrion inner membrane; NAD; Oxidoreductase; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Repeat; Respiratory chain; Transit peptide; KW Translocase; Transport; Ubiquinone. FT TRANSIT 1..34 FT /note="Mitochondrion" FT /evidence="ECO:0000250|UniProtKB:P42028" FT CHAIN 35..210 FT /note="NADH dehydrogenase [ubiquinone] iron-sulfur protein FT 8, mitochondrial" FT /id="PRO_0000020012" FT DOMAIN 102..131 FT /note="4Fe-4S ferredoxin-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711" FT DOMAIN 141..170 FT /note="4Fe-4S ferredoxin-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711" FT BINDING 111 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711" FT BINDING 114 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711" FT BINDING 117 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711" FT BINDING 121 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711" FT BINDING 150 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711" FT BINDING 153 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711" FT BINDING 156 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711" FT BINDING 160 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00711" FT VARIANT 18 FT /note="R -> C (in MC1DN2; uncertain significance; FT dbSNP:rs750062334)" FT /evidence="ECO:0000269|PubMed:16142472" FT /id="VAR_083603" FT VARIANT 63 FT /note="E -> Q (in MC1DN2; decrease in enzyme activity; FT impaired assembly of complex I; dbSNP:rs397514618)" FT /evidence="ECO:0000269|PubMed:22499348" FT /id="VAR_081440" FT VARIANT 77 FT /note="R -> W (in MC1DN2; uncertain significance; decrease FT in enzyme activity; impaired assembly of complex I; FT dbSNP:rs146766138)" FT /evidence="ECO:0000269|PubMed:22499348" FT /id="VAR_081441" FT VARIANT 79 FT /note="P -> L (in MC1DN2; dbSNP:rs28939679)" FT /evidence="ECO:0000269|PubMed:9837812" FT /id="VAR_019538" FT VARIANT 85 FT /note="P -> L (in MC1DN2; uncertain significance; FT dbSNP:rs121912639)" FT /evidence="ECO:0000269|PubMed:15159508" FT /id="VAR_081442" FT VARIANT 102 FT /note="R -> H (in MC1DN2; dbSNP:rs121912638)" FT /evidence="ECO:0000269|PubMed:9837812" FT /id="VAR_019539" FT VARIANT 138 FT /note="R -> H (in MC1DN2; uncertain significance; FT dbSNP:rs111033588)" FT /evidence="ECO:0000269|PubMed:15159508" FT /id="VAR_081443" FT VARIANT 159 FT /note="A -> D (in MC1DN2; uncertain significance; decrease FT in enzyme activity; impaired assembly of complex I; FT dbSNP:rs397514617)" FT /evidence="ECO:0000269|PubMed:22499348" FT /id="VAR_081444" FT STRAND 36..38 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 48..60 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 63..76 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 84..86 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 98..101 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 117..120 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 130..132 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 138..141 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 144..146 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 147..149 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 155..159 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 165..167 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 175..177 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 178..181 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 182..184 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 185..194 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 196..206 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 207..209 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 210 AA; 23705 MW; 8C3EBD205BFA0112 CRC64; MRCLTTPMLL RALAQAARAG PPGGRSLHSS AVAATYKYVN MQDPEMDMKS VTDRAARTLL WTELFRGLGM TLSYLFREPA TINYPFEKGP LSPRFRGEHA LRRYPSGEER CIACKLCEAI CPAQAITIEA EPRADGSRRT TRYDIDMTKC IYCGFCQEAC PVDAIVEGPN FEFSTETHEE LLYNKEKLLN NGDKWEAEIA ANIQADYLYR // ID NDUV1_HUMAN Reviewed; 464 AA. AC P49821; O60924; O60940; Q16104; Q6IBR3; Q96BF8; Q96HS7; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 02-MAY-2002, sequence version 4. DT 28-JAN-2026, entry version 231. DE RecName: Full=NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial; DE Short=NDUFV1 {ECO:0000303|PubMed:9571201}; DE EC=7.1.1.2 {ECO:0000305|PubMed:28844695}; DE AltName: Full=Complex I-51kD; DE Short=CI-51kD; DE AltName: Full=NADH dehydrogenase flavoprotein 1; DE AltName: Full=NADH-ubiquinone oxidoreductase 51 kDa subunit {ECO:0000303|PubMed:9571201}; DE Flags: Precursor; GN Name=NDUFV1 {ECO:0000312|HGNC:HGNC:7716}; Synonyms=UQOR1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9892733; DOI=10.1007/s003359900941; RA de Coo R.F.M., Buddiger P.A., Smeets H.J.M., van Oost B.A.; RT "The structure of the human NDUFV1 gene encoding the 51-kDa subunit of RT mitochondrial complex I."; RL Mamm. Genome 10:49-53(1999). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=9571201; DOI=10.1006/bbrc.1998.8486; RA Schuelke M., Loeffen J., Mariman E., Smeitink J., van den Heuvel L.; RT "Cloning of the human mitochondrial 51 kDa subunit (NDUFV1) reveals a 100% RT antisense homology of its 3'UTR with the 5'UTR of the gamma-interferon RT inducible protein (IP-30) precursor: is this a link between mitochondrial RT myopathy and inflammation?"; RL Biochem. Biophys. Res. Commun. 245:599-606(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pituitary; RX PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J., RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., RA Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis RT and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-130. RX PubMed=1478657; DOI=10.1016/s0888-7543(05)80144-2; RA Spencer S.R., Taylor J.B., Cowell I.G., Xia C.L., Pemble S.E., Ketterer B.; RT "The human mitochondrial NADH: ubiquinone oxidoreductase 51-kDa subunit RT maps adjacent to the glutathione S-transferase P1-1 gene on chromosome RT 11q13."; RL Genomics 14:1116-1118(1992). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 87-305. RC TISSUE=Kidney; RX PubMed=8288251; DOI=10.1006/geno.1993.1493; RA Ali S.T., Duncan A.M.V., Schappert K.T., Heng H.H.Q., Tsui L.-C., Chow W., RA Robinson B.H.; RT "Chromosomal localization of the human gene encoding the 51-kDa subunit of RT mitochondrial complex I (NDUFV1) to 11q13."; RL Genomics 18:435-439(1993). RN [9] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [13] {ECO:0007744|PDB:5XTB, ECO:0007744|PDB:5XTD, ECO:0007744|PDB:5XTH, ECO:0007744|PDB:5XTI} RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 27-457, FUNCTION, RP CATALYTIC ACTIVITY, COFACTOR, AND SUBUNIT. RX PubMed=28844695; DOI=10.1016/j.cell.2017.07.050; RA Guo R., Zong S., Wu M., Gu J., Yang M.; RT "Architecture of human mitochondrial respiratory megacomplex I2III2IV2."; RL Cell 170:1247-1257(2017). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH RAB5IF. RX PubMed=31536960; DOI=10.1016/j.isci.2019.08.057; RA Moutaoufik M.T., Malty R., Amin S., Zhang Q., Phanse S., Gagarinova A., RA Zilocchi M., Hoell L., Minic Z., Gagarinova M., Aoki H., Stockwell J., RA Jessulat M., Goebels F., Broderick K., Scott N.E., Vlasblom J., Musso G., RA Prasad B., Lamantea E., Garavaglia B., Rajput A., Murayama K., Okazaki Y., RA Foster L.J., Bader G.D., Cayabyab F.S., Babu M.; RT "Rewiring of the Human Mitochondrial Interactome during Neuronal RT Reprogramming Reveals Regulators of the Respirasome and Neurogenesis."; RL IScience 19:1114-1132(2019). RN [15] RP INVOLVEMENT IN MC1DN4, AND VARIANTS MC1DN4 VAL-341 AND MET-423. RX PubMed=10080174; DOI=10.1038/6772; RA Schuelke M., Smeitink J., Mariman E., Loeffen J., Plecko B., Trijbels F., RA Stockler-Ipsiroglu S., van den Heuvel L.; RT "Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and RT myoclonic epilepsy."; RL Nat. Genet. 21:260-261(1999). RN [16] RP INVOLVEMENT IN MC1DN4, AND VARIANT MC1DN4 LYS-214. RX PubMed=11349233; DOI=10.1086/320603; RA Benit P., Chretien D., Kadhom N., de Lonlay-Debeney P., Cormier-Daire V., RA Cabral A., Peudenier S., Rustin P., Munnich A., Roetig A.; RT "Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 RT genes in mitochondrial complex I deficiency."; RL Am. J. Hum. Genet. 68:1344-1352(2001). CC -!- FUNCTION: Core subunit of the mitochondrial membrane respiratory chain CC NADH dehydrogenase (Complex I) which catalyzes electron transfer from CC NADH through the respiratory chain, using ubiquinone as an electron CC acceptor (PubMed:28844695). Part of the peripheral arm of the enzyme, CC where the electrons from NADH are accepted by flavin mononucleotide CC (FMN) and then passed along a chain of iron-sulfur clusters by electron CC tunnelling to the final acceptor ubiquinone (PubMed:28844695). Contains CC FMN, which is the initial electron acceptor as well as one iron-sulfur CC cluster (PubMed:28844695). {ECO:0000269|PubMed:28844695}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ubiquinone + NADH + 5 H(+)(in) = a ubiquinol + NAD(+) + 4 CC H(+)(out); Xref=Rhea:RHEA:29091, Rhea:RHEA-COMP:9565, Rhea:RHEA- CC COMP:9566, ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=7.1.1.2; CC Evidence={ECO:0000305|PubMed:28844695}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29092; CC Evidence={ECO:0000305|PubMed:28844695}; CC -!- COFACTOR: CC Name=FMN; Xref=ChEBI:CHEBI:58210; CC Evidence={ECO:0000269|PubMed:28844695}; CC Note=Binds 1 FMN. {ECO:0000269|PubMed:28844695}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Evidence={ECO:0000269|PubMed:28844695}; CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000269|PubMed:28844695}; CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex CC I) which is composed of 45 different subunits (PubMed:12611891, CC PubMed:28844695). This is a component of the flavoprotein-sulfur (FP) CC fragment of the enzyme (PubMed:12611891). Interacts with RAB5IF CC (PubMed:31536960). {ECO:0000269|PubMed:12611891, CC ECO:0000269|PubMed:28844695, ECO:0000269|PubMed:31536960}. CC -!- INTERACTION: CC P49821; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-748312, EBI-2875816; CC P49821; Q9Y297: BTRC; NbExp=3; IntAct=EBI-748312, EBI-307461; CC P49821; P61201: COPS2; NbExp=3; IntAct=EBI-748312, EBI-1050386; CC P49821; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-748312, EBI-3867333; CC P49821; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-748312, EBI-8468186; CC P49821; Q8TCJ0-3: FBXO25; NbExp=3; IntAct=EBI-748312, EBI-6262578; CC P49821; Q6P3S6: FBXO42; NbExp=3; IntAct=EBI-748312, EBI-2506081; CC P49821; Q92993: KAT5; NbExp=3; IntAct=EBI-748312, EBI-399080; CC P49821; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-748312, EBI-11742507; CC P49821; P41218: MNDA; NbExp=3; IntAct=EBI-748312, EBI-2829677; CC P49821; P56181: NDUFV3; NbExp=5; IntAct=EBI-748312, EBI-721902; CC P49821; Q96CV9-2: OPTN; NbExp=3; IntAct=EBI-748312, EBI-9091423; CC P49821; P17252: PRKCA; NbExp=3; IntAct=EBI-748312, EBI-1383528; CC P49821; P25788-2: PSMA3; NbExp=3; IntAct=EBI-748312, EBI-348394; CC P49821; P20618: PSMB1; NbExp=3; IntAct=EBI-748312, EBI-372273; CC P49821; Q16401: PSMD5; NbExp=3; IntAct=EBI-748312, EBI-752143; CC P49821; Q7Z6E9-3: RBBP6; NbExp=3; IntAct=EBI-748312, EBI-11743772; CC P49821; Q9H871: RMND5A; NbExp=3; IntAct=EBI-748312, EBI-2797992; CC P49821; Q9NTX7-2: RNF146; NbExp=3; IntAct=EBI-748312, EBI-11750630; CC P49821; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-748312, EBI-9090795; CC P49821; Q2TAY7: SMU1; NbExp=3; IntAct=EBI-748312, EBI-298027; CC P49821; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-748312, EBI-11959123; CC P49821; Q8WUA7-2: TBC1D22A; NbExp=3; IntAct=EBI-748312, EBI-21575846; CC P49821; Q96B65: USP25; NbExp=3; IntAct=EBI-748312, EBI-25876491; CC P49821; P45880: VDAC2; NbExp=3; IntAct=EBI-748312, EBI-354022; CC P49821; P61981: YWHAG; NbExp=3; IntAct=EBI-748312, EBI-359832; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000250|UniProtKB:P25708}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P25708}; Matrix side CC {ECO:0000250|UniProtKB:P25708}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P49821-1; Sequence=Displayed; CC Name=2; CC IsoId=P49821-2; Sequence=VSP_003730; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 4 (MC1DN4) CC [MIM:618225]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN4 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:10080174, CC ECO:0000269|PubMed:11349233}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I 51 kDa subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y17379; CAA76757.1; -; Genomic_DNA. DR EMBL; Y17380; CAA76757.1; JOINED; Genomic_DNA. DR EMBL; Y17381; CAA76757.1; JOINED; Genomic_DNA. DR EMBL; Y17382; CAA76757.1; JOINED; Genomic_DNA. DR EMBL; Y17383; CAA76757.1; JOINED; Genomic_DNA. DR EMBL; AF053069; AAC39750.1; -; Genomic_DNA. DR EMBL; AF053070; AAC39722.1; -; mRNA. DR EMBL; AF092131; AAD40373.1; -; mRNA. DR EMBL; CR456739; CAG33020.1; -; mRNA. DR EMBL; CH471076; EAW74655.1; -; Genomic_DNA. DR EMBL; BC008146; AAH08146.1; -; mRNA. DR EMBL; BC015645; AAH15645.1; -; mRNA. DR EMBL; AH004147; AAB24883.1; -; Genomic_DNA. DR EMBL; S67973; AAB29698.2; ALT_SEQ; mRNA. DR CCDS; CCDS53669.1; -. [P49821-2] DR CCDS; CCDS8173.1; -. [P49821-1] DR PIR; JE0092; JE0092. DR RefSeq; NP_001159574.1; NM_001166102.2. [P49821-2] DR RefSeq; NP_009034.2; NM_007103.3. [P49821-1] DR PDB; 5XTB; EM; 3.40 A; A=27-457. DR PDB; 5XTD; EM; 3.70 A; A=27-457. DR PDB; 5XTH; EM; 3.90 A; A=27-457. DR PDB; 5XTI; EM; 17.40 A; A/BA=27-457. DR PDB; 9CWT; EM; 3.44 A; A=1-464. DR PDBsum; 5XTB; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; P49821; -. DR EMDB; EMD-45974; -. DR SMR; P49821; -. DR BioGRID; 110802; 323. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; P49821; -. DR FunCoup; P49821; 2357. DR IntAct; P49821; 110. DR MINT; P49821; -. DR STRING; 9606.ENSP00000497587; -. DR BindingDB; P49821; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; P49821; -. DR CarbonylDB; P49821; -. DR GlyGen; P49821; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P49821; -. DR PhosphoSitePlus; P49821; -. DR SwissPalm; P49821; -. DR BioMuta; NDUFV1; -. DR DMDM; 20455501; -. DR REPRODUCTION-2DPAGE; IPI00028520; -. DR REPRODUCTION-2DPAGE; IPI00221298; -. DR jPOST; P49821; -. DR MassIVE; P49821; -. DR PaxDb; 9606-ENSP00000322450; -. DR PeptideAtlas; P49821; -. DR ProteomicsDB; 56148; -. [P49821-1] DR ProteomicsDB; 56149; -. [P49821-2] DR Pumba; P49821; -. DR Antibodypedia; 30465; 258 antibodies from 30 providers. DR DNASU; 4723; -. DR Ensembl; ENST00000322776.11; ENSP00000322450.6; ENSG00000167792.14. [P49821-1] DR Ensembl; ENST00000529927.5; ENSP00000436766.1; ENSG00000167792.14. [P49821-2] DR Ensembl; ENST00000647561.1; ENSP00000497587.1; ENSG00000167792.14. [P49821-1] DR GeneID; 4723; -. DR KEGG; hsa:4723; -. DR MANE-Select; ENST00000322776.11; ENSP00000322450.6; NM_007103.4; NP_009034.2. DR UCSC; uc001omj.3; human. [P49821-1] DR AGR; HGNC:7716; -. DR ClinPGx; PA31526; -. DR CTD; 4723; -. DR DisGeNET; 4723; -. DR GeneCards; NDUFV1; -. DR GeneReviews; NDUFV1; -. DR HGNC; HGNC:7716; NDUFV1. DR HPA; ENSG00000167792; Low tissue specificity. DR MalaCards; NDUFV1; -. DR MIM; 161015; gene. DR MIM; 618225; phenotype. DR OpenTargets; ENSG00000167792; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000167792; -. DR eggNOG; KOG2658; Eukaryota. DR GeneTree; ENSGT00390000010641; -. DR HOGENOM; CLU_014881_0_1_1; -. DR InParanoid; P49821; -. DR OMA; QGDGKPH; -. DR OrthoDB; 42889at2759; -. DR PAN-GO; P49821; 2 GO annotations based on evolutionary models. DR PhylomeDB; P49821; -. DR BioCyc; MetaCyc:HS09641-MONOMER; -. DR PathwayCommons; P49821; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR Reactome; R-HSA-9837999; Mitochondrial protein degradation. DR SignaLink; P49821; -. DR SIGNOR; P49821; -. DR Agora; ENSG00000167792; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 4723; 188 hits in 1175 CRISPR screens. DR ChiTaRS; NDUFV1; human. DR GeneWiki; NDUFV1; -. DR GenomeRNAi; 4723; -. DR Pharos; P49821; Tclin. DR PRO; PR:P49821; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P49821; protein. DR Bgee; ENSG00000167792; Expressed in apex of heart and 201 other cell types or tissues. DR ExpressionAtlas; P49821; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0010181; F:FMN binding; IEA:InterPro. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0051287; F:NAD binding; IEA:InterPro. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IDA:UniProtKB. DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0042775; P:mitochondrial ATP synthesis coupled electron transport; IMP:CAFA. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IDA:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR FunFam; 1.20.1440.230:FF:000001; Mitochondrial NADH dehydrogenase flavoprotein 1; 1. DR FunFam; 3.10.20.600:FF:000001; NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial; 1. DR FunFam; 3.40.50.11540:FF:000001; NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial; 1. DR Gene3D; 3.10.20.600; -; 1. DR Gene3D; 3.40.50.11540; NADH-ubiquinone oxidoreductase 51kDa subunit; 1. DR Gene3D; 1.20.1440.230; NADH-ubiquinone oxidoreductase 51kDa subunit, iron-sulphur binding domain; 1. DR InterPro; IPR050837; ComplexI_51kDa_subunit. DR InterPro; IPR001949; NADH-UbQ_OxRdtase_51kDa_CS. DR InterPro; IPR011537; NADH-UbQ_OxRdtase_suF. DR InterPro; IPR011538; Nuo51_FMN-bd. DR InterPro; IPR037225; Nuo51_FMN-bd_sf. DR InterPro; IPR019575; Nuop51_4Fe4S-bd. DR InterPro; IPR037207; Nuop51_4Fe4S-bd_sf. DR InterPro; IPR054765; SLBB_dom. DR NCBIfam; TIGR01959; nuoF_fam; 1. DR NCBIfam; NF010120; PRK13596.1; 1. DR PANTHER; PTHR11780:SF10; NADH DEHYDROGENASE [UBIQUINONE] FLAVOPROTEIN 1, MITOCHONDRIAL; 1. DR PANTHER; PTHR11780; NADH-UBIQUINONE OXIDOREDUCTASE FLAVOPROTEIN 1 NDUFV1; 1. DR Pfam; PF01512; Complex1_51K; 1. DR Pfam; PF10589; NADH_4Fe-4S; 1. DR Pfam; PF22461; SLBB_2; 1. DR SMART; SM00928; NADH_4Fe-4S; 1. DR SUPFAM; SSF142019; Nqo1 FMN-binding domain-like; 1. DR SUPFAM; SSF142984; Nqo1 middle domain-like; 1. DR SUPFAM; SSF140490; Nqo1C-terminal domain-like; 1. DR PROSITE; PS00644; COMPLEX1_51K_1; 1. DR PROSITE; PS00645; COMPLEX1_51K_2; 1. PE 1: Evidence at protein level; KW 3D-structure; 4Fe-4S; Acetylation; Alternative splicing; Disease variant; KW Electron transport; Flavoprotein; FMN; Iron; Iron-sulfur; Leigh syndrome; KW Membrane; Metal-binding; Methylation; Mitochondrion; KW Mitochondrion inner membrane; NAD; Oxidoreductase; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transit peptide; Translocase; KW Transport; Ubiquinone. FT TRANSIT 1..20 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 21..464 FT /note="NADH dehydrogenase [ubiquinone] flavoprotein 1, FT mitochondrial" FT /id="PRO_0000019976" FT BINDING 87..96 FT /ligand="NADH" FT /ligand_id="ChEBI:CHEBI:57945" FT /evidence="ECO:0000250" FT BINDING 199..247 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250" FT BINDING 379 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000269|PubMed:28844695, FT ECO:0007744|PDB:5XTB, ECO:0007744|PDB:5XTD, FT ECO:0007744|PDB:5XTH, ECO:0007744|PDB:5XTI" FT BINDING 382 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000269|PubMed:28844695, FT ECO:0007744|PDB:5XTB, ECO:0007744|PDB:5XTD, FT ECO:0007744|PDB:5XTH, ECO:0007744|PDB:5XTI" FT BINDING 385 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000269|PubMed:28844695, FT ECO:0007744|PDB:5XTB, ECO:0007744|PDB:5XTD, FT ECO:0007744|PDB:5XTH, ECO:0007744|PDB:5XTI" FT BINDING 425 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000269|PubMed:28844695, FT ECO:0007744|PDB:5XTB, ECO:0007744|PDB:5XTD, FT ECO:0007744|PDB:5XTH, ECO:0007744|PDB:5XTI" FT MOD_RES 81 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q91YT0" FT MOD_RES 81 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:Q91YT0" FT MOD_RES 104 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q91YT0" FT MOD_RES 257 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q91YT0" FT MOD_RES 375 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q91YT0" FT VAR_SEQ 16..24 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_003730" FT VARIANT 76 FT /note="I -> V (in dbSNP:rs1800670)" FT /id="VAR_014480" FT VARIANT 214 FT /note="E -> K (in MC1DN4; dbSNP:rs121913661)" FT /evidence="ECO:0000269|PubMed:11349233" FT /id="VAR_019534" FT VARIANT 277 FT /note="N -> Y (in dbSNP:rs1043770)" FT /id="VAR_014481" FT VARIANT 341 FT /note="A -> V (in MC1DN4; dbSNP:rs121913660)" FT /evidence="ECO:0000269|PubMed:10080174" FT /id="VAR_008846" FT VARIANT 423 FT /note="T -> M (in MC1DN4; dbSNP:rs121913659)" FT /evidence="ECO:0000269|PubMed:10080174" FT /id="VAR_008847" FT CONFLICT 80 FT /note="I -> V (in Ref. 7; AAB24883)" FT /evidence="ECO:0000305" FT CONFLICT 150 FT /note="G -> A (in Ref. 8; AAB29698)" FT /evidence="ECO:0000305" FT CONFLICT 306 FT /note="G -> F (in Ref. 1; CAA76757)" FT /evidence="ECO:0000305" FT CONFLICT 313 FT /note="N -> Y (in Ref. 1; CAA76757)" FT /evidence="ECO:0000305" FT TURN 37..39 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 53..58 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 59..68 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 75..81 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 82..84 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 88..91 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 95..100 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 101..103 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 114..116 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 126..133 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 135..149 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 152..158 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 164..178 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 181..183 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 186..188 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 193..199 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 204..207 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 209..216 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 230..232 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 235..237 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 242..244 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 245..256 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 259..263 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 265..268 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 272..284 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 286..291 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 296..301 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 302..304 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 311..313 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 314..322 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 329..332 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 336..338 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 339..344 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 350..352 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 353..358 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 364..376 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 383..401 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 408..419 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 420..422 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 423..425 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 427..454 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 464 AA; 50817 MW; 8C261EA3B0267256 CRC64; MLATRRLLGW SLPARVSVRF SGDTTAPKKT SFGSLKDEDR IFTNLYGRHD WRLKGSLSRG DWYKTKEILL KGPDWILGEI KTSGLRGRGG AGFPTGLKWS FMNKPSDGRP KYLVVNADEG EPGTCKDREI LRHDPHKLLE GCLVGGRAMG ARAAYIYIRG EFYNEASNLQ VAIREAYEAG LIGKNACGSG YDFDVFVVRG AGAYICGEET ALIESIEGKQ GKPRLKPPFP ADVGVFGCPT TVANVETVAV SPTICRRGGT WFAGFGRERN SGTKLFNISG HVNHPCTVEE EMSVPLKELI EKHAGGVTGG WDNLLAVIPG GSSTPLIPKS VCETVLMDFD ALVQAQTGLG TAAVIVMDRS TDIVKAIARL IEFYKHESCG QCTPCREGVD WMNKVMARFV RGDARPAEID SLWEISKQIE GHTICALGDG AAWPVQGLIR HFRPELEERM QRFAQQHQAR QAAS // ID NDUV2_HUMAN Reviewed; 249 AA. AC P19404; Q9BV41; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 02-MAY-2002, sequence version 2. DT 28-JAN-2026, entry version 242. DE RecName: Full=NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial {ECO:0000303|PubMed:12754703}; DE Short=NDUFV2 {ECO:0000303|PubMed:12754703}; DE EC=7.1.1.2 {ECO:0000305|PubMed:28844695}; DE AltName: Full=NADH-ubiquinone oxidoreductase 24 kDa subunit; DE Flags: Precursor; GN Name=NDUFV2 {ECO:0000312|HGNC:HGNC:7717}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-29. RX PubMed=2500970; DOI=10.1021/bi00434a021; RA Pilkington S.J., Walker J.E.; RT "Mitochondrial NADH-ubiquinone reductase: complementary DNA sequences of RT import precursors of the bovine and human 24-kDa subunit."; RL Biochemistry 28:3257-3264(1989). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [5] RP PHOSPHORYLATION AT TYR-193. RX PubMed=22823520; DOI=10.1042/bj20120509; RA Ogura M., Yamaki J., Homma M.K., Homma Y.; RT "Mitochondrial c-Src regulates cell survival through phosphorylation of RT respiratory chain components."; RL Biochem. J. 447:281-289(2012). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [7] RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER ASN-32, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [8] RP INVOLVEMENT IN MC1DN7. RX PubMed=12754703; DOI=10.1002/humu.10225; RA Benit P., Beugnot R., Chretien D., Giurgea I., De Lonlay-Debeney P., RA Issartel J.P., Corral-Debrinski M., Kerscher S., Rustin P., Roetig A., RA Munnich A.; RT "Mutant NDUFV2 subunit of mitochondrial complex I causes early onset RT hypertrophic cardiomyopathy and encephalopathy."; RL Hum. Mutat. 21:582-586(2003). RN [9] RP INVOLVEMENT IN MC1DN7. RX PubMed=26008862; DOI=10.1016/j.ejpn.2015.05.002; RA Cameron J.M., MacKay N., Feigenbaum A., Tarnopolsky M., Blaser S., RA Robinson B.H., Schulze A.; RT "Exome sequencing identifies complex I NDUFV2 mutations as a novel cause of RT Leigh syndrome."; RL Eur. J. Paediatr. Neurol. 19:525-532(2015). RN [10] {ECO:0007744|PDB:5XTB, ECO:0007744|PDB:5XTD, ECO:0007744|PDB:5XTH, ECO:0007744|PDB:5XTI} RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 36-247, FUNCTION, RP CATALYTIC ACTIVITY, AND COFACTOR. RX PubMed=28844695; DOI=10.1016/j.cell.2017.07.050; RA Guo R., Zong S., Wu M., Gu J., Yang M.; RT "Architecture of human mitochondrial respiratory megacomplex I2III2IV2."; RL Cell 170:1247-1257(2017). CC -!- FUNCTION: Core subunit of the mitochondrial membrane respiratory chain CC NADH dehydrogenase (Complex I) which catalyzes electron transfer from CC NADH through the respiratory chain, using ubiquinone as an electron CC acceptor (Probable). Parts of the peripheral arm of the enzyme, where CC the electrons from NADH are accepted by flavin mononucleotide (FMN) and CC then passed along a chain of iron-sulfur clusters by electron CC tunnelling to the final acceptor ubiquinone (Probable). Contains one CC iron-sulfur cluster (Probable). {ECO:0000305|PubMed:28844695}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ubiquinone + NADH + 5 H(+)(in) = a ubiquinol + NAD(+) + 4 CC H(+)(out); Xref=Rhea:RHEA:29091, Rhea:RHEA-COMP:9565, Rhea:RHEA- CC COMP:9566, ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=7.1.1.2; CC Evidence={ECO:0000305|PubMed:28844695}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:29092; CC Evidence={ECO:0000305|PubMed:28844695}; CC -!- COFACTOR: CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135; CC Evidence={ECO:0000269|PubMed:28844695}; CC Note=Binds 1 [2Fe-2S] cluster. {ECO:0000269|PubMed:28844695}; CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex CC I) which is composed of 45 different subunits. This is a component of CC the flavoprotein-sulfur (FP) fragment of the enzyme. CC {ECO:0000269|PubMed:12611891}. CC -!