ID CMPK2_HUMAN Reviewed; 449 AA. AC Q5EBM0; A2RUB0; A5D8T2; B7ZM18; Q6ZRU2; Q96AL8; DT 29-APR-2008, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 3. DT 28-JAN-2026, entry version 147. DE RecName: Full=UMP-CMP kinase 2, mitochondrial; DE EC=2.7.4.14; DE AltName: Full=Nucleoside-diphosphate kinase; DE EC=2.7.4.6; DE Flags: Precursor; GN Name=CMPK2; 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), FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=17999954; DOI=10.1074/jbc.m707997200; RA Xu Y., Johansson M., Karlsson A.; RT "Human UMP-CMP kinase 2, a novel nucleoside monophosphate kinase localized RT in mitochondria."; RL J. Biol. Chem. 283:1563-1571(2008). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=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 MRNA] (ISOFORMS 3 AND 4), AND NUCLEOTIDE RP SEQUENCE [LARGE SCALE MRNA] OF 9-449 (ISOFORM 1). RC TISSUE=Lymph, and Prostate; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP 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 FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=23416111; DOI=10.1016/j.biocel.2013.02.004; RA Amiri M., Conserva F., Panayiotou C., Karlsson A., Solaroli N.; RT "The human adenylate kinase 9 is a nucleoside mono- and diphosphate RT kinase."; RL Int. J. Biochem. Cell Biol. 45:925-931(2013). RN [6] RP FUNCTION, AND INDUCTION BY INTERFERON-ALPHA. RX PubMed=30083606; DOI=10.1126/sciadv.aat0843; RA El-Diwany R., Soliman M., Sugawara S., Breitwieser F., Skaist A., RA Coggiano C., Sangal N., Chattergoon M., Bailey J.R., Siliciano R.F., RA Blankson J.N., Ray S.C., Wheelan S.J., Thomas D.L., Balagopal A.; RT "CMPK2 and BCL-G are associated with type 1 interferon-induced HIV RT restriction in humans."; RL Sci. Adv. 4:eaat0843-eaat0843(2018). RN [7] RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=34142025; DOI=10.1016/j.isci.2021.102498; RA Lai J.H., Wu D.W., Wu C.H., Hung L.F., Huang C.Y., Ka S.M., Chen A., RA Chang Z.F., Ho L.J.; RT "Mitochondrial CMPK2 mediates immunomodulatory and antiviral activities RT through IFN-dependent and IFN-independent pathways."; RL IScience 24:102498-102498(2021). RN [8] RP INVOLVEMENT IN IBGC10, VARIANT IBGC10 CYS-414, CHARACTERIZATION OF VARIANT RP IBGC10 CYS-414, AND SUBCELLULAR LOCATION. RX PubMed=36443312; DOI=10.1038/s41421-022-00475-2; RA Zhao M., Su H.Z., Zeng Y.H., Sun Y., Guo X.X., Li Y.L., Wang C., Zhao Z.Y., RA Huang X.J., Lin K.J., Ye Z.L., Lin B.W., Hong S., Zheng J., Liu Y.B., RA Yao X.P., Yang D., Lu Y.Q., Chen H.Z., Zuo E., Yang G., Wang H.T., RA Huang C.W., Lin X.H., Cen Z., Lai L.L., Zhang Y.K., Li X., Lai T., Lin J., RA Zuo D.D., Lin M.T., Liou C.W., Kong Q.X., Yan C.Z., Xiong Z.Q., Wang N., RA Luo W., Zhao C.P., Cheng X., Chen W.J.; RT "Loss of function of CMPK2 causes mitochondria deficiency and brain RT calcification."; RL Cell Discov. 8:128-128(2022). RN [9] RP FUNCTION. RX PubMed=36930652; DOI=10.1371/journal.pbio.3002039; RA Zhu M., Lv J., Wang W., Guo R., Zhong C., Antia A., Zeng Q., Li J., Liu Q., RA Zhou J., Zhu X., Fan B., Ding S., Li B.; RT "CMPK2 is a host restriction factor that inhibits infection of multiple RT coronaviruses in a cell-intrinsic manner."; RL PLoS Biol. 21:e3002039-e3002039(2023). RN [10] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=37075076; DOI=10.1371/journal.ppat.1011286; RA Pawlak J.B., Hsu J.C., Xia H., Han P., Suh H.W., Grove T.L., Morrison J., RA Shi P.Y., Cresswell P., Laurent-Rolle M.; RT "CMPK2 restricts Zika virus replication by inhibiting viral translation."; RL PLoS Pathog. 19:e1011286-e1011286(2023). CC -!- FUNCTION: Mitochondrial nucleotide monophosphate kinase needed for CC salvage dNTP synthesis that mediates immunomodulatory and antiviral CC activities through IFN-dependent and IFN-independent pathways CC (PubMed:17999954, PubMed:30083606, PubMed:36930652, PubMed:37075076). CC Restricts the replication of multiple viruses including flaviviruses or CC coronaviruses (PubMed:30083606, PubMed:36930652, PubMed:37075076). CC Together with viperin/RSAD2 and ddhCTP, suppresses the replication of CC several coronaviruses through inhibition of the viral RNA-dependent RNA CC polymerase activities (PubMed:36930652). Concerning flaviviruses, CC restricts RNA translation when localized to the mitochondria CC independently of its kinase activity (PubMed:37075076). Is able to CC phosphorylate dUMP, dCMP, CMP, UMP and monophosphates of the pyrimidine CC nucleoside analogs ddC, dFdC, araC, BVDU and FdUrd with ATP as CC phosphate donor. Efficacy is highest for dUMP followed by dCMP while CC CMP and UMP are poor substrates. Controls therefore mitochondrial DNA CC synthesis by supplying required deoxyribonucleotides (By similarity). CC CMPK2-dependent mitochondrial DNA synthesis is necessary for the CC production of oxidized mitochondrial DNA fragments after exposure to CC NLRP3 activators (By similarity). In turn, cytosolic oxidized mtDNA CC associates with the NLRP3 inflammasome complex and is required for its CC activation (By similarity). {ECO:0000250|UniProtKB:Q3U5Q7, CC ECO:0000269|PubMed:17999954, ECO:0000269|PubMed:23416111, CC ECO:0000269|PubMed:30083606, ECO:0000269|PubMed:34142025, CC ECO:0000269|PubMed:36930652, ECO:0000269|PubMed:37075076}. CC -!- CATALYTIC ACTIVITY: CC Reaction=CMP + ATP = CDP + ADP; Xref=Rhea:RHEA:11600, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:58069, ChEBI:CHEBI:60377, CC ChEBI:CHEBI:456216; EC=2.7.4.14; CC Evidence={ECO:0000269|PubMed:23416111}; CC -!- CATALYTIC ACTIVITY: CC Reaction=dCMP + ATP = dCDP + ADP; Xref=Rhea:RHEA:25094, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57566, ChEBI:CHEBI:58593, CC ChEBI:CHEBI:456216; EC=2.7.4.14; CC Evidence={ECO:0000269|PubMed:23416111}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 2'-deoxyribonucleoside 5'-diphosphate + ATP = a 2'- CC deoxyribonucleoside 5'-triphosphate + ADP; Xref=Rhea:RHEA:44640, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61560, ChEBI:CHEBI:73316, CC ChEBI:CHEBI:456216; EC=2.7.4.6; CC Evidence={ECO:0000269|PubMed:23416111}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a ribonucleoside 5'-diphosphate + ATP = a ribonucleoside 5'- CC triphosphate + ADP; Xref=Rhea:RHEA:18113, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557, ChEBI:CHEBI:456216; EC=2.7.4.6; CC Evidence={ECO:0000269|PubMed:23416111}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=3.09 mM for CMP; CC KM=6.3 mM for UMP; CC KM=1.31 mM for dCMP; CC KM=0.1 mM for dUMP; CC Vmax=1.64 umol/min/mg enzyme towards CMP; CC Vmax=0.19 umol/min/mg enzyme towards UMP; CC Vmax=1.77 umol/min/mg enzyme towards dCMP; CC Vmax=0.48 umol/min/mg enzyme towards dUMP; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:17999954, CC ECO:0000269|PubMed:34142025, ECO:0000269|PubMed:36443312, CC ECO:0000269|PubMed:37075076}. Note=Mitochondrial localization is CC required for its antiviral function. {ECO:0000269|PubMed:37075076}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q5EBM0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q5EBM0-2; Sequence=VSP_033238, VSP_033239; CC Name=3; CC IsoId=Q5EBM0-3; Sequence=VSP_033240; CC Name=4; CC IsoId=Q5EBM0-4; Sequence=VSP_033241; CC -!- TISSUE SPECIFICITY: High levels are observed in myeloid, lymphoid and CC mesenchymal tissues. {ECO:0000269|PubMed:34142025}. CC -!- INDUCTION: By interferon-alpha (PubMed:30083606). IRF1 is crucial for CC the transcriptional activation of CMPK2 (PubMed:36930652). CC {ECO:0000269|PubMed:30083606, ECO:0000269|PubMed:36930652}. CC -!- DISEASE: Basal ganglia calcification, idiopathic, 10, autosomal CC recessive (IBGC10) [MIM:621018]: A form of basal ganglia calcification, CC a genetically heterogeneous condition characterized by symmetric CC calcification in the basal ganglia and other brain regions. Affected CC individuals can either be asymptomatic or show a wide spectrum of CC neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, CC ataxia, dementia, psychosis, seizures, and chronic headache. Serum CC levels of calcium, phosphate, alkaline phosphatase and parathyroid CC hormone are normal. The neuropathological hallmark of the disease is CC vascular and pericapillary calcification, mainly of calcium phosphate, CC in the affected brain areas. IBGC10 is a progressive form characterized CC by motor dysfunction, speech impairment, and impaired cognition. CC {ECO:0000269|PubMed:36443312}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the thymidylate kinase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK127983; BAC87217.1; -; mRNA. DR EMBL; BC016969; AAH16969.1; -; mRNA. DR EMBL; BC141802; AAI41803.1; -; mRNA. DR EMBL; BC132821; AAI32822.1; -; mRNA. DR EMBL; BC089425; AAH89425.1; -; mRNA. DR EMBL; BC144202; AAI44203.1; -; mRNA. DR CCDS; CCDS42648.1; -. [Q5EBM0-1] DR CCDS; CCDS58695.1; -. [Q5EBM0-3] DR CCDS; CCDS58696.1; -. [Q5EBM0-4] DR RefSeq; NP_001243406.1; NM_001256477.1. [Q5EBM0-4] DR RefSeq; NP_001243407.1; NM_001256478.1. [Q5EBM0-3] DR RefSeq; NP_997198.2; NM_207315.4. [Q5EBM0-1] DR AlphaFoldDB; Q5EBM0; -. DR SMR; Q5EBM0; -. DR BioGRID; 126200; 1. DR FunCoup; Q5EBM0; 1752. DR STRING; 9606.ENSP00000256722; -. DR iPTMnet; Q5EBM0; -. DR PhosphoSitePlus; Q5EBM0; -. DR BioMuta; CMPK2; -. DR DMDM; 296439392; -. DR jPOST; Q5EBM0; -. DR MassIVE; Q5EBM0; -. DR PaxDb; 9606-ENSP00000256722; -. DR PeptideAtlas; Q5EBM0; -. DR ProteomicsDB; 62766; -. [Q5EBM0-1] DR ProteomicsDB; 62767; -. [Q5EBM0-2] DR ProteomicsDB; 62768; -. [Q5EBM0-3] DR ProteomicsDB; 62769; -. [Q5EBM0-4] DR Pumba; Q5EBM0; -. DR Antibodypedia; 26409; 91 antibodies from 21 providers. DR DNASU; 129607; -. DR Ensembl; ENST00000256722.10; ENSP00000256722.5; ENSG00000134326.12. [Q5EBM0-1] DR Ensembl; ENST00000404168.1; ENSP00000384915.1; ENSG00000134326.12. [Q5EBM0-4] DR Ensembl; ENST00000458098.5; ENSP00000396385.1; ENSG00000134326.12. [Q5EBM0-3] DR GeneID; 129607; -. DR KEGG; hsa:129607; -. DR MANE-Select; ENST00000256722.10; ENSP00000256722.5; NM_207315.4; NP_997198.2. DR UCSC; uc002qyo.5; human. [Q5EBM0-1] DR AGR; HGNC:27015; -. DR ClinPGx; PA162382556; -. DR CTD; 129607; -. DR DisGeNET; 129607; -. DR GeneCards; CMPK2; -. DR HGNC; HGNC:27015; CMPK2. DR HPA; ENSG00000134326; Tissue enhanced (salivary). DR MalaCards; CMPK2; -. DR MIM; 611787; gene. DR MIM; 621018; phenotype. DR OpenTargets; ENSG00000134326; -. DR Orphanet; 1980; Bilateral striopallidodentate calcinosis. DR VEuPathDB; HostDB:ENSG00000134326; -. DR eggNOG; KOG3327; Eukaryota. DR GeneTree; ENSGT00940000154030; -. DR HOGENOM; CLU_049896_0_0_1; -. DR InParanoid; Q5EBM0; -. DR OMA; ECTSLIP; -. DR OrthoDB; 425602at2759; -. DR PAN-GO; Q5EBM0; 9 GO annotations based on evolutionary models. DR PhylomeDB; Q5EBM0; -. DR BRENDA; 2.7.4.14; 2681. DR PathwayCommons; Q5EBM0; -. DR SABIO-RK; Q5EBM0; -. DR Agora; ENSG00000134326; -. DR BioGRID-ORCS; 129607; 17 hits in 1161 CRISPR screens. DR GenomeRNAi; 129607; -. DR Pharos; Q5EBM0; Tbio. DR PRO; PR:Q5EBM0; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q5EBM0; protein. DR Bgee; ENSG00000134326; Expressed in palpebral conjunctiva and 184 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0036430; F:CMP kinase activity; IEA:RHEA. DR GO; GO:0036431; F:dCMP kinase activity; IEA:RHEA. DR GO; GO:0004798; F:dTMP kinase activity; IBA:GO_Central. DR GO; GO:0120136; F:dUMP kinase activity; IEA:Ensembl. DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB. DR GO; GO:0033862; F:UMP kinase activity; IDA:MGI. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0006233; P:dTDP biosynthetic process; IBA:GO_Central. DR GO; GO:0006235; P:dTTP biosynthetic process; IBA:GO_Central. DR GO; GO:0006227; P:dUDP biosynthetic process; IBA:GO_Central. DR FunFam; 3.40.50.300:FF:001133; UMP-CMP kinase 2, mitochondrial; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR039430; Thymidylate_kin-like_dom. DR InterPro; IPR014505; UMP-CMP_kinase_2. DR PANTHER; PTHR10344; THYMIDYLATE KINASE; 1. DR PANTHER; PTHR10344:SF4; UMP-CMP KINASE 2, MITOCHONDRIAL; 1. DR Pfam; PF02223; Thymidylate_kin; 1. DR PIRSF; PIRSF019736; dTMP_TKRP1; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Coiled coil; Kinase; Mitochondrion; KW Nucleotide-binding; Proteomics identification; Pyrimidine biosynthesis; KW Reference proteome; Transferase; Transit peptide. FT TRANSIT 1..98 FT /note="Mitochondrion" FT /evidence="ECO:0000255" FT CHAIN 99..449 FT /note="UMP-CMP kinase 2, mitochondrial" FT /id="PRO_0000331524" FT COILED 380..412 FT /evidence="ECO:0000255" FT BINDING 259..266 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT VAR_SEQ 280..303 FT /note="LLKSPPSCIGQWRKIFDDEPTIIR -> PQPITLCTSGQRTCSNLTLSCCSL FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_033238" FT VAR_SEQ 304..449 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_033239" FT VAR_SEQ 332..449 FT /note="YWHSTATYAIATEVSGGLQHLPPAHHPVYQWPEDLLKPDLILLLTVSPEERL FT QRLQGRGMEKTREEAELEANSVFRQKVEMSYQRMENPGCHVVDASPSREKVLQTVLSLI FT QNSFSEP -> SQLGGTLYHPSLHLLGSEVCGTGILDSSHSSQGLE (in isoform FT 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_033240" FT VAR_SEQ 410..449 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_033241" FT VARIANT 414 FT /note="Y -> C (in IBGC10; uncertain significance; decreased FT protein abundance; no effect on subcellular location; FT dbSNP:rs1322954088)" FT /evidence="ECO:0000269|PubMed:36443312" FT /id="VAR_090198" FT VARIANT 433 FT /note="K -> R (in dbSNP:rs6712141)" FT /id="VAR_055997" FT CONFLICT 448 FT /note="E -> G (in Ref. 3; AAH89425)" FT /evidence="ECO:0000305" SQ SEQUENCE 449 AA; 49448 MW; 99F382E34332B6DE CRC64; MAFARRLLRG PLSGPLLGRR GVCAGAMAPP RRFVLELPDC TLAHFALGAD APGDADAPDP RLAALLGPPE RSYSLCVPVT PDAGCGARVR AARLHQRLLH QLRRGPFQRC QLLRLLCYCP GGQAGGAQQG FLLRDPLDDP DTRQALLELL GACQEAPRPH LGEFEADPRG QLWQRLWEVQ DGRRLQVGCA QVVPVPEPPL HPVVPDLPSS VVFPDREAAR AVLEECTSFI PEARAVLDLV DQCPKQIQKG KFQVVAIEGL DATGKTTVTQ SVADSLKAVL LKSPPSCIGQ WRKIFDDEPT IIRRAFYSLG NYIVASEIAK ESAKSPVIVD RYWHSTATYA IATEVSGGLQ HLPPAHHPVY QWPEDLLKPD LILLLTVSPE ERLQRLQGRG MEKTREEAEL EANSVFRQKV EMSYQRMENP GCHVVDASPS REKVLQTVLS LIQNSFSEP // ID JAM2_HUMAN Reviewed; 298 AA. AC P57087; B2R6T9; B4DGT9; Q6UXG6; Q6YNC1; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 1. DT 28-JAN-2026, entry version 210. DE RecName: Full=Junctional adhesion molecule B; DE Short=JAM-B; DE AltName: Full=Junctional adhesion molecule 2 {ECO:0000303|PubMed:10945976}; DE Short=JAM-2 {ECO:0000303|PubMed:10945976}; DE AltName: Full=Vascular endothelial junction-associated molecule {ECO:0000303|PubMed:10779521}; DE Short=VE-JAM {ECO:0000303|PubMed:10779521}; DE AltName: CD_antigen=CD322; DE Flags: Precursor; GN Name=JAM2 {ECO:0000312|HGNC:HGNC:14686}; GN Synonyms=C21orf43 {ECO:0000312|HGNC:HGNC:14686}, GN VEJAM {ECO:0000303|PubMed:10779521}; ORFNames=UNQ219/PRO245; 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), PROTEIN SEQUENCE OF 29-33, RP SUBCELLULAR LOCATION, TOPOLOGY, AND TISSUE SPECIFICITY. RC TISSUE=Vascular endothelial cell; RX PubMed=10779521; DOI=10.1074/jbc.m003189200; RA Palmeri D., van Zante A., Huang C.-C., Hemmerich S., Rosen S.D.; RT "Vascular endothelial junction-associated molecule, a novel member of the RT immunoglobulin superfamily, is localized to intercellular boundaries of RT endothelial cells."; RL J. Biol. Chem. 275:19139-19145(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Placenta; RX PubMed=10945976; DOI=10.1074/jbc.m002718200; RA Cunningham S.A., Arrate M.P., Rodriguez J.M., Bjercke R.J., Vanderslice P., RA Morris A.P., Brock T.A.; RT "A novel protein with homology to the junctional adhesion molecule: RT Characterization of leukocyte interactions."; RL J. Biol. Chem. 275:34750-34756(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=12036298; DOI=10.1006/geno.2002.6782; RA Gardiner K., Slavov D., Bechtel L., Davisson M.; RT "Annotation of human chromosome 21 for relevance to Down syndrome: gene RT structure and expression analysis."; RL Genomics 79:833-843(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U., RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [8] RP PROTEIN SEQUENCE OF 29-43. