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 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 //