- INTERACTION: CC P19404; P63010-2: AP2B1; NbExp=3; IntAct=EBI-713665, EBI-11529439; CC P19404; Q9BZZ5-2: API5; NbExp=3; IntAct=EBI-713665, EBI-10989614; CC P19404; P05067: APP; NbExp=3; IntAct=EBI-713665, EBI-77613; CC P19404; Q9Y575-3: ASB3; NbExp=3; IntAct=EBI-713665, EBI-14199987; CC P19404; Q96FT7-4: ASIC4; NbExp=3; IntAct=EBI-713665, EBI-9089489; CC P19404; Q8WXF7: ATL1; NbExp=3; IntAct=EBI-713665, EBI-2410266; CC P19404; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-713665, EBI-2837444; CC P19404; P62158: CALM3; NbExp=3; IntAct=EBI-713665, EBI-397435; CC P19404; P24863: CCNC; NbExp=7; IntAct=EBI-713665, EBI-395261; CC P19404; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-713665, EBI-350590; CC P19404; Q96HD1-2: CRELD1; NbExp=3; IntAct=EBI-713665, EBI-21536433; CC P19404; Q8IUI8: CRLF3; NbExp=3; IntAct=EBI-713665, EBI-2872414; CC P19404; P35222: CTNNB1; NbExp=3; IntAct=EBI-713665, EBI-491549; CC P19404; Q96EY1-3: DNAJA3; NbExp=3; IntAct=EBI-713665, EBI-11526226; CC P19404; P20042: EIF2S2; NbExp=3; IntAct=EBI-713665, EBI-711977; CC P19404; Q9NRY5: FAM114A2; NbExp=3; IntAct=EBI-713665, EBI-10973142; CC P19404; O15287: FANCG; NbExp=3; IntAct=EBI-713665, EBI-81610; CC P19404; Q9Y261-2: FOXA2; NbExp=3; IntAct=EBI-713665, EBI-25830360; CC P19404; P06241-3: FYN; NbExp=3; IntAct=EBI-713665, EBI-10691738; CC P19404; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-713665, EBI-712073; CC P19404; Q7L7L0: H2AC25; NbExp=3; IntAct=EBI-713665, EBI-5325551; CC P19404; Q71DI3: H3C15; NbExp=3; IntAct=EBI-713665, EBI-750650; CC P19404; P61978: HNRNPK; NbExp=3; IntAct=EBI-713665, EBI-304185; CC P19404; Q8IWL3: HSCB; NbExp=6; IntAct=EBI-713665, EBI-1805738; CC P19404; Q92613: JADE3; NbExp=3; IntAct=EBI-713665, EBI-10278909; CC P19404; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-713665, EBI-714379; CC P19404; Q14525: KRT33B; NbExp=3; IntAct=EBI-713665, EBI-1049638; CC P19404; Q96PV6: LENG8; NbExp=3; IntAct=EBI-713665, EBI-739546; CC P19404; Q6DKI2: LGALS9C; NbExp=3; IntAct=EBI-713665, EBI-9088829; CC P19404; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-713665, EBI-739832; CC P19404; P43356: MAGEA2B; NbExp=3; IntAct=EBI-713665, EBI-5650739; CC P19404; Q8N6F8: METTL27; NbExp=3; IntAct=EBI-713665, EBI-8487781; CC P19404; Q9Y3D2: MSRB2; NbExp=3; IntAct=EBI-713665, EBI-9092052; CC P19404; Q99457: NAP1L3; NbExp=3; IntAct=EBI-713665, EBI-8645631; CC P19404; Q6X4W1-6: NSMF; NbExp=3; IntAct=EBI-713665, EBI-25842707; CC P19404; O15381-5: NVL; NbExp=3; IntAct=EBI-713665, EBI-18577082; CC P19404; Q16625: OCLN; NbExp=3; IntAct=EBI-713665, EBI-2903088; CC P19404; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-713665, EBI-1058491; CC P19404; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-713665, EBI-25830200; CC P19404; P32242: OTX1; NbExp=3; IntAct=EBI-713665, EBI-740446; CC P19404; Q8N7B6-2: PACRGL; NbExp=3; IntAct=EBI-713665, EBI-10694433; CC P19404; Q16549: PCSK7; NbExp=3; IntAct=EBI-713665, EBI-8059854; CC P19404; Q5T2W1: PDZK1; NbExp=3; IntAct=EBI-713665, EBI-349819; CC P19404; Q5T6S3: PHF19; NbExp=3; IntAct=EBI-713665, EBI-2339674; CC P19404; O75925: PIAS1; NbExp=3; IntAct=EBI-713665, EBI-629434; CC P19404; Q6P1J6-2: PLB1; NbExp=3; IntAct=EBI-713665, EBI-10694821; CC P19404; Q96I34: PPP1R16A; NbExp=3; IntAct=EBI-713665, EBI-710402; CC P19404; Q6ZMI0-5: PPP1R21; NbExp=3; IntAct=EBI-713665, EBI-25835994; CC P19404; P57729: RAB38; NbExp=3; IntAct=EBI-713665, EBI-6552718; CC P19404; Q96QF0-7: RAB3IP; NbExp=3; IntAct=EBI-713665, EBI-11984839; CC P19404; Q9NS23-4: RASSF1; NbExp=6; IntAct=EBI-713665, EBI-438710; CC P19404; Q8WWW0-2: RASSF5; NbExp=3; IntAct=EBI-713665, EBI-960502; CC P19404; P57052: RBM11; NbExp=3; IntAct=EBI-713665, EBI-741332; CC P19404; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-713665, EBI-25829984; CC P19404; Q96D59: RNF183; NbExp=3; IntAct=EBI-713665, EBI-743938; CC P19404; Q8N6K7-2: SAMD3; NbExp=3; IntAct=EBI-713665, EBI-11528848; CC P19404; Q6AZY7-2: SCARA3; NbExp=3; IntAct=EBI-713665, EBI-21598366; CC P19404; Q9GZS3: SKIC8; NbExp=3; IntAct=EBI-713665, EBI-358545; CC P19404; O95391: SLU7; NbExp=3; IntAct=EBI-713665, EBI-750559; CC P19404; Q12824: SMARCB1; NbExp=3; IntAct=EBI-713665, EBI-358419; CC P19404; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-713665, EBI-358489; CC P19404; Q92673: SORL1; NbExp=3; IntAct=EBI-713665, EBI-1171329; CC P19404; Q8NHS9: SPATA22; NbExp=3; IntAct=EBI-713665, EBI-7067260; CC P19404; Q8IUW3: SPATA2L; NbExp=3; IntAct=EBI-713665, EBI-2510414; CC P19404; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-713665, EBI-5235340; CC P19404; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-713665, EBI-7082156; CC P19404; Q9BR01-2: SULT4A1; NbExp=3; IntAct=EBI-713665, EBI-25831443; CC P19404; Q9NVV9: THAP1; NbExp=3; IntAct=EBI-713665, EBI-741515; CC P19404; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-713665, EBI-11525489; CC P19404; Q86UV6-2: TRIM74; NbExp=3; IntAct=EBI-713665, EBI-10259086; CC P19404; P07437: TUBB; NbExp=3; IntAct=EBI-713665, EBI-350864; CC P19404; Q5VYS8-5: TUT7; NbExp=3; IntAct=EBI-713665, EBI-9088812; CC P19404; P10599: TXN; NbExp=3; IntAct=EBI-713665, EBI-594644; CC P19404; O75436: VPS26A; NbExp=3; IntAct=EBI-713665, EBI-1043891; CC P19404; P58304: VSX2; NbExp=3; IntAct=EBI-713665, EBI-6427899; CC P19404; Q9BRX9: WDR83; NbExp=3; IntAct=EBI-713665, EBI-7705033; CC P19404; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-713665, EBI-12040603; CC P19404; P17023: ZNF19; NbExp=3; IntAct=EBI-713665, EBI-12884200; CC P19404; Q9UNY5: ZNF232; NbExp=3; IntAct=EBI-713665, EBI-749023; CC P19404; Q86VK4-3: ZNF410; NbExp=3; IntAct=EBI-713665, EBI-11741890; CC P19404; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-713665, EBI-12010736; CC P19404; P10073: ZSCAN22; NbExp=3; IntAct=EBI-713665, EBI-10178224; CC P19404; Q86V28; NbExp=3; IntAct=EBI-713665, EBI-10259496; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000250|UniProtKB:P04394}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P04394}; Matrix side CC {ECO:0000250|UniProtKB:P04394}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 7 (MC1DN7) CC [MIM:618229]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN7 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:12754703, CC ECO:0000269|PubMed:26008862}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the complex I 24 kDa subunit family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M22538; AAA75390.1; -; mRNA. DR EMBL; BC001632; AAH01632.1; -; mRNA. DR EMBL; BC017487; AAH17487.1; -; mRNA. DR CCDS; CCDS11842.1; -. DR PIR; A30113; A30113. DR RefSeq; NP_066552.2; NM_021074.5. DR PDB; 5XTB; EM; 3.40 A; O=36-247. DR PDB; 5XTD; EM; 3.70 A; O=36-247. DR PDB; 5XTH; EM; 3.90 A; O=36-247. DR PDB; 5XTI; EM; 17.40 A; BO/O=36-247. DR PDB; 9CWT; EM; 3.44 A; O=1-249. DR PDBsum; 5XTB; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; P19404; -. DR EMDB; EMD-45974; -. DR SMR; P19404; -. DR BioGRID; 110807; 229. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; P19404; -. DR FunCoup; P19404; 1676. DR IntAct; P19404; 174. DR MINT; P19404; -. DR STRING; 9606.ENSP00000327268; -. DR BindingDB; P19404; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB00157; NADH. DR DrugCentral; P19404; -. DR GlyGen; P19404; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P19404; -. DR PhosphoSitePlus; P19404; -. DR SwissPalm; P19404; -. DR BioMuta; NDUFV2; -. DR DMDM; 20455499; -. DR jPOST; P19404; -. DR MassIVE; P19404; -. DR PaxDb; 9606-ENSP00000327268; -. DR PeptideAtlas; P19404; -. DR ProteomicsDB; 53655; -. DR Pumba; P19404; -. DR TopDownProteomics; P19404; -. DR Antibodypedia; 1273; 282 antibodies from 33 providers. DR DNASU; 4729; -. DR Ensembl; ENST00000318388.11; ENSP00000327268.6; ENSG00000178127.14. DR GeneID; 4729; -. DR KEGG; hsa:4729; -. DR MANE-Select; ENST00000318388.11; ENSP00000327268.6; NM_021074.5; NP_066552.2. DR UCSC; uc002knu.3; human. DR AGR; HGNC:7717; -. DR ClinPGx; PA31527; -. DR CTD; 4729; -. DR DisGeNET; 4729; -. DR GeneCards; NDUFV2; -. DR HGNC; HGNC:7717; NDUFV2. DR HPA; ENSG00000178127; Tissue enhanced (skeletal). DR MalaCards; NDUFV2; -. DR MIM; 600532; gene. DR MIM; 618229; phenotype. DR OpenTargets; ENSG00000178127; -. DR Orphanet; 2609; Isolated complex I deficiency. DR Orphanet; 139447; Progressive cavitating leukoencephalopathy. DR VEuPathDB; HostDB:ENSG00000178127; -. DR eggNOG; KOG3196; Eukaryota. DR GeneTree; ENSGT00390000017580; -. DR HOGENOM; CLU_054362_1_0_1; -. DR InParanoid; P19404; -. DR OMA; IMSIYPE; -. DR OrthoDB; 10254187at2759; -. DR PAN-GO; P19404; 2 GO annotations based on evolutionary models. DR PhylomeDB; P19404; -. DR BioCyc; MetaCyc:HS11253-MONOMER; -. DR PathwayCommons; P19404; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; P19404; -. DR SIGNOR; P19404; -. DR Agora; ENSG00000178127; -. DR BioGRID-ORCS; 4729; 135 hits in 1173 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; NDUFV2; human. DR GeneWiki; NDUFV2; -. DR GenomeRNAi; 4729; -. DR Pharos; P19404; Tclin. DR PRO; PR:P19404; -. DR Proteomes; UP000005640; Chromosome 18. DR RNAct; P19404; protein. DR Bgee; ENSG00000178127; Expressed in apex of heart and 100 other cell types or tissues. DR ExpressionAtlas; P19404; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IEA:UniProtKB-KW. DR GO; GO:0009055; F:electron transfer activity; NAS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IDA:UniProtKB. DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0048738; P:cardiac muscle tissue development; IMP:UniProtKB. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IDA:UniProtKB. DR GO; GO:0007399; P:nervous system development; IMP:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR CDD; cd03064; TRX_Fd_NuoE; 1. DR FunFam; 3.40.30.10:FF:000022; NADH dehydrogenase flavoprotein 2, mitochondrial; 1. DR FunFam; 1.10.10.1590:FF:000001; NADH-quinone oxidoreductase subunit E; 1. DR Gene3D; 3.40.30.10; Glutaredoxin; 1. DR Gene3D; 1.10.10.1590; NADH-quinone oxidoreductase subunit E; 1. DR InterPro; IPR002023; NuoE-like. DR InterPro; IPR042128; NuoE_dom. DR InterPro; IPR041921; NuoE_N. DR InterPro; IPR036249; Thioredoxin-like_sf. DR NCBIfam; TIGR01958; nuoE_fam; 1. DR NCBIfam; NF005722; PRK07539.1-2; 1. DR NCBIfam; NF005725; PRK07539.1-5; 1. DR PANTHER; PTHR10371:SF3; NADH DEHYDROGENASE [UBIQUINONE] FLAVOPROTEIN 2, MITOCHONDRIAL; 1. DR PANTHER; PTHR10371; NADH DEHYDROGENASE UBIQUINONE FLAVOPROTEIN 2, MITOCHONDRIAL; 1. DR Pfam; PF01257; 2Fe-2S_thioredx; 1. DR PIRSF; PIRSF000216; NADH_DH_24kDa; 1. DR SUPFAM; SSF52833; Thioredoxin-like; 1. DR PROSITE; PS01099; COMPLEX1_24K; 1. PE 1: Evidence at protein level; KW 2Fe-2S; 3D-structure; Acetylation; Electron transport; Iron; Iron-sulfur; KW Membrane; Metal-binding; Mitochondrion; Mitochondrion inner membrane; NAD; KW Oxidoreductase; Phosphoprotein; Primary mitochondrial disease; KW Proteomics identification; Reference proteome; Respiratory chain; KW Transit peptide; Translocase; Transport; Ubiquinone. FT TRANSIT 1..32 FT /note="Mitochondrion" FT /evidence="ECO:0007744|PubMed:25944712" FT CHAIN 33..249 FT /note="NADH dehydrogenase [ubiquinone] flavoprotein 2, FT mitochondrial" FT /id="PRO_0000020003" FT REGION 213..249 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 135 FT /ligand="[2Fe-2S] cluster" FT /ligand_id="ChEBI:CHEBI:190135" FT /evidence="ECO:0000250|UniProtKB:P04394" FT BINDING 140 FT /ligand="[2Fe-2S] cluster" FT /ligand_id="ChEBI:CHEBI:190135" FT /evidence="ECO:0000250|UniProtKB:P04394" FT BINDING 176 FT /ligand="[2Fe-2S] cluster" FT /ligand_id="ChEBI:CHEBI:190135" FT /evidence="ECO:0007744|PDB:5XTB, ECO:0007744|PDB:5XTD, FT ECO:0007744|PDB:5XTH, ECO:0007744|PDB:5XTI" FT BINDING 180 FT /ligand="[2Fe-2S] cluster" FT /ligand_id="ChEBI:CHEBI:190135" FT /evidence="ECO:0007744|PDB:5XTB, ECO:0007744|PDB:5XTD, FT ECO:0007744|PDB:5XTH, ECO:0007744|PDB:5XTI" FT MOD_RES 61 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9D6J6" FT MOD_RES 193 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:22823520" FT VARIANT 29 FT /note="V -> A (in dbSNP:rs906807)" FT /evidence="ECO:0000269|PubMed:2500970" FT /id="VAR_016167" FT STRAND 48..50 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 57..69 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 75..78 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 79..88 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 95..104 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 109..118 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 138..141 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 142..144 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 145..156 FT /evidence="ECO:0007829|PDB:5XTB" FT TURN 180..182 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 188..190 FT /evidence="ECO:0007829|PDB:5XTB" FT HELIX 198..208 FT /evidence="ECO:0007829|PDB:5XTB" FT STRAND 217..221 FT /evidence="ECO:0007829|PDB:5XTB" SQ SEQUENCE 249 AA; 27392 MW; AAF46ABB0908B177 CRC64; MFFSAALRAR AAGLTAHWGR HVRNLHKTVM QNGAGGALFV HRDTPENNPD TPFDFTPENY KRIEAIVKNY PEGHKAAAVL PVLDLAQRQN GWLPISAMNK VAEVLQVPPM RVYEVATFYT MYNRKPVGKY HIQVCTTTPC MLRNSDSILE AIQKKLGIKV GETTPDKLFT LIEVECLGAC VNAPMVQIND NYYEDLTAKD IEEIIDELKA GKIPKPGPRS GRFSCEPAGG LTSLTEPPKG PGFGVQAGL // ID NU3M_HUMAN Reviewed; 115 AA. AC P03897; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 28-JAN-2026, entry version 192. DE RecName: Full=NADH-ubiquinone oxidoreductase chain 3 {ECO:0000305}; DE EC=7.1.1.2 {ECO:0000269|PubMed:25118196}; DE AltName: Full=NADH dehydrogenase subunit 3; GN Name=MT-ND3 {ECO:0000312|HGNC:HGNC:7458}; Synonyms=MTND3, NADH3, ND3; OS Homo sapiens (Human). OG Mitochondrion. OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=7219534; DOI=10.1038/290457a0; RA Anderson S., Bankier A.T., Barrell B.G., de Bruijn M.H.L., Coulson A.R., RA Drouin J., Eperon I.C., Nierlich D.P., Roe B.A., Sanger F., Schreier P.H., RA Smith A.J.H., Staden R., Young I.G.; RT "Sequence and organization of the human mitochondrial genome."; RL Nature 290:457-465(1981). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=12949126; DOI=10.1093/molbev/msg230; RA Moilanen J.S., Finnila S., Majamaa K.; RT "Lineage-specific selection in human mtDNA: lack of polymorphisms in a RT segment of MTND5 gene in haplogroup J."; RL Mol. Biol. Evol. 20:2132-2142(2003). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11130070; DOI=10.1038/35047064; RA Ingman M., Kaessmann H., Paeaebo S., Gyllensten U.; RT "Mitochondrial genome variation and the origin of modern humans."; RL Nature 408:708-713(2000). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=12840039; DOI=10.1101/gr.686603; RA Ingman M., Gyllensten U.; RT "Mitochondrial genome variation and evolutionary history of Australian and RT New Guinean aborigines."; RL Genome Res. 13:1600-1606(2003). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=14760490; DOI=10.1007/s00414-004-0427-6; RA Coble M.D., Just R.S., O'Callaghan J.E., Letmanyi I.H., Peterson C.T., RA Irwin J.A., Parsons T.J.; RT "Single nucleotide polymorphisms over the entire mtDNA genome that increase RT the power of forensic testing in Caucasians."; RL Int. J. Legal Med. 118:137-146(2004). RN [6] RP IDENTIFICATION OF PROTEIN. RX PubMed=3921850; DOI=10.1038/314592a0; RA Chomyn A., Mariottini P., Cleeter M.W.J., Ragan C.I., Matsuno-Yagi A., RA Hatefi Y., Doolittle R.F., Attardi G.; RT "Six unidentified reading frames of human mitochondrial DNA encode RT components of the respiratory-chain NADH dehydrogenase."; RL Nature 314:592-597(1985). RN [7] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP INTERACTION WITH TMEM186. RX PubMed=32320651; DOI=10.1016/j.celrep.2020.107541; RA Formosa L.E., Muellner-Wong L., Reljic B., Sharpe A.J., Jackson T.D., RA Beilharz T.H., Stojanovski D., Lazarou M., Stroud D.A., Ryan M.T.; RT "Dissecting the Roles of Mitochondrial Complex I Intermediate Assembly RT Complex Factors in the Biogenesis of Complex I."; RL Cell Rep. 31:107541-107541(2020). RN [10] RP INTERACTION WITH TMEM242. RX PubMed=33753518; DOI=10.1073/pnas.2100558118; RA Carroll J., He J., Ding S., Fearnley I.M., Walker J.E.; RT "TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase RT and interact with assembly factors for complex I."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). RN [11] RP VARIANTS ASP-10 AND ALA-114. RX PubMed=6343397; DOI=10.1016/s0021-9258(20)81969-3; RA Oliver N.A., Greenberg B.D., Wallace D.C.; RT "Assignment of a polymorphic polypeptide to the human mitochondrial DNA RT unidentified reading frame 3 gene by a new peptide mapping strategy."; RL J. Biol. Chem. 258:5834-5839(1983). RN [12] RP VARIANTS VAL-53 AND ALA-114. RX PubMed=1757091; DOI=10.1007/bf00206061; RA Marzuki S., Noer A.S., Lertrit P., Thyagarajan D., Kapsa R., RA Utthanaphol P., Byrne E.; RT "Normal variants of human mitochondrial DNA and translation products: the RT building of a reference data base."; RL Hum. Genet. 88:139-145(1991). RN [13] RP VARIANT MC1DM1 PRO-45. RX PubMed=11456298; DOI=10.1002/ana.1084; RA Taylor R.W., Singh-Kler R., Hayes C.M., Smith P.E., Turnbull D.M.; RT "Progressive mitochondrial disease resulting from a novel missense mutation RT in the mitochondrial DNA ND3 gene."; RL Ann. Neurol. 50:104-107(2001). RN [14] RP VARIANT MC1DM1 PRO-34. RX PubMed=14705112; DOI=10.1002/ana.10787; RA McFarland R., Kirby D.M., Fowler K.J., Ohtake A., Ryan M.T., Amor D.J., RA Fletcher J.M., Dixon J.W., Collins F.A., Turnbull D.M., Taylor R.W., RA Thorburn D.R.; RT "De novo mutations in the mitochondrial ND3 gene as a cause of infantile RT mitochondrial encephalopathy and complex I deficiency."; RL Ann. Neurol. 55:58-64(2004). RN [15] RP VARIANT LS THR-47. RX PubMed=17152068; DOI=10.1002/ajmg.a.31565; RA Sarzi E., Brown M.D., Lebon S., Chretien D., Munnich A., Rotig A., RA Procaccio V.; RT "A novel recurrent mitochondrial DNA mutation in ND3 gene is associated RT with isolated complex I deficiency causing Leigh syndrome and dystonia."; RL Am. J. Med. Genet. A 143:33-41(2007). RN [16] RP VARIANTS MC1DM1 PRO-34; PRO-45 AND THR-47. RX PubMed=20818383; DOI=10.1038/ng.659; RA Calvo S.E., Tucker E.J., Compton A.G., Kirby D.M., Crawford G., Burtt N.P., RA Rivas M., Guiducci C., Bruno D.L., Goldberger O.A., Redman M.C., RA Wiltshire E., Wilson C.J., Altshuler D., Gabriel S.B., Daly M.J., RA Thorburn D.R., Mootha V.K.; RT "High-throughput, pooled sequencing identifies mutations in NUBPL and RT FOXRED1 in human complex I deficiency."; RL Nat. Genet. 42:851-858(2010). RN [17] RP VARIANT LS LYS-26, CHARACTERIZATION OF VARIANT LS LYS-26, FUNCTION, AND RP CATALYTIC ACTIVITY. RX PubMed=25118196; DOI=10.1371/journal.pone.0104879; RA Miller D.K., Menezes M.J., Simons C., Riley L.G., Cooper S.T., RA Grimmond S.M., Thorburn D.R., Christodoulou J., Taft R.J.; RT "Rapid identification of a novel complex I MT-ND3 m.10134C>A mutation in a RT Leigh syndrome patient."; RL PLoS ONE 9:e104879-e104879(2014). CC -!- FUNCTION: Core subunit of the mitochondrial membrane respiratory chain CC NADH dehydrogenase (Complex I) which catalyzes electron transfer from CC NADH through the respiratory chain, using ubiquinone as an electron CC acceptor (PubMed:25118196). Essential for the catalytic activity of CC complex I (PubMed:25118196). {ECO:0000269|PubMed:25118196}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a ubiquinone + NADH + 5 H(+)(in) = a ubiquinol + NAD(+) + 4 CC H(+)(out); Xref=Rhea:RHEA:29091, Rhea:RHEA-COMP:9565, Rhea:RHEA- CC COMP:9566, ChEBI:CHEBI:15378, ChEBI:CHEBI:16389, ChEBI:CHEBI:17976, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=7.1.1.2; CC Evidence={ECO:0000269|PubMed:25118196}; CC -!- SUBUNIT: Core subunit of respiratory chain NADH dehydrogenase (Complex CC I) which is composed of 45 different subunits (PubMed:12611891). CC Interacts with TMEM186 (PubMed:32320651). Interacts with TMEM242 CC (PubMed:33753518). {ECO:0000269|PubMed:12611891, CC ECO:0000269|PubMed:32320651, ECO:0000269|PubMed:33753518}. CC -!- INTERACTION: CC P03897; PRO_0000000092 [P05067]: APP; NbExp=2; IntAct=EBI-1246249, EBI-821758; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000250|UniProtKB:P03898}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- DISEASE: Leigh syndrome (LS) [MIM:256000]: An early-onset progressive CC neurodegenerative disorder characterized by the presence of focal, CC bilateral lesions in one or more areas of the central nervous system CC including the brainstem, thalamus, basal ganglia, cerebellum and spinal CC cord. Clinical features depend on which areas of the central nervous CC system are involved and include subacute onset of psychomotor CC retardation, hypotonia, ataxia, weakness, vision loss, eye movement CC abnormalities, seizures, and dysphagia. {ECO:0000269|PubMed:17152068, CC ECO:0000269|PubMed:25118196}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Mitochondrial complex I deficiency, mitochondrial type 1 CC (MC1DM1) [MIM:500014]: A form of mitochondrial complex I deficiency, CC the most common biochemical signature of mitochondrial disorders, a CC group of highly heterogeneous conditions characterized by defective CC oxidative phosphorylation, which collectively affects 1 in 5-10000 live CC births. Clinical disorders have variable severity, ranging from lethal CC neonatal disease to adult-onset neurodegenerative disorders. Phenotypes CC include macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. {ECO:0000269|PubMed:11456298, CC ECO:0000269|PubMed:14705112, ECO:0000269|PubMed:20818383}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the complex I subunit 3 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J01415; AAB58950.1; -; Genomic_DNA. DR EMBL; V00662; CAA24033.1; -; Genomic_DNA. DR EMBL; AY339402; AAP89043.1; -; Genomic_DNA. DR EMBL; AY339403; AAP89056.1; -; Genomic_DNA. DR EMBL; AY339404; AAP89069.1; -; Genomic_DNA. DR EMBL; AY339405; AAP89082.1; -; Genomic_DNA. DR EMBL; AY339406; AAP89095.1; -; Genomic_DNA. DR EMBL; AY339407; AAP89108.1; -; Genomic_DNA. DR EMBL; AY339408; AAP89121.1; -; Genomic_DNA. DR EMBL; AY339409; AAP89134.1; -; Genomic_DNA. DR EMBL; AY339410; AAP89147.1; -; Genomic_DNA. DR EMBL; AY339411; AAP89160.1; -; Genomic_DNA. DR EMBL; AY339412; AAP89173.1; -; Genomic_DNA. DR EMBL; AY339413; AAP89186.1; -; Genomic_DNA. DR EMBL; AY339414; AAP89199.1; -; Genomic_DNA. DR EMBL; AY339415; AAP89212.1; -; Genomic_DNA. DR EMBL; AY339416; AAP89225.1; -; Genomic_DNA. DR EMBL; AY339417; AAP89238.1; -; Genomic_DNA. DR EMBL; AY339418; AAP89251.1; -; Genomic_DNA. DR EMBL; AY339419; AAP89264.1; -; Genomic_DNA. DR EMBL; AY339420; AAP89277.1; -; Genomic_DNA. DR EMBL; AY339421; AAP89290.1; -; Genomic_DNA. DR EMBL; AY339422; AAP89303.1; -; Genomic_DNA. DR EMBL; AY339423; AAP89316.1; -; Genomic_DNA. DR EMBL; AY339424; AAP89329.1; -; Genomic_DNA. DR EMBL; AY339425; AAP89342.1; -; Genomic_DNA. DR EMBL; AY339426; AAP89355.1; -; Genomic_DNA. DR EMBL; AY339427; AAP89368.1; -; Genomic_DNA. DR EMBL; AY339428; AAP89381.1; -; Genomic_DNA. DR EMBL; AY339429; AAP89394.1; -; Genomic_DNA. DR EMBL; AY339430; AAP89407.1; -; Genomic_DNA. DR EMBL; AY339431; AAP89420.1; -; Genomic_DNA. DR EMBL; AY339432; AAP89433.1; -; Genomic_DNA. DR EMBL; AY339433; AAP89446.1; -; Genomic_DNA. DR EMBL; AY339434; AAP89459.1; -; Genomic_DNA. DR EMBL; AY339435; AAP89472.1; -; Genomic_DNA. DR EMBL; AY339436; AAP89485.1; -; Genomic_DNA. DR EMBL; AY339437; AAP89498.1; -; Genomic_DNA. DR EMBL; AY339438; AAP89511.1; -; Genomic_DNA. DR EMBL; AY339439; AAP89524.1; -; Genomic_DNA. DR EMBL; AY339440; AAP89537.1; -; Genomic_DNA. DR EMBL; AY339441; AAP89550.1; -; Genomic_DNA. DR EMBL; AY339442; AAP89563.1; -; Genomic_DNA. DR EMBL; AY339443; AAP89576.1; -; Genomic_DNA. DR EMBL; AY339444; AAP89589.1; -; Genomic_DNA. DR EMBL; AY339445; AAP89602.1; -; Genomic_DNA. DR EMBL; AY339446; AAP89615.1; -; Genomic_DNA. DR EMBL; AY339447; AAP89628.1; -; Genomic_DNA. DR EMBL; AY339448; AAP89641.1; -; Genomic_DNA. DR EMBL; AY339449; AAP89654.1; -; Genomic_DNA. DR EMBL; AY339450; AAP89667.1; -; Genomic_DNA. DR EMBL; AY339451; AAP89680.1; -; Genomic_DNA. DR EMBL; AY339452; AAP89693.1; -; Genomic_DNA. DR EMBL; AY339453; AAP89706.1; -; Genomic_DNA. DR EMBL; AY339454; AAP89719.1; -; Genomic_DNA. DR EMBL; AY339455; AAP89732.1; -; Genomic_DNA. DR EMBL; AY339456; AAP89745.1; -; Genomic_DNA. DR EMBL; AY339457; AAP89758.1; -; Genomic_DNA. DR EMBL; AY339458; AAP89771.1; -; Genomic_DNA. DR EMBL; AY339459; AAP89784.1; -; Genomic_DNA. DR EMBL; AY339460; AAP89797.1; -; Genomic_DNA. DR EMBL; AY339461; AAP89810.1; -; Genomic_DNA. DR EMBL; AY339462; AAP89823.1; -; Genomic_DNA. DR EMBL; AY339463; AAP89836.1; -; Genomic_DNA. DR EMBL; AY339464; AAP89849.1; -; Genomic_DNA. DR EMBL; AY339465; AAP89862.1; -; Genomic_DNA. DR EMBL; AY339475; AAP89992.1; -; Genomic_DNA. DR EMBL; AY339476; AAP90005.1; -; Genomic_DNA. DR EMBL; AY339477; AAP90018.1; -; Genomic_DNA. DR EMBL; AY339478; AAP90031.1; -; Genomic_DNA. DR EMBL; AY339479; AAP90044.1; -; Genomic_DNA. DR EMBL; AY339480; AAP90057.1; -; Genomic_DNA. DR EMBL; AY339481; AAP90070.1; -; Genomic_DNA. DR EMBL; AY339482; AAP90083.1; -; Genomic_DNA. DR EMBL; AY339483; AAP90096.1; -; Genomic_DNA. DR EMBL; AY339484; AAP90109.1; -; Genomic_DNA. DR EMBL; AY339485; AAP90122.1; -; Genomic_DNA. DR EMBL; AY339486; AAP90135.1; -; Genomic_DNA. DR EMBL; AY339487; AAP90148.1; -; Genomic_DNA. DR EMBL; AY339488; AAP90161.1; -; Genomic_DNA. DR EMBL; AY339489; AAP90174.1; -; Genomic_DNA. DR EMBL; AY339490; AAP90187.1; -; Genomic_DNA. DR EMBL; AY339491; AAP90200.1; -; Genomic_DNA. DR EMBL; AY339492; AAP90213.1; -; Genomic_DNA. DR EMBL; AY339493; AAP90226.1; -; Genomic_DNA. DR EMBL; AY339494; AAP90239.1; -; Genomic_DNA. DR EMBL; AY339495; AAP90252.1; -; Genomic_DNA. DR EMBL; AY339496; AAP90265.1; -; Genomic_DNA. DR EMBL; AY339510; AAP90447.1; -; Genomic_DNA. DR EMBL; AY339511; AAP90460.1; -; Genomic_DNA. DR EMBL; AY339512; AAP90473.1; -; Genomic_DNA. DR EMBL; AY339513; AAP90486.1; -; Genomic_DNA. DR EMBL; AY339523; AAP90616.1; -; Genomic_DNA. DR EMBL; AY339524; AAP90629.1; -; Genomic_DNA. DR EMBL; AY339525; AAP90642.1; -; Genomic_DNA. DR EMBL; AY339526; AAP90655.1; -; Genomic_DNA. DR EMBL; AY339527; AAP90668.1; -; Genomic_DNA. DR EMBL; AY339528; AAP90681.1; -; Genomic_DNA. DR EMBL; AY339529; AAP90694.1; -; Genomic_DNA. DR EMBL; AY339530; AAP90707.1; -; Genomic_DNA. DR EMBL; AY339531; AAP90720.1; -; Genomic_DNA. DR EMBL; AY339532; AAP90733.1; -; Genomic_DNA. DR EMBL; AY339533; AAP90746.1; -; Genomic_DNA. DR EMBL; AY339534; AAP90759.1; -; Genomic_DNA. DR EMBL; AY339535; AAP90772.1; -; Genomic_DNA. DR EMBL; AY339536; AAP90785.1; -; Genomic_DNA. DR EMBL; AY339537; AAP90798.1; -; Genomic_DNA. DR EMBL; AY339538; AAP90811.1; -; Genomic_DNA. DR EMBL; AY339539; AAP90824.1; -; Genomic_DNA. DR EMBL; AY339540; AAP90837.1; -; Genomic_DNA. DR EMBL; AY339541; AAP90850.1; -; Genomic_DNA. DR EMBL; AY339542; AAP90863.1; -; Genomic_DNA. DR EMBL; AY339543; AAP90876.1; -; Genomic_DNA. DR EMBL; AY339544; AAP90889.1; -; Genomic_DNA. DR EMBL; AY339545; AAP90902.1; -; Genomic_DNA. DR EMBL; AY339546; AAP90915.1; -; Genomic_DNA. DR EMBL; AY339549; AAP90954.1; -; Genomic_DNA. DR EMBL; AY339550; AAP90967.1; -; Genomic_DNA. DR EMBL; AY339551; AAP90980.1; -; Genomic_DNA. DR EMBL; AY339552; AAP90993.1; -; Genomic_DNA. DR EMBL; AY339553; AAP91006.1; -; Genomic_DNA. DR EMBL; AY339566; AAP91175.1; -; Genomic_DNA. DR EMBL; AY339567; AAP91188.1; -; Genomic_DNA. DR EMBL; AY339568; AAP91201.1; -; Genomic_DNA. DR EMBL; AY339569; AAP91214.1; -; Genomic_DNA. DR EMBL; AY339570; AAP91227.1; -; Genomic_DNA. DR EMBL; AY339571; AAP91240.1; -; Genomic_DNA. DR EMBL; AY339572; AAP91253.1; -; Genomic_DNA. DR EMBL; AY339573; AAP91266.1; -; Genomic_DNA. DR EMBL; AY339574; AAP91279.1; -; Genomic_DNA. DR EMBL; AF346963; AAK17214.1; -; Genomic_DNA. DR EMBL; AF346964; AAK17227.2; -; Genomic_DNA. DR EMBL; AF346971; AAK17318.2; -; Genomic_DNA. DR EMBL; AF346973; AAK17344.2; -; Genomic_DNA. DR EMBL; AF346974; AAK17357.2; -; Genomic_DNA. DR EMBL; AF346975; AAK17370.2; -; Genomic_DNA. DR EMBL; AF346978; AAK17409.1; -; Genomic_DNA. DR EMBL; AF346981; AAK17448.2; -; Genomic_DNA. DR EMBL; AF346982; AAK17461.1; -; Genomic_DNA. DR EMBL; AF346988; AAK17539.1; -; Genomic_DNA. DR EMBL; AF346993; AAK17604.2; -; Genomic_DNA. DR EMBL; AF347001; AAK17708.2; -; Genomic_DNA. DR EMBL; AF347002; AAK17721.2; -; Genomic_DNA. DR EMBL; AF347004; AAK17747.2; -; Genomic_DNA. DR EMBL; AF347005; AAK17760.2; -; Genomic_DNA. DR EMBL; AF347006; AAK17773.2; -; Genomic_DNA. DR EMBL; AF347007; AAK17786.2; -; Genomic_DNA. DR EMBL; AF347011; AAK17838.2; -; Genomic_DNA. DR EMBL; AY289051; AAP47887.1; -; Genomic_DNA. DR EMBL; AY289052; AAP47900.1; -; Genomic_DNA. DR EMBL; AY289053; AAP47913.1; -; Genomic_DNA. DR EMBL; AY289054; AAP47926.1; -; Genomic_DNA. DR EMBL; AY289055; AAP47939.1; -; Genomic_DNA. DR EMBL; AY289056; AAP47952.1; -; Genomic_DNA. DR EMBL; AY289058; AAP47978.1; -; Genomic_DNA. DR EMBL; AY289059; AAP47991.1; -; Genomic_DNA. DR EMBL; AY289060; AAP48004.1; -; Genomic_DNA. DR EMBL; AY289061; AAP48017.1; -; Genomic_DNA. DR EMBL; AY289062; AAP48030.1; -; Genomic_DNA. DR EMBL; AY289063; AAP48043.1; -; Genomic_DNA. DR EMBL; AY289065; AAP48069.1; -; Genomic_DNA. DR EMBL; AY289068; AAP48108.1; -; Genomic_DNA. DR EMBL; AY289069; AAP48121.1; -; Genomic_DNA. DR EMBL; AY289073; AAP48173.1; -; Genomic_DNA. DR EMBL; AY289076; AAP48212.1; -; Genomic_DNA. DR EMBL; AY289077; AAP48225.1; -; Genomic_DNA. DR EMBL; AY289080; AAP48264.1; -; Genomic_DNA. DR EMBL; AY289083; AAP48303.1; -; Genomic_DNA. DR EMBL; AY289084; AAP48316.1; -; Genomic_DNA. DR EMBL; AY289086; AAP48342.1; -; Genomic_DNA. DR EMBL; AY289087; AAP48355.1; -; Genomic_DNA. DR EMBL; AY289088; AAP48368.1; -; Genomic_DNA. DR EMBL; AY289091; AAP48407.1; -; Genomic_DNA. DR EMBL; AY289092; AAP48420.1; -; Genomic_DNA. DR EMBL; AY289093; AAP48432.1; -; Genomic_DNA. DR EMBL; AY289094; AAP48445.1; -; Genomic_DNA. DR EMBL; AY289095; AAP48458.1; -; Genomic_DNA. DR EMBL; AY289096; AAP48471.1; -; Genomic_DNA. DR EMBL; AY289099; AAP48510.1; -; Genomic_DNA. DR EMBL; AY289100; AAP48523.1; -; Genomic_DNA. DR EMBL; AY289101; AAP48536.1; -; Genomic_DNA. DR EMBL; AY289102; AAP48549.1; -; Genomic_DNA. DR EMBL; AY495090; AAR92503.1; -; Genomic_DNA. DR EMBL; AY495091; AAR92516.1; -; Genomic_DNA. DR EMBL; AY495092; AAR92529.1; -; Genomic_DNA. DR EMBL; AY495093; AAR92542.1; -; Genomic_DNA. DR EMBL; AY495094; AAR92555.1; -; Genomic_DNA. DR EMBL; AY495095; AAR92568.1; -; Genomic_DNA. DR EMBL; AY495096; AAR92581.1; -; Genomic_DNA. DR EMBL; AY495097; AAR92594.1; -; Genomic_DNA. DR EMBL; AY495098; AAR92607.1; -; Genomic_DNA. DR EMBL; AY495099; AAR92620.1; -; Genomic_DNA. DR EMBL; AY495100; AAR92633.1; -; Genomic_DNA. DR EMBL; AY495101; AAR92646.1; -; Genomic_DNA. DR EMBL; AY495102; AAR92659.1; -; Genomic_DNA. DR EMBL; AY495103; AAR92672.1; -; Genomic_DNA. DR EMBL; AY495104; AAR92685.1; -; Genomic_DNA. DR EMBL; AY495105; AAR92698.1; -; Genomic_DNA. DR EMBL; AY495106; AAR92711.1; -; Genomic_DNA. DR EMBL; AY495107; AAR92724.1; -; Genomic_DNA. DR EMBL; AY495108; AAR92737.1; -; Genomic_DNA. DR EMBL; AY495109; AAR92750.1; -; Genomic_DNA. DR EMBL; AY495110; AAR92763.1; -; Genomic_DNA. DR EMBL; AY495111; AAR92776.1; -; Genomic_DNA. DR EMBL; AY495112; AAR92789.1; -; Genomic_DNA. DR EMBL; AY495113; AAR92802.1; -; Genomic_DNA. DR EMBL; AY495114; AAR92815.1; -; Genomic_DNA. DR EMBL; AY495115; AAR92828.1; -; Genomic_DNA. DR EMBL; AY495116; AAR92841.1; -; Genomic_DNA. DR EMBL; AY495117; AAR92854.1; -; Genomic_DNA. DR EMBL; AY495118; AAR92867.1; -; Genomic_DNA. DR EMBL; AY495119; AAR92880.1; -; Genomic_DNA. DR EMBL; AY495120; AAR92893.1; -; Genomic_DNA. DR EMBL; AY495121; AAR92906.1; -; Genomic_DNA. DR EMBL; AY495122; AAR92919.1; -; Genomic_DNA. DR EMBL; AY495123; AAR92932.1; -; Genomic_DNA. DR EMBL; AY495124; AAR92945.1; -; Genomic_DNA. DR EMBL; AY495125; AAR92958.1; -; Genomic_DNA. DR EMBL; AY495126; AAR92971.1; -; Genomic_DNA. DR EMBL; AY495127; AAR92984.1; -; Genomic_DNA. DR EMBL; AY495128; AAR92997.1; -; Genomic_DNA. DR EMBL; AY495129; AAR93010.1; -; Genomic_DNA. DR EMBL; AY495130; AAR93023.1; -; Genomic_DNA. DR EMBL; AY495131; AAR93036.1; -; Genomic_DNA. DR EMBL; AY495132; AAR93049.1; -; Genomic_DNA. DR EMBL; AY495133; AAR93062.1; -; Genomic_DNA. DR EMBL; AY495134; AAR93075.1; -; Genomic_DNA. DR EMBL; AY495135; AAR93088.1; -; Genomic_DNA. DR EMBL; AY495136; AAR93101.1; -; Genomic_DNA. DR EMBL; AY495137; AAR93114.1; -; Genomic_DNA. DR EMBL; AY495138; AAR93127.1; -; Genomic_DNA. DR EMBL; AY495139; AAR93140.1; -; Genomic_DNA. DR EMBL; AY495140; AAR93153.1; -; Genomic_DNA. DR EMBL; AY495141; AAR93166.1; -; Genomic_DNA. DR EMBL; AY495142; AAR93179.1; -; Genomic_DNA. DR EMBL; AY495143; AAR93192.1; -; Genomic_DNA. DR EMBL; AY495144; AAR93205.1; -; Genomic_DNA. DR EMBL; AY495145; AAR93218.1; -; Genomic_DNA. DR EMBL; AY495146; AAR93231.1; -; Genomic_DNA. DR EMBL; AY495147; AAR93244.1; -; Genomic_DNA. DR EMBL; AY495148; AAR93257.1; -; Genomic_DNA. DR EMBL; AY495149; AAR93270.1; -; Genomic_DNA. DR EMBL; AY495150; AAR93283.1; -; Genomic_DNA. DR EMBL; AY495151; AAR93296.1; -; Genomic_DNA. DR EMBL; AY495152; AAR93309.1; -; Genomic_DNA. DR EMBL; AY495153; AAR93322.1; -; Genomic_DNA. DR EMBL; AY495154; AAR93335.1; -; Genomic_DNA. DR EMBL; AY495155; AAR93348.1; -; Genomic_DNA. DR EMBL; AY495156; AAR93361.1; -; Genomic_DNA. DR EMBL; AY495157; AAR93374.1; -; Genomic_DNA. DR EMBL; AY495158; AAR93387.1; -; Genomic_DNA. DR EMBL; AY495159; AAR93400.1; -; Genomic_DNA. DR EMBL; AY495160; AAR93413.1; -; Genomic_DNA. DR EMBL; AY495161; AAR93426.1; -; Genomic_DNA. DR EMBL; AY495162; AAR93439.1; -; Genomic_DNA. DR EMBL; AY495163; AAR93452.1; -; Genomic_DNA. DR EMBL; AY495164; AAR93465.1; -; Genomic_DNA. DR EMBL; AY495165; AAR93478.1; -; Genomic_DNA. DR EMBL; AY495166; AAR93491.1; -; Genomic_DNA. DR EMBL; AY495167; AAR93504.1; -; Genomic_DNA. DR EMBL; AY495168; AAR93517.1; -; Genomic_DNA. DR EMBL; AY495169; AAR93530.1; -; Genomic_DNA. DR EMBL; AY495171; AAR93556.1; -; Genomic_DNA. DR EMBL; AY495172; AAR93569.1; -; Genomic_DNA. DR EMBL; AY495173; AAR93582.1; -; Genomic_DNA. DR EMBL; AY495174; AAR93595.1; -; Genomic_DNA. DR EMBL; AY495175; AAR93608.1; -; Genomic_DNA. DR EMBL; AY495176; AAR93621.1; -; Genomic_DNA. DR EMBL; AY495177; AAR93634.1; -; Genomic_DNA. DR EMBL; AY495178; AAR93647.1; -; Genomic_DNA. DR EMBL; AY495179; AAR93660.1; -; Genomic_DNA. DR EMBL; AY495180; AAR93673.1; -; Genomic_DNA. DR EMBL; AY495181; AAR93686.1; -; Genomic_DNA. DR EMBL; AY495182; AAR93699.1; -; Genomic_DNA. DR EMBL; AY495183; AAR93712.1; -; Genomic_DNA. DR EMBL; AY495184; AAR93725.1; -; Genomic_DNA. DR EMBL; AY495185; AAR93738.1; -; Genomic_DNA. DR EMBL; AY495186; AAR93751.1; -; Genomic_DNA. DR EMBL; AY495187; AAR93764.1; -; Genomic_DNA. DR EMBL; AY495188; AAR93777.1; -; Genomic_DNA. DR EMBL; AY495189; AAR93790.1; -; Genomic_DNA. DR EMBL; AY495190; AAR93803.1; -; Genomic_DNA. DR EMBL; AY495191; AAR93816.1; -; Genomic_DNA. DR EMBL; AY495192; AAR93829.1; -; Genomic_DNA. DR EMBL; AY495193; AAR93842.1; -; Genomic_DNA. DR EMBL; AY495194; AAR93855.1; -; Genomic_DNA. DR EMBL; AY495239; AAR94440.1; -; Genomic_DNA. DR EMBL; AY495240; AAR94453.1; -; Genomic_DNA. DR EMBL; AY495241; AAR94466.1; -; Genomic_DNA. DR EMBL; AY495242; AAR94479.1; -; Genomic_DNA. DR EMBL; AY495244; AAR94505.1; -; Genomic_DNA. DR EMBL; AY495246; AAR94531.1; -; Genomic_DNA. DR EMBL; AY495247; AAR94544.1; -; Genomic_DNA. DR EMBL; AY495248; AAR94557.1; -; Genomic_DNA. DR EMBL; AY495249; AAR94570.1; -; Genomic_DNA. DR EMBL; AY495252; AAR94609.1; -; Genomic_DNA. DR EMBL; AY495267; AAR94804.1; -; Genomic_DNA. DR EMBL; AY495268; AAR94817.1; -; Genomic_DNA. DR EMBL; AY495269; AAR94830.1; -; Genomic_DNA. DR EMBL; AY495270; AAR94843.1; -; Genomic_DNA. DR EMBL; AY495271; AAR94856.1; -; Genomic_DNA. DR EMBL; AY495272; AAR94869.1; -; Genomic_DNA. DR EMBL; AY495273; AAR94882.1; -; Genomic_DNA. DR EMBL; AY495274; AAR94895.1; -; Genomic_DNA. DR EMBL; AY495275; AAR94908.1; -; Genomic_DNA. DR EMBL; AY495276; AAR94921.1; -; Genomic_DNA. DR EMBL; AY495277; AAR94934.1; -; Genomic_DNA. DR EMBL; AY495278; AAR94947.1; -; Genomic_DNA. DR EMBL; AY495279; AAR94960.1; -; Genomic_DNA. DR EMBL; AY495280; AAR94973.1; -; Genomic_DNA. DR EMBL; AY495281; AAR94986.1; -; Genomic_DNA. DR EMBL; AY495282; AAR94999.1; -; Genomic_DNA. DR EMBL; AY495283; AAR95012.1; -; Genomic_DNA. DR EMBL; AY495284; AAR95025.1; -; Genomic_DNA. DR EMBL; AY495285; AAR95038.1; -; Genomic_DNA. DR EMBL; AY495286; AAR95051.1; -; Genomic_DNA. DR EMBL; AY495287; AAR95064.1; -; Genomic_DNA. DR EMBL; AY495288; AAR95077.1; -; Genomic_DNA. DR EMBL; AY495289; AAR95090.1; -; Genomic_DNA. DR EMBL; AY495290; AAR95103.1; -; Genomic_DNA. DR EMBL; AY495291; AAR95116.1; -; Genomic_DNA. DR EMBL; AY495292; AAR95129.1; -; Genomic_DNA. DR EMBL; AY495293; AAR95142.1; -; Genomic_DNA. DR EMBL; AY495294; AAR95155.1; -; Genomic_DNA. DR EMBL; AY495295; AAR95168.1; -; Genomic_DNA. DR EMBL; AY495297; AAR95194.1; -; Genomic_DNA. DR EMBL; AY495298; AAR95207.1; -; Genomic_DNA. DR EMBL; AY495299; AAR95220.1; -; Genomic_DNA. DR EMBL; AY495300; AAR95233.1; -; Genomic_DNA. DR EMBL; AY495301; AAR95246.1; -; Genomic_DNA. DR EMBL; AY495302; AAR95259.1; -; Genomic_DNA. DR EMBL; AY495303; AAR95272.1; -; Genomic_DNA. DR EMBL; AY495304; AAR95285.1; -; Genomic_DNA. DR EMBL; AY495305; AAR95298.1; -; Genomic_DNA. DR EMBL; AY495306; AAR95311.1; -; Genomic_DNA. DR EMBL; AY495307; AAR95324.1; -; Genomic_DNA. DR EMBL; AY495308; AAR95337.1; -; Genomic_DNA. DR EMBL; AY495309; AAR95350.1; -; Genomic_DNA. DR EMBL; AY495310; AAR95363.1; -; Genomic_DNA. DR EMBL; AY495311; AAR95376.1; -; Genomic_DNA. DR EMBL; AY495312; AAR95389.1; -; Genomic_DNA. DR EMBL; AY495313; AAR95402.1; -; Genomic_DNA. DR EMBL; AY495314; AAR95415.1; -; Genomic_DNA. DR EMBL; AY495315; AAR95428.1; -; Genomic_DNA. DR EMBL; AY495316; AAR95441.1; -; Genomic_DNA. DR EMBL; AY495317; AAR95454.1; -; Genomic_DNA. DR EMBL; AY495318; AAR95467.1; -; Genomic_DNA. DR EMBL; AY495319; AAR95480.1; -; Genomic_DNA. DR EMBL; AY495320; AAR95493.1; -; Genomic_DNA. DR EMBL; AY495321; AAR95506.1; -; Genomic_DNA. DR EMBL; AY495322; AAR95519.1; -; Genomic_DNA. DR EMBL; AY495323; AAR95532.1; -; Genomic_DNA. DR EMBL; AY495324; AAR95545.1; -; Genomic_DNA. DR EMBL; AY495325; AAR95558.1; -; Genomic_DNA. DR EMBL; AY495326; AAR95571.1; -; Genomic_DNA. DR EMBL; AY495327; AAR95584.1; -; Genomic_DNA. DR EMBL; AY495328; AAR95597.1; -; Genomic_DNA. DR EMBL; AY495329; AAR95610.1; -; Genomic_DNA. DR EMBL; AY495330; AAR95623.1; -; Genomic_DNA. DR PIR; A00422; DNHUN3. DR RefSeq; YP_003024033.1; NC_012920.1. DR PDB; 5XTC; EM; 3.70 A; j=1-115. DR PDB; 5XTD; EM; 3.70 A; j=1-115. DR PDB; 9CWT; EM; 3.44 A; j=1-115. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; P03897; -. DR EMDB; EMD-45974; -. DR SMR; P03897; -. DR BioGRID; 110633; 3. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; P03897; -. DR FunCoup; P03897; 243. DR IntAct; P03897; 3. DR STRING; 9606.ENSP00000355206; -. DR BindingDB; P03897; -. DR ChEMBL; CHEMBL2363065; -. DR DrugBank; DB04464; N-Formylmethionine. DR DrugBank; DB00157; NADH. DR DrugCentral; P03897; -. DR GlyGen; P03897; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P03897; -. DR PhosphoSitePlus; P03897; -. DR BioMuta; MT-ND3; -. DR DMDM; 128710; -. DR jPOST; P03897; -. DR MassIVE; P03897; -. DR PaxDb; 9606-ENSP00000355206; -. DR PeptideAtlas; P03897; -. DR ProteomicsDB; 51613; -. DR Pumba; P03897; -. DR Antibodypedia; 68603; 126 antibodies from 25 providers. DR DNASU; 4537; -. DR Ensembl; ENST00000361227.2; ENSP00000355206.2; ENSG00000198840.2. DR GeneID; 4537; -. DR KEGG; hsa:4537; -. DR AGR; HGNC:7458; -. DR CTD; 4537; -. DR DisGeNET; 4537; -. DR GeneCards; MT-ND3; -. DR GeneReviews; MT-ND3; -. DR HGNC; HGNC:7458; MT-ND3. DR HPA; ENSG00000198840; Tissue enhanced (heart). DR MalaCards; MT-ND3; -. DR MIM; 256000; phenotype. DR MIM; 500014; phenotype. DR MIM; 516002; gene. DR OpenTargets; ENSG00000198840; -. DR Orphanet; 2609; Isolated complex I deficiency. DR Orphanet; 99718; Leber plus disease. DR Orphanet; 255210; Mitochondrial DNA-associated Leigh syndrome. DR VEuPathDB; HostDB:ENSG00000198840; -. DR eggNOG; KOG4662; Eukaryota. DR GeneTree; ENSGT00390000011605; -. DR HOGENOM; CLU_119549_3_1_1; -. DR InParanoid; P03897; -. DR OMA; GPRRYNR; -. DR PAN-GO; P03897; 2 GO annotations based on evolutionary models. DR PhylomeDB; P03897; -. DR BioCyc; MetaCyc:HS00032-MONOMER; -. DR PathwayCommons; P03897; -. DR Reactome; R-HSA-5419276; Mitochondrial translation termination. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; P03897; -. DR SIGNOR; P03897; -. DR Agora; ENSG00000198840; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 4537; 0 hits in 3 CRISPR screens. DR ChiTaRS; ND3; human. DR GeneWiki; MT-ND3; -. DR GenomeRNAi; 4537; -. DR Pharos; P03897; Tclin. DR PRO; PR:P03897; -. DR Proteomes; UP000005640; Mitochondrion MT. DR RNAct; P03897; protein. DR Bgee; ENSG00000198840; Expressed in right uterine tube and 95 other cell types or tissues. DR ExpressionAtlas; P03897; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0005739; C:mitochondrion; HTP:FlyBase. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0008137; F:NADH dehydrogenase (ubiquinone) activity; IMP:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEA:Ensembl. DR GO; GO:0006120; P:mitochondrial electron transport, NADH to ubiquinone; IMP:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR GO; GO:0009642; P:response to light intensity; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl. DR FunFam; 1.20.58.1610:FF:000004; NADH-quinone oxidoreductase subunit A; 1. DR Gene3D; 1.20.58.1610; NADH:ubiquinone/plastoquinone oxidoreductase, chain 3; 1. DR InterPro; IPR000440; NADH_UbQ/plastoQ_OxRdtase_su3. DR InterPro; IPR038430; NDAH_ubi_oxred_su3_sf. DR PANTHER; PTHR11058; NADH-UBIQUINONE OXIDOREDUCTASE CHAIN 3; 1. DR PANTHER; PTHR11058:SF9; NADH-UBIQUINONE OXIDOREDUCTASE CHAIN 3; 1. DR Pfam; PF00507; Oxidored_q4; 1. PE 1: Evidence at protein level; KW 3D-structure; Disease variant; Electron transport; Leigh syndrome; KW Membrane; Mitochondrion; Mitochondrion inner membrane; NAD; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Translocase; Transmembrane; KW Transmembrane helix; Transport; Ubiquinone. FT CHAIN 1..115 FT /note="NADH-ubiquinone oxidoreductase chain 3" FT /id="PRO_0000117752" FT TRANSMEM 3..23 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 55..75 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 84..104 FT /note="Helical" FT /evidence="ECO:0000255" FT VARIANT 10 FT /note="N -> D (in dbSNP:rs28358274)" FT /evidence="ECO:0000269|PubMed:6343397" FT /id="VAR_008391" FT VARIANT 26 FT /note="Q -> K (in LS; uncertain significance; decrease in FT enzyme activity; dbSNP:rs587780529)" FT /evidence="ECO:0000269|PubMed:25118196" FT /id="VAR_084384" FT VARIANT 34 FT /note="S -> P (in MC1DM1; dbSNP:rs199476117)" FT /evidence="ECO:0000269|PubMed:14705112, FT ECO:0000269|PubMed:20818383" FT /id="VAR_064564" FT VARIANT 45 FT /note="S -> P (in MC1DM1; dbSNP:rs267606890)" FT /evidence="ECO:0000269|PubMed:11456298, FT ECO:0000269|PubMed:20818383" FT /id="VAR_035091" FT VARIANT 47 FT /note="A -> T (in LS and MC1DM1; dbSNP:rs267606891)" FT /evidence="ECO:0000269|PubMed:17152068, FT ECO:0000269|PubMed:20818383" FT /id="VAR_035092" FT VARIANT 53 FT /note="M -> V" FT /evidence="ECO:0000269|PubMed:1757091" FT /id="VAR_008598" FT VARIANT 114 FT /note="T -> A (in dbSNP:rs2853826)" FT /evidence="ECO:0000269|PubMed:1757091, FT ECO:0000269|PubMed:6343397" FT /id="VAR_008392" SQ SEQUENCE 115 AA; 13186 MW; FA9E0C13B5108EE6 CRC64; MNFALILMIN TLLALLLMII TFWLPQLNGY MEKSTPYECG FDPMSPARVP FSMKFFLVAI TFLLFDLEIA LLLPLPWALQ TTNLPLMVMS SLLLIIILAL SLAYEWLQKG LDWTE // ID NUBPL_HUMAN Reviewed; 319 AA. AC Q8TB37; B4DHZ1; Q86TZ4; Q9H9M2; DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 28-JAN-2026, entry version 179. DE RecName: Full=Iron-sulfur cluster transfer protein NUBPL {ECO:0000305}; DE AltName: Full=IND1 homolog; DE AltName: Full=Nucleotide-binding protein-like; DE AltName: Full=huInd1; DE Flags: Precursor; GN Name=NUBPL; Synonyms=C14orf127; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Neuroblastoma; RA Li W.B., Gruber C., Jessee J., Polayes D.; RT "Full-length cDNA libraries and normalization."; RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Teratocarcinoma, and Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-319 (ISOFORM 1), AND VARIANT RP THR-198. RC TISSUE=Prostatic adenocarcinoma; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, IRON-SULFUR CLUSTER-BINDING, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND MUTAGENESIS OF CYS-244 AND CYS-247. RX PubMed=19752196; DOI=10.1128/mcb.00817-09; RA Sheftel A.D., Stehling O., Pierik A.J., Netz D.J., Kerscher S., RA Elsasser H.P., Wittig I., Balk J., Brandt U., Lill R.; RT "Human ind1, an iron-sulfur cluster assembly factor for respiratory complex RT I."; RL Mol. Cell. Biol. 29:6059-6073(2009). RN [6] RP INVOLVEMENT IN MC1DN21, AND VARIANT ARG-56. RX PubMed=20818383; DOI=10.1038/ng.659; RA Calvo S.E., Tucker E.J., Compton A.G., Kirby D.M., Crawford G., Burtt N.P., RA Rivas M., Guiducci C., Bruno D.L., Goldberger O.A., Redman M.C., RA Wiltshire E., Wilson C.J., Altshuler D., Gabriel S.B., Daly M.J., RA Thorburn D.R., Mootha V.K.; RT "High-throughput, pooled sequencing identifies mutations in NUBPL and RT FOXRED1 in human complex I deficiency."; RL Nat. Genet. 42:851-858(2010). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [8] RP CHARACTERIZATION OF VARIANT ARG-56. RX PubMed=22072591; DOI=10.1002/humu.21654; RA Tucker E.J., Mimaki M., Compton A.G., McKenzie M., Ryan M.T., RA Thorburn D.R.; RT "Next generation sequencing in molecular diagnosis: NUBPL mutations RT highlight the challenges of variant detection and interpretation."; RL Hum. Mutat. 33:411-418(2012). RN [9] RP VARIANTS MC1DN21 TYR-105 AND PHE-193, AND VARIANT ARG-56. RX PubMed=23553477; DOI=10.1212/wnl.0b013e31828f1914; RA Kevelam S.H., Rodenburg R.J., Wolf N.I., Ferreira P., Lunsing R.J., RA Nijtmans L.G., Mitchell A., Arroyo H.A., Rating D., Vanderver A., RA van Berkel C.G., Abbink T.E., Heutink P., van der Knaap M.S.; RT "NUBPL mutations in patients with complex I deficiency and a distinct MRI RT pattern."; RL Neurology 80:1577-1583(2013). CC -!- FUNCTION: Iron-sulfur cluster transfer protein involved in the assembly CC of the mitochondrial membrane respiratory chain NADH dehydrogenase CC (Complex I) (PubMed:19752196). May deliver one or more Fe-S clusters to CC complex I subunits (PubMed:19752196). {ECO:0000269|PubMed:19752196}. CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Note=Binds 1 [4Fe-4S] cluster.; CC -!- INTERACTION: CC Q8TB37; Q8N371-3: KDM8; NbExp=3; IntAct=EBI-12852610, EBI-12161375; CC Q8TB37; Q9Y5Y2: NUBP2; NbExp=6; IntAct=EBI-12852610, EBI-1048886; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:19752196}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8TB37-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8TB37-2; Sequence=VSP_020985, VSP_008797; CC -!- TISSUE SPECIFICITY: Highest expression in liver and kidney. expressed CC at significant levels in small intestine and brain (at protein level). CC {ECO:0000269|PubMed:19752196}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 21 (MC1DN21) CC [MIM:618242]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN21 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:20818383, CC ECO:0000269|PubMed:23553477}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 2]: May be due to exon skipping. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the Mrp/NBP35 ATP-binding proteins family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH24919.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB14203.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAD62349.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; BX248028; CAD62349.1; ALT_INIT; mRNA. DR EMBL; AK022722; BAB14203.1; ALT_INIT; mRNA. DR EMBL; AK295326; BAG58303.1; -; mRNA. DR EMBL; AK316445; BAH14816.1; -; mRNA. DR EMBL; CH471078; EAW65942.1; -; Genomic_DNA. DR EMBL; BC024919; AAH24919.1; ALT_INIT; mRNA. DR CCDS; CCDS41940.1; -. [Q8TB37-1] DR RefSeq; NP_001188502.1; NM_001201573.1. DR RefSeq; NP_079428.2; NM_025152.3. [Q8TB37-1] DR RefSeq; XP_047287744.1; XM_047431788.1. [Q8TB37-2] DR AlphaFoldDB; Q8TB37; -. DR SMR; Q8TB37; -. DR BioGRID; 123190; 91. DR FunCoup; Q8TB37; 1254. DR IntAct; Q8TB37; 41. DR STRING; 9606.ENSP00000281081; -. DR iPTMnet; Q8TB37; -. DR PhosphoSitePlus; Q8TB37; -. DR BioMuta; NUBPL; -. DR DMDM; 116242683; -. DR jPOST; Q8TB37; -. DR MassIVE; Q8TB37; -. DR PaxDb; 9606-ENSP00000281081; -. DR PeptideAtlas; Q8TB37; -. DR ProteomicsDB; 73958; -. [Q8TB37-1] DR ProteomicsDB; 73959; -. [Q8TB37-2] DR Pumba; Q8TB37; -. DR Antibodypedia; 23093; 265 antibodies from 23 providers. DR DNASU; 80224; -. DR Ensembl; ENST00000281081.12; ENSP00000281081.7; ENSG00000151413.18. [Q8TB37-1] DR Ensembl; ENST00000547839.5; ENSP00000449918.1; ENSG00000151413.18. [Q8TB37-2] DR GeneID; 80224; -. DR KEGG; hsa:80224; -. DR MANE-Select; ENST00000281081.12; ENSP00000281081.7; NM_025152.3; NP_079428.2. DR UCSC; uc059apb.1; human. [Q8TB37-1] DR AGR; HGNC:20278; -. DR ClinPGx; PA134907818; -. DR CTD; 80224; -. DR DisGeNET; 80224; -. DR GeneCards; NUBPL; -. DR HGNC; HGNC:20278; NUBPL. DR HPA; ENSG00000151413; Low tissue specificity. DR MalaCards; NUBPL; -. DR MIM; 613621; gene. DR MIM; 618242; phenotype. DR OpenTargets; ENSG00000151413; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000151413; -. DR eggNOG; KOG3022; Eukaryota. DR GeneTree; ENSGT00950000183193; -. DR HOGENOM; CLU_024839_0_2_1; -. DR InParanoid; Q8TB37; -. DR OMA; CNHESHI; -. DR OrthoDB; 1741334at2759; -. DR PAN-GO; Q8TB37; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q8TB37; -. DR PathwayCommons; Q8TB37; -. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q8TB37; -. DR Agora; ENSG00000151413; -. DR BioGRID-ORCS; 80224; 119 hits in 1159 CRISPR screens. DR ChiTaRS; NUBPL; human. DR GenomeRNAi; 80224; -. DR Pharos; Q8TB37; Tbio. DR PRO; PR:Q8TB37; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q8TB37; protein. DR Bgee; ENSG00000151413; Expressed in calcaneal tendon and 188 other cell types or tissues. DR ExpressionAtlas; Q8TB37; baseline and differential. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0140663; F:ATP-dependent FeS chaperone activity; IEA:InterPro. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0016226; P:iron-sulfur cluster assembly; IBA:GO_Central. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR GO; GO:0007005; P:mitochondrion organization; IMP:UniProtKB. DR CDD; cd02037; Mrp_NBP35; 1. DR FunFam; 3.40.50.300:FF:000709; Iron-sulfur protein NUBPL isoform X1; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR HAMAP; MF_02040; Mrp_NBP35; 1. DR InterPro; IPR000808; Mrp-like_CS. DR InterPro; IPR019591; Mrp/NBP35_ATP-bd. DR InterPro; IPR044304; NUBPL-like. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR033756; YlxH/NBP35. DR PANTHER; PTHR42961; IRON-SULFUR PROTEIN NUBPL; 1. DR PANTHER; PTHR42961:SF2; IRON-SULFUR PROTEIN NUBPL; 1. DR Pfam; PF10609; ParA; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS01215; MRP; 1. PE 1: Evidence at protein level; KW 4Fe-4S; Alternative splicing; ATP-binding; Disease variant; Iron; KW Iron-sulfur; Metal-binding; Mitochondrion; Nucleotide-binding; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Transit peptide. FT TRANSIT 1..38 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 39..319 FT /note="Iron-sulfur cluster transfer protein NUBPL" FT /id="PRO_0000184950" FT BINDING 75..82 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT VAR_SEQ 173 FT /note="D -> L (in isoform 2)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_020985" FT VAR_SEQ 174..319 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.1" FT /id="VSP_008797" FT VARIANT 56 FT /note="G -> R (found in a patient with mitochondrial FT complex I deficiency; uncertain significance; found in FT association with a nucleotide transition causing exon FT skipping; does not affect protein stability, processing and FT import in the mitochondrion; can restore complex I activity FT when overexpressed in patient fibroblasts; FT dbSNP:rs200401432)" FT /evidence="ECO:0000269|PubMed:20818383, FT ECO:0000269|PubMed:22072591, ECO:0000269|PubMed:23553477" FT /id="VAR_064570" FT VARIANT 105 FT /note="D -> Y (in MC1DN21; dbSNP:rs397515440)" FT /evidence="ECO:0000269|PubMed:23553477" FT /id="VAR_069767" FT VARIANT 193 FT /note="L -> F (in MC1DN21; dbSNP:rs552722349)" FT /evidence="ECO:0000269|PubMed:23553477" FT /id="VAR_069768" FT VARIANT 198 FT /note="N -> T (in dbSNP:rs11558436)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_027895" FT MUTAGEN 244 FT /note="C->A: Defect in complex I assembly; when associated FT with A-247." FT /evidence="ECO:0000269|PubMed:19752196" FT MUTAGEN 247 FT /note="C->A: Defect in complex I assembly; when associated FT with A-244." FT /evidence="ECO:0000269|PubMed:19752196" SQ SEQUENCE 319 AA; 34083 MW; 7A497482A4D449A4 CRC64; MGIWQRLLLF GGVSLRAGGG ATAPLGGSRA MVCGRQLSGA GSETLKQRRT QIMSRGLPKQ KPIEGVKQVI VVASGKGGVG KSTTAVNLAL ALAANDSSKA IGLLDVDVYG PSVPKMMNLK GNPELSQSNL MRPLLNYGIA CMSMGFLVEE SEPVVWRGLM VMSAIEKLLR QVDWGQLDYL VVDMPPGTGD VQLSVSQNIP ITGAVIVSTP QDIALMDAHK GAEMFRRVHV PVLGLVQNMS VFQCPKCKHK THIFGADGAR KLAQTLGLEV LGDIPLHLNI REASDTGQPI VFSQPESDEA KAYLRIAVEV VRRLPSPSE // ID PSN1_HUMAN Reviewed; 467 AA. AC P49768; B2R6D3; O95465; Q14762; Q15719; Q15720; Q96P33; Q9UIF0; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 28-JAN-2026, entry version 263. DE RecName: Full=Presenilin-1 {ECO:0000303|PubMed:9144240}; DE Short=PS-1 {ECO:0000303|PubMed:9298817}; DE EC=3.4.23.- {ECO:0000269|PubMed:10206644, ECO:0000269|PubMed:10811883, ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:12679784, ECO:0000269|PubMed:15274632, ECO:0000269|PubMed:26280335}; DE AltName: Full=Protein S182 {ECO:0000303|PubMed:7550356}; DE Contains: DE RecName: Full=Presenilin-1 NTF subunit {ECO:0000305|PubMed:9173929}; DE Contains: DE RecName: Full=Presenilin-1 CTF subunit {ECO:0000305|PubMed:9173929}; DE Contains: DE RecName: Full=Presenilin-1 CTF12 {ECO:0000305|PubMed:9485372}; DE Short=PS1-CTF12; GN Name=PSEN1 {ECO:0000312|HGNC:HGNC:9508}; Synonyms=AD3, PS1, PSNL1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), VARIANTS AD3 RP LEU-146; ARG-163; GLU-246 AND VAL-286, AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=7596406; DOI=10.1038/375754a0; RA Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M., RA Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L., Foncin J.-F., RA Bruni A.C., Montesi M.P., Sorbi S., Rainero I., Pinessi L., Nee L., RA Chumakov I., Pollen D., Brookes A., Sanseau P., Polinsky R.J., Wasco W., RA da Silva H.A.R., Haines J.L., Pericak-Vance M.A., Tanzi R.E., Roses A.D., RA Fraser P.E., Rommens J.M., St George-Hyslop P.H.; RT "Cloning of a gene bearing missense mutations in early-onset familial RT Alzheimer's disease."; RL Nature 375:754-760(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), AND TISSUE SPECIFICITY. RC TISSUE=Blood, and Brain; RX PubMed=8641442; DOI=10.1016/0014-5793(96)00054-3; RA Sahara N., Yahagi Y., Takagi H., Kondo T., Okochi M., Usami M., RA Shirasawa T., Mori H.; RT "Identification and characterization of presenilin I-467, I-463 and I- RT 374."; RL FEBS Lett. 381:7-11(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). RA Powell C.S., Gegg M.E., Palmer M.S.; RT "Human presenilin 1 gene encodes an alternative protein-minilin."; RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Rowen L., Madan A., Qin S., Abbasi N., Dors M., Ratcliffe A., Madan A., RA Dickhoff R., Shaffer T., James R., Lasky S., Hood L.; RT "Complete sequence of the gene for presenilin 1."; RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RA Kang L., Zhang B., Zhou Y., Peng X., Yuan J., Qiang B.; RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., RA Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-113. RX PubMed=9070286; DOI=10.1006/bbrc.1996.6043; RA Tsujimura A., Yasojima K., Hashimoto-Gotoh T.; RT "Cloning of Xenopus presenilin-alpha and -beta cDNAs and their differential RT expression in oogenesis and embryogenesis."; RL Biochem. Biophys. Res. Commun. 231:392-396(1997). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 24-32, AND ALTERNATIVE SPLICING (ISOFORMS 6 RP AND 7). RC TISSUE=Megakaryocyte, and Platelet; RX PubMed=8804415; DOI=10.1016/0014-5793(96)00845-9; RA Vidal R., Ghiso J., Wisniewski T., Frangione B.; RT "Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes. RT Identification of a novel splice variant."; RL FEBS Lett. 393:19-23(1996). RN [12] RP PROTEIN SEQUENCE OF 36-42; 61-76; 109-129; 217-239; 270-278; 315-320; RP 345-352 AND 381-395 (ISOFORM 1), IDENTIFICATION BY MASS SPECTROMETRY, RP IDENTIFICATION IN GAMMA-SECRETASE COMPLEX, FUNCTION, CATALYTIC ACTIVITY, RP AND SUBCELLULAR LOCATION. RX PubMed=15274632; DOI=10.1021/bi0494976; RA Fraering P.C., Ye W., Strub J.-M., Dolios G., LaVoie M.J., RA Ostaszewski B.L., van Dorsselaer A., Wang R., Selkoe D.J., Wolfe M.S.; RT "Purification and characterization of the human gamma-secretase complex."; RL Biochemistry 43:9774-9789(2004). RN [13] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=8574969; DOI=10.1038/nm0296-224; RA Kovacs D.M., Fausett H.J., Page K.J., Kim T.-W., Moir R.D., Merriam D.E., RA Hollister R.D., Hallmark O.G., Mancini R., Felsenstein K.M., Hyman B.T., RA Tanzi R.E., Wasco W.; RT "Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and RT localization to intracellular membranes in mammalian cells."; RL Nat. Med. 2:224-229(1996). RN [14] RP PROTEOLYTIC PROCESSING. RX PubMed=9173929; DOI=10.1006/nbdi.1997.0129; RA Podlisny M.B., Citron M., Amarante P., Sherrington R., Xia W., Zhang J., RA Diehl T., Levesque G., Fraser P., Haass C., Koo E.H., Seubert P., RA St George-Hyslop P.H., Teplow D.B., Selkoe D.J.; RT "Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 RT and Ala299 and occur as stable N- and C-terminal fragments in normal and RT Alzheimer brain tissue."; RL Neurobiol. Dis. 3:325-337(1997). RN [15] RP PHOSPHORYLATION. RX PubMed=9144240; DOI=10.1073/pnas.94.10.5349; RA Walter J., Gruenberg J., Capell A., Pesold B., Schindzielorz A., Citron M., RA Mendla K., St George-Hyslop P.H., Multhaup G., Selkoe D.J., Haass C.; RT "Proteolytic processing of the Alzheimer disease-associated presenilin-1 RT generates an in vivo substrate for protein kinase C."; RL Proc. Natl. Acad. Sci. U.S.A. 94:5349-5354(1997). RN [16] RP CASPASE CLEAVAGE SITE, AND MUTAGENESIS OF ASP-345; ASP-373 AND ASP-385. RX PubMed=9485372; DOI=10.1021/bi972106l; RA Gruenberg J., Walter J., Loetscher H., Deuschle U., Jacobsen H., Haass C.; RT "Alzheimer's disease associated presenilin-1 holoprotein and its 18-20 kDa RT C-terminal fragment are death substrates for proteases of the caspase RT family."; RL Biochemistry 37:2263-2270(1998). RN [17] RP FUNCTION, INTERACTION WITH CTNNB1, AND SUBCELLULAR LOCATION. RX PubMed=9738936; DOI=10.1016/s0014-5793(98)00886-2; RA Murayama M., Tanaka S., Palacino J., Murayama O., Honda T., Sun X., RA Yasutake K., Nihonmatsu N., Wolozin B., Takashima A.; RT "Direct association of presenilin-1 with beta-catenin."; RL FEBS Lett. 433:73-77(1998). RN [18] RP INTERACTION WITH FLNA AND FLNB. RX PubMed=9437013; DOI=10.1523/jneurosci.18-03-00914.1998; RA Zhang W., Han S.W., McKeel D.W., Goate A., Wu J.Y.; RT "Interaction of presenilins with the filamin family of actin-binding RT proteins."; RL J. Neurosci. 18:914-922(1998). RN [19] RP FUNCTION, MUTAGENESIS OF MET-292, AND PROTEOLYTIC PROCESSING. RX PubMed=10545183; DOI=10.1021/bi9914210; RA Steiner H., Romig H., Pesold B., Philipp U., Baader M., Citron M., RA Loetscher H., Jacobsen H., Haass C.; RT "Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 RT in the absence of endoproteolysis."; RL Biochemistry 38:14600-14605(1999). RN [20] RP INTERACTION WITH MTCH1. RX PubMed=10551805; DOI=10.1074/jbc.274.46.32543; RA Xu X., Shi Y.-C., Wu X., Gambetti P., Sui D., Cui M.-Z.; RT "Identification of a novel PSD-95/Dlg/ZO-1 (PDZ)-like protein interacting RT with the C terminus of presenilin-1."; RL J. Biol. Chem. 274:32543-32546(1999). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NOTCH. RX PubMed=10593990; DOI=10.1074/jbc.274.51.36801; RA Ray W.J., Yao M., Mumm J., Schroeter E.H., Saftig P., Wolfe M., RA Selkoe D.J., Kopan R., Goate A.M.; RT "Cell surface presenilin-1 participates in the gamma-secretase-like RT proteolysis of Notch."; RL J. Biol. Chem. 274:36801-36807(1999). RN [22] RP INTERACTION WITH CTNND2 AND CTNNB1, AND SUBCELLULAR LOCATION. RX PubMed=10037471; DOI=10.1046/j.1471-4159.1999.0720999.x; RA Levesque G., Yu G., Nishimura M., Zhang D.M., Levesque L., Yu H., Xu D., RA Liang Y., Rogaeva E.A., Ikeda M., Duthie M., Murgolo N., Wang L., RA VanderVere P., Bayne M.L., Strader C.D., Rommens J.M., Fraser P.E., RA St George-Hyslop P.H.; RT "Presenilins interact with armadillo proteins including neural-specific RT plakophilin-related protein and beta-catenin."; RL J. Neurochem. 72:999-1008(1999). RN [23] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF ASP-257 AND RP ASP-385. RX PubMed=10206644; DOI=10.1038/19077; RA Wolfe M.S., Xia W., Ostaszewski B.L., Diehl T.S., Kimberly W.T., RA Selkoe D.J.; RT "Two transmembrane aspartates in presenilin-1 required for presenilin RT endoproteolysis and gamma-secretase activity."; RL Nature 398:513-517(1999). RN [24] RP INTERACTION WITH DOCK3. RX PubMed=10854253; DOI=10.1046/j.1471-4159.2000.0750109.x; RA Kashiwa A., Yoshida H., Lee S., Paladino T., Liu Y., Chen Q., Dargusch R., RA Schubert D., Kimura H.; RT "Isolation and characterization of novel presenilin binding protein."; RL J. Neurochem. 75:109-116(2000). RN [25] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF ASP-257 AND RP ASP-385. RX PubMed=10899933; DOI=10.1046/j.1471-4159.2000.0750583.x; RA Berezovska O., Jack C., McLean P., Aster J.C., Hicks C., Xia W., RA Wolfe M.S., Kimberly W.T., Weinmaster G., Selkoe D.J., Hyman B.T.; RT "Aspartate mutations in presenilin and gamma-secretase inhibitors both RT impair notch1 proteolysis and nuclear translocation with relative RT preservation of notch1 signaling."; RL J. Neurochem. 75:583-593(2000). RN [26] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LEU-286. RX PubMed=10811883; DOI=10.1073/pnas.100049897; RA Kulic L., Walter J., Multhaup G., Teplow D.B., Baumeister R., Romig H., RA Capell A., Steiner H., Haass C.; RT "Separation of presenilin function in amyloid beta-peptide generation and RT endoproteolysis of Notch."; RL Proc. Natl. Acad. Sci. U.S.A. 97:5913-5918(2000). RN [27] RP INTERACTION WITH PARL. RX PubMed=12214059; DOI=10.3233/jad-2001-3203; RA Pellegrini L., Passer B.J., Canelles M., Lefterov I., Ganjei J.K., RA Fowlkes B.J., Koonin E.V., D'Adamio L.; RT "PAMP and PARL, two novel putative metalloproteases interacting with the RT COOH-terminus of presenilin-1 and -2."; RL J. Alzheimers Dis. 3:181-190(2001). RN [28] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=11987239; DOI=10.1006/bcmd.2002.0486; RA Mirinics Z.K., Calafat J., Udby L., Lovelock J., Kjeldsen L., RA Rothermund K., Sisodia S.S., Borregaard N., Corey S.J.; RT "Identification of the presenilins in hematopoietic cells with localization RT of presenilin 1 to neutrophil and platelet granules."; RL Blood Cells Mol. Dis. 28:28-38(2002). RN [29] RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN A COMPLEX WITH CDH1 RP AND CTNNB1. RX PubMed=11953314; DOI=10.1093/emboj/21.8.1948; RA Marambaud P., Shioi J., Serban G., Georgakopoulos A., Sarner S., Nagy V., RA Baki L., Wen P., Efthimiopoulos S., Shao Z., Wisniewski T., Robakis N.K.; RT "A presenilin-1/gamma-secretase cleavage releases the E-cadherin RT intracellular domain and regulates disassembly of adherens junctions."; RL EMBO J. 21:1948-1956(2002). RN [30] RP INTERACTION WITH HERPUD1. RX PubMed=11799129; DOI=10.1074/jbc.m112372200; RA Sai X., Kawamura Y., Kokame K., Yamaguchi H., Shiraishi H., Suzuki R., RA Suzuki T., Kawaichi M., Miyata T., Kitamura T., De Strooper B., RA Yanagisawa K., Komano H.; RT "Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin- RT mediated generation of amyloid beta-protein."; RL J. Biol. Chem. 277:12915-12920(2002). RN [31] RP INTERACTION WITH GFAP, MUTAGENESIS OF 66-ASP--ASP-72; 76-LYS-TYR-77; RP 82-VAL-ILE-83; VAL-82 AND 84-MET-LEU-85, AND CHARACTERIZATION OF VARIANTS RP AD3 VAL-79 AND LEU-82. RX PubMed=12058025; DOI=10.1074/jbc.m112121200; RA Nielsen A.L., Holm I.E., Johansen M., Bonven B., Jorgensen P., RA Jorgensen A.L.; RT "A new splice variant of glial fibrillary acidic protein GFAPepsilon, RT interacts with the presenilin proteins."; RL J. Biol. Chem. 277:29983-29991(2002). RN [32] RP INTERACTION WITH CDH2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-385. RX PubMed=14515347; DOI=10.1002/jnr.10753; RA Uemura K., Kitagawa N., Kohno R., Kuzuya A., Kageyama T., Chonabayashi K., RA Shibasaki H., Shimohama S.; RT "Presenilin 1 is involved in maturation and trafficking of N-cadherin to RT the plasma membrane."; RL J. Neurosci. Res. 74:184-191(2003). RN [33] RP ENZYME ACTIVITY OF A GAMMA-SECRETASE COMPLEX, CATALYTIC ACTIVITY, FUNCTION, RP AND SUBUNIT. RX PubMed=12679784; DOI=10.1038/ncb960; RA Edbauer D., Winkler E., Regula J.T., Pesold B., Steiner H., Haass C.; RT "Reconstitution of gamma-secretase activity."; RL Nat. Cell Biol. 5:486-488(2003). RN [34] RP COMPONENT OF A GAMMA-SECRETASE COMPLEX WITH PEN2; PSEN1/PSEN2 AND NCSTN. RX PubMed=12740439; DOI=10.1073/pnas.1037392100; RA Kimberly W.T., LaVoie M.J., Ostaszewski B.L., Ye W., Wolfe M.S., RA Selkoe D.J.; RT "Gamma-secretase is a membrane protein complex comprised of presenilin, RT nicastrin, Aph-1, and Pen-2."; RL Proc. Natl. Acad. Sci. U.S.A. 100:6382-6387(2003). RN [35] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:R8.1-R8.16(2004). RN [36] RP FUNCTION, SUBCELLULAR LOCATION, VARIANT AD3 SER-117, AND CHARACTERIZATION RP OF VARIANTS AD3 LEU-117 AND SER-117. RX PubMed=15004326; DOI=10.3233/jad-2004-6105; RA Dowjat W.K., Kuchna I., Wisniewski T., Wegiel J.; RT "A novel highly pathogenic Alzheimer presenilin-1 mutation in codon 117 RT (Pro117Ser): Comparison of clinical, neuropathological and cell culture RT phenotypes of Pro117Leu and Pro117Ser mutations."; RL J. Alzheimers Dis. 6:31-43(2004). RN [37] RP PHOSPHORYLATION AT SER-310 AND SER-346, AND MUTAGENESIS OF SER-310 AND RP SER-346. RX PubMed=14576165; DOI=10.1074/jbc.m306653200; RA Fluhrer R., Friedlein A., Haass C., Walter J.; RT "Phosphorylation of presenilin 1 at the caspase recognition site regulates RT its proteolytic processing and the progression of apoptosis."; RL J. Biol. Chem. 279:1585-1593(2004). RN [38] RP TOPOLOGY. RX PubMed=15385547; DOI=10.1074/jbc.m407898200; RA Friedmann E., Lemberg M.K., Weihofen A., Dev K.K., Dengler U., Rovelli G., RA Martoglio B.; RT "Consensus analysis of signal peptide peptidase and homologous human RT aspartic proteases reveals opposite topology of catalytic domains compared RT with presenilins."; RL J. Biol. Chem. 279:50790-50798(2004). RN [39] RP FUNCTION, ACTIVE SITES ASP-257 AND ASP-385, AND MUTAGENESIS OF TYR-256; RP ASP-257; ASP-385 AND TYR-389. RX PubMed=15341515; DOI=10.1111/j.1471-4159.2004.02596.x; RA Wrigley J.D., Nunn E.J., Nyabi O., Clarke E.E., Hunt P., Nadin A., RA De Strooper B., Shearman M.S., Beher D.; RT "Conserved residues within the putative active site of gamma-secretase RT differentially influence enzyme activity and inhibitor binding."; RL J. Neurochem. 