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND TOPOLOGY. RX PubMed=11590146; DOI=10.1074/jbc.m105972200; RA Arrate M.P., Rodriguez J.M., Tran T.M., Brock T.A., Cunningham S.A.; RT "Cloning of human junctional adhesion molecule 3 (JAM3) and its RT identification as the JAM2 counter-receptor."; RL J. Biol. Chem. 276:45826-45832(2001). RN [10] RP FUNCTION. RX PubMed=12239159; DOI=10.1182/blood-2001-11-0098; RA Johnson-Leger C.A., Aurrand-Lions M., Beltraminelli N., Fasel N., RA Imhof B.A.; RT "Junctional adhesion molecule-2 (JAM-2) promotes lymphocyte RT transendothelial migration."; RL Blood 100:2479-2486(2002). RN [11] RP FUNCTION, DOMAIN, AND MUTAGENESIS OF ASP-82. RX PubMed=12070135; DOI=10.1074/jbc.c200331200; RA Cunningham S.A., Rodriguez J.M., Arrate M.P., Tran T.M., Brock T.A.; RT "JAM2 interacts with alpha4beta1. Facilitation by JAM3."; RL J. Biol. Chem. 277:27589-27592(2002). RN [12] RP FUNCTION. RX PubMed=11823489; DOI=10.4049/jimmunol.168.4.1618; RA Liang T.W., Chiu H.H., Gurney A., Sidle A., Tumas D.B., Schow P., RA Foster J., Klassen T., Dennis K., DeMarco R.A., Pham T., Frantz G., RA Fong S.; RT "Vascular endothelial-junctional adhesion molecule (VE-JAM)/JAM 2 interacts RT with T, NK, and dendritic cells through JAM 3."; RL J. Immunol. 168:1618-1626(2002). RN [13] RP REVIEW, AND NOMENCLATURE. RX PubMed=12810109; DOI=10.1016/s1471-4906(03)00117-0; RA Muller W.A.; RT "Leukocyte-endothelial-cell interactions in leukocyte transmigration and RT the inflammatory response."; RL Trends Immunol. 24:327-334(2003). RN [14] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-98. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [15] RP FUNCTION. RX PubMed=24357068; DOI=10.1002/stem.1624; RA Arcangeli M.L., Bardin F., Frontera V., Bidaut G., Obrados E., Adams R.H., RA Chabannon C., Aurrand-Lions M.; RT "Function of Jam-B/Jam-C interaction in homing and mobilization of human RT and mouse hematopoietic stem and progenitor cells."; RL Stem Cells 32:1043-1054(2014). RN [16] RP INVOLVEMENT IN IBGC8, VARIANTS IBGC8 60-ARG--ILE-298 DEL; HIS-108 AND RP 229-ARG--ILE-298 DEL, AND CHARACTERIZATION OF VARIANT IBGC8 RP 229-ARG--ILE-298 DEL. RX PubMed=32142645; DOI=10.1016/j.ajhg.2020.02.007; RG SYNAPS Study Group; RA Schottlaender L.V., Abeti R., Jaunmuktane Z., Macmillan C., Chelban V., RA O'Callaghan B., McKinley J., Maroofian R., Efthymiou S., RA Athanasiou-Fragkouli A., Forbes R., Soutar M.P.M., Livingston J.H., RA Kalmar B., Swayne O., Hotton G., Pittman A., Mendes de Oliveira J.R., RA de Grandis M., Richard-Loendt A., Launchbury F., Althonayan J., RA McDonnell G., Carr A., Khan S., Beetz C., Bisgin A., Tug Bozdogan S., RA Begtrup A., Torti E., Greensmith L., Giunti P., Morrison P.J., Brandner S., RA Aurrand-Lions M., Houlden H.; RT "Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial RT Brain Calcification."; RL Am. J. Hum. Genet. 106:412-421(2020). RN [17] RP VARIANT IBGC8 CYS-168, CHARACTERIZATION OF VARIANT IBGC8 CYS-168, RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=31851307; DOI=10.1093/brain/awz392; RA Cen Z., Chen Y., Chen S., Wang H., Yang D., Zhang H., Wu H., Wang L., RA Tang S., Ye J., Shen J., Wang H., Fu F., Chen X., Xie F., Liu P., Xu X., RA Cao J., Cai P., Pan Q., Li J., Yang W., Shan P.F., Li Y., Liu J.Y., RA Zhang B., Luo W.; RT "Biallelic loss-of-function mutations in JAM2 cause primary familial brain RT calcification."; RL Brain 143:491-502(2020). CC -!- FUNCTION: Junctional adhesion protein that mediates heterotypic cell- CC cell interactions with its cognate receptor JAM3 to regulate different CC cellular processes (PubMed:11590146, PubMed:11823489, PubMed:24357068). CC Plays a role in homing and mobilization of hematopoietic stem and CC progenitor cells within the bone marrow (PubMed:24357068). At the CC surface of bone marrow stromal cells, it contributes to the retention CC of the hematopoietic stem and progenitor cells expressing JAM3 CC (PubMed:11590146, PubMed:24357068). Plays a central role in leukocytes CC extravasation by facilitating not only transmigration but also CC tethering and rolling of leukocytes along the endothelium CC (PubMed:12239159). Tethering and rolling of leukocytes are dependent on CC the binding by JAM2 of the integrin alpha-4/beta-1 (PubMed:12070135). CC Plays a role in spermatogenesis where JAM2 and JAM3, which are CC respectively expressed by Sertoli and germ cells, mediate an CC interaction between both cell types and play an essential role in the CC anchorage of germ cells onto Sertoli cells and the assembly of cell CC polarity complexes during spermatid differentiation (By similarity). CC Also functions as an inhibitory somatodendritic cue that prevents the CC myelination of non-axonal parts of neurons (By similarity). During CC myogenesis, it is involved in myocyte fusion (By similarity). May also CC play a role in angiogenesis (By similarity). CC {ECO:0000250|UniProtKB:A0A0R4IGV4, ECO:0000250|UniProtKB:Q9JI59, CC ECO:0000269|PubMed:11590146, ECO:0000269|PubMed:11823489, CC ECO:0000269|PubMed:12070135, ECO:0000269|PubMed:12239159, CC ECO:0000269|PubMed:24357068}. CC -!- INTERACTION: CC P57087; Q9BX67: JAM3; NbExp=4; IntAct=EBI-3918416, EBI-4314733; CC P57087; Q8TEW0: PARD3; NbExp=2; IntAct=EBI-3918416, EBI-81968; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10779521, CC ECO:0000269|PubMed:11590146, ECO:0000269|PubMed:31851307}; Single-pass CC type I membrane protein {ECO:0000269|PubMed:10779521, CC ECO:0000269|PubMed:11590146}. Cell junction CC {ECO:0000269|PubMed:10779521, ECO:0000269|PubMed:10945976}. Cell CC junction, tight junction {ECO:0000250|UniProtKB:Q9JI59}. Note=Localized CC at tight junctions of both epithelial and endothelial cells (By CC similarity). Specifically localized within the somatodendritic CC compartment of neurons and excluded from the axon (By similarity). CC {ECO:0000250|UniProtKB:Q9JI59}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P57087-1; Sequence=Displayed; CC Name=2; CC IsoId=P57087-2; Sequence=VSP_045153; CC Name=3; CC IsoId=P57087-3; Sequence=VSP_047352; CC -!- TISSUE SPECIFICITY: Highly expressed in heart, placenta, lung, foreskin CC and lymph node (PubMed:10779521, PubMed:10945976). Prominently CC expressed on high endothelial venules and also present on the CC endothelia of other vessels (at protein level) (PubMed:10779521, CC PubMed:10945976). Also expressed in the brain in the caudate nuclei CC (PubMed:31851307). {ECO:0000269|PubMed:10779521, CC ECO:0000269|PubMed:10945976, ECO:0000269|PubMed:31851307}. CC -!- DOMAIN: The Ig-like V-type domain is necessary and sufficient to CC mediate interaction with JAM3 and integrin alpha-4/beta-1. CC {ECO:0000269|PubMed:12070135}. CC -!- DISEASE: Basal ganglia calcification, idiopathic, 8, autosomal CC recessive (IBGC8) [MIM:618824]: A form of basal ganglia calcification, CC a genetically heterogeneous condition characterized by symmetric CC calcification in the basal ganglia and other brain regions. Affected CC individuals can either be asymptomatic or show a wide spectrum of CC neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, CC ataxia, dementia, psychosis, seizures, and chronic headache. Serum CC levels of calcium, phosphate, alkaline phosphatase and parathyroid CC hormone are normal. The neuropathological hallmark of the disease is CC vascular and pericapillary calcification, mainly of calcium phosphate, CC in the affected brain areas. {ECO:0000269|PubMed:31851307, CC ECO:0000269|PubMed:32142645}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the immunoglobulin superfamily. {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; AF255910; AAF81223.1; -; mRNA. DR EMBL; AY016009; AAG49022.1; -; mRNA. DR EMBL; AY077698; AAL82538.1; -; mRNA. DR EMBL; AY358361; AAQ88727.1; -; mRNA. DR EMBL; AK294769; BAG57900.1; -; mRNA. DR EMBL; AK312708; BAG35586.1; -; mRNA. DR EMBL; AP000223; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000224; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000225; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP000226; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC017779; AAH17779.1; -; mRNA. DR CCDS; CCDS42911.1; -. [P57087-1] DR CCDS; CCDS58787.1; -. [P57087-3] DR CCDS; CCDS58788.1; -. [P57087-2] DR RefSeq; NP_001257336.1; NM_001270407.2. [P57087-2] DR RefSeq; NP_001257337.1; NM_001270408.2. [P57087-3] DR RefSeq; NP_067042.1; NM_021219.4. [P57087-1] DR AlphaFoldDB; P57087; -. DR SMR; P57087; -. DR BioGRID; 121824; 12. DR CORUM; P57087; -. DR FunCoup; P57087; 431. DR IntAct; P57087; 21. DR MINT; P57087; -. DR STRING; 9606.ENSP00000383376; -. DR ChEMBL; CHEMBL5483010; -. DR GlyCosmos; P57087; 3 sites, No reported glycans. DR GlyGen; P57087; 3 sites, 4 N-linked glycans (1 site). DR iPTMnet; P57087; -. DR PhosphoSitePlus; P57087; -. DR SwissPalm; P57087; -. DR BioMuta; JAM2; -. DR DMDM; 10720348; -. DR jPOST; P57087; -. DR MassIVE; P57087; -. DR PaxDb; 9606-ENSP00000383376; -. DR PeptideAtlas; P57087; -. DR ProteomicsDB; 4159; -. DR ProteomicsDB; 56996; -. [P57087-1] DR Antibodypedia; 4909; 470 antibodies from 37 providers. DR DNASU; 58494; -. DR Ensembl; ENST00000312957.9; ENSP00000318416.6; ENSG00000154721.16. [P57087-2] DR Ensembl; ENST00000400532.5; ENSP00000383376.1; ENSG00000154721.16. [P57087-3] DR Ensembl; ENST00000480456.6; ENSP00000420419.1; ENSG00000154721.16. [P57087-1] DR GeneID; 58494; -. DR KEGG; hsa:58494; -. DR MANE-Select; ENST00000480456.6; ENSP00000420419.1; NM_021219.4; NP_067042.1. DR UCSC; uc002ylp.3; human. [P57087-1] DR AGR; HGNC:14686; -. DR ClinPGx; PA29992; -. DR CTD; 58494; -. DR DisGeNET; 58494; -. DR GeneCards; JAM2; -. DR HGNC; HGNC:14686; JAM2. DR HPA; ENSG00000154721; Tissue enhanced (placenta). DR MalaCards; JAM2; -. DR MIM; 606870; gene. DR MIM; 618824; phenotype. DR OpenTargets; ENSG00000154721; -. DR Orphanet; 1980; Bilateral striopallidodentate calcinosis. DR VEuPathDB; HostDB:ENSG00000154721; -. DR eggNOG; ENOG502QZ6E; Eukaryota. DR GeneTree; ENSGT00940000160634; -. DR HOGENOM; CLU_067351_1_0_1; -. DR InParanoid; P57087; -. DR OMA; ASEYRWY; -. DR OrthoDB; 10015491at2759; -. DR PAN-GO; P57087; 5 GO annotations based on evolutionary models. DR PhylomeDB; P57087; -. DR PathwayCommons; P57087; -. DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall. DR Reactome; R-HSA-216083; Integrin cell surface interactions. DR SignaLink; P57087; -. DR Agora; ENSG00000154721; -. DR BioGRID-ORCS; 58494; 14 hits in 1149 CRISPR screens. DR ChiTaRS; JAM2; human. DR GeneWiki; JAM2; -. DR GenomeRNAi; 58494; -. DR Pharos; P57087; Tbio. DR PRO; PR:P57087; -. DR Proteomes; UP000005640; Chromosome 21. DR RNAct; P57087; protein. DR Bgee; ENSG00000154721; Expressed in ventricular zone and 198 other cell types or tissues. DR ExpressionAtlas; P57087; baseline and differential. DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell. DR GO; GO:0009986; C:cell surface; IDA:ARUK-UCL. DR GO; GO:0044291; C:cell-cell contact zone; IDA:ARUK-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098636; C:protein complex involved in cell adhesion; IDA:UniProtKB. DR GO; GO:0036477; C:somatodendritic compartment; ISS:UniProtKB. DR GO; GO:0070160; C:tight junction; ISS:UniProtKB. DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB. DR GO; GO:0098609; P:cell-cell adhesion; IMP:UniProtKB. DR GO; GO:0045123; P:cellular extravasation; IDA:UniProtKB. DR GO; GO:0097241; P:hematopoietic stem cell migration to bone marrow; IMP:UniProtKB. DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IBA:GO_Central. DR GO; GO:0050901; P:leukocyte tethering or rolling; IDA:ARUK-UCL. DR GO; GO:0071593; P:lymphocyte aggregation; IDA:ARUK-UCL. DR GO; GO:0035633; P:maintenance of blood-brain barrier; NAS:ARUK-UCL. DR GO; GO:0031642; P:negative regulation of myelination; ISS:UniProtKB. DR GO; GO:2000403; P:positive regulation of lymphocyte migration; IDA:ARUK-UCL. DR GO; GO:0007286; P:spermatid development; ISS:UniProtKB. DR CDD; cd20946; IgV_1_JAM1-like; 1. DR FunFam; 2.60.40.10:FF:001393; Junctional adhesion molecule 2; 1. DR FunFam; 2.60.40.10:FF:000342; Junctional adhesion molecule A; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR013106; Ig_V-set. DR InterPro; IPR042625; JAM2. DR PANTHER; PTHR44663; JUNCTIONAL ADHESION MOLECULE B; 1. DR PANTHER; PTHR44663:SF2; JUNCTIONAL ADHESION MOLECULE B; 1. DR Pfam; PF13927; Ig_3; 1. DR Pfam; PF07686; V-set; 1. DR SMART; SM00409; IG; 2. DR SMART; SM00408; IGc2; 2. DR SUPFAM; SSF48726; Immunoglobulin; 2. DR PROSITE; PS50835; IG_LIKE; 2. PE 1: Evidence at protein level; KW Alternative splicing; Cell junction; Cell membrane; KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; KW Immunoglobulin domain; Membrane; Proteomics identification; KW Reference proteome; Signal; Tight junction; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..28 FT /evidence="ECO:0000269|PubMed:10779521, FT ECO:0000269|PubMed:15340161" FT CHAIN 29..298 FT /note="Junctional adhesion molecule B" FT /id="PRO_0000015069" FT TOPO_DOM 29..238 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 239..259 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 260..298 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 32..127 FT /note="Ig-like V-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DOMAIN 134..238 FT /note="Ig-like C2-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT CARBOHYD 98 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952" FT CARBOHYD 187 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 236 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 50..109 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT DISULFID 155..214 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT VAR_SEQ 44..79 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045153" FT VAR_SEQ 289..298 FT /note="DFKHTKSFII -> VQWLTPVIPALWKAAAGGSRGQEF (in isoform FT 3)" FT /evidence="ECO:0000303|PubMed:12975309" FT /id="VSP_047352" FT VARIANT 60..298 FT /note="Missing (in IBGC8)" FT /evidence="ECO:0000269|PubMed:32142645" FT /id="VAR_083943" FT VARIANT 108 FT /note="R -> H (in IBGC8; dbSNP:rs1383641309)" FT /evidence="ECO:0000269|PubMed:32142645" FT /id="VAR_083944" FT VARIANT 168 FT /note="W -> C (in IBGC8; loss of localization to the plasma FT membrane; mainly retained in the cytoplasm; FT dbSNP:rs1230941179)" FT /evidence="ECO:0000269|PubMed:31851307" FT /id="VAR_083945" FT VARIANT 229..298 FT /note="Missing (in IBGC8; loss of protein expression)" FT /evidence="ECO:0000269|PubMed:32142645" FT /id="VAR_083946" FT VARIANT 286 FT /note="S -> R (in dbSNP:rs9976382)" FT /id="VAR_049973" FT MUTAGEN 82 FT /note="D->A: No effect on binding of JAM3 or integrin." FT /evidence="ECO:0000269|PubMed:12070135" FT CONFLICT 270 FT /note="E -> G (in Ref. 3; AAL82538)" FT /evidence="ECO:0000305" SQ SEQUENCE 298 AA; 33207 MW; CA78E518E22DCAEE CRC64; MARRSRHRLL LLLLRYLVVA LGYHKAYGFS APKDQQVVTA VEYQEAILAC KTPKKTVSSR LEWKKLGRSV SFVYYQQTLQ GDFKNRAEMI DFNIRIKNVT RSDAGKYRCE VSAPSEQGQN LEEDTVTLEV LVAPAVPSCE VPSSALSGTV VELRCQDKEG NPAPEYTWFK DGIRLLENPR LGSQSTNSSY TMNTKTGTLQ FNTVSKLDTG EYSCEARNSV GYRRCPGKRM QVDDLNISGI IAAVVVVALV ISVCGLGVCY AQRKGYFSKE TSFQKSNSSS KATTMSENDF KHTKSFII // ID KLK6_HUMAN Reviewed; 244 AA. AC Q92876; A6NJA1; A8MW09; Q6H301; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 28-JAN-2026, entry version 204. DE RecName: Full=Kallikrein-6; DE EC=3.4.21.