90:1312-1320(2004). RN [40] RP INTERACTION WITH CDH1 AND CTNNB1. RX PubMed=16126725; DOI=10.1074/jbc.m507503200; RA Serban G., Kouchi Z., Baki L., Georgakopoulos A., Litterst C.M., Shioi J., RA Robakis N.K.; RT "Cadherins mediate both the association between PS1 and beta-catenin and RT the effects of PS1 on beta-catenin stability."; RL J. Biol. Chem. 280:36007-36012(2005). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [42] RP FUNCTION, AND CHARACTERIZATION OF VARIANT AD3 VAL-146. RX PubMed=16959576; DOI=10.1016/j.cell.2006.06.059; RA Tu H., Nelson O., Bezprozvanny A., Wang Z., Lee S.F., Hao Y.H., RA Serneels L., De Strooper B., Yu G., Bezprozvanny I.; RT "Presenilins form ER Ca2+ leak channels, a function disrupted by familial RT Alzheimer's disease-linked mutations."; RL Cell 126:981-993(2006). RN [43] RP FUNCTION OF PAL MOTIF, MUTAGENESIS OF PRO-433; ALA-434 AND LEU-435, AND RP CHARACTERIZATION OF VARIANT AD3 PHE-435. RX PubMed=16305624; DOI=10.1111/j.1471-4159.2005.03548.x; RA Wang J., Beher D., Nyborg A.C., Shearman M.S., Golde T.E., Goate A.; RT "C-terminal PAL motif of presenilin and presenilin homologues required for RT normal active site conformation."; RL J. Neurochem. 96:218-227(2006). RN [44] RP VARIANTS AD3 ILE-139 AND CYS-289. RX PubMed=8875251; DOI=10.1093/hmg/5.supplement_1.1449; RA Cruts M., Hendriks L., Van Broeckhoven C.; RT "The presenilin genes: a new gene family involved in Alzheimer disease RT pathology."; RL Hum. Mol. Genet. 5:1449-1455(1996). RN [45] RP REVIEW ON VARIANTS. RX PubMed=9521418; RX DOI=10.1002/(sici)1098-1004(1998)11:3<183::aid-humu1>3.0.co;2-j; RA Cruts M., van Broeckhoven C.; RT "Presenilin mutations in Alzheimer's disease."; RL Hum. Mutat. 11:183-190(1998). RN [46] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [47] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [48] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [49] RP IDENTIFICATION IN THE GAMMA-SECRETASE COMPLEX, AND INTERACTION WITH CRB2. RX PubMed=20299451; DOI=10.1074/jbc.m109.038760; RA Mitsuishi Y., Hasegawa H., Matsuo A., Araki W., Suzuki T., Tagami S., RA Okochi M., Takeda M., Roepman R., Nishimura M.; RT "Human CRB2 inhibits gamma-secretase cleavage of amyloid precursor protein RT by binding to the presenilin complex."; RL J. Biol. Chem. 285:14920-14931(2010). RN [50] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [51] RP INVOLVEMENT IN ACNINV3. RX PubMed=20929727; DOI=10.1126/science.1196284; RA Wang B., Yang W., Wen W., Sun J., Su B., Liu B., Ma D., Lv D., Wen Y., RA Qu T., Chen M., Sun M., Shen Y., Zhang X.; RT "Gamma-secretase gene mutations in familial acne inversa."; RL Science 330:1065-1065(2010). RN [52] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43 AND SER-367, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [53] RP SUBCELLULAR LOCATION, AND INTERACTION WITH UBQLN1. RX PubMed=21143716; DOI=10.1111/j.1600-0854.2010.01149.x; RA Viswanathan J., Haapasalo A., Bottcher C., Miettinen R., Kurkinen K.M., RA Lu A., Thomas A., Maynard C.J., Romano D., Hyman B.T., Berezovska O., RA Bertram L., Soininen H., Dantuma N.P., Tanzi R.E., Hiltunen M.; RT "Alzheimer's disease-associated ubiquilin-1 regulates presenilin-1 RT accumulation and aggresome formation."; RL Traffic 12:330-348(2011). RN [54] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43 AND SER-367, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [55] RP FUNCTION, INTERACTION WITH APH1A/APH1B AND PEN2, SUBCELLULAR LOCATION, AND RP CHARACTERIZATION OF VARIANT AD3 ASP-206. RX PubMed=25394380; DOI=10.1007/s12035-014-8969-1; RA Chen W.T., Hsieh Y.F., Huang Y.J., Lin C.C., Lin Y.T., Liu Y.C., Lien C.C., RA Cheng I.H.; RT "G206D mutation of presenilin-1 reduces Pen2 interaction, increases RT Abeta42/Abeta40 ratio and elevates ER Ca(2+) accumulation."; RL Mol. Neurobiol. 52:1835-1849(2015). RN [56] {ECO:0007744|PDB:2KR6} RP STRUCTURE BY NMR OF 292-467. RA Doetsch V.; RT "Solution structure of presenilin-1 CTF subunit."; RL Submitted (DEC-2009) to the PDB data bank. RN [57] RP STRUCTURE BY ELECTRON MICROSCOPY (4.5 ANGSTROMS), FUNCTION, SUBCELLULAR RP LOCATION, SUBUNIT, AND TOPOLOGY. RX PubMed=25043039; DOI=10.1038/nature13567; RA Lu P., Bai X.C., Ma D., Xie T., Yan C., Sun L., Yang G., Zhao Y., Zhou R., RA Scheres S.H., Shi Y.; RT "Three-dimensional structure of human gamma-secretase."; RL Nature 512:166-170(2014). RN [58] {ECO:0007744|PDB:5FN2, ECO:0007744|PDB:5FN3, ECO:0007744|PDB:5FN4, ECO:0007744|PDB:5FN5} RP STRUCTURE BY ELECTRON MICROSCOPY (4.00 ANGSTROMS), SUBUNIT, AND TOPOLOGY. RX PubMed=26623517; DOI=10.7554/elife.11182; RA Bai X.C., Rajendra E., Yang G., Shi Y., Scheres S.H.; RT "Sampling the conformational space of the catalytic subunit of human gamma- RT secretase."; RL Elife 4:0-0(2015). RN [59] {ECO:0007744|PDB:5A63} RP STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS), SUBCELLULAR LOCATION, RP TOPOLOGY, SUBUNIT, FUNCTION, CATALYTIC ACTIVITY, CHARACTERIZATION OF RP VARIANTS AD3 LEU-213; ILE-237 AND PHE-261, AND MUTAGENESIS OF ILE-202; RP LEU-226; LEU-248 AND LEU-424. RX PubMed=26280335; DOI=10.1038/nature14892; RA Bai X.C., Yan C., Yang G., Lu P., Ma D., Sun L., Zhou R., Scheres S.H., RA Shi Y.; RT "An atomic structure of human gamma-secretase."; RL Nature 525:212-217(2015). RN [60] {ECO:0007744|PDB:4UIS} RP STRUCTURE BY ELECTRON MICROSCOPY (4.40 ANGSTROMS) OF 81-463, SUBUNIT, AND RP TOPOLOGY. RX PubMed=25918421; DOI=10.1073/pnas.1506242112; RA Sun L., Zhao L., Yang G., Yan C., Zhou R., Zhou X., Xie T., Zhao Y., Wu S., RA Li X., Shi Y.; RT "Structural basis of human gamma-secretase assembly."; RL Proc. Natl. Acad. Sci. U.S.A. 112:6003-6008(2015). RN [61] RP STRUCTURE BY ELECTRON MICROSCOPY (2.70 ANGSTROMS) OF MUTANT ALA-385 IN RP COMPLEX WITH NOTCH1; PSENEN; APH1A AND NCSTN, SUBUNIT, TOPOLOGY, CATALYTIC RP ACTIVITY, FUNCTION, ACTIVE SITE, MUTAGENESIS OF GLN-112; 288-TYR--SER-290; RP 377-ARG--LEU-381; ASP-385; LEU-432 AND 432-LEU--ALA-434, AND DOMAIN. RX PubMed=30598546; DOI=10.1038/s41586-018-0813-8; RA Yang G., Zhou R., Zhou Q., Guo X., Yan C., Ke M., Lei J., Shi Y.; RT "Structural basis of Notch recognition by human gamma-secretase."; RL Nature 565:192-197(2019). RN [62] RP STRUCTURE BY ELECTRON MICROSCOPY (2.60 ANGSTROMS) OF MUTANT ALA-385 IN RP COMPLEX WITH APP CHAIN C83; PSENEN; APH1A AND NCSTN, SUBUNIT, TOPOLOGY, RP CATALYTIC ACTIVITY, FUNCTION, ACTIVE SITE, DOMAIN, AND MUTAGENESIS OF RP GLN-112; 288-TYR--SER-290; 377-ARG--LEU-381; ASP-385; LEU-432 AND RP 432-LEU--ALA-434. RX PubMed=30630874; DOI=10.1126/science.aaw0930; RA Zhou R., Yang G., Guo X., Zhou Q., Lei J., Shi Y.; RT "Recognition of the amyloid precursor protein by human gamma-secretase."; RL Science 0:0-0(2019). RN [63] RP VARIANTS AD3 THR-143 AND ALA-384. RX PubMed=8634711; DOI=10.1093/hmg/4.12.2363; RA Cruts M., Backhovens H., Wang S.-Y., van Gassen G., Theuns J., RA de Jonghe C., Wehnert A., de Voecht J., de Winter G., Cras P., Bruyland M., RA Datson N., Weissenbach J., den Dunnen J.T., Martin J.-J., Hendriks L., RA Van Broeckhoven C.; RT "Molecular genetic analysis of familial early-onset Alzheimer's disease RT linked to chromosome 14q24.3."; RL Hum. Mol. Genet. 4:2363-2372(1995). RN [64] RP VARIANTS AD3 LEU-82; HIS-115; THR-139; ARG-163; THR-231; LEU-264; VAL-392 RP AND TYR-410. RX PubMed=8634712; DOI=10.1093/hmg/4.12.2373; RA Campion D., Flaman J.-M., Brice A., Hannequin D., Dubois B., Martin C., RA Moreau V., Charbonnier F., Didierjean O., Tardieu S., Penet C., Puel M., RA Pasquier F., le Doze F., Bellis G., Calenda A., Heilig R., Martinez M., RA Mallet J., Bellis M., Clerget-Darpoux F., Agid Y., Frebourg T.; RT "Mutations of the presenilin I gene in families with early-onset RT Alzheimer's disease."; RL Hum. Mol. Genet. 4:2373-2377(1995). RN [65] RP VARIANTS AD3 VAL-260; VAL-285 AND VAL-392. RX PubMed=7651536; DOI=10.1038/376775a0; RA Rogaev E.I., Sherrington R., Rogaeva E.A., Levesque G., Ikeda M., Liang Y., RA Chi H., Lin C., Holman K., Tsuda T., Mar L., Sorbi S., Nacmias B., RA Piacentini S., Amaducci L., Chumakov I., Cohen D., Lannfelt L., RA Fraser P.E., Rommens J.M., St George-Hyslop P.H.; RT "Familial Alzheimer's disease in kindreds with missense mutations in a gene RT on chromosome 1 related to the Alzheimer's disease type 3 gene."; RL Nature 376:775-778(1995). RN [66] RP VARIANTS AD3 VAL-139; VAL-146; TYR-163; SER-267; ALA-280 AND GLY-280. RX PubMed=7550356; DOI=10.1038/ng1095-219; RA Clark R.F., Hutton M., Fuldner R.A., Froelich S., Karran E., Talbot C., RA Crook R., Lendon C.L., Prihar G., He C., Korenblat K., Martinez A., RA Wragg M., Busfield F., Behrens M.I., Myers A., Norton J., Morris J., RA Mehta N., Pearson C., Lincoln S., Baker M., Duff K., Zehr C., Perez-Tur J., RA Houlden H., Ruiz A., Ossa J., Lopera F., Arcos M., Madrigal L., RA Collinge J., Humphreys C., Asworth T., Sarner S., Fox N.C., Harvey R., RA Kennedy A., Roques P.K., Cline R.T., Phillips C.A., Venter J.C., Forsel L., RA Axelman K., Lilius L., Johnston J., Cowburn R., Viitanen M., Winblad B., RA Kosik K.S., Haltia M., Poyhonen M., Dickson D., Mann D., Neary D., RA Snowden J., Lantos P., Lannfelt L., Rossor M.N., Roberts G.W., Adams M.D., RA Hardy J., Goate A.M.; RT "The structure of the presenilin 1 (S182) gene and identification of six RT novel mutations in early onset AD families."; RL Nat. Genet. 11:219-222(1995). RN [67] RP VARIANT AD3 ALA-280, AND INVOLVEMENT IN AD3. RX PubMed=8837617; DOI=10.1038/nm1096-1146; RA Lemere C.A., Lopera F., Kosik K.S., Lendon C.L., Ossa J., Saido T.C., RA Yamaguchi H., Ruiz A., Martinez A., Madrigal L., Hincapie L., Arango J.C., RA Anthony D.C., Koo E.H., Goate A.M., Selkoe D.J., Arango J.C.; RT "The E280A presenilin 1 Alzheimer mutation produces increased A beta 42 RT deposition and severe cerebellar pathology."; RL Nat. Med. 2:1146-1150(1996). RN [68] RP VARIANTS AD3 PHE-96; ARG-163 AND THR-213. RX PubMed=8733303; DOI=10.1016/0304-3940(96)12587-8; RA Kamino K., Sato S., Sakaki Y., Yoshiiwa A., Nishiwaki Y., Takeda H., RA Tanabe H., Nishimura T., Li K., St George-Hyslop P.H., Miki T., Ogihara T.; RT "Three different mutations of presenilin 1 gene in early-onset Alzheimer's RT disease families."; RL Neurosci. Lett. 208:195-198(1996). RN [69] RP VARIANT AD3 ASP-135. RX PubMed=9225696; DOI=10.1002/ana.410420121; RA Crook R., Ellis R., Shanks M., Thal L.J., Perez-Tur J., Baker M., RA Hutton M., Haltia T., Hardy J., Galasko D.; RT "Early-onset Alzheimer's disease with a presenilin-1 mutation at the site RT corresponding to the Volga German presenilin-2 mutation."; RL Ann. Neurol. 42:124-128(1997). RN [70] RP VARIANT AD3 ALA-280. RX PubMed=9298817; RX DOI=10.1002/(sici)1098-1004(1997)10:3<186::aid-humu2>3.0.co;2-h; RA Lendon C.L., Martinez A., Behrens I.M., Kosik K.S., Madrigal L., Norton J., RA Neuman R., Myers A., Busfield F., Wragg M., Arcos M., Arango-Viana J.C., RA Ossa J., Ruiz A., Goate A.M., Lopera F.; RT "E280A PS-1 mutation causes Alzheimer's disease but age of onset is not RT modified by ApoE alleles."; RL Hum. Mutat. 10:186-195(1997). RN [71] RP VARIANTS AD3 THR-233 AND THR-278. RX PubMed=9172170; DOI=10.1097/00001756-199704140-00043; RA Kwok J.B.J., Taddei K., Hallupp M., Fisher C., Brooks W.S., Broe G.A., RA Hardy J., Fulham M.J., Nicholson G.A., Stell R., St George-Hyslop P.H., RA Fraser P.E., Kakulas B., Clarnette R., Relkin N., Gandy S.E., RA Schofield P.R., Martins R.N.; RT "Two novel (M233T and R278T) presenilin-1 mutations in early-onset RT Alzheimer's disease pedigrees and preliminary evidence for association of RT presenilin-1 mutations with a novel phenotype."; RL NeuroReport 8:1537-1542(1997). RN [72] RP VARIANT AD3 PRO-171. RX PubMed=9833068; RA Ramirez-Duenas M.G., Rogaeva E.A., Leal C.A., Lin C., RA Ramirez-Casillas G.A., Hernandez-Romo J.A., St George-Hyslop P.H., RA Cantu J.M.; RT "A novel Leu171Pro mutation in presenilin-1 gene in a Mexican family with RT early onset Alzheimer disease."; RL Ann. Genet. 41:149-153(1998). RN [73] RP VARIANT GLY-318. RX PubMed=9851443; DOI=10.1002/ana.410440617; RA Mattila K.M., Forsell C., Pirttila T., Rinne J.O., Lehtimaki T., Roytta M., RA Lilius L., Eerola A., St George-Hyslop P.H., Frey H., Lannfelt L.; RT "The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause RT Alzheimer's disease."; RL Ann. Neurol. 44:965-967(1998). RN [74] RP VARIANT GLY-318. RX PubMed=9851450; DOI=10.1002/ana.410440624; RA Aldudo J., Bullido M.J., Frank A., Valdivieso F.; RT "Missense mutation E318G of the presenilin-1 gene appears to be a RT nonpathogenic polymorphism."; RL Ann. Neurol. 44:985-986(1998). RN [75] RP VARIANTS AD3 VAL-79; CYS-115 AND VAL-231, AND VARIANT GLY-318. RX PubMed=9384602; DOI=10.1093/hmg/7.1.43; RA Cruts M., van Duijn C.M., Backhovens H., van den Broeck M., Wehnert A., RA Serneels S., Sherrington R., Hutton M., Hardy J., St George-Hyslop P.H., RA Hofman A., van Broeckhoven C.; RT "Estimation of the genetic contribution of presenilin-1 and -2 mutations in RT a population-based study of presenile Alzheimer disease."; RL Hum. Mol. Genet. 7:43-51(1998). RN [76] RP VARIANTS AD3 ASP-120; ARG-163; VAL-209; VAL-260; LEU-264; TYR-410 AND RP PRO-426. RX PubMed=9521423; RX DOI=10.1002/(sici)1098-1004(1998)11:3<216::aid-humu6>3.0.co;2-f; RA Poorkaj P., Sharma V., Anderson L., Nemens E., Alonso M.E., Orr H., RA White J., Heston L., Bird T.D., Schellenberg G.D.; RT "Missense mutations in the chromosome 14 familial Alzheimer's disease RT presenilin 1 gene."; RL Hum. Mutat. 11:216-221(1998). RN [77] RP VARIANT AD3 GLU-378. RX PubMed=10200054; RX DOI=10.1002/(sici)1098-1004(1998)11:6<481::aid-humu12>3.0.co;2-q; RA Besancon R., Lorenzi A., Cruts M., Radawiec S., Sturtz F., Broussolle E., RA Chazot G., van Broeckhoven C., Chamba G., Vandenberghe A.; RT "Missense mutation in exon 11 (codon 378) of the presenilin-1 gene in a RT French family with early-onset Alzheimer's disease and transmission study RT by mismatch enhanced allele specific amplification."; RL Hum. Mutat. 11:481-481(1998). RN [78] RP VARIANT AD3 LYS-139. RX PubMed=9719376; DOI=10.1136/jmg.35.8.672; RA Dumanchin C., Brice A., Campion D., Hannequin D., Martin C., Moreau V., RA Agid Y., Martinez M., Clerget-Darpoux F., Frebourg T.; RT "De novo presenilin 1 mutations are rare in clinically sporadic, early RT onset Alzheimer's disease cases."; RL J. Med. Genet. 35:672-673(1998). RN [79] RP VARIANT AD3 LEU-117. RX PubMed=9507958; DOI=10.1097/00001756-199801260-00008; RA Wisniewski T., Dowjat W.K., Buxbaum J.D., Khorkova O., Efthimiopoulos S., RA Kulczycki J., Lojkowska W., Wegiel J., Wisniewski H.M., Frangione B.; RT "A novel Polish presenilin-1 mutation (P117L) is associated with familial RT Alzheimer's disease and leads to death as early as the age of 28 years."; RL NeuroReport 9:217-221(1998). RN [80] RP VARIANTS AD3 LEU-169 AND GLN-436. RX PubMed=9831473; DOI=10.1097/00001756-199810050-00034; RA Taddei K., Kwok J.B., Kril J.J., Halliday G.M., Creasey H., Hallupp M., RA Fisher C., Brooks W.S., Chung C., Andrews C., Masters C.L., Schofield P.R., RA Martins R.N.; RT "Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with RT very early onset Alzheimer's disease."; RL NeuroReport 9:3335-3339(1998). RN [81] RP VARIANT GLY-318. RX PubMed=9915968; DOI=10.1086/302200; RA Dermaut B., Cruts M., Slooter A.J.C., van Gestel S., de Jonghe C., RA Vanderstichele H., Vanmechelen E., Breteler M.M., Hofman A., RA van Duijn C.M., van Broeckhoven C.; RT "The Glu318Gly substitution in presenilin 1 is not causally related to RT Alzheimer disease."; RL Am. J. Hum. Genet. 64:290-292(1999). RN [82] RP VARIANTS AD3 LEU-82; HIS-115; ASP-120; THR-139; LEU-146; ILE-147; ARG-163; RP CYS-165; TRP-173; THR-231; THR-233; PRO-235; LEU-264; ILE-390; VAL-392 AND RP TYR-410, AND VARIANT GLY-318. RX PubMed=10441572; DOI=10.1086/302553; RA Campion D., Dumanchin C., Hannequin D., Dubois B., Belliard S., Puel M., RA Thomas-Anterion C., Michon A., Martin C., Charbonnier F., Raux G., RA Camuzat A., Penet C., Mesnage V., Martinez M., Clerget-Darpoux F., RA Brice A., Frebourg T.; RT "Early-onset autosomal dominant Alzheimer disease: prevalence, genetic RT heterogeneity, and mutation spectrum."; RL Am. J. Hum. Genet. 65:664-670(1999). RN [83] RP VARIANTS AD3 PHE-143 AND SER-436. RX PubMed=10090481; RX DOI=10.1002/(sici)1098-1004(1999)13:3<256::aid-humu11>3.0.co;2-p; RA Palmer M.S., Beck J.A., Campbell T.A., Humphries C.B., Roques P.K., RA Fox N.C., Harvey R., Rossor M.N., Collinge J.; RT "Pathogenic presenilin 1 mutations (P436S and I143F) in early-onset RT Alzheimer's disease in the UK."; RL Hum. Mutat. 13:256-256(1999). RN [84] RP VARIANT AD3 ARG-209. RX PubMed=10447269; RX DOI=10.1002/(sici)1098-1004(1999)14:1<90::aid-humu19>3.0.co;2-s; RA Sugiyama N., Suzuki K., Matsumura T., Kawanishi C., Onishi H., Yamada Y., RA Iseki E., Kosaka K.; RT "A novel missense mutation (G209R) in exon 8 of the presenilin 1 gene in a RT Japanese family with presenile familial Alzheimer's disease."; RL Hum. Mutat. 14:90-90(1999). RN [85] RP VARIANTS AD3 LEU-233; ARG-282 AND THR-409, AND VARIANT GLY-318. RX PubMed=10533070; RX DOI=10.1002/(sici)1098-1004(199911)14:5<433::aid-humu10>3.0.co;2-k; RA Aldudo J., Bullido M.J., Valdivieso F.; RT "DGGE method for the mutational analysis of the coding and proximal RT promoter regions of the Alzheimer's disease presenilin-1 gene: two novel RT mutations."; RL Hum. Mutat. 14:433-439(1999). RN [86] RP VARIANT AD3 PRO-169. RX PubMed=10025789; DOI=10.1212/wnl.52.3.566; RA Ezquerra M., Carnero C., Blesa R., Gelpi J.L., Ballesta F., Oliva R.; RT "A presenilin 1 mutation (Ser169Pro) associated with early-onset AD and RT myoclonic seizures."; RL Neurology 52:566-570(1999). RN [87] RP VARIANT AD3 PRO-219. RX PubMed=10208579; DOI=10.1097/00001756-199902250-00011; RA Smith M.J., Gardner R.J., Knight M.A., Forrest S.M., Beyreuther K., RA Storey E., McLean C.A., Cotton R.G., Cappal R., Masters C.L.; RT "Early-onset Alzheimer's disease caused by a novel mutation at codon 219 of RT the presenilin-1 gene."; RL NeuroReport 10:503-507(1999). RN [88] RP VARIANT AD3 ASN-116. RX PubMed=10439444; DOI=10.1097/00001756-199908020-00006; RA Romero I., Joergensen P., Bolwig G., Fraser P.E., Rogaeva E., Mann D., RA Havsager A.-M., Joergensen A.L.; RT "A presenilin-1 Thr116Asn substitution in a family with early-onset RT Alzheimer's disease."; RL NeuroReport 10:2255-2260(1999). RN [89] RP VARIANTS AD3 VAL-79; LEU-105 AND VAL-139, AND VARIANT GLY-318. RX PubMed=10631141; DOI=10.1086/302702; RA Finckh U., Mueller-Thomsen T., Mann U., Eggers C., Marksteiner J., RA Meins W., Binetti G., Alberici A., Hock C., Nitsch R.M., Gal A.; RT "High prevalence of pathogenic mutations in patients with early-onset RT dementia detected by sequence analyses of four different genes."; RL Am. J. Hum. Genet. 66:110-117(2000). RN [90] RP VARIANT AD3 SER-405. RX PubMed=10644793; DOI=10.1136/jnnp.68.2.220; RA Yasuda M., Maeda S., Kawamata T., Tamaoka A., Yamamoto Y., Kuroda S., RA Maeda K., Tanaka C.; RT "Novel presenilin-1 mutation with widespread cortical amyloid deposition RT but limited cerebral amyloid angiopathy."; RL J. Neurol. Neurosurg. Psych. 68:220-223(2000). RN [91] RP VARIANT AD3 SER-92. RX PubMed=11027672; DOI=10.1006/bbrc.2000.3646; RA Lewis P.A., Perez-Tur J., Golde T.E., Hardy J.; RT "The presenilin 1 C92S mutation increases abeta 42 production."; RL Biochem. Biophys. Res. Commun. 277:261-263(2000). RN [92] RP VARIANT FTD1 PRO-113. RX PubMed=11094121; DOI=10.1212/wnl.55.10.1577; RA Raux G., Gantier R., Thomas-Anterion C., Boulliat J., Verpillat P., RA Hannequin D., Brice A., Frebourg T., Campion D.; RT "Dementia with prominent frontotemporal features associated with L113P RT presenilin 1 mutation."; RL Neurology 55:1577-1578(2000). RN [93] RP VARIANTS AD3 MET-94; THR-143 AND ALA-280, AND VARIANT GLY-318. RX PubMed=11568920; RX DOI=10.1002/1096-8628(20011001)103:2<138::aid-ajmg1529>3.0.co;2-8; RA Arango D., Cruts M., Torres O., Backhovens H., Serrano M.L., Villareal E., RA Montanes P., Matallana D., Cano C., Van Broeckhoven C., Jacquier M.; RT "Systematic genetic study of Alzheimer disease in Latin America: mutation RT frequencies of the amyloid beta precursor protein and presenilin genes in RT Colombia."; RL Am. J. Med. Genet. 103:138-143(2001). RN [94] RP VARIANT AD3 VAL-282, AND CHARACTERIZATION OF VARIANT AD3 VAL-282. RX PubMed=11701593; DOI=10.1093/brain/124.12.2383; RA Dermaut B., Kumar-Singh S., De Jonghe C., Cruts M., Loefgren A., Luebke U., RA Cras P., Dom R., De Deyn P.P., Martin J.J., Van Broeckhoven C.; RT "Cerebral amyloid angiopathy is a pathogenic lesion in Alzheimer's disease RT due to a novel presenilin 1 mutation."; RL Brain 124:2383-2392(2001). RN [95] RP ERRATUM OF PUBMED:11701593, AND VARIANT AD3 GLU-431. RA Ringman J.M., Jain V., Murrell J., Ghetti B., Cochran E.J.; RL Hum. Genet. 109:242-242(2001). RN [96] RP VARIANT AD3 ALA-206. RX PubMed=11710891; DOI=10.1001/jama.286.18.2257; RA Athan E.S., Williamson J., Ciappa A., Santana V., Romas S.N., Lee J.H., RA Rondon H., Lantigua R.A., Medrano M., Torres M., Arawaka S., Rogaeva E., RA Song Y.-Q., Sato C., Kawarai T., Fafel K.C., Boss M.A., Seltzer W.K., RA Stern Y., St George-Hyslop P.H., Tycko B., Mayeux R.; RT "A founder mutation in presenilin 1 causing early-onset Alzheimer disease RT in unrelated Caribbean Hispanic families."; RL JAMA 286:2257-2263(2001). RN [97] RP VARIANT AD3 ILE-237. RX PubMed=11561050; DOI=10.1136/jnnp.71.4.556; RA Sodeyama N., Iwata T., Ishikawa K., Mizusawa H., Yamada M., Itoh Y., RA Otomo E., Matsushita M., Komatsuzaki Y.; RT "Very early onset Alzheimer's disease with spastic paraparesis associated RT with a novel presenilin 1 mutation (Phe237Ile)."; RL J. Neurol. Neurosurg. Psych. 71:556-557(2001). RN [98] RP VARIANTS AD3 GLN-35; VAL-79; CYS-115; ASN-116; THR-143; ILE-146; LEU-146; RP VAL-146; TYR-156 DELINS PHE-THR-TYR; ARG-163; LEU-177; SER-177; PRO-178; RP ALA-206; SER-206; GLU-209; LEU-213; ARG-222; THR-231; LEU-233; PRO-235; RP PHE-261; ARG-274; ARG-352 INS; ILE-354; GLN-358; TYR-365; VAL-394; PHE-418; RP GLU-431; PHE-435 AND VAL-439, AND VARIANT GLY-318. RX PubMed=11524469; DOI=10.1212/wnl.57.4.621; RA Rogaeva E.A., Fafel K.C., Song Y.Q., Medeiros H., Sato C., Liang Y., RA Richard E., Rogaev E.I., Frommelt P., Sadovnick A.D., Meschino W., RA Rockwood K., Boss M.A., Mayeux R., St George-Hyslop P.; RT "Screening for PS1 mutations in a referral-based series of AD cases: 21 RT novel mutations."; RL Neurology 57:621-625(2001). RN [99] RP VARIANT AD3 SER-266. RX PubMed=11920851; DOI=10.1002/ajmg.10250; RA Matsubara-Tsutsui M., Yasuda M., Yamagata H., Nomura T., Taguchi K., RA Kohara K., Miyoshi K., Miki T.; RT "Molecular evidence of presenilin 1 mutation in familial early onset RT dementia."; RL Am. J. Med. Genet. 114:292-298(2002). RN [100] RP VARIANT AD3 LEU-89. RX PubMed=11796781; DOI=10.1136/jnnp.72.2.266; RA Queralt R., Ezquerra M., Lleo A., Castellvi M., Gelpi J., Ferrer I., RA Acarin N., Pasarin L., Blesa R., Oliva R.; RT "A novel mutation (V89L) in the presenilin 1 gene in a family with early RT onset Alzheimer's disease and marked behavioural disturbances."; RL J. Neurol. Neurosurg. Psych. 72:266-269(2002). RN [101] RP VARIANT AD3 GLY-280. RX PubMed=12370477; DOI=10.1212/wnl.59.7.1108; RA O'Riordan S., McMonagle P., Janssen J.C., Fox N.C., Farrell M., RA Collinge J., Rossor M.N., Hutchinson M.; RT "Presenilin-1 mutation (E280G), spastic paraparesis, and cranial MRI white- RT matter abnormalities."; RL Neurology 59:1108-1110(2002). RN [102] RP VARIANT AD3 PRO-166. RX PubMed=12048239; DOI=10.1073/pnas.112686799; RA Moehlmann T., Winkler E., Xia X., Edbauer D., Murrell J., Capell A., RA Kaether C., Zheng H., Ghetti B., Haass C., Steiner H.; RT "Presenilin-1 mutations of leucine 166 equally affect the generation of the RT Notch and APP intracellular domains independent of their effect on Abeta 42 RT production."; RL Proc. Natl. Acad. Sci. U.S.A. 99:8025-8030(2002). RN [103] RP VARIANT AD3 MET-174. RX PubMed=12484344; DOI=10.1007/s10048-002-0136-6; RA Bertoli-Avella A.M., Marcheco Teruel B., Llibre Rodriguez J.J., RA Gomez Viera N., Borrajero-Martinez I., Severijnen E.A., Joosse M., RA van Duijn C.M., Heredero Baute L., Heutink P.; RT "A novel presenilin 1 mutation (L174 M) in a large Cuban family with early RT onset Alzheimer disease."; RL Neurogenetics 4:97-104(2002). RN [104] RP VARIANT AD3 VAL-271. RX PubMed=12493737; DOI=10.1074/jbc.m211827200; RA Kwok J.B.J., Halliday G.M., Brooks W.S., Dolios G., Laudon H., Murayama O., RA Hallupp M., Badenhop R.F., Vickers J., Wang R., Naslund J., Takashima A., RA Gandy S.E., Schofield P.R.; RT "Presenilin-1 mutation L271V results in altered exon 8 splicing and RT Alzheimer's disease with non-cored plaques and no neuritic dystrophy."; RL J. Biol. Chem. 278:6748-6754(2003). RN [105] RP VARIANTS AD3 CYS-115; ILE-146; VAL-153; CYS-154; ILE-168 DEL; PRO-171; RP ASP-184; PHE-229; VAL-235; LEU-237; VAL-260; PHE-263; HIS-269; MET-377 AND RP VAL-378, AND VARIANT GLY-318. RX PubMed=12552037; DOI=10.1212/01.wnl.0000042088.22694.e3; RA Janssen J.C., Beck J.A., Campbell T.A., Dickinson A., Fox N.C., RA Harvey R.J., Houlden H., Rossor M.N., Collinge J.; RT "Early onset familial Alzheimer's disease: Mutation frequency in 31 RT families."; RL Neurology 60:235-239(2003). RN [106] RP VARIANT PIDB VAL-183, CHARACTERIZATION OF VARIANTS AD3 THR-143 AND VAL-282, RP AND CHARACTERIZATION OF VARIANT PIDB VAL-183. RX PubMed=15122701; DOI=10.1002/ana.20083; RA Dermaut B., Kumar-Singh S., Engelborghs S., Theuns J., Rademakers R., RA Saerens J., Pickut B.A., Peeters K., van den Broeck M., Vennekens K., RA Claes S., Cruts M., Cras P., Martin J.J., Van Broeckhoven C., De Deyn P.P.; RT "A novel presenilin 1 mutation associated with Pick's disease but not beta- RT amyloid plaques."; RL Ann. Neurol. 55:617-626(2004). RN [107] RP VARIANT AD3 PRO-85, AND CHARACTERIZATION OF VARIANT AD3 PRO-85. RX PubMed=15534188; DOI=10.1001/archneur.61.11.1773; RA Ataka S., Tomiyama T., Takuma H., Yamashita T., Shimada H., Tsutada T., RA Kawabata K., Mori H., Miki T.; RT "A novel presenilin-1 mutation (Leu85Pro) in early-onset Alzheimer disease RT with spastic paraparesis."; RL Arch. Neurol. 61:1773-1776(2004). RN [108] RP VARIANT AD3 ILE-278. RX PubMed=15534260; DOI=10.1212/01.wnl.0000143060.98164.1a; RA Godbolt A.K., Beck J.A., Collinge J., Garrard P., Warren J.D., Fox N.C., RA Rossor M.N.; RT "A presenilin 1 R278I mutation presenting with language impairment."; RL Neurology 63:1702-1704(2004). RN [109] RP VARIANT AD3 ASN-154. RX PubMed=15364419; DOI=10.1016/j.neulet.2004.07.057; RA Hattori S., Sakuma K., Wakutani Y., Wada K., Shimoda M., Urakami K., RA Kowa H., Nakashima K.; RT "A novel presenilin 1 mutation (Y154N) in a patient with early onset RT Alzheimer's disease with spastic paraparesis."; RL Neurosci. Lett. 368:319-322(2004). RN [110] RP VARIANT AD3 PHE-170. RX PubMed=16344340; DOI=10.1001/archneur.62.12.1821; RA Snider B.J., Norton J., Coats M.A., Chakraverty S., Hou C.E., Jervis R., RA Lendon C.L., Goate A.M., McKeel D.W. Jr., Morris J.C.; RT "Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy RT bodies in the third decade of life."; RL Arch. Neurol. 62:1821-1830(2005). RN [111] RP VARIANT AD3 LEU-97. RX PubMed=15851849; DOI=10.3233/jad-2005-7204; RA Jia J., Xu E., Shao Y., Jia J., Sun Y., Li D.; RT "One novel presenilin-1 gene mutation in a Chinese pedigree of familial RT Alzheimer's disease."; RL J. Alzheimers Dis. 7:119-124(2005). RN [112] RP VARIANT CMD1U GLY-333. RX PubMed=17186461; DOI=10.1086/509900; RA Li D., Parks S.B., Kushner J.D., Nauman D., Burgess D., Ludwigsen S., RA Partain J., Nixon R.R., Allen C.N., Irwin R.P., Jakobs P.M., Litt M., RA Hershberger R.E.; RT "Mutations of presenilin genes in dilated cardiomyopathy and heart RT failure."; RL Am. J. Hum. Genet. 79:1030-1039(2006). RN [113] RP CHARACTERIZATION OF VARIANTS AD3 VAL-79; THR-143; VAL-231; PHE-262; RP PHE-263; VAL-282 AND ALA-384. RX PubMed=16752394; DOI=10.1002/humu.20336; RA Kumar-Singh S., Theuns J., Van Broeck B., Pirici D., Vennekens K., RA Corsmit E., Cruts M., Dermaut B., Wang R., Van Broeckhoven C.; RT "Mean age-of-onset of familial alzheimer disease caused by presenilin RT mutations correlates with both increased Abeta42 and decreased Abeta40."; RL Hum. Mutat. 27:686-695(2006). RN [114] RP VARIANT AD3 GLU-431. RX PubMed=16628450; DOI=10.1007/s10048-006-0043-3; RA Yescas P., Huertas-Vazquez A., Villarreal-Molina M.T., Rasmussen A., RA Tusie-Luna M.T., Lopez M., Canizales-Quinteros S., Alonso M.E.; RT "Founder effect for the Ala431Glu mutation of the presenilin 1 gene causing RT early-onset Alzheimer's disease in Mexican families."; RL Neurogenetics 7:195-200(2006). RN [115] RP VARIANT AD3 GLU-431. RX PubMed=16897084; DOI=10.1007/s10048-006-0053-1; RA Murrell J., Ghetti B., Cochran E., Macias-Islas M.A., Medina L., RA Varpetian A., Cummings J.L., Mendez M.F., Kawas C., Chui H., Ringman J.M.; RT "The A431E mutation in PSEN1 causing familial Alzheimer's disease RT originating in Jalisco State, Mexico: an additional fifteen families."; RL Neurogenetics 7:277-279(2006). RN [116] RP VARIANT AD3 VAL-79, AND CHARACTERIZATION OF VARIANT AD3 VAL-79. RX PubMed=17366635; DOI=10.1002/ana.21099; RA Kauwe J.S., Jacquart S., Chakraverty S., Wang J., Mayo K., Fagan A.M., RA Holtzman D.M., Morris J.C., Goate A.M.; RT "Extreme cerebrospinal fluid amyloid beta levels identify family with late- RT onset Alzheimer's disease presenilin 1 mutation."; RL Ann. Neurol. 61:446-453(2007). RN [117] RP VARIANT AD3 PHE-170. RX PubMed=17502474; DOI=10.1001/archneur.64.5.738; RA Piccini A., Zanusso G., Borghi R., Noviello C., Monaco S., Russo R., RA Damonte G., Armirotti A., Gelati M., Giordano R., Zambenedetti P., RA Russo C., Ghetti B., Tabaton M.; RT "Association of a presenilin 1 S170F mutation with a novel Alzheimer RT disease molecular phenotype."; RL Arch. Neurol. 64:738-745(2007). RN [118] RP CHARACTERIZATION OF VARIANTS AD3 LEU-117; LEU-146; GLU-246; VAL-260; RP LEU-264 AND GLY-280, FUNCTION, AND MUTAGENESIS OF ASP-257. RX PubMed=17428795; DOI=10.1074/jbc.m611449200; RA Litterst C., Georgakopoulos A., Shioi J., Ghersi E., Wisniewski T., RA Wang R., Ludwig A., Robakis N.K.; RT "Ligand binding and calcium influx induce distinct ectodomain/gamma- RT secretase-processing pathways of EphB2 receptor."; RL J. Biol. Chem. 282:16155-16163(2007). RN [119] RP VARIANT GLY-318. RX PubMed=18485326; DOI=10.1016/j.ajhg.2008.04.014; RA Cornier A.S., Staehling-Hampton K., Delventhal K.M., Saga Y., Caubet J.-F., RA Sasaki N., Ellard S., Young E., Ramirez N., Carlo S.E., Torres J., RA Emans J.B., Turnpenny P.D., Pourquie O.; RT "Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin RT syndrome."; RL Am. J. Hum. Genet. 82:1334-1341(2008). RN [120] RP CHARACTERIZATION OF VARIANT AD3 THR-213. RX PubMed=18430735; DOI=10.1074/jbc.m801279200; RA Shimojo M., Sahara N., Mizoroki T., Funamoto S., Morishima-Kawashima M., RA Kudo T., Takeda M., Ihara Y., Ichinose H., Takashima A.; RT "Enzymatic characteristics of I213T mutant presenilin-1/gamma-secretase in RT cell models and knock-in mouse brains: familial Alzheimer disease-linked RT mutation impairs gamma-site cleavage of amyloid precursor protein C- RT terminal fragment beta."; RL J. Biol. Chem. 283:16488-16496(2008). RN [121] RP VARIANT AD3 VAL-381. RX PubMed=19797784; DOI=10.1177/1533317509341464; RA Dintchov Traykov L., Mehrabian S., Van den Broeck M., RA Radoslavova Raycheva M., Cruts M., Kirilova Jordanova A., RA Van Broeckhoven C.; RT "Novel PSEN1 mutation in a Bulgarian patient with very early-onset RT Alzheimer's disease, spastic paraparesis, and extrapyramidal signs."; RL Am. J. Alzheimers Dis. Other Demen. 24:404-407(2009). RN [122] RP VARIANT AD3 ARG-217, AND CHARACTERIZATION OF VARIANT AD3 ARG-217. RX PubMed=19667325; DOI=10.1212/wnl.0b013e3181b163ba; RA Norton J.B., Cairns N.J., Chakraverty S., Wang J., Levitch D., Galvin J.E., RA Goate A.; RT "Presenilin1 G217R mutation linked to Alzheimer disease with cotton wool RT plaques."; RL Neurology 73:480-482(2009). RN [123] RP VARIANT AD3 LEU-146. RX PubMed=20164095; DOI=10.1212/wnl.0b013e3181d52785; RA Bruni A.C., Bernardi L., Colao R., Rubino E., Smirne N., Frangipane F., RA Terni B., Curcio S.A., Mirabelli M., Clodomiro A., Di Lorenzo R., RA Maletta R., Anfossi M., Gallo M., Geracitano S., Tomaino C., Muraca M.G., RA Leotta A., Lio S.G., Pinessi L., Rainero I., Sorbi S., Nee L., Milan G., RA Pappata S., Postiglione A., Abbamondi N., Forloni G., St George Hyslop P., RA Rogaeva E., Bugiani O., Giaccone G., Foncin J.F., Spillantini M.G., RA Puccio G.; RT "Worldwide distribution of PSEN1 Met146Leu mutation: a large variability RT for a founder mutation."; RL Neurology 74:798-806(2010). RN [124] RP VARIANT AD3 PHE-435, CHARACTERIZATION OF VARIANTS AD3 PHE-435; GLN-436 AND RP SER-436, MUTAGENESIS OF PRO-433 AND LEU-435, AND FUNCTION. RX PubMed=20460383; DOI=10.1074/jbc.m110.116962; RA Heilig E.A., Xia W., Shen J., Kelleher R.J. III; RT "A presenilin-1 mutation identified in familial Alzheimer disease with RT cotton wool plaques causes a nearly complete loss of gamma-secretase RT activity."; RL J. Biol. Chem. 285:22350-22359(2010). RN [125] RP VARIANT AD3 ASP-206. RX PubMed=21335660; DOI=10.3233/jad-2011-102031; RA Wu Y.Y., Cheng I.H., Lee C.C., Chiu M.J., Lee M.J., Chen T.F., Hsu J.L.; RT "Clinical phenotype of G206D mutation in the presenilin 1 gene in RT pathologically confirmed familial Alzheimer's disease."; RL J. Alzheimers Dis. 25:145-150(2011). RN [126] RP VARIANT CYS-315. RX PubMed=21248752; DOI=10.1038/nature09639; RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M., RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.; RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene RT PBRM1 in renal carcinoma."; RL Nature 469:539-542(2011). RN [127] RP VARIANT AD3 ARG-235. RX PubMed=21501661; DOI=10.1016/j.neulet.2011.03.084; RA Antonell A., Balasa M., Oliva R., Llado A., Bosch B., Fabregat N., RA Fortea J., Molinuevo J.L., Sanchez-Valle R.; RT "A novel PSEN1 gene mutation (L235R) associated with familial early-onset RT Alzheimer's disease."; RL Neurosci. Lett. 496:40-42(2011). RN [128] RP CHARACTERIZATION OF VARIANTS AD3 LEU-146; ARG-163 AND ALA-280. RX PubMed=22461631; DOI=10.1074/jbc.m111.300483; RA Chau D.M., Crump C.J., Villa J.C., Scheinberg D.A., Li Y.M.; RT "Familial Alzheimer disease presenilin-1 mutations alter the active site RT conformation of gamma-secretase."; RL J. Biol. Chem. 287:17288-17296(2012). RN [129] RP VARIANTS AD3 ARG-134; ARG-163 AND VAL-262, AND VARIANT TYR-214. RX PubMed=22503161; DOI=10.1016/j.neurobiolaging.2012.02.020; RA Lohmann E., Guerreiro R.J., Erginel-Unaltuna N., Gurunlian N., Bilgic B., RA Gurvit H., Hanagasi H.A., Luu N., Emre M., Singleton A.; RT "Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish RT dementia patients."; RL Neurobiol. Aging 33:1850.E17-1850.E27(2012). RN [130] RP VARIANT AD3 PHE-159. RX PubMed=23123781; DOI=10.1016/j.neulet.2012.10.037; RA Kerchner G.A., Holbrook K.; RT "Novel presenilin-1 Y159F sequence variant associated with early-onset RT Alzheimer's disease."; RL Neurosci. Lett. 531:142-144(2012). RN [131] RP CHARACTERIZATION OF VARIANTS AD3 PRO-166 AND GLN-436, AND MUTAGENESIS OF RP ASP-257 AND ASP-385. RX PubMed=22529981; DOI=10.1371/journal.pone.0035133; RA Cacquevel M., Aeschbach L., Houacine J., Fraering P.C.; RT "Alzheimer's disease-linked mutations in presenilin-1 result in a drastic RT loss of activity in purified gamma-secretase complexes."; RL PLoS ONE 7:E35133-E35133(2012). RN [132] RP CHARACTERIZATION OF VARIANTS AD3 PRO-166; ILE-278; ALA-384; VAL-392; RP TYR-410 AND PHE-435. RX PubMed=23843529; DOI=10.1523/jneurosci.0954-13.2013; RA Heilig E.A., Gutti U., Tai T., Shen J., Kelleher R.J. III; RT "Trans-dominant negative effects of pathogenic PSEN1 mutations on gamma- RT secretase activity and Abeta production."; RL J. Neurosci. 33:11606-11617(2013). RN [133] RP VARIANT AD3 PHE-381. RX PubMed=24121961; DOI=10.3233/jad-131340; RA Dolzhanskaya N., Gonzalez M.A., Sperziani F., Stefl S., Messing J., RA Wen G.Y., Alexov E., Zuchner S., Velinov M.; RT "A novel p.Leu(381)Phe mutation in presenilin 1 is associated with very RT early onset and unusually fast progressing dementia as well as lysosomal RT inclusions typically seen in Kufs disease."; RL J. Alzheimers Dis. 39:23-27(2014). RN [134] RP VARIANT AD3 VAL-153. RX PubMed=24495933; DOI=10.1016/j.neulet.2014.01.016; RA Cornejo-Olivas M.R., Yu C.E., Mazzetti P., Mata I.F., Meza M., RA Lindo-Samanamud S., Leverenz J.B., Bird T.D.; RT "Clinical and molecular studies reveal a PSEN1 mutation (L153V) in a RT Peruvian family with early-onset Alzheimer's disease."; RL Neurosci. Lett. 563:140-143(2014). RN [135] RP VARIANT AD3 VAL-275. RX PubMed=24582897; DOI=10.1016/j.neulet.2014.02.034; RA Luedecke D., Becktepe J.S., Lehmbeck J.T., Finckh U., Yamamoto R., Jahn H., RA Boelmans K.; RT "A novel presenilin 1 mutation (Ala275Val) as cause of early-onset familial RT Alzheimer disease."; RL Neurosci. Lett. 566:115-119(2014). RN [136] RP VARIANT AD3 THR-83. RX PubMed=26145164; DOI=10.1016/j.neurobiolaging.2015.06.007; RA Achouri-Rassas A., Ben Ali N., Fray S., Hadj Fredj S., Kechaou M., RA Zakraoui N.O., Cherif A., Chabbi S., Anane N., Messaoud T., Gouider R., RA Belal S.; RT "Novel presenilin 1 mutation (p.I83T) in Tunisian family with early-onset RT Alzheimer's disease."; RL Neurobiol. Aging 36:2904.E09-2904.E11(2015). RN [137] RP VARIANTS AD3 ALA-206 AND VAL-378. RX PubMed=27073747; RA Ravenscroft T.A., Pottier C., Murray M.E., Baker M., Christopher E., RA Levitch D., Brown P.H., Barker W., Duara R., Greig-Custo M., Betancourt A., RA English M., Sun X., Ertekin-Taner N., Graff-Radford N.R., Dickson D.W., RA Rademakers R.; RT "The presenilin 1 p.Gly206Ala mutation is a frequent cause of early-onset RT Alzheimer's disease in Hispanics in Florida."; RL Am. J. Neurodegener. Dis. 5:94-101(2016). RN [138] RP VARIANT AD3 THR-408. RX PubMed=26549787; DOI=10.1016/j.neulet.2015.11.004; RA Tedde A., Bartoli A., Piaceri I., Ferrara S., Bagnoli S., Serio A., RA Sorbi S., Nacmias B.; RT "Novel presenilin 1 mutation (Ile408Thr) in an Italian family with late- RT onset Alzheimer's disease."; RL Neurosci. Lett. 610:150-153(2016). RN [139] RP VARIANT ARG-311, CHARACTERIZATION OF VARIANTS ALA-280 AND ARG-311, AND RP FUNCTION. RX PubMed=28269784; DOI=10.3233/jad-161188; RA Dong J., Qin W., Wei C., Tang Y., Wang Q., Jia J.; RT "A novel PSEN1 K311R mutation discovered in Chinese families with late- RT onset Alzheimer's disease affects amyloid-beta production and tau RT phosphorylation."; RL J. Alzheimers Dis. 57:613-623(2017). RN [140] RP CHARACTERIZATION OF VARIANTS AD3 GLN-35; VAL-79; LEU-82; PRO-85; LEU-89; RP SER-92; MET-94; PHE-96; LEU-97; HIS-115; ASN-116; ASP-120; LYS-120; RP ARG-134; ASP-135; VAL-139; THR-143; LEU-146; ILE-147; VAL-153; ASN-154; RP ARG-163; TYR-163; PRO-166; PRO-169; PHE-170; PRO-171; TRP-173; MET-174; RP LEU-177; PRO-178; VAL-183; ASP-184; ALA-206; SER-206; ARG-209; VAL-209; RP LEU-213; ARG-217; ARG-222; PHE-229; THR-231; LEU-233; THR-233; ARG-235; RP PRO-235; VAL-235; ILE-237; GLU-246; SER-250; VAL-260; PHE-261; PHE-262; RP ARG-263; LEU-264; SER-266; SER-267; GLY-269; VAL-271; ARG-274; VAL-275; RP ALA-280; GLY-280; ARG-282; VAL-285; VAL-286; ILE-354; GLN-358; GLU-378; RP VAL-378; VAL-381; ALA-384; ILE-390; VAL-392; VAL-394; THR-396; SER-405; RP THR-409; TYR-410; PHE-418; PRO-426; GLU-431; PHE-435; SER-436 AND VAL-439, RP CHARACTERIZATION OF VARIANT CMD1U GLY-333, AND MUTAGENESIS OF THR-99; RP PHE-105; ARG-108; LEU-113; PRO-117; GLU-123; HIS-131; ALA-136; ILE-143; RP LEU-150; TRP-165; ILE-168; PHE-176; GLU-184; ILE-202; SER-212; HIS-214; RP LEU-219; GLN-223; LEU-226; SER-230; ILE-238; LYS-239; THR-245; LEU-248; RP TYR-256; VAL-272; GLU-273; ARG-278; PRO-284; THR-291; ARG-352; SER-365; RP ARG-377; PHE-386; VAL-391; VAL-412; LEU-420; LEU-424; ALA-434 AND ILE-437. RX PubMed=27930341; DOI=10.1073/pnas.1618657114; RA Sun L., Zhou R., Yang G., Shi Y.; RT "Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro RT production of Abeta42 and Abeta40 peptides by gamma-secretase."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E476-E485(2017). RN [141] RP VARIANT AD3 ILE-116. RX PubMed=30200536; DOI=10.3390/ijms19092604; RA Bagyinszky E., Lee H.M., Van Giau V., Koh S.B., Jeong J.H., An S.S.A., RA Kim S.; RT "PSEN1 p.Thr116Ile variant in two Korean families with young onset RT Alzheimer's disease."; RL Int. J. Mol. Sci. 19:0-0(2018). RN [142] RP VARIANT AD3 ASN-116. RX PubMed=29404783; DOI=10.1007/s00702-018-1850-z; RA Sutovsky S., Smolek T., Turcani P., Petrovic R., Brandoburova P., RA Jadhav S., Novak P., Attems J., Zilka N.; RT "Neuropathology and biochemistry of early onset familial Alzheimer's RT disease caused by presenilin-1 missense mutation Thr116Asn."; RL J. Neural Transm. 125:965-976(2018). RN [143] RP VARIANTS AD3 PHE-142 AND ASP-206. RX PubMed=29175279; DOI=10.1016/j.neurobiolaging.2017.10.011; RA Wang J.C., Alinaghi S., Tafakhori A., Sikora E., Azcona L.J., RA Karkheiran S., Goate A., Paisan-Ruiz C., Darvish H.; RT "Genetic screening in two Iranian families with early-onset Alzheimer's RT disease identified a novel PSEN1 mutation."; RL Neurobiol. Aging 62:E15-E17(2018). RN [144] RP VARIANT AD3 ALA-417. RX PubMed=30180983; DOI=10.1016/j.neurobiolaging.2018.08.003; RA Giau V.V., Wang M.J., Bagyinszky E., Youn Y.C., An S.S.A., Kim S.; RT "Novel PSEN1 p.Gly417Ala mutation in a Korean patient with early-onset RT Alzheimer's disease with parkinsonism."; RL Neurobiol. Aging 72:E13-E17(2018). RN [145] RP VARIANT AD3 PHE-170. RX PubMed=29466804; DOI=10.1159/000485899; RA Tiedt H.O., Benjamin B., Niedeggen M., Lueschow A.; RT "Phenotypic variability in autosomal dominant familial Alzheimer disease RT due to the S170F mutation of presenilin-1."; RL Neurodegener. Dis. 18:57-68(2018). CC -!- FUNCTION: Catalytic subunit of the gamma-secretase complex, an CC endoprotease complex that catalyzes the intramembrane cleavage of CC integral membrane proteins such as Notch receptors and APP (amyloid- CC beta precursor protein) (PubMed:10206644, PubMed:10545183, CC PubMed:10593990, PubMed:10811883, PubMed:10899933, PubMed:12679784, CC PubMed:12740439, PubMed:15274632, PubMed:20460383, PubMed:25043039, CC PubMed:26280335, PubMed:28269784, PubMed:30598546, PubMed:30630874). CC Requires the presence of the other members of the gamma-secretase CC complex for protease activity (PubMed:15274632, PubMed:25043039, CC PubMed:26280335, PubMed:30598546, PubMed:30630874). Plays a role in CC Notch and Wnt signaling cascades and regulation of downstream processes CC via its role in processing key regulatory proteins, and by regulating CC cytosolic CTNNB1 levels (PubMed:10593990, PubMed:10811883, CC PubMed:10899933, PubMed:9738936). Stimulates cell-cell adhesion via its CC interaction with CDH1; this stabilizes the complexes between CDH1 (E- CC cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 CC and JUP (gamma-catenin) (PubMed:11953314). Under conditions of CC apoptosis or calcium influx, cleaves CDH1 (PubMed:11953314). This CC promotes the disassembly of the complexes between CDH1 and CTNND1, JUP CC and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby CC negatively regulates Wnt signaling (PubMed:11953314, PubMed:9738936). CC Required for normal embryonic brain and skeleton development, and for CC normal angiogenesis (By similarity). Mediates the proteolytic cleavage CC of EphB2/CTF1 into EphB2/CTF2 (PubMed:17428795, PubMed:28269784). The CC holoprotein functions as a calcium-leak channel that allows the passive CC movement of calcium from endoplasmic reticulum to cytosol and is CC therefore involved in calcium homeostasis (PubMed:16959576, CC PubMed:25394380). Involved in the regulation of neurite outgrowth CC (PubMed:15004326, PubMed:20460383). Is a regulator of presynaptic CC facilitation, spike transmission and synaptic vesicles replenishment in CC a process that depends on gamma-secretase activity. It acts through the CC control of SYT7 presynaptic expression (By similarity). CC {ECO:0000250|UniProtKB:P49769, ECO:0000269|PubMed:10206644, CC ECO:0000269|PubMed:10545183, ECO:0000269|PubMed:10593990, CC ECO:0000269|PubMed:10811883, ECO:0000269|PubMed:10899933, CC ECO:0000269|PubMed:11953314, ECO:0000269|PubMed:12679784, CC ECO:0000269|PubMed:12740439, ECO:0000269|PubMed:15004326, CC ECO:0000269|PubMed:15274632, ECO:0000269|PubMed:15341515, CC ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:16959576, CC ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:20460383, CC ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:25394380, CC ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:28269784, CC ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874, CC ECO:0000269|PubMed:9738936}. CC -!- SUBUNIT: Homodimer. The functional gamma-secretase complex is composed CC of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), CC nicastrin (NCSTN), APH1 (APH1A/APH1B) and PEN2 (PubMed:12679784, CC PubMed:12740439, PubMed:15274632, PubMed:25043039, PubMed:25394380, CC PubMed:26280335, PubMed:30598546, PubMed:30630874). Such minimal CC complex is sufficient for secretase activity (PubMed:12679784, CC PubMed:12740439, PubMed:15274632, PubMed:25043039, PubMed:26280335, CC PubMed:30598546, PubMed:30630874). Other components which are CC associated with the complex include SLC25A64, SLC5A7, PHB and PSEN1 CC isoform 3. As part of the gamma-secretase complex, interacts with CRB2 CC (via transmembrane domain) (PubMed:20299451). Predominantly heterodimer CC of a N-terminal (NTF) and a C-terminal (CTF) endoproteolytical fragment CC (PubMed:15274632). Associates with proteolytic processed C-terminal CC fragments C83 and C99 of the amyloid precursor protein (APP) (via CC transmembrane domain) (PubMed:30630874). Associates with NOTCH1 (via CC transmembrane domain) (PubMed:10593990, PubMed:30598546). Associates CC with cadherin/catenin adhesion complexes through direct binding to CDH1 CC or CDH2 (PubMed:11953314, PubMed:14515347, PubMed:16126725). CC Interaction with CDH1 stabilizes the complex and stimulates cell-cell CC aggregation (PubMed:11953314). Interaction with CDH2 is essential for CC trafficking of CDH2 from the endoplasmic reticulum to the plasma CC membrane (PubMed:14515347). Interacts with CTNND2, CTNNB1, CTNND1, JUP, CC HERPUD1, FLNA, FLNB, MTCH1, PKP4 and PARL (PubMed:10037471, CC PubMed:10551805, PubMed:11799129, PubMed:11953314, PubMed:12214059, CC PubMed:16126725, PubMed:9437013, PubMed:9738936). Interacts through its CC N-terminus with GFAP (isoform 2) (PubMed:12058025). Interacts with CC DOCK3; this interaction mediates the membrane association of DOCK3 CC (PubMed:10854253). Interacts with isoform 1 and isoform 3 of UBQLN1 CC (PubMed:21143716). {ECO:0000250|UniProtKB:P49769, CC ECO:0000269|PubMed:10037471, ECO:0000269|PubMed:10551805, CC ECO:0000269|PubMed:10854253, ECO:0000269|PubMed:11799129, CC ECO:0000269|PubMed:11953314, ECO:0000269|PubMed:12058025, CC ECO:0000269|PubMed:12214059, ECO:0000269|PubMed:12679784, CC ECO:0000269|PubMed:12740439, ECO:0000269|PubMed:14515347, CC ECO:0000269|PubMed:15274632, ECO:0000269|PubMed:16126725, CC ECO:0000269|PubMed:20299451, ECO:0000269|PubMed:21143716, CC ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:25394380, CC ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:30598546, CC ECO:0000269|PubMed:30630874, ECO:0000269|PubMed:9437013, CC ECO:0000269|PubMed:9738936}. CC -!- INTERACTION: CC P49768; Q02410: APBA1; NbExp=4; IntAct=EBI-297277, EBI-368690; CC P49768; Q96BI3: APH1A; NbExp=3; IntAct=EBI-297277, EBI-2606935; CC P49768; P05067: APP; NbExp=6; IntAct=EBI-297277, EBI-77613; CC P49768; P05067-4: APP; NbExp=4; IntAct=EBI-297277, EBI-302641; CC P49768; P56817: BACE1; NbExp=6; IntAct=EBI-297277, EBI-2433139; CC P49768; Q16543: CDC37; NbExp=3; IntAct=EBI-297277, EBI-295634; CC P49768; P12830: CDH1; NbExp=2; IntAct=EBI-297277, EBI-727477; CC P49768; Q9BQ95: ECSIT; NbExp=4; IntAct=EBI-297277, EBI-712452; CC P49768; P21333: FLNA; NbExp=2; IntAct=EBI-297277, EBI-350432; CC P49768; O75369: FLNB; NbExp=2; IntAct=EBI-297277, EBI-352089; CC P49768; Q92542: NCSTN; NbExp=6; IntAct=EBI-297277, EBI-998440; CC P49768; Q99569: PKP4; NbExp=3; IntAct=EBI-297277, EBI-726447; CC P49768; Q9NZ42: PSENEN; NbExp=4; IntAct=EBI-297277, EBI-998468; CC P49768; P50502: ST13; NbExp=3; IntAct=EBI-297277, EBI-357285; CC P49768; P55061: TMBIM6; NbExp=12; IntAct=EBI-297277, EBI-1045825; CC P49768; P49755: TMED10; NbExp=4; IntAct=EBI-297277, EBI-998422; CC P49768; Q9NZC2: TREM2; NbExp=5; IntAct=EBI-297277, EBI-14036387; CC P49768; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-297277, EBI-741480; CC P49768; O35430: Apba1; Xeno; NbExp=2; IntAct=EBI-297277, EBI-704760; CC P49768; P98084: Apba2; Xeno; NbExp=2; IntAct=EBI-297277, EBI-81669; CC P49768; P62493: RAB11A; Xeno; NbExp=2; IntAct=EBI-297277, EBI-7030357; CC P49768-2; P63010-2: AP2B1; NbExp=6; IntAct=EBI-11047108, EBI-11529439; CC P49768-2; P05067: APP; NbExp=6; IntAct=EBI-11047108, EBI-77613; CC P49768-2; P16870: CPE; NbExp=3; IntAct=EBI-11047108, EBI-711320; CC P49768-2; Q5D0E6-2: DALRD3; NbExp=3; IntAct=EBI-11047108, EBI-9090939; CC P49768-2; Q9H816: DCLRE1B; NbExp=3; IntAct=EBI-11047108, EBI-3508943; CC P49768-2; Q9UHY8: FEZ2; NbExp=3; IntAct=EBI-11047108, EBI-396453; CC P49768-2; Q06787-7: FMR1; NbExp=3; IntAct=EBI-11047108, EBI-25856644; CC P49768-2; P02792: FTL; NbExp=3; IntAct=EBI-11047108, EBI-713279; CC P49768-2; P68431: H3C12; NbExp=6; IntAct=EBI-11047108, EBI-79722; CC P49768-2; Q12891: HYAL2; NbExp=3; IntAct=EBI-11047108, EBI-2806068; CC P49768-2; Q6DN90-2: IQSEC1; NbExp=6; IntAct=EBI-11047108, EBI-21911304; CC P49768-2; Q9NVX7-2: KBTBD4; NbExp=3; IntAct=EBI-11047108, EBI-25871195; CC P49768-2; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-11047108, EBI-1044640; CC P49768-2; Q9BYZ2: LDHAL6B; NbExp=6; IntAct=EBI-11047108, EBI-1108377; CC P49768-2; Q8TDB4: MGARP; NbExp=6; IntAct=EBI-11047108, EBI-4397720; CC P49768-2; A4FUJ8: MKL1; NbExp=6; IntAct=EBI-11047108, EBI-21250407; CC P49768-2; Q9Y605: MRFAP1; NbExp=3; IntAct=EBI-11047108, EBI-995714; CC P49768-2; Q86WS3: OOSP2; NbExp=3; IntAct=EBI-11047108, EBI-25888682; CC P49768-2; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-11047108, EBI-1058491; CC P49768-2; Q13113: PDZK1IP1; NbExp=6; IntAct=EBI-11047108, EBI-716063; CC P49768-2; P53350: PLK1; NbExp=3; IntAct=EBI-11047108, EBI-476768; CC P49768-2; O14494: PLPP1; NbExp=3; IntAct=EBI-11047108, EBI-2865290; CC P49768-2; Q9NZ42: PSENEN; NbExp=3; IntAct=EBI-11047108, EBI-998468; CC P49768-2; Q6ZNA4-2: RNF111; NbExp=6; IntAct=EBI-11047108, EBI-21535400; CC P49768-2; Q9ULX5: RNF112; NbExp=6; IntAct=EBI-11047108, EBI-25829984; CC P49768-2; Q8N488: RYBP; NbExp=6; IntAct=EBI-11047108, EBI-752324; CC P49768-2; Q2NKQ1-4: SGSM1; NbExp=3; IntAct=EBI-11047108, EBI-10182463; CC P49768-2; Q9GZS3: SKIC8; NbExp=6; IntAct=EBI-11047108, EBI-358545; CC P49768-2; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-11047108, EBI-18159983; CC P49768-2; Q99932-2: SPAG8; NbExp=6; IntAct=EBI-11047108, EBI-11959123; CC P49768-2; O00300: TNFRSF11B; NbExp=3; IntAct=EBI-11047108, EBI-15481185; CC P49768-2; Q96NC0: ZMAT2; NbExp=6; IntAct=EBI-11047108, EBI-2682299; CC PRO_0000025591; Q63053: Arc; Xeno; NbExp=3; IntAct=EBI-2606326, EBI-5275794; CC PRO_0000025592; P35613: BSG; NbExp=6; IntAct=EBI-2606356, EBI-750709; CC PRO_0000025592; Q92542: NCSTN; NbExp=2; IntAct=EBI-2606356, EBI-998440; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum CC {ECO:0000269|PubMed:25394380}. Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:10593990, ECO:0000269|PubMed:8574969, CC ECO:0000269|PubMed:9738936, ECO:0000305|PubMed:10037471, CC ECO:0000305|PubMed:15274632}; Multi-pass membrane protein CC {ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:25918421, CC ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26623517, CC ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874}. Golgi CC apparatus membrane {ECO:0000269|PubMed:10593990, CC ECO:0000269|PubMed:8574969, ECO:0000305|PubMed:10037471, CC ECO:0000305|PubMed:15274632}; Multi-pass membrane protein CC {ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:25918421, CC ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26623517, CC ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874}. Cytoplasmic CC granule {ECO:0000269|PubMed:11987239}. Cell membrane CC {ECO:0000269|PubMed:10593990, ECO:0000269|PubMed:11953314, CC ECO:0000269|PubMed:11987239, ECO:0000269|PubMed:21143716}; Multi-pass CC membrane protein {ECO:0000269|PubMed:25918421, CC ECO:0000269|PubMed:26623517, ECO:0000269|PubMed:30598546, CC ECO:0000269|PubMed:30630874}. Cell projection, growth cone CC {ECO:0000269|PubMed:15004326}. Early endosome CC {ECO:0000269|PubMed:25394380}. Early endosome membrane CC {ECO:0000305|PubMed:25394380}; Multi-pass membrane protein CC {ECO:0000269|PubMed:25918421, ECO:0000269|PubMed:26623517, CC ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874}. Cell CC projection, neuron projection {ECO:0000269|PubMed:15004326}. Cell CC projection, axon {ECO:0000250|UniProtKB:Q4JIM4}. Synapse CC {ECO:0000250|UniProtKB:Q4JIM4}. Note=Translocates with bound NOTCH1 CC from the endoplasmic reticulum and/or Golgi to the cell surface CC (PubMed:10593990). Colocalizes with CDH1/2 at sites of cell-cell CC contact. Colocalizes with CTNNB1 in the endoplasmic reticulum and the CC proximity of the plasma membrane (PubMed:9738936). Also present in CC azurophil granules of neutrophils (PubMed:11987239). Colocalizes with CC UBQLN1 in the cell membrane and in cytoplasmic juxtanuclear structures CC called aggresomes (PubMed:21143716). Also highly enriched in CC mitochondria-associated endoplasmic reticulum membrane contact site (By CC similarity). {ECO:0000250|UniProtKB:P49769, CC ECO:0000269|PubMed:10593990, ECO:0000269|PubMed:11987239, CC ECO:0000269|PubMed:21143716, ECO:0000269|PubMed:9738936}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1; Synonyms=I-467; CC IsoId=P49768-1; Sequence=Displayed; CC Name=2; Synonyms=I-463; CC IsoId=P49768-2; Sequence=VSP_005191; CC Name=3; Synonyms=I-374; CC IsoId=P49768-3; Sequence=VSP_005191, VSP_005192; CC Name=4; Synonyms=Minilin; CC IsoId=P49768-4; Sequence=VSP_007986, VSP_007987; CC Name=5; CC IsoId=P49768-5; Sequence=VSP_005192; CC Name=6; CC IsoId=P49768-6; Sequence=VSP_012288; CC Name=7; CC IsoId=P49768-7; Sequence=VSP_041440; CC -!- TISSUE SPECIFICITY: Detected in azurophile granules in neutrophils and CC in platelet cytoplasmic granules (at protein level) (PubMed:11987239). CC Expressed in a wide range of tissues including various regions of the CC brain, liver, spleen and lymph nodes (PubMed:7596406, PubMed:8574969, CC PubMed:8641442). {ECO:0000269|PubMed:11987239, CC ECO:0000269|PubMed:7596406, ECO:0000269|PubMed:8574969, CC ECO:0000269|PubMed:8641442}. CC -!- DOMAIN: The PAL motif is required for normal active site conformation. CC {ECO:0000269|PubMed:16305624}. CC -!- DOMAIN: Substrates, such as NOTCH1 and APP peptides, are bound between CC PSEN1 transmembrane domains and via the first lumenal loop and the CC cytoplasmic loop between the sixth and seventh transmembrane domains. CC Substrate binding causes a conformation change and formation of an CC intermolecular antiparallel beta-sheet between PSEN1 and its CC substrates. {ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874}. CC -!- PTM: Heterogeneous proteolytic processing generates N-terminal (NTF) CC and C-terminal (CTF) fragments of approximately 35 and 20 kDa, CC respectively. During apoptosis, the C-terminal fragment (CTF) is CC further cleaved by caspase-3 to produce the fragment, PS1-CTF12. CC {ECO:0000269|PubMed:10545183, ECO:0000269|PubMed:15274632, CC ECO:0000269|PubMed:9173929, ECO:0000269|PubMed:9485372}. CC -!- PTM: After endoproteolysis, the C-terminal fragment (CTF) is CC phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on CC Ser-346 inhibits endoproteolysis. {ECO:0000269|PubMed:14576165, CC ECO:0000269|PubMed:9144240}. CC -!- DISEASE: Alzheimer disease 3 (AD3) [MIM:607822]: A familial early-onset CC form of Alzheimer disease. Alzheimer disease is a neurodegenerative CC disorder characterized by progressive dementia, loss of cognitive CC abilities, and deposition of fibrillar amyloid proteins as CC intraneuronal neurofibrillary tangles, extracellular amyloid plaques CC and vascular amyloid deposits. The major constituents of these plaques CC are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, CC that are produced by the proteolysis of the transmembrane APP protein. CC The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved CC products, such as C31, are also implicated in neuronal death. CC {ECO:0000269|PubMed:10025789, ECO:0000269|PubMed:10090481, CC ECO:0000269|PubMed:10200054, ECO:0000269|PubMed:10208579, CC ECO:0000269|PubMed:10439444, ECO:0000269|PubMed:10441572, CC ECO:0000269|PubMed:10447269, ECO:0000269|PubMed:10533070, CC ECO:0000269|PubMed:10631141, ECO:0000269|PubMed:10644793, CC ECO:0000269|PubMed:11027672, ECO:0000269|PubMed:11524469, CC ECO:0000269|PubMed:11561050, ECO:0000269|PubMed:11568920, CC ECO:0000269|PubMed:11701593, ECO:0000269|PubMed:11710891, CC ECO:0000269|PubMed:11796781, ECO:0000269|PubMed:11920851, CC ECO:0000269|PubMed:12048239, ECO:0000269|PubMed:12058025, CC ECO:0000269|PubMed:12370477, ECO:0000269|PubMed:12484344, CC ECO:0000269|PubMed:12493737, ECO:0000269|PubMed:12552037, CC ECO:0000269|PubMed:15004326, ECO:0000269|PubMed:15122701, CC ECO:0000269|PubMed:15364419, ECO:0000269|PubMed:15534188, CC ECO:0000269|PubMed:15534260, ECO:0000269|PubMed:15851849, CC ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:16344340, CC ECO:0000269|PubMed:16628450, ECO:0000269|PubMed:16752394, CC ECO:0000269|PubMed:16897084, ECO:0000269|PubMed:16959576, CC ECO:0000269|PubMed:17366635, ECO:0000269|PubMed:17428795, CC ECO:0000269|PubMed:17502474, ECO:0000269|PubMed:18430735, CC ECO:0000269|PubMed:19667325, ECO:0000269|PubMed:19797784, CC ECO:0000269|PubMed:20164095, ECO:0000269|PubMed:20460383, CC ECO:0000269|PubMed:21335660, ECO:0000269|PubMed:21501661, CC ECO:0000269|PubMed:22461631, ECO:0000269|PubMed:22503161, CC ECO:0000269|PubMed:22529981, ECO:0000269|PubMed:23123781, CC ECO:0000269|PubMed:23843529, ECO:0000269|PubMed:24121961, CC ECO:0000269|PubMed:24495933, ECO:0000269|PubMed:24582897, CC ECO:0000269|PubMed:25394380, ECO:0000269|PubMed:26145164, CC ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26549787, CC ECO:0000269|PubMed:27073747, ECO:0000269|PubMed:27930341, CC ECO:0000269|PubMed:29175279, ECO:0000269|PubMed:29404783, CC ECO:0000269|PubMed:29466804, ECO:0000269|PubMed:30180983, CC ECO:0000269|PubMed:30200536, ECO:0000269|PubMed:7550356, CC ECO:0000269|PubMed:7596406, ECO:0000269|PubMed:7651536, CC ECO:0000269|PubMed:8634711, ECO:0000269|PubMed:8634712, CC ECO:0000269|PubMed:8733303, ECO:0000269|PubMed:8837617, CC ECO:0000269|PubMed:8875251, ECO:0000269|PubMed:9172170, CC ECO:0000269|PubMed:9225696, ECO:0000269|PubMed:9298817, CC ECO:0000269|PubMed:9384602, ECO:0000269|PubMed:9507958, CC ECO:0000269|PubMed:9521423, ECO:0000269|PubMed:9719376, CC ECO:0000269|PubMed:9831473, ECO:0000269|PubMed:9833068, CC ECO:0000269|Ref.95}. Note=The disease is caused by variants affecting CC the gene represented in this entry. CC -!