-; DE AltName: Full=Neurosin; DE AltName: Full=Protease M; DE AltName: Full=SP59; DE AltName: Full=Serine protease 18; DE AltName: Full=Serine protease 9; DE AltName: Full=Zyme; DE Flags: Precursor; GN Name=KLK6; Synonyms=PRSS18, PRSS9; 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=8898378; DOI=10.1007/bf03401646; RA Anisowicz A., Sotiropoulou G., Stenman G., Mok S.C., Sager R.; RT "A novel protease homolog differentially expressed in breast and ovarian RT cancer."; RL Mol. Med. 2:624-636(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Colon; RX PubMed=9003450; DOI=10.1016/s0167-4781(96)00187-x; RA Yamashiro K., Tsuruoka N., Kodama S., Tsujimoto M., Yamamura Y., Tanaka T., RA Nakazato H., Yamaguchi N.; RT "Molecular cloning of a novel trypsin-like serine protease (neurosin) RT preferentially expressed in brain."; RL Biochim. Biophys. Acta 1350:11-14(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9312124; DOI=10.1074/jbc.272.40.25135; RA Little S.P., Dixon E.P., Norris F., Buckley W., Becker G.W., Johnson M., RA Dobbins J.R., Wyrick T., Miller J.R., Mackellar W., Hepburn D., RA Corvalan J., McClure D., Liu X., Stephenson D., Clemens J., Johnstone E.M.; RT "Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from RT Alzheimer's disease brain."; RL J. Biol. Chem. 272:25135-25142(1997). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10610719; DOI=10.1006/geno.1999.6012; RA Yousef G.M., Luo L.Y., Scherer S.W., Sotiropoulou G., Diamandis E.P.; RT "Molecular characterization of Zyme/protease M/neurosin(PRSS9), a RT hormonally regulated kallikrein-like serine protease."; RL Genomics 62:251-259(1999). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11054574; DOI=10.1016/s0378-1119(00)00382-6; RA Gan L., Lee I., Smith R., Argonza-Barrett R., Lei H., McCuaig J., Moss P., RA Paeper B., Wang K.; RT "Sequencing and expression analysis of the serine protease gene cluster RT located in chromosome 19q13 region."; RL Gene 257:119-130(2000). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Testis; RX PubMed=15207701; DOI=10.1016/j.bbrc.2004.04.205; RA Pampalakis G., Kurlender L., Diamandis E.P., Sotiropoulou G.; RT "Cloning and characterization of novel isoforms of the human kallikrein 6 RT gene."; RL Biochem. Biophys. Res. Commun. 320:54-61(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=16800739; DOI=10.1515/bc.2006.097; RA Pampalakis G., Sotiropoulou G.; RT "Multiple mechanisms underlie the aberrant expression of the human RT kallikrein 6 gene in breast cancer."; RL Biol. Chem. 387:773-782(2006). RN [8] 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 [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [10] 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 [11] 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 [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon; 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 [13] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11018688; DOI=10.1016/s0009-9120(00)00145-4; RA Diamandis E.P., Yousef G.M., Soosaipillai A.R., Grass L., Porter A., RA Little S., Sotiropoulou G.; RT "Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) RT and preliminary clinical applications."; RL Clin. Biochem. 33:369-375(2000). RN [14] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=10997858; DOI=10.1046/j.1440-1819.2000.00731.x; RA Ogawa K., Yamada T., Tsujioka Y., Taguchi J., Takahashi M., Tsuboi Y., RA Fujino Y., Nakajima M., Yamamoto T., Akatsu H., Mitsui S., Yamaguchi N.; RT "Localization of a novel type trypsin-like serine protease, neurosin, in RT brain tissues of Alzheimer's disease and Parkinson's disease."; RL Psychiatry Clin. Neurosci. 54:419-426(2000). RN [15] RP TISSUE SPECIFICITY. RX PubMed=11668196; DOI=10.1177/002215540104901111; RA Petraki C.D., Karavana V.N., Skoufogiannis P.T., Little S.P., RA Howarth D.J.C., Yousef G.M., Diamandis E.P.; RT "The spectrum of human kallikrein 6 (zyme/protease M/neurosin) expression RT in human tissues as assessed by immunohistochemistry."; RL J. Histochem. Cytochem. 49:1431-1441(2001). RN [16] RP FUNCTION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND RP AUTOCATALYTIC CLEAVAGE. RX PubMed=12878203; DOI=10.1016/s0006-291x(03)01271-3; RA Magklara A., Mellati A.A., Wasney G.A., Little S.P., Sotiropoulou G., RA Becker G.W., Diamandis E.P.; RT "Characterization of the enzymatic activity of human kallikrein 6: RT autoactivation, substrate specificity, and regulation by inhibitors."; RL Biochem. Biophys. Res. Commun. 307:948-955(2003). RN [17] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=12928483; DOI=10.1093/hmg/ddg283; RA Iwata A., Maruyama M., Akagi T., Hashikawa T., Kanazawa I., Tsuji S., RA Nukina N.; RT "Alpha-synuclein degradation by serine protease neurosin: implication for RT pathogenesis of synucleinopathies."; RL Hum. Mol. Genet. 12:2625-2635(2003). RN [18] RP FUNCTION. RX PubMed=15557757; DOI=10.1159/000081102; RA Ghosh M.C., Grass L., Soosaipillai A., Sotiropoulou G., Diamandis E.P.; RT "Human kallikrein 6 degrades extracellular matrix proteins and may enhance RT the metastatic potential of tumour cells."; RL Tumor Biol. 25:193-199(2004). RN [19] RP FUNCTION, AND INDUCTION. RX PubMed=16987227; DOI=10.1111/j.1460-9568.2006.05021.x; RA Scarisbrick I.A., Sabharwal P., Cruz H., Larsen N., Vandell A.G., RA Blaber S.I., Ameenuddin S., Papke L.M., Fehlings M.G., Reeves R.K., RA Blaber M., Windebank A.J., Rodriguez M.; RT "Dynamic role of kallikrein 6 in traumatic spinal cord injury."; RL Eur. J. Neurosci. 24:1457-1469(2006). RN [20] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=16321973; DOI=10.1074/jbc.m510096200; RA Angelo P.F., Lima A.R., Alves F.M., Blaber S.I., Scarisbrick I.A., RA Blaber M., Juliano L., Juliano M.A.; RT "Substrate specificity of human kallikrein 6: salt and glycosaminoglycan RT activation effects."; RL J. Biol. Chem. 281:3116-3126(2006). RN [21] RP AUTOCATALYTIC CLEAVAGE. RX PubMed=17417874; DOI=10.1021/bi6025006; RA Blaber S.I., Yoon H., Scarisbrick I.A., Juliano M.A., Blaber M.; RT "The autolytic regulation of human kallikrein-related peptidase 6."; RL Biochemistry 46:5209-5217(2007). RN [22] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 21-243, AUTOCATALYTIC CLEAVAGE, RP ACTIVE SITES, AND DISULFIDE BONDS. RX PubMed=12016211; DOI=10.1074/jbc.m201534200; RA Gomis-Rueth F.X., Bayes A., Sotiropoulou G., Pampalakis G., Tsetsenis T., RA Villegas V., Aviles F.X., Coll M.; RT "The structure of human prokallikrein 6 reveals a novel activation RT mechanism for the kallikrein family."; RL J. Biol. Chem. 277:27273-27281(2002). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 22-244, PROTEIN SEQUENCE OF RP 22-25, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AUTOCATALYTIC CLEAVAGE, RP DISULFIDE BONDS, AND MASS SPECTROMETRY. RX PubMed=11983703; DOI=10.1074/jbc.m202392200; RA Bernett M.J., Blaber S.I., Scarisbrick I.A., Dhanarajan P., Thompson S.M., RA Blaber M.; RT "Crystal structure and biochemical characterization of human kallikrein 6 RT reveals that a trypsin-like kallikrein is expressed in the central nervous RT system."; RL J. Biol. Chem. 277:24562-24570(2002). CC -!- FUNCTION: Serine protease which exhibits a preference for Arg over Lys CC in the substrate P1 position and for Ser or Pro in the P2 position. CC Shows activity against amyloid precursor protein, myelin basic protein, CC gelatin, casein and extracellular matrix proteins such as fibronectin, CC laminin, vitronectin and collagen. Degrades alpha-synuclein and CC prevents its polymerization, indicating that it may be involved in the CC pathogenesis of Parkinson disease and other synucleinopathies. May be CC involved in regulation of axon outgrowth following spinal cord injury. CC Tumor cells treated with a neutralizing KLK6 antibody migrate less than CC control cells, suggesting a role in invasion and metastasis. CC {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203, CC ECO:0000269|PubMed:12928483, ECO:0000269|PubMed:15557757, CC ECO:0000269|PubMed:16321973, ECO:0000269|PubMed:16987227}. CC -!- ACTIVITY REGULATION: Inhibited by a range of serine protease inhibitors CC including soybean trypsin inhibitor, benzamidine and serpins. Activated CC by a range of glycosaminoglycans including chondroitin sulfate, CC dermatan sulfate, heparan sulfate and heparin. CC {ECO:0000269|PubMed:12878203, ECO:0000269|PubMed:16321973}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1562 uM for Tosyl-Gly-Pro-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=777 uM for Tosyl-Gly-Pro-Lys-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=0.410 mM for Phe-Ser-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=0.455 mM for Gly-Gly-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=0.335 mM for Asp-Pro-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=0.758 mM for Gln-Gly-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=0.625 mM for Pro-Phe-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=0.271 mM for Val-Pro-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=1.72 mM for Val-Leu-Lys-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC -!- INTERACTION: CC Q92876; Q8NC06-3: ACBD4; NbExp=3; IntAct=EBI-2432309, EBI-12811089; CC Q92876; P11117: ACP2; NbExp=3; IntAct=EBI-2432309, EBI-2907070; CC Q92876; Q53FZ2-2: ACSM3; NbExp=3; IntAct=EBI-2432309, EBI-25887341; CC Q92876; Q96BT7-2: ALKBH8; NbExp=3; IntAct=EBI-2432309, EBI-13329511; CC Q92876; P05067: APP; NbExp=3; IntAct=EBI-2432309, EBI-77613; CC Q92876; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-2432309, EBI-2875816; CC Q92876; Q5H9R4-2: ARMCX4; NbExp=3; IntAct=EBI-2432309, EBI-21899904; CC Q92876; Q8WXK3-2: ASB13; NbExp=3; IntAct=EBI-2432309, EBI-12015080; CC Q92876; Q12797-6: ASPH; NbExp=3; IntAct=EBI-2432309, EBI-12092171; CC Q92876; Q9Y6H3: ATP23; NbExp=3; IntAct=EBI-2432309, EBI-12811889; CC Q92876; P27449: ATP6V0C; NbExp=3; IntAct=EBI-2432309, EBI-721179; CC Q92876; O95817: BAG3; NbExp=3; IntAct=EBI-2432309, EBI-747185; CC Q92876; Q8TBE0: BAHD1; NbExp=3; IntAct=EBI-2432309, EBI-742750; CC Q92876; Q9UQB8-3: BAIAP2; NbExp=3; IntAct=EBI-2432309, EBI-9091996; CC Q92876; Q9UQB8-6: BAIAP2; NbExp=3; IntAct=EBI-2432309, EBI-9092016; CC Q92876; P51572: BCAP31; NbExp=3; IntAct=EBI-2432309, EBI-77683; CC Q92876; O15155-2: BET1; NbExp=3; IntAct=EBI-2432309, EBI-25846497; CC Q92876; Q9BXY8: BEX2; NbExp=3; IntAct=EBI-2432309, EBI-745073; CC Q92876; Q7L1Q6-2: BZW1; NbExp=3; IntAct=EBI-2432309, EBI-21557060; CC Q92876; Q9H0W9-3: C11orf54; NbExp=3; IntAct=EBI-2432309, EBI-12108466; CC Q92876; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-2432309, EBI-11530605; CC Q92876; Q86XM0: CATSPERD; NbExp=3; IntAct=EBI-2432309, EBI-10260328; CC Q92876; O75309: CDH16; NbExp=3; IntAct=EBI-2432309, EBI-2837263; CC Q92876; P49336-2: CDK8; NbExp=3; IntAct=EBI-2432309, EBI-11039720; CC Q92876; Q9Y281: CFL2; NbExp=3; IntAct=EBI-2432309, EBI-351218; CC Q92876; Q8NE62: CHDH; NbExp=3; IntAct=EBI-2432309, EBI-7127986; CC Q92876; O75508: CLDN11; NbExp=3; IntAct=EBI-2432309, EBI-12820543; CC Q92876; Q9BT09: CNPY3; NbExp=3; IntAct=EBI-2432309, EBI-2835965; CC Q92876; P20849: COL9A1; NbExp=3; IntAct=EBI-2432309, EBI-2528238; CC Q92876; Q86WV2: COX4I1; NbExp=3; IntAct=EBI-2432309, EBI-10260134; CC Q92876; P68400: CSNK2A1; NbExp=3; IntAct=EBI-2432309, EBI-347804; CC Q92876; P09668: CTSH; NbExp=3; IntAct=EBI-2432309, EBI-6189940; CC Q92876; P09172: DBH; NbExp=3; IntAct=EBI-2432309, EBI-8589586; CC Q92876; P61962: DCAF7; NbExp=3; IntAct=EBI-2432309, EBI-359808; CC Q92876; Q9BTE7: DCUN1D5; NbExp=3; IntAct=EBI-2432309, EBI-3924013; CC Q92876; Q6ZPD9-2: DPY19L3; NbExp=3; IntAct=EBI-2432309, EBI-25888224; CC Q92876; P63167: DYNLL1; NbExp=3; IntAct=EBI-2432309, EBI-349105; CC Q92876; Q13144: EIF2B5; NbExp=3; IntAct=EBI-2432309, EBI-4401110; CC Q92876; P23588: EIF4B; NbExp=3; IntAct=EBI-2432309, EBI-970310; CC Q92876; P16452: EPB42; NbExp=3; IntAct=EBI-2432309, EBI-1182496; CC Q92876; Q5RHP9-3: ERICH3; NbExp=3; IntAct=EBI-2432309, EBI-20839496; CC Q92876; Q6NXG1: ESRP1; NbExp=3; IntAct=EBI-2432309, EBI-10213520; CC Q92876; Q6NXG1-3: ESRP1; NbExp=3; IntAct=EBI-2432309, EBI-21567429; CC Q92876; Q7L5A8: FA2H; NbExp=3; IntAct=EBI-2432309, EBI-11337888; CC Q92876; Q6NZ36-4: FAAP20; NbExp=3; IntAct=EBI-2432309, EBI-12013806; CC Q92876; Q14296: FASTK; NbExp=3; IntAct=EBI-2432309, EBI-1754067; CC Q92876; P62861: FAU; NbExp=3; IntAct=EBI-2432309, EBI-358093; CC Q92876; P31994: FCGR2B; NbExp=3; IntAct=EBI-2432309, EBI-724784; CC Q92876; Q7L622: G2E3; NbExp=3; IntAct=EBI-2432309, EBI-751757; CC Q92876; P24522: GADD45A; NbExp=3; IntAct=EBI-2432309, EBI-448167; CC Q92876; P15976-2: GATA1; NbExp=3; IntAct=EBI-2432309, EBI-9090198; CC Q92876; Q9NXC2: GFOD1; NbExp=3; IntAct=EBI-2432309, EBI-8799578; CC Q92876; B2RAF7: hCG_1818547; NbExp=3; IntAct=EBI-2432309, EBI-25844370; CC Q92876; P52790: HK3; NbExp=3; IntAct=EBI-2432309, EBI-2965780; CC Q92876; Q9P0W2: HMG20B; NbExp=3; IntAct=EBI-2432309, EBI-713401; CC Q92876; Q4VB01: HOXB1; NbExp=3; IntAct=EBI-2432309, EBI-17494170; CC Q92876; Q7LGA3-3: HS2ST1; NbExp=3; IntAct=EBI-2432309, EBI-25887463; CC Q92876; Q96D96-2: HVCN1; NbExp=3; IntAct=EBI-2432309, EBI-25888137; CC Q92876; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-2432309, EBI-8638439; CC Q92876; Q14005-2: IL16; NbExp=3; IntAct=EBI-2432309, EBI-17178971; CC Q92876; Q0VD86: INCA1; NbExp=3; IntAct=EBI-2432309, EBI-6509505; CC Q92876; Q9BT40: INPP5K; NbExp=3; IntAct=EBI-2432309, EBI-749162; CC Q92876; Q9Y283-3: INVS; NbExp=3; IntAct=EBI-2432309, EBI-11944909; CC Q92876; P57682: KLF3; NbExp=3; IntAct=EBI-2432309, EBI-8472267; CC Q92876; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-2432309, EBI-714379; CC Q92876; O60259: KLK8; NbExp=3; IntAct=EBI-2432309, EBI-3915857; CC Q92876; P08727: KRT19; NbExp=3; IntAct=EBI-2432309, EBI-742756; CC Q92876; Q14533: KRT81; NbExp=3; IntAct=EBI-2432309, EBI-739648; CC Q92876; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-2432309, EBI-1048945; CC Q92876; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-2432309, EBI-10241353; CC Q92876; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-2432309, EBI-10261141; CC Q92876; Q92615: LARP4B; NbExp=3; IntAct=EBI-2432309, EBI-1052558; CC Q92876; Q14847-2: LASP1; NbExp=3; IntAct=EBI-2432309, EBI-9088686; CC Q92876; Q6DKI2: LGALS9C; NbExp=3; IntAct=EBI-2432309, EBI-9088829; CC Q92876; Q8TE12-2: LMX1A; NbExp=3; IntAct=EBI-2432309, EBI-25846312; CC Q92876; O95332: LOC57228; NbExp=3; IntAct=EBI-2432309, EBI-25846778; CC Q92876; Q96JB6: LOXL4; NbExp=3; IntAct=EBI-2432309, EBI-749562; CC Q92876; Q99683: MAP3K5; NbExp=3; IntAct=EBI-2432309, EBI-476263; CC Q92876; Q15759: MAPK11; NbExp=3; IntAct=EBI-2432309, EBI-298304; CC Q92876; P42679: MATK; NbExp=3; IntAct=EBI-2432309, EBI-751664; CC Q92876; Q8N6R0: METTL13; NbExp=3; IntAct=EBI-2432309, EBI-1053295; CC Q92876; Q14728: MFSD10; NbExp=3; IntAct=EBI-2432309, EBI-11337904; CC Q92876; A0A0A0MR05: MLST8; NbExp=3; IntAct=EBI-2432309, EBI-25835557; CC Q92876; Q9BRA0: NAA38; NbExp=3; IntAct=EBI-2432309, EBI-9106509; CC Q92876; Q92886: NEUROG1; NbExp=3; IntAct=EBI-2432309, EBI-10279647; CC Q92876; P48645: NMU; NbExp=3; IntAct=EBI-2432309, EBI-10210351; CC Q92876; Q9Y239: NOD1; NbExp=3; IntAct=EBI-2432309, EBI-1051262; CC Q92876; P06748: NPM1; NbExp=3; IntAct=EBI-2432309, EBI-78579; CC Q92876; Q6P4D5-2: PABIR3; NbExp=3; IntAct=EBI-2432309, EBI-9091052; CC Q92876; Q8WW12: PCNP; NbExp=3; IntAct=EBI-2432309, EBI-10972020; CC Q92876; Q16549: PCSK7; NbExp=3; IntAct=EBI-2432309, EBI-8059854; CC Q92876; Q13371: PDCL; NbExp=3; IntAct=EBI-2432309, EBI-5772890; CC Q92876; Q9NZ53-2: PODXL2; NbExp=3; IntAct=EBI-2432309, EBI-25887738; CC Q92876; Q9GZS1: POLR1E; NbExp=3; IntAct=EBI-2432309, EBI-359458; CC Q92876; P19388: POLR2E; NbExp=3; IntAct=EBI-2432309, EBI-395189; CC Q92876; Q6ZMI0-5: PPP1R21; NbExp=3; IntAct=EBI-2432309, EBI-25835994; CC Q92876; Q96QH2: PRAM1; NbExp=3; IntAct=EBI-2432309, EBI-2860740; CC Q92876; Q86UA1: PRPF39; NbExp=3; IntAct=EBI-2432309, EBI-2803203; CC Q92876; P61289: PSME3; NbExp=3; IntAct=EBI-2432309, EBI-355546; CC Q92876; P21246: PTN; NbExp=3; IntAct=EBI-2432309, EBI-473725; CC Q92876; P53801: PTTG1IP; NbExp=3; IntAct=EBI-2432309, EBI-3906138; CC Q92876; Q9NWB1-5: RBFOX1; NbExp=3; IntAct=EBI-2432309, EBI-12123390; CC Q92876; Q9BWF3: RBM4; NbExp=3; IntAct=EBI-2432309, EBI-2856454; CC Q92876; P52756: RBM5; NbExp=3; IntAct=EBI-2432309, EBI-714003; CC Q92876; P47804-3: RGR; NbExp=3; IntAct=EBI-2432309, EBI-25834767; CC Q92876; Q9H0X6: RNF208; NbExp=3; IntAct=EBI-2432309, EBI-751555; CC Q92876; Q969K3: RNF34; NbExp=3; IntAct=EBI-2432309, EBI-2340642; CC Q92876; Q9BY12-3: SCAPER; NbExp=3; IntAct=EBI-2432309, EBI-25837959; CC Q92876; Q86SQ7-2: SDCCAG8; NbExp=3; IntAct=EBI-2432309, EBI-10696955; CC Q92876; Q9NTN9-3: SEMA4G; NbExp=3; IntAct=EBI-2432309, EBI-9089805; CC Q92876; Q8IUQ4-2: SIAH1; NbExp=3; IntAct=EBI-2432309, EBI-11522811; CC Q92876; Q9H2B4-2: SLC26A1; NbExp=3; IntAct=EBI-2432309, EBI-12908340; CC Q92876; Q99717: SMAD5; NbExp=3; IntAct=EBI-2432309, EBI-6391136; CC Q92876; P37840: SNCA; NbExp=3; IntAct=EBI-2432309, EBI-985879; CC Q92876; Q5T0L3: SPATA46; NbExp=3; IntAct=EBI-2432309, EBI-750105; CC Q92876; Q496A3: SPATS1; NbExp=3; IntAct=EBI-2432309, EBI-3923692; CC Q92876; Q9BUD6: SPON2; NbExp=3; IntAct=EBI-2432309, EBI-10298801; CC Q92876; Q9C004: SPRY4; NbExp=3; IntAct=EBI-2432309, EBI-354861; CC Q92876; Q99469: STAC; NbExp=3; IntAct=EBI-2432309, EBI-2652799; CC Q92876; O75558: STX11; NbExp=3; IntAct=EBI-2432309, EBI-714135; CC Q92876; Q9UMX1: SUFU; NbExp=3; IntAct=EBI-2432309, EBI-740595; CC Q92876; O43463: SUV39H1; NbExp=3; IntAct=EBI-2432309, EBI-349968; CC Q92876; O60506-4: SYNCRIP; NbExp=3; IntAct=EBI-2432309, EBI-11123832; CC Q92876; Q8TDR4: TCP10L; NbExp=3; IntAct=EBI-2432309, EBI-3923210; CC Q92876; Q96A09: TENT5B; NbExp=3; IntAct=EBI-2432309, EBI-752030; CC Q92876; Q01664: TFAP4; NbExp=3; IntAct=EBI-2432309, EBI-2514218; CC Q92876; Q6YHU6: THADA; NbExp=3; IntAct=EBI-2432309, EBI-2824523; CC Q92876; Q9H808: TLE6; NbExp=3; IntAct=EBI-2432309, EBI-3921684; CC Q92876; Q8IU80-2: TMPRSS6; NbExp=3; IntAct=EBI-2432309, EBI-25839648; CC Q92876; Q8IUR5-4: TMTC1; NbExp=3; IntAct=EBI-2432309, EBI-9089156; CC Q92876; Q8WVP5: TNFAIP8L1; NbExp=3; IntAct=EBI-2432309, EBI-752102; CC Q92876; Q96KP6: TNIP3; NbExp=3; IntAct=EBI-2432309, EBI-2509913; CC Q92876; O14787-2: TNPO2; NbExp=3; IntAct=EBI-2432309, EBI-12076664; CC Q92876; O94900: TOX; NbExp=3; IntAct=EBI-2432309, EBI-9088321; CC Q92876; P06753-2: TPM3; NbExp=3; IntAct=EBI-2432309, EBI-10977875; CC Q92876; Q9NX07: TRNAU1AP; NbExp=3; IntAct=EBI-2432309, EBI-12581310; CC Q92876; O60636: TSPAN2; NbExp=3; IntAct=EBI-2432309, EBI-3914288; CC Q92876; Q86UF1: TSPAN33; NbExp=3; IntAct=EBI-2432309, EBI-12045841; CC Q92876; Q5VYS8-5: TUT7; NbExp=3; IntAct=EBI-2432309, EBI-9088812; CC Q92876; Q9GZX9: TWSG1; NbExp=3; IntAct=EBI-2432309, EBI-10304067; CC Q92876; Q13404: UBE2V1; NbExp=3; IntAct=EBI-2432309, EBI-1050671; CC Q92876; Q9H9P5-5: UNKL; NbExp=3; IntAct=EBI-2432309, EBI-12817837; CC Q92876; Q9NVA1: UQCC1; NbExp=3; IntAct=EBI-2432309, EBI-11911675; CC Q92876; P61964: WDR5; NbExp=3; IntAct=EBI-2432309, EBI-540834; CC Q92876; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-2432309, EBI-12040603; CC Q92876; O00308: WWP2; NbExp=3; IntAct=EBI-2432309, EBI-743923; CC Q92876; Q9HAV4: XPO5; NbExp=3; IntAct=EBI-2432309, EBI-517949; CC Q92876; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-2432309, EBI-12010736; CC Q92876; Q7Z783; NbExp=3; IntAct=EBI-2432309, EBI-9088990; CC Q92876; Q96EJ4; NbExp=3; IntAct=EBI-2432309, EBI-750454; CC -!- SUBCELLULAR LOCATION: Secreted. Nucleus, nucleolus. Cytoplasm. CC Mitochondrion. Microsome. Note=In brain, detected in the nucleus of CC glial cells and in the nucleus and cytoplasm of neurons. Detected in CC the mitochondrial and microsomal fractions of HEK-293 cells and CC released into the cytoplasm following cell stress. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q92876-1; Sequence=Displayed; CC Name=2; CC IsoId=Q92876-2; Sequence=VSP_034403; CC Name=3; CC IsoId=Q92876-3; Sequence=VSP_034404, VSP_034405; CC -!- TISSUE SPECIFICITY: In fluids, highest levels found in milk of CC lactating women followed by cerebrospinal fluid, nipple aspirate fluid CC and breast cyst fluid. Also found in serum, seminal plasma and some CC amniotic fluids and breast tumor cytosolic extracts. Not detected in CC urine. At the tissue level, highest concentrations found in glandular CC tissues such as salivary glands followed by lung, colon, fallopian CC tube, placenta, breast, pituitary and kidney. Not detected in skin, CC spleen, bone, thyroid, heart, ureter, liver, muscle, endometrium, CC testis, pancreas, seminal vesicle, ovary, adrenals and prostate. In CC brain, detected in gray matter neurons (at protein level). Colocalizes CC with pathological inclusions such as Lewy bodies and glial cytoplasmic CC inclusions. Overexpressed in primary breast tumors but not expressed in CC metastatic tumors. {ECO:0000269|PubMed:10997858, CC ECO:0000269|PubMed:11018688, ECO:0000269|PubMed:11668196, CC ECO:0000269|PubMed:12928483, ECO:0000269|PubMed:16800739}. CC -!- INDUCTION: By spinal cord injury. This effect is particularly prominent CC in macrophages, microglia and reactive astrocytes. CC {ECO:0000269|PubMed:16987227}. CC -!- PTM: Inactivated by autolytic cleavage after Arg-80. CC -!- MASS SPECTROMETRY: Mass=25866; Method=MALDI; CC Evidence={ECO:0000269|PubMed:11983703}; CC -!- SIMILARITY: Belongs to the peptidase S1 family. Kallikrein subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00274}. 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; U62801; AAB07113.1; -; mRNA. DR EMBL; D78203; BAA11306.1; -; mRNA. DR EMBL; AF013988; AAB66483.1; -; mRNA. DR EMBL; AF149289; AAD51475.1; -; Genomic_DNA. DR EMBL; AF243527; AAG33359.1; -; Genomic_DNA. DR EMBL; AY318867; AAP82446.1; -; mRNA. DR EMBL; AY318868; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AY318869; AAP82448.1; -; mRNA. DR EMBL; AY318870; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; DQ223012; ABB04464.1; -; mRNA. DR EMBL; AK314897; BAG37411.1; -; mRNA. DR EMBL; BT006852; AAP35498.1; -; mRNA. DR EMBL; AC011483; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471135; EAW71953.1; -; Genomic_DNA. DR EMBL; CH471135; EAW71954.1; -; Genomic_DNA. DR EMBL; BC015525; AAH15525.1; -; mRNA. DR CCDS; CCDS12811.1; -. [Q92876-1] DR CCDS; CCDS42599.1; -. [Q92876-2] DR RefSeq; NP_001012982.1; NM_001012964.3. [Q92876-1] DR RefSeq; NP_001012983.1; NM_001012965.3. [Q92876-2] DR RefSeq; NP_001306877.1; NM_001319948.2. [Q92876-2] DR RefSeq; NP_001306878.1; NM_001319949.2. [Q92876-2] DR RefSeq; NP_002765.1; NM_002774.4. [Q92876-1] DR RefSeq; XP_024307379.1; XM_024451611.2. [Q92876-2] DR PDB; 1GVL; X-ray; 1.80 A; A=21-243. DR PDB; 1L2E; X-ray; 1.75 A; A=22-244. DR PDB; 1LO6; X-ray; 1.56 A; A=22-244. DR PDB; 3VFE; X-ray; 1.88 A; A=22-244. DR PDB; 4D8N; X-ray; 1.68 A; A=22-244. DR PDB; 5NX1; X-ray; 1.85 A; A=22-244. DR PDB; 5NX3; X-ray; 2.30 A; A=22-244. DR PDB; 6QFF; X-ray; 1.64 A; A/B=22-243. DR PDB; 6QFG; X-ray; 1.68 A; A/B=22-244. DR PDB; 6QFH; X-ray; 1.65 A; A/B=22-243. DR PDB; 6QH9; X-ray; 2.27 A; A/B=22-244. DR PDB; 6QHA; X-ray; 1.82 A; A/B=22-244. DR PDB; 6QHB; X-ray; 1.84 A; A/B=22-244. DR PDB; 6QHC; X-ray; 1.87 A; A/B=22-244. DR PDB; 6SKB; X-ray; 1.84 A; A/B/C=12-244. DR PDB; 6SKC; X-ray; 2.18 A; A/B=22-244. DR PDB; 6SKD; X-ray; 2.26 A; A/B=22-244. DR PDB; 7QFT; X-ray; 1.47 A; A/B=22-244. DR PDB; 7QFV; X-ray; 1.56 A; A/B=22-244. DR PDB; 7QHZ; X-ray; 1.50 A; A=22-244. DR PDB; 7QI0; X-ray; 1.88 A; A/B=22-244. DR PDBsum; 1GVL; -. DR PDBsum; 1L2E; -. DR PDBsum; 1LO6; -. DR PDBsum; 3VFE; -. DR PDBsum; 4D8N; -. DR PDBsum; 5NX1; -. DR PDBsum; 5NX3; -. DR PDBsum; 6QFF; -. DR PDBsum; 6QFG; -. DR PDBsum; 6QFH; -. DR PDBsum; 6QH9; -. DR PDBsum; 6QHA; -. DR PDBsum; 6QHB; -. DR PDBsum; 6QHC; -. DR PDBsum; 6SKB; -. DR PDBsum; 6SKC; -. DR PDBsum; 6SKD; -. DR PDBsum; 7QFT; -. DR PDBsum; 7QFV; -. DR PDBsum; 7QHZ; -. DR PDBsum; 7QI0; -. DR AlphaFoldDB; Q92876; -. DR SMR; Q92876; -. DR BioGRID; 111634; 63. DR CORUM; Q92876; -. DR FunCoup; Q92876; 77. DR IntAct; Q92876; 191. DR MINT; Q92876; -. DR STRING; 9606.ENSP00000366047; -. DR BindingDB; Q92876; -. DR ChEMBL; CHEMBL4448; -. DR DrugBank; DB03127; Benzamidine. DR GuidetoPHARMACOLOGY; 2376; -. DR MEROPS; S01.236; -. DR GlyConnect; 2937; 2 N-Linked glycans (1 site). DR GlyCosmos; Q92876; 1 site, 18 glycans. DR GlyGen; Q92876; 1 site, 18 N-linked glycans (1 site). DR iPTMnet; Q92876; -. DR PhosphoSitePlus; Q92876; -. DR BioMuta; KLK6; -. DR DMDM; 3914480; -. DR jPOST; Q92876; -. DR MassIVE; Q92876; -. DR PaxDb; 9606-ENSP00000366047; -. DR PeptideAtlas; Q92876; -. DR ProteomicsDB; 75559; -. [Q92876-1] DR ProteomicsDB; 75560; -. [Q92876-2] DR Pumba; Q92876; -. DR Antibodypedia; 32402; 345 antibodies from 33 providers. DR DNASU; 5653; -. DR Ensembl; ENST00000310157.7; ENSP00000309148.1; ENSG00000167755.16. [Q92876-1] DR Ensembl; ENST00000376851.7; ENSP00000366047.2; ENSG00000167755.16. [Q92876-1] DR Ensembl; ENST00000391808.5; ENSP00000375684.1; ENSG00000167755.16. [Q92876-2] DR Ensembl; ENST00000594641.1; ENSP00000470482.1; ENSG00000167755.16. [Q92876-1] DR Ensembl; ENST00000597379.5; ENSP00000469630.1; ENSG00000167755.16. [Q92876-3] DR Ensembl; ENST00000599881.5; ENSP00000471948.1; ENSG00000167755.16. [Q92876-3] DR GeneID; 5653; -. DR KEGG; hsa:5653; -. DR MANE-Select; ENST00000310157.7; ENSP00000309148.1; NM_002774.4; NP_002765.1. DR UCSC; uc002pui.4; human. [Q92876-1] DR AGR; HGNC:6367; -. DR ClinPGx; PA30156; -. DR CTD; 5653; -. DR DisGeNET; 5653; -. DR GeneCards; KLK6; -. DR HGNC; HGNC:6367; KLK6. DR HPA; ENSG00000167755; Tissue enriched (brain). DR MIM; 602652; gene. DR OpenTargets; ENSG00000167755; -. DR VEuPathDB; HostDB:ENSG00000167755; -. DR eggNOG; KOG3627; Eukaryota. DR GeneTree; ENSGT01030000234551; -. DR HOGENOM; CLU_006842_1_1_1; -. DR InParanoid; Q92876; -. DR OMA; RHDNDIM; -. DR OrthoDB; 10059102at2759; -. DR PAN-GO; Q92876; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q92876; -. DR BRENDA; 3.4.21.104; 2681. DR BRENDA; 3.4.21.34; 2681. DR BRENDA; 3.4.21.B10; 2681. DR PathwayCommons; Q92876; -. DR SABIO-RK; Q92876; -. DR SignaLink; Q92876; -. DR Agora; ENSG00000167755; -. DR BioGRID-ORCS; 5653; 20 hits in 1159 CRISPR screens. DR ChiTaRS; KLK6; human. DR EvolutionaryTrace; Q92876; -. DR GeneWiki; KLK6; -. DR GenomeRNAi; 5653; -. DR Pharos; Q92876; Tchem. DR PRO; PR:Q92876; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q92876; protein. DR Bgee; ENSG00000167755; Expressed in C1 segment of cervical spinal cord and 145 other cell types or tissues. DR ExpressionAtlas; Q92876; baseline and differential. DR GO; GO:0001533; C:cornified envelope; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0045171; C:intercellular bridge; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0031965; C:nuclear membrane; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0030141; C:secretory granule; IBA:GO_Central. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0042982; P:amyloid precursor protein metabolic process; NAS:UniProtKB. DR GO; GO:0007417; P:central nervous system development; NAS:UniProtKB. DR GO; GO:0030574; P:collagen catabolic process; NAS:UniProtKB. DR GO; GO:0042445; P:hormone metabolic process; NAS:UniProtKB. DR GO; GO:0042552; P:myelination; NAS:UniProtKB. DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0016540; P:protein autoprocessing; NAS:UniProtKB. DR GO; GO:0051604; P:protein maturation; IBA:GO_Central. DR GO; GO:0045595; P:regulation of cell differentiation; NAS:UniProtKB. DR GO; GO:0010975; P:regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0009611; P:response to wounding; NAS:UniProtKB. DR GO; GO:0042246; P:tissue regeneration; NAS:UniProtKB. DR CDD; cd00190; Tryp_SPc; 1. DR FunFam; 2.40.10.10:FF:000088; kallikrein-6 isoform X1; 1. DR FunFam; 2.40.10.10:FF:000041; kallikrein-6 isoform X2; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24271:SF19; KALLIKREIN-6; 1. DR PANTHER; PTHR24271; KALLIKREIN-RELATED; 1. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Autocatalytic cleavage; KW Cleavage on pair of basic residues; Cytoplasm; Direct protein sequencing; KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Hydrolase; Microsome; KW Mitochondrion; Nucleus; Protease; Proteomics identification; KW Reference proteome; Secreted; Serine protease; Signal; Zymogen. FT SIGNAL 1..16 FT /evidence="ECO:0000255" FT PROPEP 17..21 FT /note="Activation peptide" FT /evidence="ECO:0000255" FT /id="PRO_0000027940" FT CHAIN 22..244 FT /note="Kallikrein-6" FT /id="PRO_0000027941" FT DOMAIN 22..242 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 62 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:12016211" FT ACT_SITE 106 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:12016211" FT ACT_SITE 197 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:12016211" FT SITE 80..81 FT /note="Cleavage; by autolysis" FT CARBOHYD 134 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 28..157 FT DISULFID 47..63 FT DISULFID 131..231 FT DISULFID 138..203 FT DISULFID 168..182 FT DISULFID 193..218 FT VAR_SEQ 1..107 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15207701" FT /id="VSP_034403" FT VAR_SEQ 14..40 FT /note="AWAEEQNKLVHGGPCDKTSHPYQAALY -> GIFRSSWGSITFGKGRVPRSR FT VLLSGL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15207701" FT /id="VSP_034404" FT VAR_SEQ 41..244 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15207701" FT /id="VSP_034405" FT VARIANT 78 FT /note="R -> W (in dbSNP:rs61469141)" FT /id="VAR_061776" FT HELIX 27..29 FT /evidence="ECO:0007829|PDB:1GVL" FT STRAND 36..41 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 44..53 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 56..59 FT /evidence="ECO:0007829|PDB:7QFT" FT HELIX 61..63 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 69..73 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 75..77 FT /evidence="ECO:0007829|PDB:1GVL" FT STRAND 85..94 FT /evidence="ECO:0007829|PDB:7QFT" FT TURN 100..103 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 108..114 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 120..122 FT /evidence="ECO:0007829|PDB:7QI0" FT STRAND 137..144 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 146..149 FT /evidence="ECO:0007829|PDB:1GVL" FT STRAND 156..163 FT /evidence="ECO:0007829|PDB:7QFT" FT HELIX 165..171 FT /evidence="ECO:0007829|PDB:7QFT" FT TURN 173..175 FT /evidence="ECO:0007829|PDB:1LO6" FT STRAND 180..184 FT /evidence="ECO:0007829|PDB:7QFT" FT TURN 186..188 FT /evidence="ECO:0007829|PDB:7QFT" FT TURN 194..198 FT /evidence="ECO:0007829|PDB:1LO6" FT STRAND 200..203 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 206..213 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 216..218 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 221..223 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 225..229 FT /evidence="ECO:0007829|PDB:7QFT" FT HELIX 230..233 FT /evidence="ECO:0007829|PDB:7QFT" FT HELIX 234..242 FT /evidence="ECO:0007829|PDB:7QFT" SQ SEQUENCE 244 AA; 26856 MW; AEA03F9145D87AAB CRC64; MKKLMVVLSL IAAAWAEEQN KLVHGGPCDK TSHPYQAALY TSGHLLCGGV LIHPLWVLTA AHCKKPNLQV FLGKHNLRQR ESSQEQSSVV RAVIHPDYDA ASHDQDIMLL RLARPAKLSE LIQPLPLERD CSANTTSCHI LGWGKTADGD FPDTIQCAYI HLVSREECEH AYPGQITQNM LCAGDEKYGK DSCQGDSGGP LVCGDHLRGL VSWGNIPCGS KEKPGVYTNV CRYTNWIQKT IQAK // ID MYORG_HUMAN Reviewed; 714 AA. AC Q6NSJ0; Q5T587; Q5T588; Q9ULQ9; DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot. DT 24-JUL-2007, sequence version 2. DT 28-JAN-2026, entry version 153. DE RecName: Full=Alpha-galactosidase MYORG {ECO:0000305|PubMed:36129849}; DE EC=3.2.1.22 {ECO:0000305|PubMed:36129849}; DE AltName: Full=Myogenesis regulating glycosidase {ECO:0000312|HGNC:HGNC:19918}; DE AltName: Full=Nuclear envelope transmembrane protein 37 {ECO:0000303|PubMed:19706595}; GN Name=MYORG {ECO:0000312|HGNC:HGNC:19918}; GN Synonyms=KIAA1161 {ECO:0000312|EMBL:BAA86475.2}, GN NET37 {ECO:0000303|PubMed:19706595}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ILE-4 AND GLU-53. RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 35-714, AND VARIANT GLU-53. RC TISSUE=Brain; RX PubMed=10574461; DOI=10.1093/dnares/6.5.329; RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.; RT "Characterization of cDNA clones selected by the GeneMark analysis from RT size-fractionated cDNA libraries from human brain."; RL DNA Res. 6:329-336(1999). RN [4] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-250. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [5] RP SUBCELLULAR LOCATION, FUNCTION, AND MUTAGENESIS OF ASP-463. RX PubMed=19706595; DOI=10.1074/jbc.m109.034041; RA Datta K., Guan T., Gerace L.; RT "NET37, a nuclear envelope transmembrane protein with glycosidase homology, RT is involved in myoblast differentiation."; RL J. Biol. Chem. 284:29666-29676(2009). 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] {ECO:0007744|PDB:7QQF, ECO:0007744|PDB:7QQG, ECO:0007744|PDB:7QQH} RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 80-714 IN COMPLEX WITH RP GAL-ALPHA1,4-GLC, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL RP PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, ACTIVE SITE, GLYCOSYLATION AT RP ASN-240; ASN-250; ASN-346; ASN-372; ASN-398 AND ASN-511, AND DISULFIDE RP BONDS. RX PubMed=36129849; DOI=10.1371/journal.pbio.3001764; RA Meek R.W., Brockerman J., Fordwour O.B., Zandberg W.F., Davies G.J., RA Vocadlo D.J.; RT "The primary familial brain calcification-associated protein MYORG is an RT alpha-galactosidase with restricted substrate specificity."; RL PLoS Biol. 20:e3001764-e3001764(2022). RN [8] RP SUBCELLULAR LOCATION, INVOLVEMENT IN IBGC7, AND VARIANTS IBGC7 VAL-35; RP 75-TRP--SER-714 DEL; LEU-ALA-PHE-ARG-116 INS; 203-GLN--SER-714 DEL; RP LEU-232; LEU-261; 365-PHE-ASP-366 DEL; GLY-441 AND 443-TRP--SER-714 DEL. RX PubMed=29910000; DOI=10.1016/j.neuron.2018.05.037; RA Yao X.P., Cheng X., Wang C., Zhao M., Guo X.X., Su H.Z., Lai L.L., RA Zou X.H., Chen X.J., Zhao Y., Dong E.L., Lu Y.Q., Wu S., Li X., Fan G., RA Yu H., Xu J., Wang N., Xiong Z.Q., Chen W.J.; RT "Biallelic mutations in MYORG cause autosomal recessive primary familial RT brain calcification."; RL Neuron 98:1116-1123(2018). RN [9] RP INVOLVEMENT IN IBGC7, AND VARIANT IBGC7 ASP-354 DEL. RX PubMed=30656188; DOI=10.1002/acn3.684; RA Arkadir D., Lossos A., Rahat D., Abu Snineh M., Schueler-Furman O., RA Nitschke S., Minassian B.A., Sadaka Y., Lerer I., Tabach Y., Meiner V.; RT "MYORG is associated with recessive primary familial brain calcification."; RL Ann. Clin. Transl. Neurol. 6:106-113(2019). RN [10] RP INVOLVEMENT IN IBGC7, AND VARIANTS IBGC7 GLU-64; ARG-113; RP LEU-ALA-PHE-ARG-116 INS; ALA-236 INS; CYS-249; ASP-373; HIS-434; RP 445-GLN--SER-714 DEL; ASN-476; SER-513 DEL; TRP-611; PRO-622; THR-656 AND RP GLN-660. RX PubMed=31009047; DOI=10.1093/brain/awz095; RG French PFBC study group; RA Grangeon L., Wallon D., Charbonnier C., Quenez O., Richard A.C., RA Rousseau S., Budowski C., Lebouvier T., Corbille A.G., Vidailhet M., RA Meneret A., Roze E., Anheim M., Tranchant C., Favrole P., Antoine J.C., RA Defebvre L., Ayrignac X., Labauge P., Pariente J., Clanet M., Maltete D., RA Rovelet-Lecrux A., Boland A., Deleuze J.F., Frebourg T., Hannequin D., RA Campion D., Nicolas G.; RT "Biallelic MYORG mutation carriers exhibit primary brain calcification with RT a distinct phenotype."; RL Brain 142:1573-1586(2019). RN [11] RP INVOLVEMENT IN IBGC7, AND VARIANT IBGC7 445-GLN--SER-714 DEL. RX PubMed=30460687; DOI=10.1111/cge.13467; RA Peng Y., Wang P., Chen Z., Jiang H.; RT "A novel mutation in MYORG causes primary familial brain calcification with RT central neuropathic pain."; RL Clin. Genet. 95:433-435(2019). RN [12] RP INVOLVEMENT IN IBGC7, AND VARIANTS IBGC7 LEU-ALA-PHE-ARG-116 INS; RP 143-LEU--ILE-147 DEL; CYS-229 AND 477-TYR--SER-714 DEL. RX PubMed=30589467; DOI=10.1002/mds.27582; RA Chen Y., Fu F., Chen S., Cen Z., Tang H., Huang J., Xie F., Zheng X., RA Yang D., Wang H., Huang X., Zhang Y., Zhou Y., Liu J.Y., Luo W.; RT "Evaluation of MYORG mutations as a novel cause of primary familial brain RT calcification."; RL Mov. Disord. 34:291-297(2019). RN [13] RP INVOLVEMENT IN IBGC7. RX PubMed=30895394; DOI=10.1007/s10048-019-00571-8; RA Ramos E.M., Roca A., Chumchim N., Dokuru D.R., Van Berlo V., De Michele G., RA Lieto M., Tedeschi E., De Michele G., Coppola G.; RT "Primary familial brain calcification caused by a novel homozygous MYORG RT mutation in a consanguineous Italian family."; RL Neurogenetics 20:99-102(2019). CC -!- FUNCTION: Alpha-galactosidase with unusual specificity for the Gal- CC alpha1,4-Glc structure, whose in vivo substrate is still unknown CC (PubMed:36129849). Promotes myogenesis by activating AKT signaling CC through the maturation and secretion of IGF2 (By similarity). CC {ECO:0000250|UniProtKB:Q69ZQ1, ECO:0000269|PubMed:36129849}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Hydrolysis of terminal, non-reducing alpha-D-galactose CC residues in alpha-D-galactosides, including galactose CC oligosaccharides, galactomannans and galactolipids.; EC=3.2.1.22; CC Evidence={ECO:0000305|PubMed:36129849}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=980 uM for Gal-alpha1,4-Glc {ECO:0000269|PubMed:36129849}; CC Note=kcat is 0.047 min-1 with the disaccharide Gal-alpha1,4-Glc as CC substrate. {ECO:0000269|PubMed:36129849}; CC pH dependence: CC Optimum pH is 6.0. {ECO:0000269|PubMed:36129849}; CC -!- SUBUNIT: Homodimer (PubMed:36129849). Interacts with IGF2; this CC interaction is required for IGF2 secretion. CC {ECO:0000250|UniProtKB:Q69ZQ1, ECO:0000269|PubMed:36129849}. CC -!- SUBCELLULAR LOCATION: Nucleus membrane {ECO:0000250|UniProtKB:Q69ZQ1}; CC Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q69ZQ1}. CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:29910000, CC ECO:0000269|PubMed:36129849}; Single-pass type II membrane protein CC {ECO:0000250|UniProtKB:Q69ZQ1}. Note=Only a minor fraction is present CC in the peripheral endoplasmic reticulum. CC {ECO:0000250|UniProtKB:Q69ZQ1}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:36129849}. CC -!- DISEASE: Basal ganglia calcification, idiopathic, 7, autosomal CC recessive (IBGC7) [MIM:618317]: A form of basal ganglia calcification, CC a genetically heterogeneous condition characterized by symmetric CC calcification in the basal ganglia and other brain regions. Affected CC individuals can either be asymptomatic or show a wide spectrum of CC neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, CC ataxia, dementia, psychosis, seizures, and chronic headache. Serum CC levels of calcium, phosphate, alkaline phosphatase and parathyroid CC hormone are normal. The neuropathological hallmark of the disease is CC vascular and pericapillary calcification, mainly of calcium phosphate, CC in the affected brain areas. {ECO:0000269|PubMed:29910000, CC ECO:0000269|PubMed:30460687, ECO:0000269|PubMed:30589467, CC ECO:0000269|PubMed:30656188, ECO:0000269|PubMed:30895394, CC ECO:0000269|PubMed:31009047}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 31 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AL356494; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC070098; AAH70098.1; -; mRNA. DR EMBL; BC110493; AAI10494.1; -; mRNA. DR EMBL; AB032987; BAA86475.2; -; mRNA. DR CCDS; CCDS78391.1; -. DR RefSeq; NP_065753.2; NM_020702.5. DR RefSeq; XP_011516268.1; XM_011517966.4. DR RefSeq; XP_016870419.1; XM_017014930.3. DR PDB; 7QQF; X-ray; 2.43 A; A/B/C/D=80-714. DR PDB; 7QQG; X-ray; 2.43 A; A/B/C/D=80-714. DR PDB; 7QQH; X-ray; 2.25 A; A/B/C/D=80-714. DR PDBsum; 7QQF; -. DR PDBsum; 7QQG; -. DR PDBsum; 7QQH; -. DR AlphaFoldDB; Q6NSJ0; -. DR SMR; Q6NSJ0; -. DR BioGRID; 121532; 64. DR FunCoup; Q6NSJ0; 461. DR IntAct; Q6NSJ0; 55. DR STRING; 9606.ENSP00000297625; -. DR CAZy; GH31; Glycoside Hydrolase Family 31. DR GlyConnect; 1882; 2 N-Linked glycans (1 site). DR GlyCosmos; Q6NSJ0; 3 sites, 2 glycans. DR GlyGen; Q6NSJ0; 6 sites, 13 N-linked glycans (5 sites). DR iPTMnet; Q6NSJ0; -. DR PhosphoSitePlus; Q6NSJ0; -. DR SwissPalm; Q6NSJ0; -. DR BioMuta; MYORG; -. DR DMDM; 158563982; -. DR jPOST; Q6NSJ0; -. DR MassIVE; Q6NSJ0; -. DR PaxDb; 9606-ENSP00000297625; -. DR PeptideAtlas; Q6NSJ0; -. DR ProteomicsDB; 66636; -. DR Pumba; Q6NSJ0; -. DR Antibodypedia; 55615; 40 antibodies from 12 providers. DR DNASU; 57462; -. DR Ensembl; ENST00000297625.8; ENSP00000297625.8; ENSG00000164976.10. DR GeneID; 57462; -. DR KEGG; hsa:57462; -. DR MANE-Select; ENST00000297625.8; ENSP00000297625.8; NM_020702.5; NP_065753.2. DR UCSC; uc033cpb.2; human. DR AGR; HGNC:19918; -. DR ClinPGx; PA134929853; -. DR CTD; 57462; -. DR DisGeNET; 57462; -. DR GeneCards; MYORG; -. DR HGNC; HGNC:19918; MYORG. DR HPA; ENSG00000164976; Tissue enhanced (skeletal). DR MalaCards; MYORG; -. DR MIM; 618255; gene. DR MIM; 618317; phenotype. DR OpenTargets; ENSG00000164976; -. DR Orphanet; 1980; Bilateral striopallidodentate calcinosis. DR VEuPathDB; HostDB:ENSG00000164976; -. DR eggNOG; KOG1065; Eukaryota. DR GeneTree; ENSGT00940000161008; -. DR HOGENOM; CLU_008294_0_0_1; -. DR InParanoid; Q6NSJ0; -. DR OMA; AFFTWVH; -. DR OrthoDB; 10070917at2759; -. DR PAN-GO; Q6NSJ0; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q6NSJ0; -. DR PathwayCommons; Q6NSJ0; -. DR SignaLink; Q6NSJ0; -. DR Agora; ENSG00000164976; -. DR BioGRID-ORCS; 57462; 9 hits in 392 CRISPR screens. DR ChiTaRS; MYORG; human. DR GenomeRNAi; 57462; -. DR Pharos; Q6NSJ0; Tbio. DR PRO; PR:Q6NSJ0; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; Q6NSJ0; protein. DR Bgee; ENSG00000164976; Expressed in ventricular zone and 122 other cell types or tissues. DR ExpressionAtlas; Q6NSJ0; baseline and differential. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB. DR GO; GO:0004557; F:alpha-galactosidase activity; IDA:UniProtKB. DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro. DR GO; GO:0043568; P:positive regulation of insulin-like growth factor receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISS:UniProtKB. DR GO; GO:0048741; P:skeletal muscle fiber development; IMP:UniProtKB. DR CDD; cd06592; GH31_NET37; 1. DR FunFam; 2.60.40.1180:FF:000006; Putative family 31 glucosidase KIAA1161; 1. DR FunFam; 3.20.20.80:FF:000037; Putative family 31 glucosidase KIAA1161; 1. DR Gene3D; 3.20.20.80; Glycosidases; 1. DR Gene3D; 2.60.40.1180; Golgi alpha-mannosidase II; 1. DR InterPro; IPR050985; Alpha-glycosidase_related. DR InterPro; IPR017853; GH. DR InterPro; IPR048395; Glyco_hydro_31_C. DR InterPro; IPR000322; Glyco_hydro_31_TIM. DR InterPro; IPR013780; Glyco_hydro_b. DR PANTHER; PTHR43053; GLYCOSIDASE FAMILY 31; 1. DR PANTHER; PTHR43053:SF4; MYOGENESIS-REGULATING GLYCOSIDASE; 1. DR Pfam; PF01055; Glyco_hydro_31_2nd; 2. DR Pfam; PF21365; Glyco_hydro_31_3rd; 1. DR SUPFAM; SSF51445; (Trans)glycosidases; 1. DR SUPFAM; SSF51011; Glycosyl hydrolase domain; 1. PE 1: Evidence at protein level; KW 3D-structure; Disease variant; Disulfide bond; Endoplasmic reticulum; KW Glycoprotein; Glycosidase; Hydrolase; Membrane; Nucleus; KW Proteomics identification; Reference proteome; Signal-anchor; KW Transmembrane; Transmembrane helix. FT CHAIN 1..714 FT /note="Alpha-galactosidase MYORG" FT /id="PRO_0000295752" FT TOPO_DOM 1..56 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q69ZQ1" FT TRANSMEM 57..77 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255" FT TOPO_DOM 78..714 FT /note="Lumenal" FT /evidence="ECO:0000250|UniProtKB:Q69ZQ1" FT ACT_SITE 463 FT /note="Nucleophile" FT /evidence="ECO:0000305|PubMed:36129849" FT ACT_SITE 520 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000305|PubMed:36129849" FT BINDING 213 FT /ligand="an alpha-D-galactoside" FT /ligand_id="ChEBI:CHEBI:46953" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQH" FT BINDING 353 FT /ligand="an alpha-D-galactoside" FT /ligand_id="ChEBI:CHEBI:46953" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQH" FT BINDING 354 FT /ligand="an alpha-D-galactoside" FT /ligand_id="ChEBI:CHEBI:46953" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQH" FT BINDING 426 FT /ligand="an alpha-D-galactoside" FT /ligand_id="ChEBI:CHEBI:46953" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQH" FT BINDING 461 FT /ligand="an alpha-D-galactoside" FT /ligand_id="ChEBI:CHEBI:46953" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQH" FT BINDING 504 FT /ligand="an alpha-D-galactoside" FT /ligand_id="ChEBI:CHEBI:46953" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQH" FT BINDING 517 FT /ligand="an alpha-D-galactoside" FT /ligand_id="ChEBI:CHEBI:46953" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQH" FT BINDING 520 FT /ligand="an alpha-D-galactoside" FT /ligand_id="ChEBI:CHEBI:46953" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQH" FT CARBOHYD 240 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQF, ECO:0007744|PDB:7QQG, FT ECO:0007744|PDB:7QQH" FT CARBOHYD 250 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQH" FT CARBOHYD 346 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQF, ECO:0007744|PDB:7QQG, FT ECO:0007744|PDB:7QQH" FT CARBOHYD 372 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQF, ECO:0007744|PDB:7QQG" FT CARBOHYD 398 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQF, ECO:0007744|PDB:7QQG" FT CARBOHYD 511 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQF, ECO:0007744|PDB:7QQG, FT ECO:0007744|PDB:7QQH" FT DISULFID 125..134 FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQF, ECO:0007744|PDB:7QQG, FT ECO:0007744|PDB:7QQH" FT DISULFID 158..284 FT /evidence="ECO:0000269|PubMed:36129849, FT ECO:0007744|PDB:7QQF, ECO:0007744|PDB:7QQG, FT ECO:0007744|PDB:7QQH" FT VARIANT 4 FT /note="N -> I (in dbSNP:rs2297776)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_033359" FT VARIANT 35 FT /note="M -> V (in IBGC7; dbSNP:rs765483979)" FT /evidence="ECO:0000269|PubMed:29910000" FT /id="VAR_081940" FT VARIANT 53 FT /note="D -> E (in dbSNP:rs4879781)" FT /evidence="ECO:0000269|PubMed:10574461, FT ECO:0000269|PubMed:15489334" FT /id="VAR_033360" FT VARIANT 64 FT /note="G -> E (in IBGC7; uncertain significance; FT dbSNP:rs756514041)" FT /evidence="ECO:0000269|PubMed:31009047" FT /id="VAR_081941" FT VARIANT 75..714 FT /note="Missing (in IBGC7)" FT /evidence="ECO:0000269|PubMed:29910000" FT /id="VAR_081942" FT VARIANT 113 FT /note="L -> R (in IBGC7; uncertain significance; FT dbSNP:rs753277260)" FT /evidence="ECO:0000269|PubMed:31009047" FT /id="VAR_081943" FT VARIANT 116 FT /note="R -> RLAFR (in IBGC7)" FT /evidence="ECO:0000269|PubMed:29910000, FT ECO:0000269|PubMed:30589467, ECO:0000269|PubMed:31009047" FT /id="VAR_081944" FT VARIANT 143..147 FT /note="Missing (in IBGC7; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30589467" FT /id="VAR_081945" FT VARIANT 199 FT /note="R -> S (in dbSNP:rs12377)" FT /id="VAR_033361" FT VARIANT 203..714 FT /note="Missing (in IBGC7)" FT /evidence="ECO:0000269|PubMed:29910000" FT /id="VAR_081946" FT VARIANT 229 FT /note="W -> C (in IBGC7; uncertain significance; FT dbSNP:rs1588004637)" FT /evidence="ECO:0000269|PubMed:30589467" FT /id="VAR_081947" FT VARIANT 232 FT /note="S -> L (in IBGC7; uncertain significance; FT dbSNP:rs757434146)" FT /evidence="ECO:0000269|PubMed:29910000" FT /id="VAR_081948" FT VARIANT 236 FT /note="A -> AA (in IBGC7; uncertain significance)" FT /evidence="ECO:0000269|PubMed:31009047" FT /id="VAR_081949" FT VARIANT 249 FT /note="W -> C (in IBGC7; uncertain significance; FT dbSNP:rs1356560096)" FT /evidence="ECO:0000269|PubMed:31009047" FT /id="VAR_081950" FT VARIANT 261 FT /note="R -> L (in IBGC7; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29910000" FT /id="VAR_081951" FT VARIANT 354 FT /note="Missing (in IBGC7; uncertain significance; FT dbSNP:rs1180204613)" FT /evidence="ECO:0000269|PubMed:30656188" FT /id="VAR_081952" FT VARIANT 365..366 FT /note="Missing (in IBGC7; uncertain significance)" FT /evidence="ECO:0000269|PubMed:29910000" FT /id="VAR_081953" FT VARIANT 373 FT /note="A -> D (in IBGC7; uncertain significance; FT dbSNP:rs1588004082)" FT /evidence="ECO:0000269|PubMed:31009047" FT /id="VAR_081954" FT VARIANT 385 FT /note="F -> Y (in dbSNP:rs7852399)" FT /id="VAR_033362" FT VARIANT 434 FT /note="D -> H (in IBGC7; uncertain significance; FT dbSNP:rs916933188)" FT /evidence="ECO:0000269|PubMed:31009047" FT /id="VAR_081955" FT VARIANT 441 FT /note="R -> G (in IBGC7; dbSNP:rs749427106)" FT /evidence="ECO:0000269|PubMed:29910000" FT /id="VAR_081956" FT VARIANT 443..714 FT /note="Missing (in IBGC7)" FT /evidence="ECO:0000269|PubMed:29910000" FT /id="VAR_081957" FT VARIANT 445..714 FT /note="Missing (in IBGC7)" FT /evidence="ECO:0000269|PubMed:30460687, FT ECO:0000269|PubMed:31009047" FT /id="VAR_081958" FT VARIANT 476 FT /note="T -> N (in IBGC7; uncertain significance; FT dbSNP:rs769099047)" FT /evidence="ECO:0000269|PubMed:31009047" FT /id="VAR_081959" FT VARIANT 477..714 FT /note="Missing (in IBGC7)" FT /evidence="ECO:0000269|PubMed:30589467" FT /id="VAR_081960" FT VARIANT 513 FT /note="Missing (in IBGC7; uncertain significance)" FT /evidence="ECO:0000269|PubMed:31009047" FT /id="VAR_081961" FT VARIANT 611 FT /note="R -> W (in IBGC7; uncertain significance; FT dbSNP:rs536187898)" FT /evidence="ECO:0000269|PubMed:31009047" FT /id="VAR_081962" FT VARIANT 622 FT /note="L -> P (in IBGC7; uncertain significance; FT dbSNP:rs1239594469)" FT /evidence="ECO:0000269|PubMed:31009047" FT /id="VAR_081963" FT VARIANT 656 FT /note="I -> T (in IBGC7; uncertain significance; FT dbSNP:rs370944350)" FT /evidence="ECO:0000269|PubMed:31009047" FT /id="VAR_081964" FT VARIANT 660 FT /note="L -> Q (in IBGC7; uncertain significance; FT dbSNP:rs1588002920)" FT /evidence="ECO:0000269|PubMed:31009047" FT /id="VAR_081965" FT MUTAGEN 463 FT /note="D->A: Does not change nuclear membrane localization. FT Does not rescue the myogenetic defect induced by depletion FT of endogenous MYORG." FT /evidence="ECO:0000269|PubMed:19706595" FT STRAND 93..96 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 99..103 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 109..117 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 122..124 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 125..128 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 131..137 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 142..153 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 156..164 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 166..168 FT /evidence="ECO:0007829|PDB:7QQF" FT STRAND 172..177 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 185..189 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 202..208 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 214..216 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 218..220 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 223..231 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 234..239 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 245..250 FT /evidence="ECO:0007829|PDB:7QQH" FT TURN 251..254 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 255..260 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 263..266 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 278..285 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 289..300 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 310..313 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 317..320 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 321..324 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 325..327 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 330..342 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 350..352 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 357..359 FT /evidence="ECO:0007829|PDB:7QQH" FT TURN 367..369 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 373..382 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 387..391 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 393..396 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 402..408 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 417..420 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 423..425 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 428..433 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 438..455 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 459..462 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 467..469 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 485..491 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 492..500 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 502..504 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 506..508 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 514..517 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 523..526 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 531..533 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 534..543 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 548..550 FT /evidence="ECO:0007829|PDB:7QQH" FT TURN 564..567 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 571..581 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 584..586 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 588..591 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 593..595 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 598..613 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 615..629 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 633..635 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 637..639 FT /evidence="ECO:0007829|PDB:7QQH" FT HELIX 645..649 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 654..656 FT /evidence="ECO:0007829|PDB:7QQH" FT TURN 657..659 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 660..663 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 671..677 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 679..684 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 694..701 FT /evidence="ECO:0007829|PDB:7QQH" FT STRAND 708..713 FT /evidence="ECO:0007829|PDB:7QQH" SQ SEQUENCE 714 AA; 81087 MW; D17E4A75A81DBB46 CRC64; MLQNPQEKSQ AYPRRRRPGC YAYRQNPEAI AAAAMYTFLP DNFSPAKPKP SKDLKPLLGS AVLGLLLVLA AVVAWCYYSV SLRKAERLRA ELLDLKAGGF SIRNQKGEQV FRLAFRSGAL DLDSCSRDGA LLGCSLTADG LPLHFFIQTV RPKDTVMCYR VRWEEAAPGR AVEHAMFLGD AAAHWYGGAE MRTQHWPIRL DGQQEPQPFV TSDVYSSDAA FGGILERYWL SSRAAAIKVN DSVPFHLGWN STERSLRLQA RYHDTPYKPP AGRAAAPELS YRVCVGSDVT SIHKYMVRRY FNKPSRVPAP EAFRDPIWST WALYGRAVDQ DKVLRFAQQI RLHHFNSSHL EIDDMYTPAY GDFDFDEVKF PNASDMFRRL RDAGFRVTLW VHPFVNYNSS RFGEGVEREL FVREPTGRLP ALVRWWNGIG AVLDFTHPKA RDWFQGHLRR LRSRYSVASF KFDAGEVSYL PRDFSTYRPL PDPSVWSRRY TEMALPFFSL AEVRVGYQSQ NISCFFRLVD RDSVWGYDLG LRSLIPAVLT VSMLGYPFIL PDMVGGNAVP QRTAGGDVPE RELYIRWLEV AAFMPAMQFS IPPWRYDAEV VAIAQKFAAL RASLVAPLLL ELAGEVTDTG DPIVRPLWWI APGDETAHRI DSQFLIGDTL LVAPVLEPGK QERDVYLPAG KWRSYKGELF DKTPVLLTDY PVDLDEIAYF TWAS // ID NAA60_HUMAN Reviewed; 242 AA. AC Q9H7X0; B3KRQ0; B4DLZ0; B4DPZ8; B4DYC4; D3DUC2; E7EQ65; Q6IA31; Q6UX26; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 28-JAN-2026, entry version 163. DE RecName: Full=N-alpha-acetyltransferase 60 {ECO:0000303|PubMed:25732826, ECO:0000312|HGNC:HGNC:25875}; DE Short=hNaa60 {ECO:0000303|PubMed:27320834, ECO:0000303|PubMed:27550639}; DE EC=2.3.1.259 {ECO:0000269|PubMed:25732826}; DE AltName: Full=Histone acetyltransferase type B protein 4 {ECO:0000303|PubMed:21981917}; DE Short=HAT4 {ECO:0000303|PubMed:21981917}; DE EC=2.3.1.48 {ECO:0000305|PubMed:21981917}; DE AltName: Full=N-acetyltransferase 15; DE AltName: Full=N-alpha-acetyltransferase F; DE Short=NatF; GN Name=NAA60 {ECO:0000303|PubMed:25732826, ECO:0000312|HGNC:HGNC:25875}; GN Synonyms=HAT4 {ECO:0000303|PubMed:21981917}, NAT15; GN ORFNames=UNQ2771/PRO7155; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2; 3; 4 AND 5). RC TISSUE=Fetal brain, Mesangial cell, 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 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.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] (ISOFORM 1). 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 [7] RP IMPRINTING, AND INDUCTION. RX PubMed=21593219; DOI=10.1093/hmg/ddr224; RA Nakabayashi K., Trujillo A.M., Tayama C., Camprubi C., Yoshida W., RA Lapunzina P., Sanchez A., Soejima H., Aburatani H., Nagae G., Ogata T., RA Hata K., Monk D.; RT "Methylation screening of reciprocal genome-wide UPDs identifies novel RT human-specific imprinted genes."; RL Hum. Mol. Genet. 20:3188-3197(2011). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACETYLATION AT LYS-79; RP LYS-105; LYS-109; LYS-121 AND LYS-156, AND MUTAGENESIS OF LYS-79; LYS-105; RP LYS-109; GLY-111; LYS-121 AND LYS-156. RX PubMed=21981917; DOI=10.1016/j.molcel.2011.07.032; RA Yang X., Yu W., Shi L., Sun L., Liang J., Yi X., Li Q., Zhang Y., Yang F., RA Han X., Zhang D., Yang J., Yao Z., Shang Y.; RT "HAT4, a Golgi apparatus-anchored B-type histone acetyltransferase, RT acetylates free histone H4 and facilitates chromatin assembly."; RL Mol. Cell 44:39-50(2011). RN [9] RP FUNCTION. RX PubMed=21750686; DOI=10.1371/journal.pgen.1002169; RA Van Damme P., Hole K., Pimenta-Marques A., Helsens K., Vandekerckhove J., RA Martinho R.G., Gevaert K., Arnesen T.; RT "NatF contributes to an evolutionary shift in protein N-terminal RT acetylation and is important for normal chromosome segregation."; RL PLoS Genet. 7:E1002169-E1002169(2011). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TOPOLOGY, AND RP MUTAGENESIS OF CYS-19; CYS-30; CYS-132; CYS-207; 221-LEU-LEU-222 AND RP CYS-222. RX PubMed=25732826; DOI=10.1016/j.celrep.2015.01.053; RA Aksnes H., Van Damme P., Goris M., Starheim K.K., Marie M., Stoeve S.I., RA Hoel C., Kalvik T.V., Hole K., Glomnes N., Furnes C., Ljostveit S., RA Ziegler M., Niere M., Gevaert K., Arnesen T.; RT "An organellar nalpha-acetyltransferase, naa60, acetylates cytosolic N RT termini of transmembrane proteins and maintains Golgi integrity."; RL Cell Rep. 10:1362-1374(2015). RN [11] RP INVOLVEMENT IN IBGC9, VARIANTS IBGC9 ARG-17; CYS-44; TYR-131 AND THR-143, RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS IBGC9 RP ARG-17; CYS-44; TYR-131 AND THR-143. RX PubMed=38480682; DOI=10.1038/s41467-024-46354-0; RA Chelban V., Aksnes H., Maroofian R., LaMonica L.C., Seabra L., RA Siggervaag A., Devic P., Shamseldin H.E., Vandrovcova J., Murphy D., RA Richard A.C., Quenez O., Bonnevalle A., Zanetti M.N., Kaiyrzhanov R., RA Salpietro V., Efthymiou S., Schottlaender L.V., Morsy H., Scardamaglia A., RA Tariq A., Pagnamenta A.T., Pennavaria A., Krogstad L.S., Bekkelund A.K., RA Caiella A., Glomnes N., Broenstad K.M., Tury S., Moreno De Luca A., RA Boland-Auge A., Olaso R., Deleuze J.F., Anheim M., Cretin B., Vona B., RA Alajlan F., Abdulwahab F., Battini J.L., Ipek R., Bauer P., Zifarelli G., RA Gungor S., Kurul S.H., Lochmuller H., Da'as S.I., Fakhro K.A., RA Gomez-Pascual A., Botia J.A., Wood N.W., Horvath R., Ernst A.M., RA Rothman J.E., McEntagart M., Crow Y.J., Alkuraya F.S., Nicolas G., RA Arnesen T., Houlden H.; RT "Biallelic NAA60 variants with impaired n-terminal acetylation capacity RT cause autosomal recessive primary familial brain calcifications."; RL Nat. Commun. 15:2269-2269(2024). RN [12] {ECO:0000312|PDB:5HGZ, ECO:0000312|PDB:5HH0, ECO:0000312|PDB:5HH1} RP X-RAY CRYSTALLOGRAPHY (1.38 ANGSTROMS) OF 4-242 IN COMPLEX WITH ACETYL-COA, RP FUNCTION, ACTIVE SITES, AND MUTAGENESIS OF PHE-34; GLU-37; TYR-38; LYS-79; RP GLU-80; ASP-81; ASP-83; TYR-97; HIS-138; ASN-143 AND TYR-165. RX PubMed=27550639; DOI=10.1038/srep31425; RA Chen J.Y., Liu L., Cao C.L., Li M.J., Tan K., Yang X., Yun C.H.; RT "Structure and function of human Naa60 (NatF), a Golgi-localized bi- RT functional acetyltransferase."; RL Sci. Rep. 6:31425-31425(2016). RN [13] {ECO:0000312|PDB:5ICV, ECO:0000312|PDB:5ICW} RP X-RAY CRYSTALLOGRAPHY (1.53 ANGSTROMS) OF 3-184 IN COMPLEX WITH ACETYL-COA RP AND SUBSTRATE, FUNCTION, ACTIVE SITES, SUBUNIT, AND MUTAGENESIS OF PRO-35; RP ILE-36; TYR-38; ASP-81; ILE-84; TYR-97; HIS-138; LEU-140; TYR-164; TYR-165 RP AND ILE-167. RX PubMed=27320834; DOI=10.1016/j.str.2016.04.020; RA Stoeve S.I., Magin R.S., Foyn H., Haug B.E., Marmorstein R., Arnesen T.; RT "Crystal structure of the Golgi-associated human Nalpha-Acetyltransferase RT 60 Reveals the molecular determinants for substrate-specific acetylation."; RL Structure 24:1044-1056(2016). CC -!- FUNCTION: N-alpha-acetyltransferase that specifically mediates the CC acetylation of N-terminal residues of the transmembrane proteins, with CC a strong preference for N-termini facing the cytosol (PubMed:25732826, CC PubMed:38480682). Displays N-terminal acetyltransferase activity CC towards a range of N-terminal sequences including those starting with CC Met-Lys, Met-Val, Met-Ala and Met-Met (PubMed:21750686, CC PubMed:25732826, PubMed:27320834, PubMed:27550639). Required for normal CC chromosomal segregation during anaphase (PubMed:21750686). May also CC show histone acetyltransferase activity; such results are however CC unclear in vivo and would require additional experimental evidences CC (PubMed:21981917). {ECO:0000269|PubMed:21750686, CC ECO:0000269|PubMed:25732826, ECO:0000269|PubMed:27320834, CC ECO:0000269|PubMed:27550639, ECO:0000269|PubMed:38480682, CC ECO:0000305|PubMed:21981917}. CC -!- CATALYTIC ACTIVITY: CC Reaction=N-terminal L-methionyl-[transmembrane protein] + acetyl-CoA = CC N-terminal N(alpha)-acetyl-L-methionyl-[transmembrane protein] + CoA CC + H(+); Xref=Rhea:RHEA:50604, Rhea:RHEA-COMP:12745, Rhea:RHEA- CC COMP:12746, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, CC ChEBI:CHEBI:64731, ChEBI:CHEBI:133414; EC=2.3.1.259; CC Evidence={ECO:0000269|PubMed:25732826}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] CC + CoA + H(+); Xref=Rhea:RHEA:45948, Rhea:RHEA-COMP:9752, Rhea:RHEA- CC COMP:10731, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57287, CC ChEBI:CHEBI:57288, ChEBI:CHEBI:61930; EC=2.3.1.48; CC Evidence={ECO:0000305|PubMed:21981917}; CC -!- SUBUNIT: Monomer and homodimer; monomer in presence of substrate and CC homodimer in its absence (PubMed:27320834). CC {ECO:0000269|PubMed:27320834}. CC -!- INTERACTION: CC Q9H7X0; P55212: CASP6; NbExp=3; IntAct=EBI-12260336, EBI-718729; CC Q9H7X0; P13473-2: LAMP2; NbExp=3; IntAct=EBI-12260336, EBI-21591415; CC Q9H7X0; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-12260336, EBI-16439278; CC Q9H7X0; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-12260336, EBI-5280197; CC Q9H7X0; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-12260336, EBI-2623095; CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000269|PubMed:21981917, ECO:0000269|PubMed:25732826, CC ECO:0000269|PubMed:38480682}; Peripheral membrane protein CC {ECO:0000269|PubMed:25732826}; Cytoplasmic side CC {ECO:0000269|PubMed:25732826}. Note=Probably forms an intramembrane CC hairpin-like structure in the membrane. {ECO:0000305|PubMed:25732826}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=Q9H7X0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H7X0-2; Sequence=VSP_044123; CC Name=3; CC IsoId=Q9H7X0-3; Sequence=VSP_044122; CC Name=4; CC IsoId=Q9H7X0-4; Sequence=VSP_044124; CC Name=5; CC IsoId=Q9H7X0-5; Sequence=VSP_044125; CC -!- INDUCTION: Isoform 2: Imprinted (PubMed:21593219). Promoter methylation CC of the paternal allele may restrict expression to the maternal allele CC in placenta and leukocytes (PubMed:21593219). Isoform 1: Biallelically CC expressed (PubMed:21593219). {ECO:0000269|PubMed:21593219}. CC -!- PTM: Acetylated: autoacetylation is required for optimal CC acetyltransferase activity. {ECO:0000269|PubMed:21981917}. CC -!- DISEASE: Basal ganglia calcification, idiopathic, 9, autosomal CC recessive (IBGC9) [MIM:620786]: A form of basal ganglia calcification, CC a genetically heterogeneous condition characterized by symmetric CC calcification in the basal ganglia and other brain regions. Affected CC individuals can either be asymptomatic or show a wide spectrum of CC neuropsychiatric symptoms, including parkinsonism, dystonia, tremor, CC ataxia, dementia, psychosis, seizures, and chronic headache. Serum CC levels of calcium, phosphate, alkaline phosphatase and parathyroid CC hormone are normal. The neuropathological hallmark of the disease is CC vascular and pericapillary calcification, mainly of calcium phosphate, CC in the affected brain areas. {ECO:0000269|PubMed:38480682}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 2]: In placenta and leukocytes, expressed from CC the maternal allele, due to imprinting of the paternal allele. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative splicing. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative splicing. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: Produced by alternative splicing. CC {ECO:0000305}. CC -!- SIMILARITY: Belongs to the acetyltransferase family. NAA60 subfamily. CC {ECO:0000305}. CC -!- CAUTION: According to a report, displays histone acetyltransferase CC activity while localized in the Golgi apparatus (PubMed:21981917). May CC mediate acetylation of free histone H4 and promote nucleosome assembly CC (PubMed:21981917). Such results are however unclear in vivo and recent CC reports strongly suggest that it acts as a N-alpha-acetyltransferase CC that specifically targets N-terminal residues of transmembrane proteins CC (PubMed:21750686, PubMed:25732826). {ECO:0000269|PubMed:21750686, CC ECO:0000269|PubMed:21981917, ECO:0000269|PubMed:25732826}. 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; AY358543; AAQ88907.1; -; mRNA. DR EMBL; AK024216; BAB14853.1; -; mRNA. DR EMBL; AK092005; BAG52462.1; -; mRNA. DR EMBL; AK297219; BAG59702.1; -; mRNA. DR EMBL; AK298566; BAG60760.1; -; mRNA. DR EMBL; AK302361; BAG63686.1; -; mRNA. DR EMBL; CR457324; CAG33605.1; -; mRNA. DR EMBL; AC004224; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC025283; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471112; EAW85358.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85359.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85360.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85361.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85362.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85363.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85364.1; -; Genomic_DNA. DR EMBL; BC011267; AAH11267.1; -; mRNA. DR CCDS; CCDS45396.1; -. [Q9H7X0-1] DR CCDS; CCDS81937.1; -. [Q9H7X0-2] DR CCDS; CCDS81938.1; -. [Q9H7X0-5] DR CCDS; CCDS81939.1; -. [Q9H7X0-4] DR CCDS; CCDS81941.1; -. [Q9H7X0-3] DR RefSeq; NP_001077069.1; NM_001083600.3. [Q9H7X0-1] DR RefSeq; NP_001077070.1; NM_001083601.3. [Q9H7X0-1] DR RefSeq; NP_001304022.1; NM_001317093.1. [Q9H7X0-2] DR RefSeq; NP_001304023.1; NM_001317094.1. DR RefSeq; NP_001304024.1; NM_001317095.2. [Q9H7X0-3] DR RefSeq; NP_001304025.1; NM_001317096.2. [Q9H7X0-5] DR RefSeq; NP_001304026.1; NM_001317097.2. [Q9H7X0-4] DR RefSeq; NP_001304027.1; NM_001317098.2. [Q9H7X0-4] DR RefSeq; NP_079121.1; NM_024845.4. [Q9H7X0-1] DR PDB; 5HGZ; X-ray; 1.38 A; A=4-242. DR PDB; 5HH0; X-ray; 1.60 A; A=4-199. DR PDB; 5HH1; X-ray; 1.80 A; A=4-199. DR PDB; 5ICV; X-ray; 1.53 A; A/B=5-184. DR PDB; 5ICW; X-ray; 1.95 A; A/B/C/D=3-184. DR PDBsum; 5HGZ; -. DR PDBsum; 5HH0; -. DR PDBsum; 5HH1; -. DR PDBsum; 5ICV; -. DR PDBsum; 5ICW; -. DR AlphaFoldDB; Q9H7X0; -. DR SMR; Q9H7X0; -. DR BioGRID; 122986; 47. DR DIP; DIP-62077N; -. DR FunCoup; Q9H7X0; 1077. DR IntAct; Q9H7X0; 6. DR MINT; Q9H7X0; -. DR STRING; 9606.ENSP00000401237; -. DR ChEMBL; CHEMBL4630856; -. DR iPTMnet; Q9H7X0; -. DR PhosphoSitePlus; Q9H7X0; -. DR SwissPalm; Q9H7X0; -. DR BioMuta; NAA60; -. DR DMDM; 74733721; -. DR jPOST; Q9H7X0; -. DR MassIVE; Q9H7X0; -. DR PaxDb; 9606-ENSP00000385903; -. DR PeptideAtlas; Q9H7X0; -. DR ProteomicsDB; 17514; -. DR ProteomicsDB; 5517; -. DR ProteomicsDB; 81152; -. [Q9H7X0-1] DR Pumba; Q9H7X0; -. DR Antibodypedia; 24137; 148 antibodies from 19 providers. DR DNASU; 79903; -. DR Ensembl; ENST00000360862.9; ENSP00000354108.5; ENSG00000122390.20. [Q9H7X0-3] DR Ensembl; ENST00000407558.9; ENSP00000385903.4; ENSG00000122390.20. [Q9H7X0-1] DR Ensembl; ENST00000414063.6; ENSP00000393224.2; ENSG00000122390.20. [Q9H7X0-1] DR Ensembl; ENST00000421765.7; ENSP00000405873.3; ENSG00000122390.20. [Q9H7X0-5] DR Ensembl; ENST00000424546.6; ENSP00000401237.2; ENSG00000122390.20. [Q9H7X0-2] DR Ensembl; ENST00000570819.5; ENSP00000460763.1; ENSG00000122390.20. [Q9H7X0-4] DR Ensembl; ENST00000572169.6; ENSP00000458928.2; ENSG00000122390.20. [Q9H7X0-1] DR Ensembl; ENST00000572584.2; ENSP00000459057.1; ENSG00000122390.20. [Q9H7X0-1] DR Ensembl; ENST00000572942.5; ENSP00000461730.1; ENSG00000122390.20. [Q9H7X0-4] DR Ensembl; ENST00000573580.5; ENSP00000459055.1; ENSG00000122390.20. [Q9H7X0-3] DR Ensembl; ENST00000575076.5; ENSP00000458667.1; ENSG00000122390.20. [Q9H7X0-1] DR Ensembl; ENST00000577013.6; ENSP00000458575.2; ENSG00000122390.20. [Q9H7X0-3] DR Ensembl; ENST00000649205.1; ENSP00000497988.1; ENSG00000122390.20. [Q9H7X0-1] DR Ensembl; ENST00000649360.1; ENSP00000497411.1; ENSG00000122390.20. [Q9H7X0-1] DR GeneID; 79903; -. DR KEGG; hsa:79903; -. DR MANE-Select; ENST00000407558.9; ENSP00000385903.4; NM_001083601.3; NP_001077070.1. DR UCSC; uc002cvg.3; human. [Q9H7X0-1] DR AGR; HGNC:25875; -. DR ClinPGx; PA164723438; -. DR CTD; 79903; -. DR DisGeNET; 79903; -. DR GeneCards; NAA60; -. DR HGNC; HGNC:25875; NAA60. DR HPA; ENSG00000122390; Low tissue specificity. DR MalaCards; NAA60; -. DR MIM; 614246; gene. DR MIM; 620786; phenotype. DR OpenTargets; ENSG00000122390; -. DR Orphanet; 1980; Bilateral striopallidodentate calcinosis. DR VEuPathDB; HostDB:ENSG00000122390; -. DR eggNOG; KOG3138; Eukaryota. DR GeneTree; ENSGT00390000008314; -. DR HOGENOM; CLU_1427523_0_0_1; -. DR InParanoid; Q9H7X0; -. DR OMA; IHFYKKM; -. DR OrthoDB; 47017at2759; -. DR PAN-GO; Q9H7X0; 6 GO annotations based on evolutionary models. DR PhylomeDB; Q9H7X0; -. DR BioCyc; MetaCyc:ENSG00000122390-MONOMER; -. DR BRENDA; 2.3.1.259; 2681. DR PathwayCommons; Q9H7X0; -. DR SignaLink; Q9H7X0; -. DR Agora; ENSG00000122390; -. DR BioGRID-ORCS; 79903; 11 hits in 1166 CRISPR screens. DR ChiTaRS; NAA60; human. DR GenomeRNAi; 79903; -. DR Pharos; Q9H7X0; Tbio. DR PRO; PR:Q9H7X0; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q9H7X0; protein. DR Bgee; ENSG00000122390; Expressed in pancreatic ductal cell and 198 other cell types or tissues. DR ExpressionAtlas; Q9H7X0; baseline and differential. DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB. DR GO; GO:0004402; F:histone acetyltransferase activity; IBA:GO_Central. DR GO; GO:0010485; F:histone H4 acetyltransferase activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0120518; F:protein N-terminal-methionine acetyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0004596; F:protein-N-terminal amino-acid acetyltransferase activity; IDA:UniProtKB. DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB. DR GO; GO:0007059; P:chromosome segregation; ISS:UniProtKB. DR GO; GO:0017196; P:N-terminal peptidyl-methionine acetylation; IDA:UniProtKB. DR GO; GO:0006474; P:N-terminal protein amino acid acetylation; IDA:UniProtKB. DR GO; GO:0006334; P:nucleosome assembly; IDA:UniProtKB. DR CDD; cd04301; NAT_SF; 1. DR FunFam; 3.40.630.30:FF:000028; N-alpha-acetyltransferase 60 isoform X1; 1. DR Gene3D; 3.40.630.30; -; 1. DR InterPro; IPR016181; Acyl_CoA_acyltransferase. DR InterPro; IPR000182; GNAT_dom. DR InterPro; IPR045141; NAA60-like. DR PANTHER; PTHR14744; N-ALPHA-ACETYLTRANSFERASE 60; 1. DR PANTHER; PTHR14744:SF15; N-ALPHA-ACETYLTRANSFERASE 60; 1. DR Pfam; PF00583; Acetyltransf_1; 1. DR SUPFAM; SSF55729; Acyl-CoA N-acyltransferases (Nat); 1. DR PROSITE; PS51186; GNAT; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Acyltransferase; Alternative promoter usage; KW Alternative splicing; Chromatin regulator; Chromosome partition; KW Golgi apparatus; Membrane; Proteomics identification; Reference proteome; KW Transferase. FT CHAIN 1..242 FT /note="N-alpha-acetyltransferase 60" FT /id="PRO_0000321566" FT TOPO_DOM 1..192 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:25732826" FT INTRAMEM 193..236 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:25732826" FT TOPO_DOM 237..242 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:25732826" FT DOMAIN 13..182 FT /note="N-acetyltransferase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00532" FT REGION 162..173 FT /note="Required for homodimerization" FT /evidence="ECO:0000269|PubMed:27320834" FT ACT_SITE 97 FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000269|PubMed:27550639" FT ACT_SITE 138 FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000269|PubMed:27550639" FT BINDING 38 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000312|PDB:5ICV, ECO:0000312|PDB:5ICW" FT BINDING 99 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000312|PDB:5ICV, ECO:0000312|PDB:5ICW" FT BINDING 101..103 FT /ligand="acetyl-CoA" FT /ligand_id="ChEBI:CHEBI:57288" FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000269|PubMed:27550639, ECO:0000312|PDB:5HGZ, FT ECO:0000312|PDB:5HH0, ECO:0000312|PDB:5HH1, FT ECO:0000312|PDB:5ICV, ECO:0000312|PDB:5ICW" FT BINDING 109..114 FT /ligand="acetyl-CoA" FT /ligand_id="ChEBI:CHEBI:57288" FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000269|PubMed:27550639, ECO:0000312|PDB:5HGZ, FT ECO:0000312|PDB:5HH0, ECO:0000312|PDB:5HH1, FT ECO:0000312|PDB:5ICV, ECO:0000312|PDB:5ICW" FT BINDING 143 FT /ligand="acetyl-CoA" FT /ligand_id="ChEBI:CHEBI:57288" FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000269|PubMed:27550639, ECO:0000312|PDB:5HGZ, FT ECO:0000312|PDB:5HH0, ECO:0000312|PDB:5HH1, FT ECO:0000312|PDB:5ICV, ECO:0000312|PDB:5ICW" FT BINDING 150..153 FT /ligand="acetyl-CoA" FT /ligand_id="ChEBI:CHEBI:57288" FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000269|PubMed:27550639, ECO:0000312|PDB:5HGZ, FT ECO:0000312|PDB:5HH0, ECO:0000312|PDB:5HH1, FT ECO:0000312|PDB:5ICV, ECO:0000312|PDB:5ICW" FT BINDING 165 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000312|PDB:5ICV, ECO:0000312|PDB:5ICW" FT SITE 34 FT /note="Required to position thioacetyl group" FT /evidence="ECO:0000269|PubMed:27550639" FT MOD_RES 79 FT /note="N6-acetyllysine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:21981917" FT MOD_RES 105 FT /note="N6-acetyllysine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:21981917" FT MOD_RES 109 FT /note="N6-acetyllysine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:21981917" FT MOD_RES 121 FT /note="N6-acetyllysine; by autocatalysis" FT /evidence="ECO:0000305|PubMed:21981917" FT MOD_RES 156 FT /note="N6-acetyllysine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:21981917" FT VAR_SEQ 1..65 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044122" FT VAR_SEQ 1..36 FT /note="MTEVVPSSALSEVSLRLLCHDDIDTVKHLCGDWFPI -> MFPRRRTERRLG FT DTGTRKKIAYRKAVPGGRKCGASLSWEKSSR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044123" FT VAR_SEQ 113..242 FT /note="GSLLLESLKDHISTTAQDHCKAIYLHVLTTNNTAINFYENRDFKQHHYLPYY FT YSIRGVLKDGFTYVLYINGGHPPWTILDYIQHLGSALASLSPCSIPHRVYRQAHSLLCS FT FLPWSGISSKSGIEYSRTM -> ESTARPTACSAASCHGRASLPRVASSTAGPCDVGWA FT AATRPHPSAARRARLPVHLTPSVFCKELPAI (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044124" FT VAR_SEQ 113..242 FT /note="GSLLLESLKDHISTTAQDHCKAIYLHVLTTNNTAINFYENRDFKQHHYLPYY FT YSIRGVLKDGFTYVLYINGGHPPWTILDYIQHLGSALASLSPCSIPHRVYRQAHSLLCS FT FLPWSGISSKSGIEYSRTM -> EPHGLHPAPGLCTSQPEPLLHSAQSLPPGPQPALQL FT PAMVGHLFQEWHRVQPDHVMSAGQPPPGPTLRPPAEPAFLSI (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044125" FT VARIANT 17 FT /note="L -> R (in IBGC9; uncertain significance; when FT transfected RPE-1 cells, does not affect subcellular FT localization to the Golgi apparatus)" FT /evidence="ECO:0000269|PubMed:38480682" FT /id="VAR_089549" FT VARIANT 44 FT /note="R -> C (in IBGC9; uncertain significance; decreased FT activity of N-terminal protein amino acid acetylation; when FT transfected RPE-1 cells, does not affect subcellular FT localization to the Golgi apparatus)" FT /evidence="ECO:0000269|PubMed:38480682" FT /id="VAR_089550" FT VARIANT 131 FT /note="H -> Y (in IBGC9; uncertain significance; decreased FT activity of N-terminal protein amino acid acetylation; when FT transfected RPE-1 cells, does not affect subcellular FT localization to the Golgi apparatus)" FT /evidence="ECO:0000269|PubMed:38480682" FT /id="VAR_089551" FT VARIANT 143 FT /note="N -> T (in IBGC9; uncertain significance; may FT strongly decrease protein expression levels; when FT transfected RPE-1 cells, does not affect subcellular FT localization to the Golgi apparatus)" FT /evidence="ECO:0000269|PubMed:38480682" FT /id="VAR_089552" FT VARIANT 218 FT /note="H -> Q (in dbSNP:rs34464545)" FT /id="VAR_060995" FT MUTAGEN 19 FT /note="C->S: Does not affect localization to the Golgi FT apparatus; when associated with S-30; S-132; S-207 and S- FT 222." FT /evidence="ECO:0000269|PubMed:25732826" FT MUTAGEN 30 FT /note="C->S: Does not affect localization to the Golgi FT apparatus; when associated with S-19; S-132; S-207 and S- FT 222." FT /evidence="ECO:0000269|PubMed:25732826" FT MUTAGEN 34 FT /note="F->A: Abolished acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:27550639" FT MUTAGEN 35 FT /note="P->A: Reduced acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:27320834" FT MUTAGEN 36 FT /note="I->A: Reduced acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:27320834" FT MUTAGEN 37 FT /note="E->A,F: Only slightly affects acetyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:27550639" FT MUTAGEN 38 FT /note="Y->A: Strongly reduced acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000269|PubMed:27550639" FT MUTAGEN 79 FT /note="K->A: Slightly reduced acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:27550639" FT MUTAGEN 79 FT /note="K->R,Q: Increased acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:27550639" FT MUTAGEN 79 FT /note="K->R: Decreased acetyltransferase activity; when FT associated with R-105, R-109, R-121 and R-156." FT /evidence="ECO:0000269|PubMed:21981917" FT MUTAGEN 80 FT /note="E->A: Slightly increased acetyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:27550639" FT MUTAGEN 81 FT /note="D->A: Slightly increased acetyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000269|PubMed:27550639" FT MUTAGEN 83 FT /note="D->A: Slightly increased acetyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:27550639" FT MUTAGEN 84 FT /note="I->A: Slightly altered acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:27320834" FT MUTAGEN 97 FT /note="Y->A,F: Abolished acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000269|PubMed:27550639" FT MUTAGEN 105 FT /note="K->R: Decreased acetyltransferase activity; when FT associated with R-79, R-109, R-121 and R-156." FT /evidence="ECO:0000269|PubMed:21981917" FT MUTAGEN 109 FT /note="K->R: Decreased acetyltransferase activity; when FT associated with R-79, R-105, R-121 and R-156." FT /evidence="ECO:0000269|PubMed:21981917" FT MUTAGEN 111 FT /note="G->A: Abolishes acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:21981917" FT MUTAGEN 121 FT /note="K->R: Decreased acetyltransferase activity; when FT associated with R-79, R-105, R-109 and R-156." FT /evidence="ECO:0000269|PubMed:21981917" FT MUTAGEN 132 FT /note="C->S: Does not affect localization to the Golgi FT apparatus; when associated with S-19; S-30; S-207 and S- FT 222." FT /evidence="ECO:0000269|PubMed:25732826" FT MUTAGEN 138 FT /note="H->A,F: Abolished acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000269|PubMed:27550639" FT MUTAGEN 140 FT /note="L->A: Decreased acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:27320834" FT MUTAGEN 143 FT /note="N->A: Strongly reduced acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:27550639" FT MUTAGEN 156 FT /note="K->R: Decreased histone acetyltransferase activity; FT when associated with R-79, R-105, R-109 and R-121." FT /evidence="ECO:0000269|PubMed:21981917" FT MUTAGEN 164 FT /note="Y->A,F: Slightly altered acetyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:27320834" FT MUTAGEN 165 FT /note="Y->A,F: Strongly reduced acetyltransferase FT activity." FT /evidence="ECO:0000269|PubMed:27320834, FT ECO:0000269|PubMed:27550639" FT MUTAGEN 167 FT /note="I->A: Reduced acetyltransferase