- DISEASE: Frontotemporal dementia 1 (FTD1) [MIM:600274]: A form of CC dementia characterized by pathologic finding of frontotemporal lobar CC degeneration, presenile dementia with behavioral changes, deterioration CC of cognitive capacities and loss of memory. In some cases, parkinsonian CC symptoms are prominent. Neuropathological changes include CC frontotemporal atrophy often associated with atrophy of the basal CC ganglia, substantia nigra, amygdala. In most cases, protein tau CC deposits are found in glial cells and/or neurons. CC {ECO:0000269|PubMed:11094121}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Cardiomyopathy, dilated, 1U (CMD1U) [MIM:613694]: A disorder CC characterized by ventricular dilation and impaired systolic function, CC resulting in congestive heart failure and arrhythmia. Patients are at CC risk of premature death. {ECO:0000269|PubMed:17186461, CC ECO:0000269|PubMed:27930341}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Acne inversa, familial, 3 (ACNINV3) [MIM:613737]: A chronic CC relapsing inflammatory disease of the hair follicles characterized by CC recurrent draining sinuses, painful skin abscesses, and disfiguring CC scars. Manifestations typically appear after puberty. CC {ECO:0000269|PubMed:20929727}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Pick disease of the brain (PIDB) [MIM:172700]: A rare form of CC dementia pathologically defined by severe atrophy, neuronal loss and CC gliosis. It is characterized by the occurrence of tau-positive CC inclusions, swollen neurons (Pick cells) and argentophilic neuronal CC inclusions known as Pick bodies that disproportionally affect the CC frontal and temporal cortical regions. Clinical features include CC aphasia, apraxia, confusion, anomia, memory loss and personality CC deterioration. {ECO:0000269|PubMed:15122701}. Note=The gene represented CC in this entry may be involved in disease pathogenesis. CC -!- MISCELLANEOUS: [Isoform 3]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: May be produced at very low levels due to a CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA CC decay. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the peptidase A22A family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Alzheimer Research Forum; Note=Presenilins CC mutations; CC URL="https://www.alzforum.org/mutations/psen-1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L42110; AAB46416.1; -; mRNA. DR EMBL; L76517; AAB46370.1; -; mRNA. DR EMBL; L76528; AAB46371.1; -; Genomic_DNA. DR EMBL; L76519; AAB46371.1; JOINED; Genomic_DNA. DR EMBL; L76520; AAB46371.1; JOINED; Genomic_DNA. DR EMBL; L76521; AAB46371.1; JOINED; Genomic_DNA. DR EMBL; L76522; AAB46371.1; JOINED; Genomic_DNA. DR EMBL; L76523; AAB46371.1; JOINED; Genomic_DNA. DR EMBL; L76524; AAB46371.1; JOINED; Genomic_DNA. DR EMBL; L76525; AAB46371.1; JOINED; Genomic_DNA. DR EMBL; L76526; AAB46371.1; JOINED; Genomic_DNA. DR EMBL; L76527; AAB46371.1; JOINED; Genomic_DNA. DR EMBL; U40379; AAB05894.1; -; mRNA. DR EMBL; U40380; AAB05895.1; -; mRNA. DR EMBL; AJ008005; CAA07825.1; -; mRNA. DR EMBL; AF109907; AAC97960.1; -; Genomic_DNA. DR EMBL; AF416717; AAL16811.1; -; mRNA. DR EMBL; AK312531; BAG35430.1; -; mRNA. DR EMBL; AC004858; AAF19253.1; -; Genomic_DNA. DR EMBL; AC004858; AAF19254.1; -; Genomic_DNA. DR EMBL; CH471061; EAW81092.1; -; Genomic_DNA. DR EMBL; BC011729; AAH11729.1; -; mRNA. DR EMBL; D84149; BAA20883.1; -; Genomic_DNA. DR CCDS; CCDS9812.1; -. [P49768-1] DR CCDS; CCDS9813.1; -. [P49768-2] DR PIR; S58396; S58396. DR PIR; S63683; S63683. DR PIR; S63684; S63684. DR RefSeq; NP_000012.1; NM_000021.4. [P49768-1] DR RefSeq; NP_015557.2; NM_007318.3. [P49768-2] DR RefSeq; XP_005267921.1; XM_005267864.4. [P49768-1] DR RefSeq; XP_005267923.1; XM_005267866.3. [P49768-2] DR RefSeq; XP_011535274.1; XM_011536972.3. [P49768-1] DR RefSeq; XP_011535275.1; XM_011536973.3. [P49768-2] DR RefSeq; XP_011535276.1; XM_011536974.3. [P49768-2] DR RefSeq; XP_047287556.1; XM_047431600.1. [P49768-1] DR RefSeq; XP_047287557.1; XM_047431601.1. [P49768-1] DR RefSeq; XP_047287558.1; XM_047431602.1. [P49768-2] DR RefSeq; XP_054232388.1; XM_054376413.1. [P49768-1] DR RefSeq; XP_054232389.1; XM_054376414.1. [P49768-1] DR RefSeq; XP_054232390.1; XM_054376415.1. [P49768-1] DR RefSeq; XP_054232391.1; XM_054376416.1. [P49768-1] DR RefSeq; XP_054232392.1; XM_054376417.1. [P49768-2] DR RefSeq; XP_054232393.1; XM_054376418.1. [P49768-2] DR RefSeq; XP_054232394.1; XM_054376419.1. [P49768-2] DR RefSeq; XP_054232395.1; XM_054376420.1. [P49768-2] DR PDB; 2KR6; NMR; -; A=292-467. DR PDB; 4UIS; EM; 4.40 A; B=81-463. DR PDB; 5A63; EM; 3.40 A; B=1-467. DR PDB; 5FN2; EM; 4.20 A; B=1-467. DR PDB; 5FN3; EM; 4.10 A; B=1-467. DR PDB; 5FN4; EM; 4.00 A; B=1-467. DR PDB; 5FN5; EM; 4.30 A; B=1-467. DR PDB; 6IDF; EM; 2.70 A; B=1-467. DR PDB; 6IYC; EM; 2.60 A; B=1-467. DR PDB; 6LQG; EM; 3.10 A; B=1-467. DR PDB; 6LR4; EM; 3.00 A; B=1-467. DR PDB; 7C9I; EM; 3.10 A; B=1-467. DR PDB; 7D8X; EM; 2.60 A; B=1-467. DR PDB; 7Y5T; EM; 2.90 A; B=1-467. DR PDB; 8IM7; EM; 3.40 A; B=1-467. DR PDB; 8K8E; EM; 2.60 A; B=1-467. DR PDB; 8KCO; EM; 2.80 A; B=1-467. DR PDB; 8KCP; EM; 3.00 A; B=1-467. DR PDB; 8KCS; EM; 2.40 A; B=1-467. DR PDB; 8KCT; EM; 2.60 A; B=1-467. DR PDB; 8KCU; EM; 2.70 A; B=1-467. DR PDB; 8OQY; EM; 3.30 A; B=1-467. DR PDB; 8OQZ; EM; 3.40 A; B=1-467. DR PDB; 8X52; EM; 2.90 A; B=1-467. DR PDB; 8X53; EM; 3.00 A; B=1-467. DR PDB; 8X54; EM; 2.90 A; B=1-467. DR PDBsum; 2KR6; -. DR PDBsum; 4UIS; -. DR PDBsum; 5A63; -. DR PDBsum; 5FN2; -. DR PDBsum; 5FN3; -. DR PDBsum; 5FN4; -. DR PDBsum; 5FN5; -. DR PDBsum; 6IDF; -. DR PDBsum; 6IYC; -. DR PDBsum; 6LQG; -. DR PDBsum; 6LR4; -. DR PDBsum; 7C9I; -. DR PDBsum; 7D8X; -. DR PDBsum; 7Y5T; -. DR PDBsum; 8IM7; -. DR PDBsum; 8K8E; -. DR PDBsum; 8KCO; -. DR PDBsum; 8KCP; -. DR PDBsum; 8KCS; -. DR PDBsum; 8KCT; -. DR PDBsum; 8KCU; -. DR PDBsum; 8OQY; -. DR PDBsum; 8OQZ; -. DR PDBsum; 8X52; -. DR PDBsum; 8X53; -. DR PDBsum; 8X54; -. DR AlphaFoldDB; P49768; -. DR EMDB; EMD-0944; -. DR EMDB; EMD-0957; -. DR EMDB; EMD-17112; -. DR EMDB; EMD-17113; -. DR EMDB; EMD-2477; -. DR EMDB; EMD-2478; -. DR EMDB; EMD-30312; -. DR EMDB; EMD-30614; -. DR EMDB; EMD-33624; -. DR EMDB; EMD-35572; -. DR EMDB; EMD-36948; -. DR EMDB; EMD-37106; -. DR EMDB; EMD-37107; -. DR EMDB; EMD-37108; -. DR EMDB; EMD-37109; -. DR EMDB; EMD-37110; -. DR EMDB; EMD-38059; -. DR EMDB; EMD-38060; -. DR EMDB; EMD-38061; -. DR EMDB; EMD-9648; -. DR EMDB; EMD-9751; -. DR SMR; P49768; -. DR BioGRID; 111642; 203. DR ComplexPortal; CPX-2176; Gamma-secretase complex, APH1A-PSEN1 variant. DR ComplexPortal; CPX-4233; Gamma-secretase complex, APH1B-PSEN1 variant. DR CORUM; P49768; -. DR DIP; DIP-1134N; -. DR ELM; P49768; -. DR FunCoup; P49768; 2287. DR IntAct; P49768; 299. DR MINT; P49768; -. DR STRING; 9606.ENSP00000326366; -. DR BindingDB; P49768; -. DR ChEMBL; CHEMBL2473; -. DR DrugBank; DB11893; Avagacestat. DR DrugBank; DB12263; Begacestat. DR DrugBank; DB05171; E-2012. DR DrugBank; DB16159; Esflurbiprofen. DR DrugBank; DB12819; GSI-136. DR DrugBank; DB16825; Itanapraced. DR DrugBank; DB12852; MK-0752. DR DrugBank; DB12005; Nirogacestat. DR DrugBank; DB11870; RG-4733. DR DrugBank; DB12463; Semagacestat. DR DrugBank; DB05289; Tarenflurbil. DR GuidetoPHARMACOLOGY; 2402; -. DR MEROPS; A22.001; -. DR TCDB; 1.A.54.1.1; the presenilin er ca(2+) leak channel (presenilin) family. DR iPTMnet; P49768; -. DR PhosphoSitePlus; P49768; -. DR SwissPalm; P49768; -. DR BioMuta; PSEN1; -. DR DMDM; 1709856; -. DR jPOST; P49768; -. DR MassIVE; P49768; -. DR PaxDb; 9606-ENSP00000326366; -. DR PeptideAtlas; P49768; -. DR ProteomicsDB; 56106; -. [P49768-1] DR ProteomicsDB; 56107; -. [P49768-2] DR ProteomicsDB; 56108; -. [P49768-3] DR ProteomicsDB; 56109; -. [P49768-4] DR ProteomicsDB; 56110; -. [P49768-5] DR ProteomicsDB; 56111; -. [P49768-6] DR ProteomicsDB; 56112; -. [P49768-7] DR Pumba; P49768; -. DR Antibodypedia; 3480; 972 antibodies from 47 providers. DR DNASU; 5663; -. DR Ensembl; ENST00000324501.10; ENSP00000326366.5; ENSG00000080815.21. [P49768-1] DR Ensembl; ENST00000357710.8; ENSP00000350342.4; ENSG00000080815.21. [P49768-2] DR Ensembl; ENST00000394157.7; ENSP00000377712.3; ENSG00000080815.21. [P49768-4] DR Ensembl; ENST00000394164.5; ENSP00000377719.1; ENSG00000080815.21. [P49768-2] DR Ensembl; ENST00000553599.6; ENSP00000452477.2; ENSG00000080815.21. [P49768-2] DR Ensembl; ENST00000553855.5; ENSP00000452242.1; ENSG00000080815.21. [P49768-5] DR Ensembl; ENST00000554131.6; ENSP00000451915.2; ENSG00000080815.21. [P49768-1] DR Ensembl; ENST00000555386.6; ENSP00000450845.1; ENSG00000080815.21. [P49768-3] DR Ensembl; ENST00000556951.6; ENSP00000450551.2; ENSG00000080815.21. [P49768-2] DR Ensembl; ENST00000557511.5; ENSP00000451429.1; ENSG00000080815.21. [P49768-6] DR Ensembl; ENST00000700265.1; ENSP00000514901.1; ENSG00000080815.21. [P49768-2] DR Ensembl; ENST00000700267.1; ENSP00000514903.1; ENSG00000080815.21. [P49768-1] DR Ensembl; ENST00000700268.1; ENSP00000514904.1; ENSG00000080815.21. [P49768-1] DR Ensembl; ENST00000700269.1; ENSP00000514905.1; ENSG00000080815.21. [P49768-1] DR Ensembl; ENST00000700273.1; ENSP00000514908.1; ENSG00000080815.21. [P49768-2] DR Ensembl; ENST00000700306.1; ENSP00000514933.1; ENSG00000080815.21. [P49768-1] DR Ensembl; ENST00000700313.1; ENSP00000514940.1; ENSG00000080815.21. [P49768-2] DR Ensembl; ENST00000700317.1; ENSP00000514944.1; ENSG00000080815.21. [P49768-1] DR Ensembl; ENST00000700321.1; ENSP00000514948.1; ENSG00000080815.21. [P49768-1] DR Ensembl; ENST00000700322.1; ENSP00000514949.1; ENSG00000080815.21. [P49768-2] DR Ensembl; ENST00000700323.1; ENSP00000514950.1; ENSG00000080815.21. [P49768-1] DR Ensembl; ENST00000700324.1; ENSP00000514951.1; ENSG00000080815.21. [P49768-2] DR Ensembl; ENST00000700375.1; ENSP00000514966.1; ENSG00000080815.21. [P49768-1] DR Ensembl; ENST00000700378.1; ENSP00000514968.1; ENSG00000080815.21. [P49768-1] DR Ensembl; ENST00000700389.1; ENSP00000514970.1; ENSG00000080815.21. [P49768-2] DR Ensembl; ENST00000700436.1; ENSP00000514987.1; ENSG00000080815.21. [P49768-5] DR Ensembl; ENST00000700469.1; ENSP00000515002.1; ENSG00000080815.21. [P49768-2] DR GeneID; 5663; -. DR KEGG; hsa:5663; -. DR MANE-Select; ENST00000324501.10; ENSP00000326366.5; NM_000021.4; NP_000012.1. DR UCSC; uc001xnq.5; human. [P49768-1] DR AGR; HGNC:9508; -. DR ClinPGx; PA33855; -. DR CTD; 5663; -. DR DisGeNET; 5663; -. DR GeneCards; PSEN1; -. DR GeneReviews; PSEN1; -. DR HGNC; HGNC:9508; PSEN1. DR HPA; ENSG00000080815; Low tissue specificity. DR MalaCards; PSEN1; -. DR MIM; 104311; gene. DR MIM; 172700; phenotype. DR MIM; 600274; phenotype. DR MIM; 607822; phenotype. DR MIM; 613694; phenotype. DR MIM; 613737; phenotype. DR OpenTargets; ENSG00000080815; -. DR Orphanet; 275864; Behavioral variant of frontotemporal dementia. DR Orphanet; 1020; Early-onset autosomal dominant Alzheimer disease. DR Orphanet; 154; Familial isolated dilated cardiomyopathy. DR Orphanet; 100070; Progressive non-fluent aphasia. DR Orphanet; 100069; Semantic dementia. DR VEuPathDB; HostDB:ENSG00000080815; -. DR eggNOG; KOG2736; Eukaryota. DR GeneTree; ENSGT00940000158751; -. DR HOGENOM; CLU_022975_3_0_1; -. DR InParanoid; P49768; -. DR OMA; NATCNQQ; -. DR OrthoDB; 20287at2759; -. DR PAN-GO; P49768; 26 GO annotations based on evolutionary models. DR PhylomeDB; P49768; -. DR PathwayCommons; P49768; -. DR Reactome; R-HSA-1251985; Nuclear signaling by ERBB4. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-193692; Regulated proteolysis of p75NTR. DR Reactome; R-HSA-205043; NRIF signals cell death from the nucleus. DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus. DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants. DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants. DR Reactome; R-HSA-2979096; NOTCH2 Activation and Transmission of Signal to the Nucleus. DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus. DR Reactome; R-HSA-9013700; NOTCH4 Activation and Transmission of Signal to the Nucleus. DR Reactome; R-HSA-9017802; Noncanonical activation of NOTCH3. DR Reactome; R-HSA-9839383; TGFBR3 PTM regulation. DR SignaLink; P49768; -. DR SIGNOR; P49768; -. DR Agora; ENSG00000080815; -. DR BioGRID-ORCS; 5663; 16 hits in 1162 CRISPR screens. DR CD-CODE; 8C2F96ED; Centrosome. DR ChiTaRS; PSEN1; human. DR EvolutionaryTrace; P49768; -. DR GeneWiki; PSEN1; -. DR GenomeRNAi; 5663; -. DR Pharos; P49768; Tchem. DR PRO; PR:P49768; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P49768; protein. DR Bgee; ENSG00000080815; Expressed in middle frontal gyrus and 202 other cell types or tissues. DR ExpressionAtlas; P49768; baseline and differential. DR GO; GO:0016235; C:aggresome; IDA:UniProtKB. DR GO; GO:0035577; C:azurophil granule membrane; TAS:Reactome. DR GO; GO:0005938; C:cell cortex; IEA:Ensembl. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0035253; C:ciliary rootlet; IEA:Ensembl. DR GO; GO:0030425; C:dendrite; IDA:ARUK-UCL. DR GO; GO:0043198; C:dendritic shaft; IEA:Ensembl. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HGNC-UCL. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0070765; C:gamma-secretase complex; IDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0030426; C:growth cone; IDA:UniProtKB. DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:Ensembl. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl. DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB. DR GO; GO:0005640; C:nuclear outer membrane; IDA:MGI. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IMP:CAFA. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098794; C:postsynapse; IEA:GOC. DR GO; GO:0042734; C:presynaptic membrane; IEA:Ensembl. DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA. DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0042383; C:sarcolemma; IEA:Ensembl. DR GO; GO:0005790; C:smooth endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl. DR GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; IDA:UniProtKB. DR GO; GO:0004190; F:aspartic-type endopeptidase activity; NAS:ARUK-UCL. DR GO; GO:0051117; F:ATPase binding; IPI:ARUK-UCL. DR GO; GO:0008013; F:beta-catenin binding; IPI:UniProtKB. DR GO; GO:0045296; F:cadherin binding; IEA:Ensembl. DR GO; GO:0005262; F:calcium channel activity; IMP:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; IDA:MGI. DR GO; GO:0070851; F:growth factor receptor binding; IPI:ARUK-UCL. DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProtKB. DR GO; GO:0030165; F:PDZ domain binding; IPI:UniProtKB. DR GO; GO:0042987; P:amyloid precursor protein catabolic process; IDA:ARUK-UCL. DR GO; GO:0042982; P:amyloid precursor protein metabolic process; IDA:UniProtKB. DR GO; GO:0034205; P:amyloid-beta formation; IDA:ARUK-UCL. DR GO; GO:0097190; P:apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0048143; P:astrocyte activation; IGI:ARUK-UCL. DR GO; GO:0002265; P:astrocyte activation involved in immune response; IGI:ARUK-UCL. DR GO; GO:0000045; P:autophagosome assembly; IEA:Ensembl. DR GO; GO:0001568; P:blood vessel development; IEA:Ensembl. DR GO; GO:0048854; P:brain morphogenesis; IEA:Ensembl. DR GO; GO:0021870; P:Cajal-Retzius cell differentiation; IEA:Ensembl. DR GO; GO:0055074; P:calcium ion homeostasis; IBA:GO_Central. DR GO; GO:0001708; P:cell fate specification; IEA:Ensembl. DR GO; GO:0098609; P:cell-cell adhesion; IMP:MGI. DR GO; GO:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL. DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl. DR GO; GO:0021795; P:cerebral cortex cell migration; IEA:Ensembl. DR GO; GO:0015871; P:choline transport; IEA:Ensembl. DR GO; GO:0006974; P:DNA damage response; IDA:ARUK-UCL. DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IEA:Ensembl. DR GO; GO:0030326; P:embryonic limb morphogenesis; IEA:Ensembl. DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IDA:MGI. DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0001947; P:heart looping; IEA:Ensembl. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IEA:Ensembl. DR GO; GO:0035556; P:intracellular signal transduction; IMP:UniProtKB. DR GO; GO:0098712; P:L-glutamate import across plasma membrane; IEA:Ensembl. DR GO; GO:0007611; P:learning or memory; IGI:ARUK-UCL. DR GO; GO:0040011; P:locomotion; IEA:Ensembl. DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:HGNC-UCL. DR GO; GO:0007613; P:memory; IGI:ARUK-UCL. DR GO; GO:0006839; P:mitochondrial transport; IEA:Ensembl. DR GO; GO:0043011; P:myeloid dendritic cell differentiation; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0050771; P:negative regulation of axonogenesis; IEA:Ensembl. DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IGI:ARUK-UCL. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; IEA:Ensembl. DR GO; GO:0003407; P:neural retina development; IEA:Ensembl. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:0070050; P:neuron cellular homeostasis; IEA:Ensembl. DR GO; GO:0048666; P:neuron development; IEA:Ensembl. DR GO; GO:0001764; P:neuron migration; IEA:Ensembl. DR GO; GO:1990535; P:neuron projection maintenance; IGI:ARUK-UCL. DR GO; GO:0007220; P:Notch receptor processing; IDA:ARUK-UCL. DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central. DR GO; GO:1905908; P:positive regulation of amyloid fibril formation; IGI:ARUK-UCL. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0050820; P:positive regulation of coagulation; IEA:Ensembl. DR GO; GO:0060999; P:positive regulation of dendritic spine development; IMP:CACAO. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:CACAO. DR GO; GO:0010628; P:positive regulation of gene expression; IGI:ARUK-UCL. DR GO; GO:0045821; P:positive regulation of glycolytic process; IGI:ARUK-UCL. DR GO; GO:0002038; P:positive regulation of L-glutamate import across plasma membrane; IEA:Ensembl. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl. DR GO; GO:0001921; P:positive regulation of receptor recycling; IEA:Ensembl. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IGI:ARUK-UCL. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0140249; P:protein catabolic process at postsynapse; IEA:Ensembl. DR GO; GO:0016485; P:protein processing; IDA:HGNC-UCL. DR GO; GO:0015031; P:protein transport; IEA:Ensembl. DR GO; GO:0060828; P:regulation of canonical Wnt signaling pathway; ISS:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; IGI:ARUK-UCL. DR GO; GO:0010975; P:regulation of neuron projection development; IMP:UniProtKB. DR GO; GO:0099175; P:regulation of postsynapse organization; IEA:Ensembl. DR GO; GO:0060075; P:regulation of resting membrane potential; IEA:Ensembl. DR GO; GO:0048167; P:regulation of synaptic plasticity; IEA:Ensembl. DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IEA:Ensembl. DR GO; GO:0098693; P:regulation of synaptic vesicle cycle; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; IEA:Ensembl. DR GO; GO:0051208; P:sequestering of calcium ion; IEA:Ensembl. DR GO; GO:0048705; P:skeletal system morphogenesis; IEA:Ensembl. DR GO; GO:0043589; P:skin morphogenesis; IEA:Ensembl. DR GO; GO:0051563; P:smooth endoplasmic reticulum calcium ion homeostasis; IEA:Ensembl. DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl. DR GO; GO:0050808; P:synapse organization; IGI:ARUK-UCL. DR GO; GO:0016080; P:synaptic vesicle targeting; IEA:Ensembl. DR GO; GO:0002286; P:T cell activation involved in immune response; IEA:Ensembl. DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:Ensembl. DR GO; GO:0048538; P:thymus development; IEA:Ensembl. DR DisProt; DP01292; -. DR FunFam; 1.10.472.100:FF:000001; Presenilin; 1. DR Gene3D; 1.10.472.100; Presenilin; 1. DR InterPro; IPR002031; Pept_A22A_PS1. DR InterPro; IPR001108; Peptidase_A22A. DR InterPro; IPR006639; Preselin/SPP. DR InterPro; IPR042524; Presenilin_C. DR PANTHER; PTHR10202; PRESENILIN; 1. DR PANTHER; PTHR10202:SF18; PRESENILIN-1; 1. DR Pfam; PF01080; Presenilin; 1. DR PRINTS; PR01072; PRESENILIN. DR PRINTS; PR01073; PRESENILIN1. DR SMART; SM00730; PSN; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Alzheimer disease; Amyloidosis; KW Apoptosis; Cardiomyopathy; Cell adhesion; Cell membrane; Cell projection; KW Direct protein sequencing; Disease variant; Endoplasmic reticulum; KW Endosome; Golgi apparatus; Hydrolase; Membrane; Neurodegeneration; KW Notch signaling pathway; Phosphoprotein; Protease; KW Proteomics identification; Reference proteome; Synapse; Transmembrane; KW Transmembrane helix. FT CHAIN 1..298 FT /note="Presenilin-1 NTF subunit" FT /evidence="ECO:0000269|PubMed:9173929" FT /id="PRO_0000025591" FT CHAIN 299..467 FT /note="Presenilin-1 CTF subunit" FT /evidence="ECO:0000269|PubMed:9173929" FT /id="PRO_0000025592" FT CHAIN 346..467 FT /note="Presenilin-1 CTF12" FT /evidence="ECO:0000269|PubMed:9485372" FT /id="PRO_0000236055" FT TOPO_DOM 1..82 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:26280335" FT TRANSMEM 83..103 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:26280335" FT TOPO_DOM 104..132 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:26280335" FT TRANSMEM 133..153 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:26280335" FT TOPO_DOM 154..166 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:26280335" FT TRANSMEM 167..189 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:26280335" FT TOPO_DOM 190..194 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:26280335" FT TRANSMEM 195..216 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:26280335" FT TOPO_DOM 217..220 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:26280335" FT TRANSMEM 221..241 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:26280335" FT TOPO_DOM 242..248 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:26280335" FT TRANSMEM 249..272 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:26280335" FT TOPO_DOM 273..380 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:26280335" FT TRANSMEM 381..401 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:26280335" FT TOPO_DOM 402..407 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:26280335" FT TRANSMEM 408..428 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:26280335" FT TOPO_DOM 429..432 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:26280335" FT TRANSMEM 433..453 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:26280335" FT TOPO_DOM 454..467 FT /note="Lumenal" FT /evidence="ECO:0000269|PubMed:26280335" FT REGION 13..68 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 288..290 FT /note="Important for cleavage of target proteins" FT /evidence="ECO:0000269|PubMed:30598546" FT REGION 305..333 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 322..450 FT /note="Required for interaction with CTNNB1" FT /evidence="ECO:0000269|PubMed:9738936" FT REGION 372..399 FT /note="Required for interaction with CTNND2" FT /evidence="ECO:0000269|PubMed:10037471" FT REGION 377..381 FT /note="Important for cleavage of target proteins" FT /evidence="ECO:0000269|PubMed:30598546" FT REGION 432..434 FT /note="Important for cleavage of target proteins" FT /evidence="ECO:0000269|PubMed:30598546" FT REGION 464..467 FT /note="Interaction with MTCH1" FT /evidence="ECO:0000269|PubMed:10551805" FT MOTIF 433..435 FT /note="PAL" FT /evidence="ECO:0000305|PubMed:16305624" FT COMPBIAS 13..29 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 30..45 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 257 FT /evidence="ECO:0000305|PubMed:10206644, FT ECO:0000305|PubMed:10899933, ECO:0000305|PubMed:15341515" FT ACT_SITE 385 FT /evidence="ECO:0000305|PubMed:10206644, FT ECO:0000305|PubMed:10899933, ECO:0000305|PubMed:15341515, FT ECO:0000305|PubMed:30598546, ECO:0000305|PubMed:30630874" FT SITE 291..292 FT /note="Cleavage; alternate" FT /evidence="ECO:0000269|PubMed:9173929" FT SITE 292..293 FT /note="Cleavage; alternate" FT /evidence="ECO:0000269|PubMed:9173929" FT SITE 298..299 FT /note="Cleavage" FT /evidence="ECO:0000269|PubMed:9173929" FT SITE 345..346 FT /note="Cleavage; by caspase" FT /evidence="ECO:0000269|PubMed:9485372" FT MOD_RES 43 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 51 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P97887" FT MOD_RES 310 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:14576165" FT MOD_RES 346 FT /note="Phosphoserine; by PKC" FT /evidence="ECO:0000269|PubMed:14576165" FT MOD_RES 367 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT VAR_SEQ 26..29 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:7596406, ECO:0000303|PubMed:8641442" FT /id="VSP_005191" FT VAR_SEQ 162..184 FT /note="IHAWLIISSLLLLFFFSFIYLGE -> SMRHRSLLSTLFFLWLGILVTVT FT (in isoform 4)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_007986" FT VAR_SEQ 185..467 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|Ref.3" FT /id="VSP_007987" FT VAR_SEQ 257..289 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000305" FT /id="VSP_041440" FT VAR_SEQ 319..467 FT /note="STERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAAVQELSSSILA FT GEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCLTLLLLAIFK FT KALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI -> RACLPPAAINLLSIAPM FT APRLFMPKGACRPTAQKGSHKTLLQRMMMAGSVRNGKPRGTVI (in isoform 3 FT and isoform 5)" FT /evidence="ECO:0000303|PubMed:8641442, ECO:0000303|Ref.5" FT /id="VSP_005192" FT VAR_SEQ 319..376 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000305" FT /id="VSP_012288" FT VARIANT 35 FT /note="R -> Q (in AD3; uncertain significance; decreased FT protease activity with APP; dbSNP:rs63750592)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:27930341" FT /id="VAR_075260" FT VARIANT 79 FT /note="A -> V (in AD3; also found in late-onset Alzheimer FT disease; impaired protease activity with APP; results in FT altered amyloid-beta production and increased amyloid-beta FT 42/amyloid-beta 40 ratio; no effect on interaction with FT GFAP; dbSNP:rs63749824)" FT /evidence="ECO:0000269|PubMed:10631141, FT ECO:0000269|PubMed:11524469, ECO:0000269|PubMed:12058025, FT ECO:0000269|PubMed:16752394, ECO:0000269|PubMed:17366635, FT ECO:0000269|PubMed:27930341, ECO:0000269|PubMed:9384602" FT /id="VAR_006413" FT VARIANT 82 FT /note="V -> L (in AD3; decreased protease activity with FT APP; no effect on interaction with GFAP; dbSNP:rs63749967)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:12058025, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:8634712" FT /id="VAR_006414" FT VARIANT 83 FT /note="I -> T (in AD3)" FT /evidence="ECO:0000269|PubMed:26145164" FT /id="VAR_075261" FT VARIANT 85 FT /note="L -> P (in AD3; the patient also manifest spastic FT paraparesis and apraxia; loss of protease activity with APP FT in vitro; altered amyloid-beta production in cells FT transfected with the mutant and increased amyloid-beta 42/ FT amyloid-beta 40 ratio; dbSNP:rs63750599)" FT /evidence="ECO:0000269|PubMed:15534188, FT ECO:0000269|PubMed:27930341" FT /id="VAR_081228" FT VARIANT 89 FT /note="V -> L (in AD3; decreased protease activity with FT APP; increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63750815)" FT /evidence="ECO:0000269|PubMed:11796781" FT /id="VAR_081229" FT VARIANT 92 FT /note="C -> S (in AD3; loss of protease activity with APP; FT dbSNP:rs63751141)" FT /evidence="ECO:0000269|PubMed:11027672, FT ECO:0000269|PubMed:27930341" FT /id="VAR_016214" FT VARIANT 94 FT /note="V -> M (in AD3; uncertain significance; reduced FT protease activity with APP; no relevant change in amyloid- FT beta 42/amyloid-beta 40 ratio; dbSNP:rs63750831)" FT /evidence="ECO:0000269|PubMed:11568920" FT /id="VAR_081230" FT VARIANT 96 FT /note="V -> F (in AD3; loss of protease activity with APP; FT dbSNP:rs63750601)" FT /evidence="ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:8733303" FT /id="VAR_006415" FT VARIANT 97 FT /note="V -> L (in AD3; uncertain significance; slightly FT reduced protease activity with APP; dbSNP:rs63750852)" FT /evidence="ECO:0000269|PubMed:15851849, FT ECO:0000269|PubMed:27930341" FT /id="VAR_081231" FT VARIANT 105 FT /note="F -> L (in AD3; dbSNP:rs63750321)" FT /evidence="ECO:0000269|PubMed:10631141" FT /id="VAR_009208" FT VARIANT 113 FT /note="L -> P (in FTD1; dbSNP:rs63751399)" FT /evidence="ECO:0000269|PubMed:11094121" FT /id="VAR_016215" FT VARIANT 115 FT /note="Y -> C (in AD3; dbSNP:rs63750450)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:12552037, ECO:0000269|PubMed:9384602" FT /id="VAR_006416" FT VARIANT 115 FT /note="Y -> H (in AD3; impaired protease activity with APP FT and increased amyloid-beta 42/amyloid-beta 40 ratio)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:27930341, ECO:0000269|PubMed:8634712" FT /id="VAR_006417" FT VARIANT 116 FT /note="T -> I (in AD3; dbSNP:rs63750730)" FT /evidence="ECO:0000269|PubMed:30200536" FT /id="VAR_081232" FT VARIANT 116 FT /note="T -> N (in AD3; unusual amyloid cotton wool plaques FT detected in one patient's brain; severe decrease of FT protease activity with APP; results in increased amyloid- FT beta 42/amyloid-beta 40 ratio; dbSNP:rs63750730)" FT /evidence="ECO:0000269|PubMed:10439444, FT ECO:0000269|PubMed:11524469, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:29404783" FT /id="VAR_010120" FT VARIANT 117 FT /note="P -> L (in AD3; impaired ability to cleave Ephb2/ FT CTF1; results in altered amyloid-beta production and FT increased amyloid-beta 42/amyloid-beta 40 ratio; impaired FT regulation of neurite outgrowth; dbSNP:rs63749805)" FT /evidence="ECO:0000269|PubMed:15004326, FT ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:9507958" FT /id="VAR_009209" FT VARIANT 117 FT /note="P -> S (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; impaired regulation of neurite outgrowth; FT dbSNP:rs63750550)" FT /evidence="ECO:0000269|PubMed:15004326" FT /id="VAR_081233" FT VARIANT 120 FT /note="E -> D (in AD3; impaired protease activity with APP FT and increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63751272)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:27930341, ECO:0000269|PubMed:9521423" FT /id="VAR_006418" FT VARIANT 120 FT /note="E -> K (in AD3; impaired protease activity with APP FT and increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63750800)" FT /evidence="ECO:0000269|PubMed:27930341" FT /id="VAR_006419" FT VARIANT 134 FT /note="L -> R (in AD3; uncertain significance; loss of FT protease activity with APP; dbSNP:rs1595002439)" FT /evidence="ECO:0000269|PubMed:22503161, FT ECO:0000269|PubMed:27930341" FT /id="VAR_070023" FT VARIANT 135 FT /note="N -> D (in AD3; impaired protease activity with APP FT and increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63750353)" FT /evidence="ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:9225696" FT /id="VAR_010121" FT VARIANT 139 FT /note="M -> I (in AD3; dbSNP:rs63750522)" FT /evidence="ECO:0000269|PubMed:8875251" FT /id="VAR_006420" FT VARIANT 139 FT /note="M -> K (in AD3; dbSNP:rs63751106)" FT /evidence="ECO:0000269|PubMed:9719376" FT /id="VAR_010122" FT VARIANT 139 FT /note="M -> T (in AD3; dbSNP:rs63751106)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:8634712" FT /id="VAR_006421" FT VARIANT 139 FT /note="M -> V (in AD3; increased amyloid-beta 42/amyloid- FT beta 40 ratio; dbSNP:rs63751037)" FT /evidence="ECO:0000269|PubMed:10631141, FT ECO:0000269|PubMed:27930341, ECO:0000269|PubMed:7550356" FT /id="VAR_006422" FT VARIANT 142 FT /note="V -> F (in AD3; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29175279" FT /id="VAR_081234" FT VARIANT 143 FT /note="I -> F (in AD3; dbSNP:rs63750322)" FT /evidence="ECO:0000269|PubMed:10090481" FT /id="VAR_006423" FT VARIANT 143 FT /note="I -> T (in AD3; impaired protease activity with APP; FT results in altered amyloid-beta production and increased FT amyloid-beta 42/amyloid-beta 40 ratio; dbSNP:rs63750004)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:11568920, ECO:0000269|PubMed:15122701, FT ECO:0000269|PubMed:16752394, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:8634711" FT /id="VAR_006424" FT VARIANT 146 FT /note="M -> I (in AD3; dbSNP:rs63750391)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:12552037" FT /id="VAR_006425" FT VARIANT 146 FT /note="M -> L (in AD3; disease phenotype shows high FT clinical variability; founder mutation originating from FT Southern Italy and distributed worldwide; alters the FT conformation of the active site; slightly increased FT protease activity with APP; decreased activity for Notch1 FT cleavage; no loss of its ability to cleave Ephb2/CTF1; FT dbSNP:rs63750306)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:11524469, ECO:0000269|PubMed:17428795, FT ECO:0000269|PubMed:20164095, ECO:0000269|PubMed:22461631, FT ECO:0000269|PubMed:27930341, ECO:0000269|PubMed:7596406" FT /id="VAR_006426" FT VARIANT 146 FT /note="M -> V (in AD3; loss of function as calcium-leak FT channel; results in calcium overload in the endoplasmic FT reticulum; dbSNP:rs63750306)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:16959576, ECO:0000269|PubMed:7550356" FT /id="VAR_006427" FT VARIANT 147 FT /note="T -> I (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63750907)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:27930341" FT /id="VAR_010123" FT VARIANT 153 FT /note="L -> V (in AD3; abolishes protease activity with APP FT resulting in decreased amyloid-beta 42 and amyloid-beta 40 FT production; dbSNP:rs63751441)" FT /evidence="ECO:0000269|PubMed:12552037, FT ECO:0000269|PubMed:24495933, ECO:0000269|PubMed:27930341" FT /id="VAR_081235" FT VARIANT 154 FT /note="Y -> C (in AD3; uncertain significance; FT dbSNP:rs63751292)" FT /evidence="ECO:0000269|PubMed:12552037" FT /id="VAR_081236" FT VARIANT 154 FT /note="Y -> N (in AD3; disease phenotype includes spastic FT paraparesis; abolishes protease activity with APP resulting FT in decreased amyloid-beta 42 and amyloid-beta 40 FT production; dbSNP:rs63750588)" FT /evidence="ECO:0000269|PubMed:15364419, FT ECO:0000269|PubMed:27930341" FT /id="VAR_081237" FT VARIANT 156 FT /note="Y -> FTY (in AD3; uncertain significance)" FT /evidence="ECO:0000269|PubMed:11524469" FT /id="VAR_075262" FT VARIANT 159 FT /note="Y -> F (in AD3; uncertain significance; FT dbSNP:rs778630379)" FT /evidence="ECO:0000269|PubMed:23123781" FT /id="VAR_081238" FT VARIANT 163 FT /note="H -> R (in AD3; abolishes protease activity with FT APP; decreased activity for Notch cleavage; FT dbSNP:rs63750590)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:11524469, ECO:0000269|PubMed:22461631, FT ECO:0000269|PubMed:22503161, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:7596406, ECO:0000269|PubMed:8634712, FT ECO:0000269|PubMed:8733303, ECO:0000269|PubMed:9521423" FT /id="VAR_006428" FT VARIANT 163 FT /note="H -> Y (in AD3; slightly increased protease activity FT with APP and slightly increased amyloid-beta 42 production; FT dbSNP:rs63749885)" FT /evidence="ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:7550356" FT /id="VAR_006429" FT VARIANT 165 FT /note="W -> C (in AD3; dbSNP:rs63751484)" FT /evidence="ECO:0000269|PubMed:10441572" FT /id="VAR_010124" FT VARIANT 166 FT /note="L -> P (in AD3; onset in adolescence; severe FT decrease of protease activity with APP; results in altered FT amyloid-beta production and increased amyloid-beta 42/ FT amyloid-beta 40 ratio; results in reduced Notch FT proteolysis; dbSNP:rs63750265)" FT /evidence="ECO:0000269|PubMed:12048239, FT ECO:0000269|PubMed:22529981, ECO:0000269|PubMed:23843529, FT ECO:0000269|PubMed:27930341" FT /id="VAR_016216" FT VARIANT 168 FT /note="Missing (in AD3; uncertain significance; abolishes FT protease activity with APP resulting in decreased amyloid- FT beta 42 and amyloid-beta 40 production)" FT /evidence="ECO:0000269|PubMed:12552037" FT /id="VAR_081239" FT VARIANT 169 FT /note="S -> L (in AD3; dbSNP:rs63751210)" FT /evidence="ECO:0000269|PubMed:9831473" FT /id="VAR_006430" FT VARIANT 169 FT /note="S -> P (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63750418)" FT /evidence="ECO:0000269|PubMed:10025789, FT ECO:0000269|PubMed:27930341" FT /id="VAR_006431" FT VARIANT 170 FT /note="S -> F (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63750577)" FT /evidence="ECO:0000269|PubMed:16344340, FT ECO:0000269|PubMed:17502474, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:29466804" FT /id="VAR_081240" FT VARIANT 171 FT /note="L -> P (in AD3; abolishes protease activity with FT APP; dbSNP:rs63750963)" FT /evidence="ECO:0000269|PubMed:12552037, FT ECO:0000269|PubMed:27930341, ECO:0000269|PubMed:9833068" FT /id="VAR_006432" FT VARIANT 173 FT /note="L -> W (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63750299)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:27930341" FT /id="VAR_010125" FT VARIANT 174 FT /note="L -> M (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63751144)" FT /evidence="ECO:0000269|PubMed:12484344, FT ECO:0000269|PubMed:27930341" FT /id="VAR_016217" FT VARIANT 177 FT /note="F -> L (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63749911)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:27930341" FT /id="VAR_075263" FT VARIANT 177 FT /note="F -> S (in AD3; uncertain significance; FT dbSNP:rs63749806)" FT /evidence="ECO:0000269|PubMed:11524469" FT /id="VAR_075264" FT VARIANT 178 FT /note="S -> P (in AD3; uncertain significance; abolishes FT protease activity with APP; dbSNP:rs63750155)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:27930341" FT /id="VAR_075265" FT VARIANT 183 FT /note="G -> V (in PIDB and AD3; uncertain significance; FT neuropathologic examination of brain sections from a FT patient shows the presence of Pick bodies and absence of FT beta-amyloid plaques; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio in vitro; dbSNP:rs63751068)" FT /evidence="ECO:0000269|PubMed:15122701, FT ECO:0000269|PubMed:27930341" FT /id="VAR_081241" FT VARIANT 184 FT /note="E -> D (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63750311)" FT /evidence="ECO:0000269|PubMed:12552037, FT ECO:0000269|PubMed:27930341" FT /id="VAR_081242" FT VARIANT 205 FT /note="F -> L (in dbSNP:rs1042864)" FT /id="VAR_011876" FT VARIANT 206 FT /note="G -> A (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63750082)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:11710891, ECO:0000269|PubMed:27073747, FT ECO:0000269|PubMed:27930341" FT /id="VAR_016218" FT VARIANT 206 FT /note="G -> D (in AD3; affects APP processing resulting in FT increased amyloid-beta 42/amyloid-beta 40 ratio; does not FT affect NOTCH processing; does not affect endoproteolysis; FT reduced interaction with PEN2; results in decreased protein FT levels in the endoplasmic reticulum but increased levels in FT early endosome; reduced ability to maintain ER calcium FT homeostasis; dbSNP:rs63750082)" FT /evidence="ECO:0000269|PubMed:21335660, FT ECO:0000269|PubMed:25394380, ECO:0000269|PubMed:29175279" FT /id="VAR_081243" FT VARIANT 206 FT /note="G -> S (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63750569)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:27930341" FT /id="VAR_075266" FT VARIANT 209 FT /note="G -> E (in AD3; uncertain significance; FT dbSNP:rs63750053)" FT /evidence="ECO:0000269|PubMed:11524469" FT /id="VAR_075267" FT VARIANT 209 FT /note="G -> R (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63749880)" FT /evidence="ECO:0000269|PubMed:10447269, FT ECO:0000269|PubMed:27930341" FT /id="VAR_009210" FT VARIANT 209 FT /note="G -> V (in AD3; abolishes protease activity with FT APP; dbSNP:rs63750053)" FT /evidence="ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:9521423" FT /id="VAR_006433" FT VARIANT 213 FT /note="I -> L (in AD3; increases protease activity with APP FT resulting in altered amyloid-beta production and increased FT amyloid-beta 42/amyloid-beta 40 ratio; dbSNP:rs63750861)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:27930341" FT /id="VAR_075268" FT VARIANT 213 FT /note="I -> T (in AD3; decreased protease activity with APP FT resulting in altered amyloid-beta production and increased FT amyloid-beta 42/amyloid-beta 40 ratio; dbSNP:rs63751309)" FT /evidence="ECO:0000269|PubMed:18430735, FT ECO:0000269|PubMed:8733303" FT /id="VAR_006434" FT VARIANT 214 FT /note="H -> Y (found in a patient with dementia; uncertain FT significance; dbSNP:rs63751003)" FT /evidence="ECO:0000269|PubMed:22503161" FT /id="VAR_070024" FT VARIANT 217 FT /note="G -> R (in AD3; with unusual amyloid cotton wool FT plaques; decreased protease activity with APP resulting in FT altered amyloid-beta production and increased amyloid-beta FT 42/amyloid-beta 40 ratio; dbSNP:rs267606983)" FT /evidence="ECO:0000269|PubMed:19667325, FT ECO:0000269|PubMed:27930341" FT /id="VAR_081244" FT VARIANT 219 FT /note="L -> P (in AD3; dbSNP:rs63750761)" FT /evidence="ECO:0000269|PubMed:10208579" FT /id="VAR_010126" FT VARIANT 222 FT /note="Q -> R (in AD3; uncertain significance; slightly FT increased protease activity with APP and slightly increased FT amyloid-beta 42/amyloid-beta 40 ratio; dbSNP:rs63750009)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:27930341" FT /id="VAR_075269" FT VARIANT 229 FT /note="I -> F (in AD3; decreased protease activity with APP FT resulting in altered amyloid-beta production and increased FT amyloid-beta 42/amyloid-beta 40 ratio; dbSNP:rs63749970)" FT /evidence="ECO:0000269|PubMed:12552037, FT ECO:0000269|PubMed:27930341" FT /id="VAR_081245" FT VARIANT 231 FT /note="A -> T (in AD3; decreased protease activity with APP FT resulting in altered amyloid-beta production and increased FT amyloid-beta 42/amyloid-beta 40 ratio; dbSNP:rs63749836)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:11524469, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:8634712" FT /id="VAR_006435" FT VARIANT 231 FT /note="A -> V (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63750799)" FT /evidence="ECO:0000269|PubMed:16752394, FT ECO:0000269|PubMed:9384602" FT /id="VAR_006436" FT VARIANT 233 FT /note="M -> L (in AD3; slightly decreased protease activity FT with APP resulting in altered amyloid-beta production and FT mildly increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63751287)" FT /evidence="ECO:0000269|PubMed:10533070, FT ECO:0000269|PubMed:11524469, ECO:0000269|PubMed:27930341" FT /id="VAR_009211" FT VARIANT 233 FT /note="M -> T (in AD3; decreased protease activity with APP FT resulting in altered amyloid-beta production and increased FT amyloid-beta 42/amyloid-beta 40 ratio; dbSNP:rs63751024)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:27930341, ECO:0000269|PubMed:9172170" FT /id="VAR_006437" FT VARIANT 235 FT /note="L -> P (in AD3; abolishes protease activity with FT APP; dbSNP:rs63749835)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:11524469, ECO:0000269|PubMed:27930341" FT /id="VAR_006438" FT VARIANT 235 FT /note="L -> R (in AD3; abolishes protease activity with FT APP)" FT /evidence="ECO:0000269|PubMed:21501661, FT ECO:0000269|PubMed:27930341" FT /id="VAR_081246" FT VARIANT 235 FT /note="L -> V (in AD3; reduced APP cleavage resulting in FT decreased amyloid-beta 42 and amyloid-beta 40 production; FT no relevant change in amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63751130)" FT /evidence="ECO:0000269|PubMed:12552037, FT ECO:0000269|PubMed:27930341" FT /id="VAR_081247" FT VARIANT 237 FT /note="F -> I (in AD3; uncertain significance; disease FT phenotype includes spastic paraparesis; severe decrease of FT protease activity with APP; results in decreased amyloid- FT beta 42 and amyloid-beta 40 production; dbSNP:rs63750858)" FT /evidence="ECO:0000269|PubMed:11561050, FT ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:27930341" FT /id="VAR_081248" FT VARIANT 237 FT /note="F -> L (in AD3; uncertain significance; FT dbSNP:rs63750858)" FT /evidence="ECO:0000269|PubMed:12552037" FT /id="VAR_081249" FT VARIANT 246 FT /note="A -> E (in AD3; nearly abolishes protease activity FT with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; FT no loss of its ability to cleave Ephb2/CTF1; FT dbSNP:rs63750526)" FT /evidence="ECO:0000269|PubMed:17428795, FT ECO:0000269|PubMed:27930341, ECO:0000269|PubMed:7596406" FT /id="VAR_006439" FT VARIANT 250 FT /note="L -> S (in AD3; nearly abolishes protease activity FT with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63751163)" FT /evidence="ECO:0000269|PubMed:27930341" FT /id="VAR_006440" FT VARIANT 260 FT /note="A -> V (in AD3; nearly abolishes protease activity FT with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; FT impaired ability to cleave Ephb2/CTF1; dbSNP:rs63751420)" FT /evidence="ECO:0000269|PubMed:12552037, FT ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:7651536, ECO:0000269|PubMed:9521423" FT /id="VAR_006441" FT VARIANT 261 FT /note="V -> F (in AD3; nearly abolishes protease activity FT with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63750964)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:27930341" FT /id="VAR_075270" FT VARIANT 262 FT /note="L -> F (in AD3; decreased protease activity with APP FT resulting in altered amyloid-beta production and increased FT amyloid-beta 42/amyloid-beta 40 ratio; dbSNP:rs63750248)" FT /evidence="ECO:0000269|PubMed:16752394, FT ECO:0000269|PubMed:27930341" FT /id="VAR_006442" FT VARIANT 262 FT /note="L -> V (in AD3)" FT /evidence="ECO:0000269|PubMed:22503161" FT /id="VAR_070025" FT VARIANT 263 FT /note="C -> F (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63751102)" FT /evidence="ECO:0000269|PubMed:12552037, FT ECO:0000269|PubMed:16752394" FT /id="VAR_081250" FT VARIANT 263 FT /note="C -> R (in AD3; decreased protease activity with FT APP; increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63750543)" FT /evidence="ECO:0000269|PubMed:27930341" FT /id="VAR_006443" FT VARIANT 264 FT /note="P -> L (in AD3; decreased protease activity with FT APP; increased amyloid-beta 42/amyloid-beta 40 ratio; FT impaired ability to cleave Ephb2/CTF1; dbSNP:rs63750301)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:8634712, ECO:0000269|PubMed:9521423" FT /id="VAR_006444" FT VARIANT 266 FT /note="G -> S (in AD3; nearly abolishes protease activity FT with APP; increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs121917807)" FT /evidence="ECO:0000269|PubMed:11920851, FT ECO:0000269|PubMed:27930341" FT /id="VAR_016219" FT VARIANT 267 FT /note="P -> S (in AD3; decreased protease activity with FT APP; increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63751229)" FT /evidence="ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:7550356" FT /id="VAR_006445" FT VARIANT 269 FT /note="R -> G (in AD3; decreased protease activity with FT APP; increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63751019)" FT /evidence="ECO:0000269|PubMed:27930341" FT /id="VAR_006447" FT VARIANT 269 FT /note="R -> H (in AD3; dbSNP:rs63750900)" FT /evidence="ECO:0000269|PubMed:12552037" FT /id="VAR_006448" FT VARIANT 271 FT /note="L -> V (in AD3; abolishes protease activity with FT APP; dbSNP:rs63750886)" FT /evidence="ECO:0000269|PubMed:12493737, FT ECO:0000269|PubMed:27930341" FT /id="VAR_016220" FT VARIANT 274 FT /note="T -> R (in AD3; uncertain significance; abolishes FT protease activity with APP; dbSNP:rs63750284)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:27930341" FT /id="VAR_075271" FT VARIANT 275 FT /note="A -> V (in AD3; uncertain significance; reduced FT protease activity with APP resulting in reduced amyloid- FT beta 40 levels but no relevant changes in amyloid-beta 42/ FT amyloid-beta 40 ratio; dbSNP:rs1555355869)" FT /evidence="ECO:0000269|PubMed:24582897, FT ECO:0000269|PubMed:27930341" FT /id="VAR_081251" FT VARIANT 278 FT /note="R -> I (in AD3; atypical phenotype presenting as FT language impairment, impaired frontal executive function FT and relative preservation of memory; severe decrease of APP FT and Notch proteolysis; dbSNP:rs63749891)" FT /evidence="ECO:0000269|PubMed:15534260, FT ECO:0000269|PubMed:23843529" FT /id="VAR_081252" FT VARIANT 278 FT /note="R -> T (in AD3; dbSNP:rs63749891)" FT /evidence="ECO:0000269|PubMed:9172170" FT /id="VAR_006449" FT VARIANT 280 FT /note="E -> A (in AD3; strong deposition of amyloid-beta 42 FT is observed in brain regions of AD3 patients; decreased FT protease activity with APP resulting in altered amyloid- FT beta production and increased amyloid-beta 42/amyloid-beta FT 40 ratio; decreased activity for Notch1 cleavage; FT dbSNP:rs63750231)" FT /evidence="ECO:0000269|PubMed:11568920, FT ECO:0000269|PubMed:22461631, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:28269784, ECO:0000269|PubMed:7550356, FT ECO:0000269|PubMed:8837617, ECO:0000269|PubMed:9298817" FT /id="VAR_006450" FT VARIANT 280 FT /note="E -> G (in AD3; some AD3 patients manifest spastic FT paraparesis and unusual amyloid plaques with prominent FT amyloid angiopathy on brain biopsy; decreased protease FT activity with APP; increased amyloid-beta 42/amyloid-beta FT 40 ratio; impaired ability to cleave Ephb2/CTF1; FT dbSNP:rs63750231)" FT /evidence="ECO:0000269|PubMed:12370477, FT ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:7550356" FT /id="VAR_006451" FT VARIANT 282 FT /note="L -> R (in AD3; abolishes protease activity with FT APP; dbSNP:rs63750050)" FT /evidence="ECO:0000269|PubMed:10533070, FT ECO:0000269|PubMed:27930341" FT /id="VAR_009212" FT VARIANT 282 FT /note="L -> V (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63749937)" FT /evidence="ECO:0000269|PubMed:11701593, FT ECO:0000269|PubMed:15122701, ECO:0000269|PubMed:16752394" FT /id="VAR_081253" FT VARIANT 285 FT /note="A -> V (in AD3; slightly decreased protease activity FT with APP and slightly decreased amyloid-beta 42/amyloid- FT beta 40 ratio; dbSNP:rs63751139)" FT /evidence="ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:7651536" FT /id="VAR_006452" FT VARIANT 286 FT /note="L -> V (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63751235)" FT /evidence="ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:7596406" FT /id="VAR_006453" FT VARIANT 289 FT /note="S -> C (in AD3)" FT /evidence="ECO:0000269|PubMed:8875251" FT /id="VAR_010127" FT VARIANT 311 FT /note="K -> R (found in patients with late-onset Alzheimer FT disease; uncertain significance; results in altered FT amyloid-beta production and increased amyloid-beta 42/ FT amyloid-beta 40 ratio; dbSNP:rs115865530)" FT /evidence="ECO:0000269|PubMed:28269784" FT /id="VAR_081254" FT VARIANT 315 FT /note="Y -> C (found in a renal cell carcinoma sample; FT somatic mutation)" FT /evidence="ECO:0000269|PubMed:21248752" FT /id="VAR_064747" FT VARIANT 318 FT /note="E -> G (in dbSNP:rs17125721)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:10533070, ECO:0000269|PubMed:10631141, FT ECO:0000269|PubMed:11524469, ECO:0000269|PubMed:11568920, FT ECO:0000269|PubMed:12552037, ECO:0000269|PubMed:18485326, FT ECO:0000269|PubMed:9384602, ECO:0000269|PubMed:9851443, FT ECO:0000269|PubMed:9851450, ECO:0000269|PubMed:9915968" FT /id="VAR_006454" FT VARIANT 333 FT /note="D -> G (in CMD1U; results in slightly decreased FT protease activity with APP and slightly decreased amyloid- FT beta 42/amyloid-beta 40 ratio; dbSNP:rs121917809)" FT /evidence="ECO:0000269|PubMed:17186461, FT ECO:0000269|PubMed:27930341" FT /id="VAR_064902" FT VARIANT 352 FT /note="R -> RR (in AD3; uncertain significance)" FT /evidence="ECO:0000269|PubMed:11524469" FT /id="VAR_075272" FT VARIANT 354 FT /note="T -> I (in AD3; uncertain significance; results in FT decreased protease activity with APP and decreased amyloid- FT beta 42/amyloid-beta 40 ratio; dbSNP:rs63751164)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:27930341" FT /id="VAR_075273" FT VARIANT 358 FT /note="R -> Q (in AD3; uncertain significance; results in FT altered amyloid-beta production and increased amyloid-beta FT 42/amyloid-beta 40 ratio; dbSNP:rs63751174)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:27930341" FT /id="VAR_075274" FT VARIANT 365 FT /note="S -> Y (in AD3; uncertain significance; FT dbSNP:rs63750941)" FT /evidence="ECO:0000269|PubMed:11524469" FT /id="VAR_075275" FT VARIANT 377 FT /note="R -> M (in AD3; uncertain significance)" FT /evidence="ECO:0000269|PubMed:12552037" FT /id="VAR_081255" FT VARIANT 378 FT /note="G -> E (in AD3; decreased protease activity with FT APP; results in altered amyloid-beta production and FT increased amyloid-beta 42/amyloid-beta 40 ratio)" FT /evidence="ECO:0000269|PubMed:10200054, FT ECO:0000269|PubMed:27930341" FT /id="VAR_006455" FT VARIANT 378 FT /note="G -> V (in AD3; abolishes protease activity with FT APP; dbSNP:rs63750323)" FT /evidence="ECO:0000269|PubMed:12552037, FT ECO:0000269|PubMed:27073747, ECO:0000269|PubMed:27930341" FT /id="VAR_081256" FT VARIANT 381 FT /note="L -> F (in AD3; dbSNP:rs63750687)" FT /evidence="ECO:0000269|PubMed:24121961" FT /id="VAR_081257" FT VARIANT 381 FT /note="L -> V (in AD3; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio; dbSNP:rs63750687)" FT /evidence="ECO:0000269|PubMed:19797784, FT ECO:0000269|PubMed:27930341" FT /id="VAR_081258" FT VARIANT 384 FT /note="G -> A (in AD3; results in reduced APP and Notch FT proteolysis; results in altered amyloid-beta production and FT increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63750646)" FT /evidence="ECO:0000269|PubMed:16752394, FT ECO:0000269|PubMed:23843529, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:8634711" FT /id="VAR_006456" FT VARIANT 390 FT /note="S -> I (in AD3; abolishes protease activity with FT APP; dbSNP:rs63750883)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:27930341" FT /id="VAR_010128" FT VARIANT 392 FT /note="L -> V (in AD3; results in reduced APP and Notch FT proteolysis; results in altered amyloid-beta production and FT increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63751416)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:23843529, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:7651536, ECO:0000269|PubMed:8634712" FT /id="VAR_006457" FT VARIANT 394 FT /note="G -> V (in AD3; uncertain significance; abolishes FT protease activity with APP; dbSNP:rs63750929)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:27930341" FT /id="VAR_075276" FT VARIANT 396 FT /note="A -> T (in AD3; uncertain significance; decreased FT protease activity with APP; results in altered amyloid-beta FT production and increased amyloid-beta 42/amyloid-beta 40 FT ratio)" FT /evidence="ECO:0000269|PubMed:27930341" FT /id="VAR_070026" FT VARIANT 405 FT /note="N -> S (in AD3; uncertain significance; decreased FT protease activity with APP; dbSNP:rs63751254)" FT /evidence="ECO:0000269|PubMed:10644793, FT ECO:0000269|PubMed:27930341" FT /id="VAR_010129" FT VARIANT 408 FT /note="I -> T (in AD3; dbSNP:rs906454643)" FT /evidence="ECO:0000269|PubMed:26549787" FT /id="VAR_075277" FT VARIANT 409 FT /note="A -> T (in AD3; uncertain significance; decreased FT protease activity with APP; dbSNP:rs63750227)" FT /evidence="ECO:0000269|PubMed:10533070, FT ECO:0000269|PubMed:27930341" FT /id="VAR_009213" FT VARIANT 410 FT /note="C -> Y (in AD3; results in reduced APP and Notch FT proteolysis; dbSNP:rs661)" FT /evidence="ECO:0000269|PubMed:10441572, FT ECO:0000269|PubMed:23843529, ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:8634712, ECO:0000269|PubMed:9521423" FT /id="VAR_006458" FT VARIANT 417 FT /note="G -> A (in AD3; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30180983" FT /id="VAR_081259" FT VARIANT 418 FT /note="L -> F (in AD3; uncertain significance; nearly FT abolishes protease activity with APP; dbSNP:rs63751316)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:27930341" FT /id="VAR_075278" FT VARIANT 426 FT /note="A -> P (in AD3; uncertain significance; slightly FT decreased protease activity with APP; dbSNP:rs63751223)" FT /evidence="ECO:0000269|PubMed:27930341, FT ECO:0000269|PubMed:9521423" FT /id="VAR_006459" FT VARIANT 431 FT /note="A -> E (in AD3; decreased protease activity with FT APP; results in altered amyloid-beta production and FT increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63750083)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:16628450, ECO:0000269|PubMed:16897084, FT ECO:0000269|PubMed:27930341, ECO:0000269|Ref.95" FT /id="VAR_025605" FT VARIANT 435 FT /note="L -> F (in AD3; with unusual amyloid cotton wool FT plaques; almost abolishes gamma-secretase activity; no FT endoproteolytic cleavage; no APP nor NOTCH1 processing; no FT detectable amyloid-beta; dbSNP:rs63750001)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:16305624, ECO:0000269|PubMed:20460383, FT ECO:0000269|PubMed:23843529, ECO:0000269|PubMed:27930341" FT /id="VAR_075280" FT VARIANT 436 FT /note="P -> Q (in AD3; severe decrease of protease activity FT with APP; dbSNP:rs121917808)" FT /evidence="ECO:0000269|PubMed:22529981, FT ECO:0000269|PubMed:9831473" FT /id="VAR_006460" FT VARIANT 436 FT /note="P -> S (in AD3; partially abolishes gamma-secretase FT activity; results in altered amyloid-beta production and FT increased amyloid-beta 42/amyloid-beta 40 ratio; FT dbSNP:rs63749925)" FT /evidence="ECO:0000269|PubMed:10090481, FT ECO:0000269|PubMed:21248752, ECO:0000269|PubMed:27930341" FT /id="VAR_008141" FT VARIANT 439 FT /note="I -> V (in AD3; uncertain significance; no FT significant change of protease activity with APP; FT dbSNP:rs63750249)" FT /evidence="ECO:0000269|PubMed:11524469, FT ECO:0000269|PubMed:27930341" FT /id="VAR_075282" FT MUTAGEN 66..72 FT /note="Missing: No effect on interaction with GFAP." FT /evidence="ECO:0000269|PubMed:12058025" FT MUTAGEN 76..77 FT /note="KY->AA: No effect on interaction with GFAP." FT /evidence="ECO:0000269|PubMed:12058025" FT MUTAGEN 82..83 FT /note="VI->EE: Loss of interaction with GFAP." FT /evidence="ECO:0000269|PubMed:12058025" FT MUTAGEN 82 FT /note="V->K,E: Loss of interaction with GFAP." FT /evidence="ECO:0000269|PubMed:12058025" FT MUTAGEN 84..85 FT /note="ML->EE: Loss of interaction with GFAP." FT /evidence="ECO:0000269|PubMed:12058025" FT MUTAGEN 99 FT /note="T->A: Nearly abolishes protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 105 FT /note="F->I: Nearly abolishes protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 108 FT /note="R->Q: Nearly abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 112 FT /note="Q->C: Formation of an artifactual disulfide bond FT with a substrate protein." FT /evidence="ECO:0000269|PubMed:30598546, FT ECO:0000269|PubMed:30630874" FT MUTAGEN 113 FT /note="L->Q: Severe decrease of protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 117 FT /note="P->A: Nearly abolishes protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 123 FT /note="E->K: Nearly abolishes protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 131 FT /note="H->R: Severe decrease of protease activity with FT APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 136 FT /note="A->G: Decreased protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 143 FT /note="I->V: Increased amyloid-beta 42/amyloid-beta 40 FT ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 150 FT /note="L->P: Nearly abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 165 FT /note="W->G: Decreased protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 168 FT /note="I->T: Nearly abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 176 FT /note="F->L: Nearly abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 184 FT /note="E->G: Nearly abolishes protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 202 FT /note="I->F: Nearly abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:26280335, FT ECO:0000269|PubMed:27930341" FT MUTAGEN 212 FT /note="S->Y: Nearly abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 214 FT /note="H->D: Nearly abolishes protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 219 FT /note="L->F: Decreased protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 223 FT /note="Q->R: Abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 226 FT /note="L->F: Increases protease activity with APP." FT /evidence="ECO:0000269|PubMed:26280335, FT ECO:0000269|PubMed:27930341" FT MUTAGEN 230 FT /note="S->I: Abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 238 FT /note="I->M: Abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 239 FT /note="K->N: Abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 245 FT /note="T->P: Abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 248 FT /note="L->R: Nearly abolishes protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:26280335, FT ECO:0000269|PubMed:27930341" FT MUTAGEN 256 FT /note="Y->F: Alters gamma-secretase cleavage specificity. FT Increased production of amyloid-beta protein 42. No effect FT on enzymatic activity." FT /evidence="ECO:0000269|PubMed:15341515" FT MUTAGEN 256 FT /note="Y->S: Nearly abolishes protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 257 FT /note="D->A: Loss of endoproteolytic cleavage. Severe FT decrease of protease activity with APP. Reduces production FT of amyloid-beta. Reduces production of NICD in NOTCH1 FT processing. Impaired ability to cleave Ephb2/CTF1." FT /evidence="ECO:0000269|PubMed:10206644, FT ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:15341515, FT ECO:0000269|PubMed:17428795, ECO:0000269|PubMed:22529981" FT MUTAGEN 257 FT /note="D->E: Abolishes gamma-secretase activity. Reduces FT production of amyloid-beta in APP processing. Accumulation FT of full-length PS1. Loss of binding of transition state FT analog gamma-secretase inhibitor." FT /evidence="ECO:0000269|PubMed:10206644, FT ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:15341515" FT MUTAGEN 272 FT /note="V->A: Increased amyloid-beta 42/amyloid-beta 40 FT ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 273 FT /note="E->A: Decreased protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 278 FT /note="R->K: Nearly abolishes protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 284 FT /note="P->S: No significant change of protease activity FT with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 286 FT /note="L->A,E,P,Q,R,W: Increases production of amyloid-beta FT in APP processing." FT /evidence="ECO:0000269|PubMed:10811883" FT MUTAGEN 286 FT /note="L->E,R: Reduces production of NICD in NOTCH1 FT processing." FT /evidence="ECO:0000269|PubMed:10811883" FT MUTAGEN 288..290 FT /note="Missing: Loss of NOTCH1 and APP C83 cleavage." FT /evidence="ECO:0000269|PubMed:30598546, FT ECO:0000269|PubMed:30630874" FT MUTAGEN 291 FT /note="T->P: Abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 292 FT /note="M->D: Loss of endoproteolytic cleavage." FT /evidence="ECO:0000269|PubMed:10545183" FT MUTAGEN 310 FT /note="S->A: Abolishes PKA-mediated phosphorylation; no FT effect on caspase-mediated cleavage." FT /evidence="ECO:0000269|PubMed:14576165" FT MUTAGEN 345 FT /note="D->N: Abolishes caspase cleavage." FT /evidence="ECO:0000269|PubMed:9485372" FT MUTAGEN 346 FT /note="S->A: Abolishes PKC-mediated phosphorylation; no FT effect on PKA-mediated phosphorylation." FT /evidence="ECO:0000269|PubMed:14576165" FT MUTAGEN 346 FT /note="S->E: Inhibits caspase-mediated cleavage. Modulates FT progression of apoptosis." FT /evidence="ECO:0000269|PubMed:14576165" FT MUTAGEN 352 FT /note="R->C: Decreased protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 365 FT /note="S->A: Slightly increased protease activity with FT APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 373 FT /note="D->N: No effect on caspase cleavage." FT /evidence="ECO:0000269|PubMed:9485372" FT MUTAGEN 377..381 FT /note="Missing: Loss of NOTCH1 and APP C83 cleavage." FT /evidence="ECO:0000269|PubMed:30598546, FT ECO:0000269|PubMed:30630874" FT MUTAGEN 377 FT /note="R->W: Nearly abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 385 FT /note="D->A: Loss of endoproteolytic cleavage. Severe FT decrease of protease activity with APP. Reduces production FT of amyloid-beta. Loss of NOTCH1 cleavage. Disassembly of FT the N-cadherin/PS1 complex at the cell surface. Impairs FT CDH2 processing." FT /evidence="ECO:0000269|PubMed:10206644, FT ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:14515347, FT ECO:0000269|PubMed:15341515, ECO:0000269|PubMed:22529981, FT ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874, FT ECO:0000269|PubMed:9485372" FT MUTAGEN 385 FT /note="D->E: Abolishes gamma-secretase activity. Reduces FT production of amyloid-beta in APP processing. Accumulation FT of full-length PS1. Loss of binding of transition state FT analog gamma-secretase inhibitor." FT /evidence="ECO:0000269|PubMed:10206644, FT ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:14515347, FT ECO:0000269|PubMed:15341515, ECO:0000269|PubMed:9485372" FT MUTAGEN 385 FT /note="D->N: No effect on caspase cleavage." FT /evidence="ECO:0000269|PubMed:10206644, FT ECO:0000269|PubMed:10899933, ECO:0000269|PubMed:14515347, FT ECO:0000269|PubMed:15341515, ECO:0000269|PubMed:9485372" FT MUTAGEN 386 FT /note="F->S: Nearly abolishes protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 389 FT /note="Y->F: Alters gamma-secretase cleavage specificity. FT Increased production of amyloid-beta protein 42. No effect FT on enzymatic activity." FT /evidence="ECO:0000269|PubMed:15341515" FT MUTAGEN 391 FT /note="V->F: Decreased protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 412 FT /note="V->I: Abolishes protease activity with APP." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 420 FT /note="L->R: Decreased protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT MUTAGEN 424 FT /note="L->V: Increases protease activity with APP." FT /evidence="ECO:0000269|PubMed:26280335, FT ECO:0000269|PubMed:27930341" FT MUTAGEN 432..434 FT /note="Missing: Loss of NOTCH1 and APP C83 cleavage." FT /evidence="ECO:0000269|PubMed:30598546, FT ECO:0000269|PubMed:30630874" FT MUTAGEN 432 FT /note="L->P: Loss of NOTCH1 and APP C83 cleavage." FT /evidence="ECO:0000269|PubMed:30598546, FT ECO:0000269|PubMed:30630874" FT MUTAGEN 433 FT /note="P->A: No effect on endoproteolytic cleavage. No FT effect on APP nor NOTCH1 processing. Slightly increased FT amyloid-beta protein 42/40 ratio." FT /evidence="ECO:0000269|PubMed:16305624" FT MUTAGEN 433 FT /note="P->D,F,L,N,V: No endoproteolytic cleavage; no APP, FT nor NOTCH1 processing. No detectable amyloid-beta." FT /evidence="ECO:0000269|PubMed:16305624, FT ECO:0000269|PubMed:20460383" FT MUTAGEN 433 FT /note="P->G: Very little endoproteolysis. Little APP FT processing. No NOTCH1 processing. Very low levels amyloid- FT beta protein 40 and no detectable amyloid-beta protein 42." FT /evidence="ECO:0000269|PubMed:16305624" FT MUTAGEN 434 FT /note="A->C: Some loss of endoproteolytic cleavage. Some FT loss of APP and NOTCH1 processing. 6 to 13-fold increase in FT amyloid-beta protein 42/40 ratio." FT /evidence="ECO:0000269|PubMed:16305624, FT ECO:0000269|PubMed:27930341" FT MUTAGEN 434 FT /note="A->D,I,L,V: No endoproteolytic cleavage. No APP nor FT NOTCH1 processing. No detectable amyloid-beta." FT /evidence="ECO:0000269|PubMed:16305624" FT MUTAGEN 434 FT /note="A->G: No effect on endoproteolytic cleavage. No FT effect on APP nor NOTCH1 processing. Reduced amyloid-beta FT protein 42/40 ratio." FT /evidence="ECO:0000269|PubMed:16305624" FT MUTAGEN 435 FT /note="L->A: No effect on endoproteolytic cleavage. No FT effect on APP processing. Impaired NOTCH1 processing. FT Greatly reduced amyloid-beta protein 42/40 ratio." FT /evidence="ECO:0000269|PubMed:16305624" FT MUTAGEN 435 FT /note="L->G: Greatly reduced endoproteolytic cleavage. Very FT little APP and NOTCH1 processing. Very low levels of FT amyloid-beta protein 40 and no detectable amyloid-beta FT protein 42." FT /evidence="ECO:0000269|PubMed:16305624" FT MUTAGEN 435 FT /note="L->I: No effect on endoproteolytic cleavage. No FT effect on APP nor NOTCH1 processing." FT /evidence="ECO:0000269|PubMed:16305624" FT MUTAGEN 435 FT /note="L->R: No endoproteolytic cleavage; no APP, nor FT NOTCH1 processing. No detectable amyloid-beta." FT /evidence="ECO:0000269|PubMed:20460383" FT MUTAGEN 435 FT /note="L->V: No effect on endoproteolytic cleavage. No FT effect on APP processing. Impaired NOTCH1 processing. Some FT increase in amyloid-beta protein 42/40 ratio." FT /evidence="ECO:0000269|PubMed:16305624" FT MUTAGEN 437 FT /note="I->V: Decreased protease activity with APP. FT Increased amyloid-beta 42/amyloid-beta 40 ratio in vitro." FT /evidence="ECO:0000269|PubMed:27930341" FT CONFLICT 128 FT /note="R -> G (in Ref. 7; AAL16811)" FT /evidence="ECO:0000305" FT STRAND 77..80 FT /evidence="ECO:0007829|PDB:6LR4" FT HELIX 83..102 FT /evidence="ECO:0007829|PDB:8KCS" FT HELIX 105..107 FT /evidence="ECO:0007829|PDB:6IYC" FT STRAND 114..116 FT /evidence="ECO:0007829|PDB:8X52" FT STRAND 120..123 FT /evidence="ECO:0007829|PDB:6IYC" FT HELIX 125..155 FT /evidence="ECO:0007829|PDB:8KCS" FT HELIX 159..175 FT /evidence="ECO:0007829|PDB:8KCS" FT HELIX 177..188 FT /evidence="ECO:0007829|PDB:8KCS" FT HELIX 195..214 FT /evidence="ECO:0007829|PDB:8KCS" FT HELIX 219..240 FT /evidence="ECO:0007829|PDB:8KCS" FT HELIX 243..262 FT /evidence="ECO:0007829|PDB:8KCS" FT STRAND 263..266 FT /evidence="ECO:0007829|PDB:6IDF" FT HELIX 267..277 FT /evidence="ECO:0007829|PDB:8KCS" FT STRAND 278..280 FT /evidence="ECO:0007829|PDB:6IDF" FT TURN 284..286 FT /evidence="ECO:0007829|PDB:8KCU" FT STRAND 287..289 FT /evidence="ECO:0007829|PDB:8KCS" FT HELIX 293..299 FT /evidence="ECO:0007829|PDB:2KR6" FT STRAND 341..345 FT /evidence="ECO:0007829|PDB:2KR6" FT HELIX 356..368 FT /evidence="ECO:0007829|PDB:2KR6" FT STRAND 380..382 FT /evidence="ECO:0007829|PDB:8KCS" FT HELIX 383..398 FT /evidence="ECO:0007829|PDB:8KCS" FT STRAND 400..402 FT /evidence="ECO:0007829|PDB:8OQY" FT HELIX 403..428 FT /evidence="ECO:0007829|PDB:8KCS" FT STRAND 432..434 FT /evidence="ECO:0007829|PDB:6IDF" FT HELIX 435..451 FT /evidence="ECO:0007829|PDB:8KCS" FT HELIX 454..463 FT /evidence="ECO:0007829|PDB:8KCS" SQ SEQUENCE 467 AA; 52668 MW; 5E0F451EF82BCF20 CRC64; MTELPAPLSY FQNAQMSEDN HLSNTVRSQN DNRERQEHND RRSLGHPEPL SNGRPQGNSR QVVEQDEEED EELTLKYGAK HVIMLFVPVT LCMVVVVATI KSVSFYTRKD GQLIYTPFTE DTETVGQRAL HSILNAAIMI SVIVVMTILL VVLYKYRCYK VIHAWLIISS LLLLFFFSFI YLGEVFKTYN VAVDYITVAL LIWNFGVVGM ISIHWKGPLR LQQAYLIMIS ALMALVFIKY LPEWTAWLIL AVISVYDLVA VLCPKGPLRM LVETAQERNE TLFPALIYSS TMVWLVNMAE GDPEAQRRVS KNSKYNAEST ERESQDTVAE NDDGGFSEEW EAQRDSHLGP HRSTPESRAA VQELSSSILA GEDPEERGVK LGLGDFIFYS VLVGKASATA SGDWNTTIAC FVAILIGLCL TLLLLAIFKK ALPALPISIT FGLVFYFATD YLVQPFMDQL AFHQFYI // ID T126B_HUMAN Reviewed; 230 AA. AC Q8IUX1; A8K535; A8MSS0; Q32Q09; Q8WVU3; Q96EP3; Q9NZ29; DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot. DT 20-MAR-2007, sequence version 2. DT 28-JAN-2026, entry version 146. DE RecName: Full=Complex I assembly factor TMEM126B, mitochondrial {ECO:0000305}; DE AltName: Full=Transmembrane protein 126B; GN Name=TMEM126B {ECO:0000312|HGNC:HGNC:30883}; ORFNames=HT007; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Hypothalamus; RX PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J., RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., RA Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis RT and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Cervix carcinoma; RA Li W.B., Gruber C., Jessee J., Polayes D.; RT "Full-length cDNA libraries and normalization."; RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4 AND 5), AND VARIANT RP VAL-198. RC TISSUE=B-cell, Blood vessel, and Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-34, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=24191001; DOI=10.1073/pnas.1319247110; RA Andrews B., Carroll J., Ding S., Fearnley I.M., Walker J.E.; RT "Assembly factors for the membrane arm of human complex I."; RL Proc. Natl. Acad. Sci. U.S.A. 110:18934-18939(2013). RN [9] RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [10] RP IDENTIFICATION IN THE MCIA COMPLEX, AND FUNCTION. RX PubMed=32320651; DOI=10.1016/j.celrep.2020.107541; RA Formosa L.E., Muellner-Wong L., Reljic B., Sharpe A.J., Jackson T.D., RA Beilharz T.H., Stojanovski D., Lazarou M., Stroud D.A., Ryan M.T.; RT "Dissecting the Roles of Mitochondrial Complex I Intermediate Assembly RT Complex Factors in the Biogenesis of Complex I."; RL Cell Rep. 31:107541-107541(2020). RN [11] RP INTERACTION WITH TMEM70. RX PubMed=33753518; DOI=10.1073/pnas.2100558118; RA Carroll J., He J., Ding S., Fearnley I.M., Walker J.E.; RT "TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase RT and interact with assembly factors for complex I."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). RN [12] RP INVOLVEMENT IN MC1DN29, VARIANTS MC1DN29 70-GLN--GLU-230 DEL AND VAL-212, RP AND CHARACTERIZATION OF VARIANTS MC1DN29 70-GLN--GLU-230 DEL AND VAL-212. RX PubMed=27374773; DOI=10.1016/j.ajhg.2016.05.022; RA Sanchez-Caballero L., Ruzzenente B., Bianchi L., Assouline Z., Barcia G., RA Metodiev M.D., Rio M., Funalot B., van den Brand M.A., RA Guerrero-Castillo S., Molenaar J.P., Koolen D., Brandt U., Rodenburg R.J., RA Nijtmans L.G., Roetig A.; RT "Mutations in complex I assembly factor TMEM126B result in muscle weakness RT and isolated complex I deficiency."; RL Am. J. Hum. Genet. 99:208-216(2016). RN [13] RP INVOLVEMENT IN MC1DN29, VARIANT MC1DN29 VAL-212, AND CHARACTERIZATION OF RP VARIANT MC1DN29 VAL-212. RX PubMed=27374774; DOI=10.1016/j.ajhg.2016.05.021; RA Alston C.L., Compton A.G., Formosa L.E., Strecker V., Olahova M., RA Haack T.B., Smet J., Stouffs K., Diakumis P., Ciara E., Cassiman D., RA Romain N., Yarham J.W., He L., De Paepe B., Vanlander A.V., Seneca S., RA Feichtinger R.G., Ploski R., Rokicki D., Pronicka E., Haller R.G., RA Van Hove J.L., Bahlo M., Mayr J.A., Van Coster R., Prokisch H., Wittig I., RA Ryan M.T., Thorburn D.R., Taylor R.W.; RT "Biallelic mutations in TMEM126B cause severe complex I deficiency with a RT variable clinical phenotype."; RL Am. J. Hum. Genet. 99:217-227(2016). CC -!- FUNCTION: As part of the MCIA complex, involved in the assembly of the CC mitochondrial complex I (PubMed:27374773, PubMed:27374774, CC PubMed:32320651). Participates in constructing the membrane arm of CC complex I (PubMed:24191001). {ECO:0000269|PubMed:24191001, CC ECO:0000269|PubMed:27374773, ECO:0000269|PubMed:27374774, CC ECO:0000269|PubMed:32320651}. CC -!- SUBUNIT: Part of the mitochondrial complex I assembly/MCIA complex that CC comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 CC and complement subunits such as COA1 and TMEM186 (PubMed:32320651). CC Associates with the intermediate 370 kDa subcomplex of incompletely CC assembled complex I (PubMed:24191001). Interacts with TMEM70 CC (PubMed:33753518). {ECO:0000269|PubMed:24191001, CC ECO:0000269|PubMed:32320651, ECO:0000269|PubMed:33753518}. CC -!- INTERACTION: CC Q8IUX1; Q96HT8: MRFAP1L1; NbExp=3; IntAct=EBI-2800657, EBI-748896; CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane CC {ECO:0000269|PubMed:24191001}; Multi-pass membrane protein CC {ECO:0000269|PubMed:24191001}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=Q8IUX1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8IUX1-2; Sequence=VSP_023871, VSP_023872; CC Name=3; CC IsoId=Q8IUX1-3; Sequence=VSP_023870, VSP_023873, VSP_023874; CC Name=4; CC IsoId=Q8IUX1-4; Sequence=VSP_023875; CC Name=5; CC IsoId=Q8IUX1-5; Sequence=VSP_023870; CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 29 (MC1DN29) CC [MIM:618250]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN29 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:27374773, CC ECO:0000269|PubMed:27374774}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the TMEM126 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAI07901.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF220193; AAF67658.1; -; mRNA. DR EMBL; CR612738; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK291150; BAF83839.1; -; mRNA. DR EMBL; AP000642; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471076; EAW75098.1; -; Genomic_DNA. DR EMBL; BC012065; AAH12065.1; -; mRNA. DR EMBL; BC017574; AAH17574.1; -; mRNA. DR EMBL; BC038933; AAH38933.1; -; mRNA. DR EMBL; BC107900; AAI07901.1; ALT_FRAME; mRNA. DR CCDS; CCDS53686.1; -. [Q8IUX1-5] DR CCDS; CCDS8267.2; -. [Q8IUX1-1] DR RefSeq; NP_001180467.1; NM_001193538.3. [Q8IUX1-5] DR RefSeq; NP_001243475.1; NM_001256546.2. [Q8IUX1-5] DR RefSeq; NP_001337325.1; NM_001350396.2. [Q8IUX1-3] DR RefSeq; NP_060950.3; NM_018480.4. [Q8IUX1-1] DR AlphaFoldDB; Q8IUX1; -. DR BioGRID; 120965; 56. DR ComplexPortal; CPX-6322; Mitochondrial complex I intermediate assembly (MCIA) complex. DR FunCoup; Q8IUX1; 761. DR IntAct; Q8IUX1; 35. DR MINT; Q8IUX1; -. DR STRING; 9606.ENSP00000351737; -. DR TCDB; 9.B.317.1.1; the complex i integral membrane chaperone, tmem126 (tmem126) family. DR iPTMnet; Q8IUX1; -. DR PhosphoSitePlus; Q8IUX1; -. DR SwissPalm; Q8IUX1; -. DR BioMuta; TMEM126B; -. DR DMDM; 134035041; -. DR jPOST; Q8IUX1; -. DR MassIVE; Q8IUX1; -. DR PaxDb; 9606-ENSP00000351737; -. DR PeptideAtlas; Q8IUX1; -. DR ProteomicsDB; 70618; -. [Q8IUX1-1] DR ProteomicsDB; 70619; -. [Q8IUX1-2] DR ProteomicsDB; 70620; -. [Q8IUX1-3] DR ProteomicsDB; 70621; -. [Q8IUX1-4] DR ProteomicsDB; 70622; -. [Q8IUX1-5] DR Pumba; Q8IUX1; -. DR Antibodypedia; 17580; 57 antibodies from 12 providers. DR DNASU; 55863; -. DR Ensembl; ENST00000358867.11; ENSP00000351737.7; ENSG00000171204.13. [Q8IUX1-1] DR Ensembl; ENST00000393375.5; ENSP00000377039.1; ENSG00000171204.13. [Q8IUX1-5] DR Ensembl; ENST00000534341.1; ENSP00000433471.1; ENSG00000171204.13. [Q8IUX1-4] DR GeneID; 55863; -. DR KEGG; hsa:55863; -. DR MANE-Select; ENST00000358867.11; ENSP00000351737.7; NM_018480.7; NP_060950.3. DR UCSC; uc001pao.4; human. [Q8IUX1-1] DR AGR; HGNC:30883; -. DR ClinPGx; PA143485646; -. DR CTD; 55863; -. DR DisGeNET; 55863; -. DR GeneCards; TMEM126B; -. DR HGNC; HGNC:30883; TMEM126B. DR HPA; ENSG00000171204; Low tissue specificity. DR MalaCards; TMEM126B; -. DR MIM; 615533; gene. DR MIM; 618250; phenotype. DR OpenTargets; ENSG00000171204; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000171204; -. DR eggNOG; ENOG502SQEZ; Eukaryota. DR GeneTree; ENSGT00520000055616; -. DR HOGENOM; CLU_105475_0_0_1; -. DR InParanoid; Q8IUX1; -. DR OMA; QHYARFE; -. DR OrthoDB; 6234762at2759; -. DR PAN-GO; Q8IUX1; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q8IUX1; -. DR PathwayCommons; Q8IUX1; -. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q8IUX1; -. DR Agora; ENSG00000171204; -. DR BioGRID-ORCS; 55863; 37 hits in 1168 CRISPR screens. DR ChiTaRS; TMEM126B; human. DR GeneWiki; TMEM126B; -. DR GenomeRNAi; 55863; -. DR Pharos; Q8IUX1; Tbio. DR PRO; PR:Q8IUX1; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q8IUX1; protein. DR Bgee; ENSG00000171204; Expressed in pigmented layer of retina and 203 other cell types or tissues. DR ExpressionAtlas; Q8IUX1; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR GO; GO:0032094; P:response to food; IEA:Ensembl. DR InterPro; IPR009801; TMEM126. DR PANTHER; PTHR16296:SF3; COMPLEX I ASSEMBLY FACTOR TMEM126B, MITOCHONDRIAL; 1. DR PANTHER; PTHR16296; UNCHARACTERIZED HYPOTHALAMUS PROTEIN HT007; 1. DR Pfam; PF07114; TMEM126; 1. PE 1: Evidence at protein level; KW Alternative splicing; Chaperone; Disease variant; Membrane; Mitochondrion; KW Phosphoprotein; Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Transmembrane; Transmembrane helix. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:25944712" FT CHAIN 2..230 FT /note="Complex I assembly factor TMEM126B, mitochondrial" FT /id="PRO_0000280716" FT TRANSMEM 72..92 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 110..130 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 141..161 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 199..219 FT /note="Helical" FT /evidence="ECO:0000255" FT MOD_RES 34 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..30 FT /note="Missing (in isoform 3 and isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_023870" FT VAR_SEQ 1..18 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10931946" FT /id="VSP_023871" FT VAR_SEQ 19 FT /note="P -> MWIQVWMT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10931946" FT /id="VSP_023872" FT VAR_SEQ 133..140 FT /note="DNISKENC -> GEFKFTNV (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023873" FT VAR_SEQ 141..230 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023874" FT VAR_SEQ 171..230 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_023875" FT VARIANT 70..230 FT /note="Missing (in MC1DN29; loss of function in complex I FT assembly)" FT /evidence="ECO:0000269|PubMed:27374773" FT /id="VAR_081464" FT VARIANT 198 FT /note="A -> V (in dbSNP:rs17850847)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_031188" FT VARIANT 212 FT /note="G -> V (in MC1DN29; decreased function in complex I FT assembly; dbSNP:rs141542003)" FT /evidence="ECO:0000269|PubMed:27374773, FT ECO:0000269|PubMed:27374774" FT /id="VAR_081465" SQ SEQUENCE 230 AA; 25943 MW; B0EB374211C3CF52 CRC64; MVVFGYEAGT KPRDSGVVPV GTEEAPKVFK MAASMHGQPS PSLEDAKLRR PMVIEIIEKN FDYLRKEMTQ NIYQMATFGT TAGFSGIFSN FLFRRCFKVK HDALKTYASL ATLPFLSTVV TDKLFVIDAL YSDNISKENC VFRSSLIGIV CGVFYPSSLA FTKNGRLATK YHTVPLPPKG RVLIHWMTLC QTQMKLMAIP LVFQIMFGIL NGLYHYAVFE ETLEKTIHEE // ID TIDC1_HUMAN Reviewed; 285 AA. AC Q9NPL8; D3DN81; Q6IAJ7; Q6UWU6; Q9NPR3; Q9NPS5; Q9P0Y6; DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 28-JAN-2026, entry version 160. DE RecName: Full=Complex I assembly factor TIMMDC1, mitochondrial {ECO:0000305}; DE AltName: Full=Protein M5-14; DE AltName: Full=Translocase of inner mitochondrial membrane domain-containing protein 1; DE Short=TIMM domain containing-protein 1; GN Name=TIMMDC1 {ECO:0000312|HGNC:HGNC:1321}; Synonyms=C3orf1; GN ORFNames=UNQ247/PRO284; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ASP-76 AND ILE-217, AND TISSUE RP SPECIFICITY. RX PubMed=11092749; DOI=10.3109/10425170009033252; RA Escarceller M., Pluvinet R., Sumoy L., Estivill X.; RT "Identification and expression analysis of C3orf1, a novel human gene RT homologous to the Drosophila RP140-upstream gene."; RL DNA Seq. 11:335-338(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Li D.X., Roberts R.; RT "Identification of a novel transcript, M5-14, preferentially expressed in RT cardiac and skeletal muscle."; RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-217. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=B-cell; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=24191001; DOI=10.1073/pnas.1319247110; RA Andrews B., Carroll J., Ding S., Fearnley I.M., Walker J.E.; RT "Assembly factors for the membrane arm of human complex I."; RL Proc. Natl. Acad. Sci. U.S.A. 110:18934-18939(2013). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [12] RP INTERACTION WITH TMEM70. RX PubMed=33753518; DOI=10.1073/pnas.2100558118; RA Carroll J., He J., Ding S., Fearnley I.M., Walker J.E.; RT "TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase RT and interact with assembly factors for complex I."; RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021). RN [13] RP INVOLVEMENT IN MC1DN31. RX PubMed=28604674; DOI=10.1038/ncomms15824; RA Kremer L.S., Bader D.M., Mertes C., Kopajtich R., Pichler G., Iuso A., RA Haack T.B., Graf E., Schwarzmayr T., Terrile C., Konarikova E., Repp B., RA Kastenmueller G., Adamski J., Lichtner P., Leonhardt C., Funalot B., RA Donati A., Tiranti V., Lombes A., Jardel C., Glaeser D., Taylor R.W., RA Ghezzi D., Mayr J.A., Roetig A., Freisinger P., Distelmaier F., Strom T.M., RA Meitinger T., Gagneur J., Prokisch H.; RT "Genetic diagnosis of Mendelian disorders via RNA sequencing."; RL Nat. Commun. 8:15824-15824(2017). CC -!- FUNCTION: Chaperone protein involved in the assembly of the CC mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). CC Participates in constructing the membrane arm of complex I. CC {ECO:0000269|PubMed:24191001}. CC -!- SUBUNIT: Associates with the intermediate 315 kDa subcomplex of CC incompletely assembled complex I. Interacts with TMEM70 CC (PubMed:33753518). {ECO:0000269|PubMed:24191001, CC ECO:0000269|PubMed:33753518}. CC -!- INTERACTION: CC Q9NPL8; Q8TD06: AGR3; NbExp=3; IntAct=EBI-6268651, EBI-3925742; CC Q9NPL8; Q86W74-2: ANKRD46; NbExp=3; IntAct=EBI-6268651, EBI-12109402; CC Q9NPL8; P55056: APOC4; NbExp=3; IntAct=EBI-6268651, EBI-18302142; CC Q9NPL8; O95236-2: APOL3; NbExp=3; IntAct=EBI-6268651, EBI-11976321; CC Q9NPL8; Q8N6S5: ARL6IP6; NbExp=3; IntAct=EBI-6268651, EBI-2808844; CC Q9NPL8; Q8WVX3-2: ARLN; NbExp=3; IntAct=EBI-6268651, EBI-12003442; CC Q9NPL8; O75787: ATP6AP2; NbExp=3; IntAct=EBI-6268651, EBI-2512037; CC Q9NPL8; P51572: BCAP31; NbExp=3; IntAct=EBI-6268651, EBI-77683; CC Q9NPL8; Q6UWT4: C5orf46; NbExp=3; IntAct=EBI-6268651, EBI-11986083; CC Q9NPL8; P13236: CCL4; NbExp=3; IntAct=EBI-6268651, EBI-2873970; CC Q9NPL8; O95674: CDS2; NbExp=3; IntAct=EBI-6268651, EBI-3913685; CC Q9NPL8; Q8TAZ6: CMTM2; NbExp=3; IntAct=EBI-6268651, EBI-2339374; CC Q9NPL8; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-6268651, EBI-6942903; CC Q9NPL8; Q9HCS2: CYP4F12; NbExp=3; IntAct=EBI-6268651, EBI-3918831; CC Q9NPL8; Q96PD2-2: DCBLD2; NbExp=3; IntAct=EBI-6268651, EBI-12135455; CC Q9NPL8; Q9NR28: DIABLO; NbExp=3; IntAct=EBI-6268651, EBI-517508; CC Q9NPL8; Q8N682: DRAM1; NbExp=3; IntAct=EBI-6268651, EBI-10305400; CC Q9NPL8; Q6UW88-2: EPGN; NbExp=3; IntAct=EBI-6268651, EBI-17468158; CC Q9NPL8; O75063: FAM20B; NbExp=3; IntAct=EBI-6268651, EBI-11090967; CC Q9NPL8; Q96KR6: FAM210B; NbExp=3; IntAct=EBI-6268651, EBI-18938272; CC Q9NPL8; Q969F0: FATE1; NbExp=4; IntAct=EBI-6268651, EBI-743099; CC Q9NPL8; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-6268651, EBI-12175685; CC Q9NPL8; P29033: GJB2; NbExp=3; IntAct=EBI-6268651, EBI-3905204; CC Q9NPL8; Q8TDV0: GPR151; NbExp=3; IntAct=EBI-6268651, EBI-11955647; CC Q9NPL8; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-6268651, EBI-13345167; CC Q9NPL8; Q8TED1: GPX8; NbExp=3; IntAct=EBI-6268651, EBI-11721746; CC Q9NPL8; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-6268651, EBI-18053395; CC Q9NPL8; P01563: IFNA2; NbExp=3; IntAct=EBI-6268651, EBI-4394394; CC Q9NPL8; Q99706: KIR2DL4; NbExp=3; IntAct=EBI-6268651, EBI-10294579; CC Q9NPL8; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-6268651, EBI-2820517; CC Q9NPL8; Q9NX47: MARCHF5; NbExp=3; IntAct=EBI-6268651, EBI-2341610; CC Q9NPL8; Q5SR56: MFSD14B; NbExp=3; IntAct=EBI-6268651, EBI-373355; CC Q9NPL8; Q6N075: MFSD5; NbExp=3; IntAct=EBI-6268651, EBI-3920969; CC Q9NPL8; Q9NX14: NDUFB11; NbExp=4; IntAct=EBI-6268651, EBI-1246182; CC Q9NPL8; Q92982: NINJ1; NbExp=3; IntAct=EBI-6268651, EBI-2802124; CC Q9NPL8; Q8N912: NRAC; NbExp=3; IntAct=EBI-6268651, EBI-12051377; CC Q9NPL8; P50542-3: PEX5; NbExp=3; IntAct=EBI-6268651, EBI-12181987; CC Q9NPL8; Q07326: PIGF; NbExp=3; IntAct=EBI-6268651, EBI-17180304; CC Q9NPL8; P18031: PTPN1; NbExp=3; IntAct=EBI-6268651, EBI-968788; CC Q9NPL8; Q16849-3: PTPRN; NbExp=3; IntAct=EBI-6268651, EBI-10200782; CC Q9NPL8; Q9Y225-2: RNF24; NbExp=3; IntAct=EBI-6268651, EBI-13044680; CC Q9NPL8; Q8TAC9: SCAMP5; NbExp=3; IntAct=EBI-6268651, EBI-2695784; CC Q9NPL8; O00767: SCD; NbExp=3; IntAct=EBI-6268651, EBI-2684237; CC Q9NPL8; O75920: SERF1B; NbExp=3; IntAct=EBI-6268651, EBI-2115181; CC Q9NPL8; Q8N6R1: SERP2; NbExp=3; IntAct=EBI-6268651, EBI-749270; CC Q9NPL8; Q6ICL7: SLC35E4; NbExp=3; IntAct=EBI-6268651, EBI-12867720; CC Q9NPL8; Q8N357: SLC35F6; NbExp=3; IntAct=EBI-6268651, EBI-713484; CC Q9NPL8; Q96JF0-2: ST6GAL2; NbExp=3; IntAct=EBI-6268651, EBI-12908338; CC Q9NPL8; Q86Y82: STX12; NbExp=3; IntAct=EBI-6268651, EBI-2691717; CC Q9NPL8; O43752: STX6; NbExp=3; IntAct=EBI-6268651, EBI-2695795; CC Q9NPL8; Q7Z5S9: TMEM144; NbExp=3; IntAct=EBI-6268651, EBI-12876358; CC Q9NPL8; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-6268651, EBI-8638294; CC Q9NPL8; Q96HP8: TMEM176A; NbExp=3; IntAct=EBI-6268651, EBI-2800645; CC Q9NPL8; Q969S6: TMEM203; NbExp=3; IntAct=EBI-6268651, EBI-12274070; CC Q9NPL8; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-6268651, EBI-11528917; CC Q9NPL8; Q969K7: TMEM54; NbExp=3; IntAct=EBI-6268651, EBI-3922833; CC Q9NPL8; Q6PI78: TMEM65; NbExp=3; IntAct=EBI-6268651, EBI-6656213; CC Q9NPL8; Q8N2M4: TMEM86A; NbExp=3; IntAct=EBI-6268651, EBI-12015604; CC Q9NPL8; Q5BVD1: TTMP; NbExp=3; IntAct=EBI-6268651, EBI-10243654; CC Q9NPL8; Q9NYZ1: TVP23B; NbExp=3; IntAct=EBI-6268651, EBI-11343401; CC Q9NPL8; Q86WB7-2: UNC93A; NbExp=3; IntAct=EBI-6268651, EBI-13356252; CC Q9NPL8; Q8N511: VMA12; NbExp=3; IntAct=EBI-6268651, EBI-10265825; CC Q9NPL8; O95070: YIF1A; NbExp=3; IntAct=EBI-6268651, EBI-2799703; CC Q9NPL8; Q9Y548: YIPF1; NbExp=3; IntAct=EBI-6268651, EBI-7850136; CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane CC {ECO:0000269|PubMed:24191001}; Multi-pass membrane protein CC {ECO:0000269|PubMed:24191001}. CC -!- TISSUE SPECIFICITY: Generalized expression enhanced in heart and CC skeletal muscle. {ECO:0000269|PubMed:11092749}. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 31 (MC1DN31) CC [MIM:618251]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN31 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:28604674}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the Tim17/Tim22/Tim23 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF210057; AAG43510.1; -; mRNA. DR EMBL; AL390077; CAB98201.1; -; mRNA. DR EMBL; AL390090; CAB98212.1; -; mRNA. DR EMBL; AL390094; CAB98251.1; -; mRNA. DR EMBL; AF139077; AAF62372.1; -; mRNA. DR EMBL; AL136622; CAB66557.1; -; mRNA. DR EMBL; AY358633; AAQ88996.1; -; mRNA. DR EMBL; CR457158; CAG33439.1; -; mRNA. DR EMBL; CR533524; CAG38555.1; -; mRNA. DR EMBL; CH471052; EAW79566.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79568.1; -; Genomic_DNA. DR EMBL; BC012341; AAH12341.1; -; mRNA. DR CCDS; CCDS33831.1; -. DR RefSeq; NP_057673.2; NM_016589.4. DR AlphaFoldDB; Q9NPL8; -. DR BioGRID; 119451; 266. DR FunCoup; Q9NPL8; 2200. DR IntAct; Q9NPL8; 181. DR MINT; Q9NPL8; -. DR STRING; 9606.ENSP00000418803; -. DR iPTMnet; Q9NPL8; -. DR PhosphoSitePlus; Q9NPL8; -. DR SwissPalm; Q9NPL8; -. DR BioMuta; TIMMDC1; -. DR DMDM; 116243026; -. DR jPOST; Q9NPL8; -. DR MassIVE; Q9NPL8; -. DR PaxDb; 9606-ENSP00000418803; -. DR PeptideAtlas; Q9NPL8; -. DR ProteomicsDB; 82035; -. DR Pumba; Q9NPL8; -. DR Antibodypedia; 53806; 35 antibodies from 16 providers. DR DNASU; 51300; -. DR Ensembl; ENST00000494664.6; ENSP00000418803.1; ENSG00000113845.11. DR GeneID; 51300; -. DR KEGG; hsa:51300; -. DR MANE-Select; ENST00000494664.6; ENSP00000418803.1; NM_016589.4; NP_057673.2. DR UCSC; uc003ecn.4; human. DR AGR; HGNC:1321; -. DR ClinPGx; PA25900; -. DR CTD; 51300; -. DR DisGeNET; 51300; -. DR GeneCards; TIMMDC1; -. DR HGNC; HGNC:1321; TIMMDC1. DR HPA; ENSG00000113845; Low tissue specificity. DR MalaCards; TIMMDC1; -. DR MIM; 615534; gene. DR MIM; 618251; phenotype. DR OpenTargets; ENSG00000113845; -. DR Orphanet; 2609; Isolated complex I deficiency. DR VEuPathDB; HostDB:ENSG00000113845; -. DR eggNOG; KOG4608; Eukaryota. DR GeneTree; ENSGT00390000013817; -. DR HOGENOM; CLU_068982_0_0_1; -. DR InParanoid; Q9NPL8; -. DR OMA; SYMNFME; -. DR OrthoDB; 5826189at2759; -. DR PAN-GO; Q9NPL8; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q9NPL8; -. DR PathwayCommons; Q9NPL8; -. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR SignaLink; Q9NPL8; -. DR Agora; ENSG00000113845; -. DR BioGRID-ORCS; 51300; 186 hits in 1168 CRISPR screens. DR ChiTaRS; TIMMDC1; human. DR GeneWiki; C3orf1; -. DR GenomeRNAi; 51300; -. DR Pharos; Q9NPL8; Tbio. DR PRO; PR:Q9NPL8; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9NPL8; protein. DR Bgee; ENSG00000113845; Expressed in left ventricle myocardium and 187 other cell types or tissues. DR ExpressionAtlas; Q9NPL8; baseline and differential. DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:LIFEdb. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IEA:InterPro. DR InterPro; IPR055299; TIMMDC1. DR PANTHER; PTHR13002; C3ORF1 PROTEIN-RELATED; 1. DR PANTHER; PTHR13002:SF1; COMPLEX I ASSEMBLY FACTOR TIMMDC1, MITOCHONDRIAL; 1. DR Pfam; PF02466; Tim17; 1. PE 1: Evidence at protein level; KW Chaperone; Membrane; Mitochondrion; Phosphoprotein; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Transmembrane; Transmembrane helix. FT CHAIN 1..285 FT /note="Complex I assembly factor TIMMDC1, mitochondrial" FT /id="PRO_0000252478" FT TRANSMEM 80..100 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 137..159 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 165..185 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 189..209 FT /note="Helical" FT /evidence="ECO:0000255" FT MOD_RES 277 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VARIANT 76 FT /note="N -> D (in dbSNP:rs11539377)" FT /evidence="ECO:0000269|PubMed:11092749" FT /id="VAR_027885" FT VARIANT 217 FT /note="V -> I (in dbSNP:rs57168946)" FT /evidence="ECO:0000269|PubMed:11092749, ECO:0000269|Ref.5" FT /id="VAR_061572" FT CONFLICT 156 FT /note="L -> P (in Ref. 5; CAG33439)" FT /evidence="ECO:0000305" FT CONFLICT 213 FT /note="S -> A (in Ref. 4; AAQ88996)" FT /evidence="ECO:0000305" FT CONFLICT 255 FT /note="Q -> R (in Ref. 4; AAQ88996)" FT /evidence="ECO:0000305" SQ SEQUENCE 285 AA; 32178 MW; 5AA6474C3ABCCFA2 CRC64; MEVPPPAPRS FLCRALCLFP RVFAAEAVTA DSEVLEERQK RLPYVPEPYY PESGWDRLRE LFGKDEQQRI SKDLANICKT AATAGIIGWV YGGIPAFIHA KQQYIEQSQA EIYHNRFDAV QSAHRAATRG FIRYGWRWGW RTAVFVTIFN TVNTSLNVYR NKDALSHFVI AGAVTGSLFR INVGLRGLVA GGIIGALLGT PVGGLLMAFQ KYSGETVQER KQKDRKALHE LKLEEWKGRL QVTEHLPEKI ESSLQEDEPE NDAKKIEALL NLPRNPSVID KQDKD //