activity." FT /evidence="ECO:0000269|PubMed:27320834" FT MUTAGEN 207 FT /note="C->S: Does not affect localization to the Golgi FT apparatus; when associated with S-19; S-30; S-132 and S- FT 222." FT /evidence="ECO:0000269|PubMed:25732826" FT MUTAGEN 220..221 FT /note="LL->AA: Does not affect localization to the Golgi FT apparatus." FT /evidence="ECO:0000269|PubMed:25732826" FT MUTAGEN 222 FT /note="C->S: Does not affect localization to the Golgi FT apparatus; when associated with S-19; S-30; S-132 and S- FT 207." FT /evidence="ECO:0000269|PubMed:25732826" FT CONFLICT 87 FT /note="S -> T (in Ref. 1; AAQ88907)" FT /evidence="ECO:0000305" FT CONFLICT 242 FT /note="M -> I (in Ref. 3; CAG33605)" FT /evidence="ECO:0000305" FT HELIX 3..9 FT /evidence="ECO:0007829|PDB:5HGZ" FT STRAND 12..17 FT /evidence="ECO:0007829|PDB:5HGZ" FT HELIX 20..22 FT /evidence="ECO:0007829|PDB:5HGZ" FT HELIX 23..33 FT /evidence="ECO:0007829|PDB:5HGZ" FT HELIX 40..48 FT /evidence="ECO:0007829|PDB:5HGZ" FT STRAND 52..59 FT /evidence="ECO:0007829|PDB:5HGZ" FT STRAND 62..73 FT /evidence="ECO:0007829|PDB:5HGZ" FT HELIX 74..76 FT /evidence="ECO:0007829|PDB:5HGZ" FT HELIX 79..81 FT /evidence="ECO:0007829|PDB:5HGZ" FT TURN 82..87 FT /evidence="ECO:0007829|PDB:5ICV" FT STRAND 94..103 FT /evidence="ECO:0007829|PDB:5HGZ" FT HELIX 105..107 FT /evidence="ECO:0007829|PDB:5HGZ" FT HELIX 112..128 FT /evidence="ECO:0007829|PDB:5HGZ" FT TURN 129..131 FT /evidence="ECO:0007829|PDB:5HGZ" FT STRAND 132..140 FT /evidence="ECO:0007829|PDB:5HGZ" FT HELIX 144..151 FT /evidence="ECO:0007829|PDB:5HGZ" FT TURN 152..154 FT /evidence="ECO:0007829|PDB:5HGZ" FT STRAND 156..167 FT /evidence="ECO:0007829|PDB:5HGZ" FT STRAND 170..180 FT /evidence="ECO:0007829|PDB:5HGZ" FT HELIX 190..201 FT /evidence="ECO:0007829|PDB:5HGZ" FT HELIX 206..208 FT /evidence="ECO:0007829|PDB:5HGZ" FT CONFLICT Q9H7X0-5:180 FT /note="R -> Q (in Ref. 2; BAG60760)" FT /evidence="ECO:0000305" SQ SEQUENCE 242 AA; 27451 MW; 11234F2C51DF55DE CRC64; MTEVVPSSAL SEVSLRLLCH DDIDTVKHLC GDWFPIEYPD SWYRDITSNK KFFSLAATYR GAIVGMIVAE IKNRTKIHKE DGDILASNFS VDTQVAYILS LGVVKEFRKH GIGSLLLESL KDHISTTAQD HCKAIYLHVL TTNNTAINFY ENRDFKQHHY LPYYYSIRGV LKDGFTYVLY INGGHPPWTI LDYIQHLGSA LASLSPCSIP HRVYRQAHSL LCSFLPWSGI SSKSGIEYSR TM // ID NDUAD_HUMAN Reviewed; 144 AA. AC Q9P0J0; B4DF76; K7EK58; Q6PKI0; Q9H2L3; Q9Y327; DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 28-JAN-2026, entry version 216. DE RecName: Full=NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13; DE AltName: Full=Cell death regulatory protein GRIM-19; DE AltName: Full=Complex I-B16.6; DE Short=CI-B16.6; DE AltName: Full=Gene associated with retinoic and interferon-induced mortality 19 protein; DE Short=GRIM-19; DE Short=Gene associated with retinoic and IFN-induced mortality 19 protein; DE AltName: Full=NADH-ubiquinone oxidoreductase B16.6 subunit; GN Name=NDUFA13; Synonyms=GRIM19; ORFNames=CDA016, CGI-39; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Mammary carcinoma; RX PubMed=10924506; DOI=10.1074/jbc.m003929200; RA Angell J.E., Lindner D.J., Shapiro P.S., Hofmann E.R., Kalvakolanu D.V.; RT "Identification of GRIM-19, a novel cell death-regulatory gene induced by RT the interferon-beta and retinoic acid combination, using a genetic RT approach."; RL J. Biol. Chem. 275:33416-33426(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Adrenal gland; RX PubMed=10931946; DOI=10.1073/pnas.160270997; RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J., RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., RA Chen M.-D., Chen J.-L.; RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis RT and full-length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=10810093; DOI=10.1101/gr.10.5.703; RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.; RT "Identification of novel human genes evolutionarily conserved in RT Caenorhabditis elegans by comparative proteomics."; RL Genome Res. 10:703-713(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pheochromocytoma; RA Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z.; RT "A novel gene expressed in human pheochromocytoma."; RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP INTERACTION WITH HHV-8 IRF1; HPV-16 E6 AND SV40 LT (MICROBIAL INFECTION). RX PubMed=12163600; DOI=10.1128/jvi.76.17.8797-8807.2002; RA Seo T., Lee D., Shim Y.S., Angell J.E., Chidambaram N.V., Kalvakolanu D.V., RA Choe J.; RT "Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated RT herpesvirus interacts with a cell death regulator, GRIM19, and inhibits RT interferon/retinoic acid-induced cell death."; RL J. Virol. 76:8797-8807(2002). RN [9] RP FUNCTION, INTERACTION WITH STAT3, AND SUBCELLULAR LOCATION. RX PubMed=12628925; DOI=10.1093/emboj/cdg135; RA Lufei C., Ma J., Huang G., Zhang T., Novotny-Diermayr V., Ong C.T., Cao X.; RT "GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via RT functional interaction."; RL EMBO J. 22:1325-1335(2003). RN [10] RP IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12611891; DOI=10.1074/jbc.c300064200; RA Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., RA Ghosh S.S., Capaldi R.A.; RT "The subunit composition of the human NADH dehydrogenase obtained by rapid RT one-step immunopurification."; RL J. Biol. Chem. 278:13619-13622(2003). RN [11] RP FUNCTION, AND INTERACTION WITH STAT3. RX PubMed=12867595; DOI=10.1073/pnas.1633516100; RA Zhang J., Yang J., Roy S.K., Tininini S., Hu J., Bromberg J.F., Poli V., RA Stark G.R., Kalvakolanu D.V.; RT "The cell death regulator GRIM-19 is an inhibitor of signal transducer and RT activator of transcription 3."; RL Proc. Natl. Acad. Sci. U.S.A. 100:9342-9347(2003). RN [12] RP SUBCELLULAR LOCATION. RX PubMed=15367666; DOI=10.1128/mcb.24.19.8447-8456.2004; RA Huang G., Lu H., Hao A., Ng D.C.H., Ponniah S., Guo K., Lufei C., Zeng Q., RA Cao X.; RT "GRIM-19, a cell death regulatory protein, is essential for assembly and RT function of mitochondrial complex I."; RL Mol. Cell. Biol. 24:8447-8456(2004). RN [13] RP SUBCELLULAR LOCATION, AND INTERACTION WITH OLFM4. RX PubMed=15059901; DOI=10.1158/0008-5472.can-03-3443; RA Zhang X., Huang Q., Yang Z., Li Y., Li C.-Y.; RT "GW112, a novel antiapoptotic protein that promotes tumor growth."; RL Cancer Res. 64:2474-2481(2004). RN [14] RP FUNCTION, AND INTERACTION WITH CARD15. RX PubMed=15753091; DOI=10.1074/jbc.m413776200; RA Barnich N., Hisamatsu T., Aguirre J.E., Xavier R., Reinecker H.-C., RA Podolsky D.K.; RT "GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as RT downstream effector of anti-bacterial function in intestinal epithelial RT cells."; RL J. Biol. Chem. 280:19021-19026(2005). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [17] RP FUNCTION, AND IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX. RX PubMed=27626371; DOI=10.1038/nature19754; RA Stroud D.A., Surgenor E.E., Formosa L.E., Reljic B., Frazier A.E., RA Dibley M.G., Osellame L.D., Stait T., Beilharz T.H., Thorburn D.R., RA Salim A., Ryan M.T.; RT "Accessory subunits are integral for assembly and function of human RT mitochondrial complex I."; RL Nature 538:123-126(2016). RN [18] RP VARIANTS ASN-5 AND PRO-115, AND INVOLVEMENT IN SUSCEPTIBILITY TO HURTHLE RP CELL THYROID CARCINOMA. RX PubMed=15841082; DOI=10.1038/sj.bjc.6602547; RA Maximo V., Botelho T., Capela J., Soares P., Lima J., Taveira A., Amaro T., RA Barbosa A.P., Preto A., Harach H.R., Williams D., Sobrinho-Simoes M.; RT "Somatic and germline mutation in GRIM-19, a dual function gene involved in RT mitochondrial metabolism and cell death, is linked to mitochondrion-rich RT (Hurthle cell) tumours of the thyroid."; RL Br. J. Cancer 92:1892-1898(2005). RN [19] RP VARIANT MC1DN28 HIS-57, INVOLVEMENT IN MC1DN28, AND CHARACTERIZATION OF RP VARIANT MC1DN28 HIS-57. RX PubMed=25901006; DOI=10.1093/hmg/ddv133; RA Angebault C., Charif M., Guegen N., Piro-Megy C., Mousson de Camaret B., RA Procaccio V., Guichet P.O., Hebrard M., Manes G., Leboucq N., Rivier F., RA Hamel C.P., Lenaers G., Roubertie A.; RT "Mutation in NDUFA13/GRIM19 leads to early onset hypotonia, dyskinesia and RT sensorial deficiencies, and mitochondrial complex I instability."; RL Hum. Mol. Genet. 24:3948-3955(2015). CC -!- FUNCTION: Accessory subunit of the mitochondrial membrane respiratory CC chain NADH dehydrogenase (Complex I), that is believed not to be CC involved in catalysis (PubMed:27626371). Complex I functions in the CC transfer of electrons from NADH to the respiratory chain. The immediate CC electron acceptor for the enzyme is believed to be ubiquinone CC (PubMed:27626371). Involved in the interferon/all-trans-retinoic acid CC (IFN/RA) induced cell death. This apoptotic activity is inhibited by CC interaction with viral IRF1. Prevents the transactivation of STAT3 CC target genes. May play a role in CARD15-mediated innate mucosal CC responses and serve to regulate intestinal epithelial cell responses to CC microbes (PubMed:15753091). {ECO:0000269|PubMed:12628925, CC ECO:0000269|PubMed:12867595, ECO:0000269|PubMed:15753091, CC ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: Complex I is composed of 45 different subunits CC (PubMed:27626371). Interacts with CARD15, but not with CARD4 CC (PubMed:12611891, PubMed:15753091). Interacts with STAT3, but not with CC STAT1, STAT2 and STAT5A (PubMed:12628925, PubMed:12867595). Interacts CC with OLFM4 (PubMed:15059901). {ECO:0000269|PubMed:12163600, CC ECO:0000269|PubMed:12611891, ECO:0000269|PubMed:12628925, CC ECO:0000269|PubMed:12867595, ECO:0000269|PubMed:15059901, CC ECO:0000269|PubMed:15753091, ECO:0000269|PubMed:27626371}. CC -!- SUBUNIT: (Microbial infection) Interacts with HHV-8 IRF1, in the CC nucleus, with HPV-16 E6 and SV40 LT (PubMed:12163600). CC {ECO:0000269|PubMed:12163600}. CC -!- INTERACTION: CC Q9P0J0; O43464: HTRA2; NbExp=8; IntAct=EBI-372742, EBI-517086; CC Q9P0J0; P42858: HTT; NbExp=4; IntAct=EBI-372742, EBI-466029; CC Q9P0J0; Q9HC29: NOD2; NbExp=6; IntAct=EBI-372742, EBI-7445625; CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000269|PubMed:12628925, ECO:0000269|PubMed:15059901, CC ECO:0000269|PubMed:15367666}; Single-pass membrane protein CC {ECO:0000255}; Matrix side. Nucleus {ECO:0000269|PubMed:12628925}. CC Note=Localizes mainly in the mitochondrion (PubMed:12628925). May be CC translocated into the nucleus upon IFN/RA treatment. CC {ECO:0000269|PubMed:12628925, ECO:0000269|PubMed:15059901}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9P0J0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9P0J0-2; Sequence=VSP_056644; CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in heart, CC skeletal muscle, liver, kidney and placenta. In intestinal mucosa, CC down-regulated in areas involved in Crohn disease and ulcerative CC colitis. {ECO:0000269|PubMed:10924506}. CC -!- DEVELOPMENTAL STAGE: Expressed in numerous fetal tissues. CC -!- INDUCTION: By IFNB1/IFN-beta combined with all-trans-retinoic acid CC (ATRA). CC -!- DISEASE: Hurthle cell thyroid carcinoma (HCTC) [MIM:607464]: A rare CC type of thyroid cancer accounting for only about 3-10% of all CC differentiated thyroid cancers. These neoplasms are considered a CC variant of follicular carcinoma of the thyroid and are referred to as CC follicular carcinoma, oxyphilic type. {ECO:0000269|PubMed:15841082}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- DISEASE: Mitochondrial complex I deficiency, nuclear type 28 (MC1DN28) CC [MIM:618249]: A form of mitochondrial complex I deficiency, the most CC common biochemical signature of mitochondrial disorders, a group of CC highly heterogeneous conditions characterized by defective oxidative CC phosphorylation, which collectively affects 1 in 5-10000 live births. CC Clinical disorders have variable severity, ranging from lethal neonatal CC disease to adult-onset neurodegenerative disorders. Phenotypes include CC macrocephaly with progressive leukodystrophy, non-specific CC encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh CC syndrome, Leber hereditary optic neuropathy, and some forms of CC Parkinson disease. MC1DN28 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:25901006}. CC Note=The disease may be caused by variants affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the complex I NDUFA13 subunit family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD27748.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAG44670.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAH00589.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF286697; AAG28167.1; -; mRNA. DR EMBL; AF155662; AAF67481.1; -; mRNA. DR EMBL; AF132973; AAD27748.1; ALT_INIT; mRNA. DR EMBL; AF261134; AAG44670.1; ALT_INIT; mRNA. DR EMBL; AK293965; BAG57337.1; -; mRNA. DR EMBL; AC011448; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000589; AAH00589.2; ALT_INIT; mRNA. DR EMBL; BC009189; AAH09189.1; -; mRNA. DR CCDS; CCDS12404.2; -. [Q9P0J0-1] DR RefSeq; NP_057049.5; NM_015965.6. [Q9P0J0-1] DR PDB; 5XTB; EM; 3.40 A; W=7-28. DR PDB; 5XTC; EM; 3.70 A; W=29-144. DR PDB; 5XTD; EM; 3.70 A; W=7-144. DR PDB; 5XTH; EM; 3.90 A; W=7-144. DR PDB; 5XTI; EM; 17.40 A; BW/W=7-144. DR PDB; 9CWT; EM; 3.44 A; W=1-144. DR PDBsum; 5XTB; -. DR PDBsum; 5XTC; -. DR PDBsum; 5XTD; -. DR PDBsum; 5XTH; -. DR PDBsum; 5XTI; -. DR PDBsum; 9CWT; -. DR AlphaFoldDB; Q9P0J0; -. DR EMDB; EMD-45974; -. DR SMR; Q9P0J0; -. DR BioGRID; 119270; 182. DR ComplexPortal; CPX-577; Mitochondrial respiratory chain complex I. DR CORUM; Q9P0J0; -. DR DIP; DIP-31180N; -. DR FunCoup; Q9P0J0; 2355. DR IntAct; Q9P0J0; 126. DR MINT; Q9P0J0; -. DR STRING; 9606.ENSP00000423673; -. DR BindingDB; Q9P0J0; -. DR ChEMBL; CHEMBL4105781; -. DR DrugBank; DB18773; Flurpiridaz F-18. DR DrugBank; DB00157; NADH. DR DrugCentral; Q9P0J0; -. DR iPTMnet; Q9P0J0; -. DR PhosphoSitePlus; Q9P0J0; -. DR SwissPalm; Q9P0J0; -. DR BioMuta; NDUFA13; -. DR DMDM; 20139242; -. DR jPOST; Q9P0J0; -. DR MassIVE; Q9P0J0; -. DR PaxDb; 9606-ENSP00000423673; -. DR PeptideAtlas; Q9P0J0; -. DR ProteomicsDB; 83552; -. [Q9P0J0-1] DR Pumba; Q9P0J0; -. DR TopDownProteomics; Q9P0J0-1; -. [Q9P0J0-1] DR Antibodypedia; 28492; 294 antibodies from 38 providers. DR DNASU; 51079; -. DR Ensembl; ENST00000507754.9; ENSP00000423673.1; ENSG00000186010.20. [Q9P0J0-1] DR GeneID; 51079; -. DR KEGG; hsa:51079; -. DR MANE-Select; ENST00000507754.9; ENSP00000423673.1; NM_015965.7; NP_057049.5. DR UCSC; uc021uqu.2; human. [Q9P0J0-1] DR AGR; HGNC:17194; -. DR ClinPGx; PA142671270; -. DR CTD; 51079; -. DR DisGeNET; 51079; -. DR GeneCards; NDUFA13; -. DR HGNC; HGNC:17194; NDUFA13. DR HPA; ENSG00000186010; Low tissue specificity. DR MalaCards; NDUFA13; -. DR MIM; 607464; phenotype. DR MIM; 609435; gene. DR MIM; 618249; phenotype. DR OpenTargets; ENSG00000186010; -. DR Orphanet; 146; Differentiated thyroid carcinoma. DR VEuPathDB; HostDB:ENSG00000186010; -. DR eggNOG; KOG3300; Eukaryota. DR GeneTree; ENSGT00390000000719; -. DR HOGENOM; CLU_119720_0_0_1; -. DR InParanoid; Q9P0J0; -. DR OrthoDB; 3308at2759; -. DR PAN-GO; Q9P0J0; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q9P0J0; -. DR BioCyc; MetaCyc:HS05364-MONOMER; -. DR PathwayCommons; Q9P0J0; -. DR Reactome; R-HSA-611105; Respiratory electron transport. DR Reactome; R-HSA-6799198; Complex I biogenesis. DR Reactome; R-HSA-9837999; Mitochondrial protein degradation. DR SignaLink; Q9P0J0; -. DR SIGNOR; Q9P0J0; -. DR Agora; ENSG00000186010; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 51079; 225 hits in 1162 CRISPR screens. DR ChiTaRS; NDUFA13; human. DR GeneWiki; NDUFA13; -. DR GenomeRNAi; 51079; -. DR Pharos; Q9P0J0; Tclin. DR PRO; PR:Q9P0J0; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q9P0J0; protein. DR Bgee; ENSG00000186010; Expressed in apex of heart and 99 other cell types or tissues. DR ExpressionAtlas; Q9P0J0; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:ComplexPortal. DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0098803; C:respiratory chain complex; IDA:UniProtKB. DR GO; GO:0045271; C:respiratory chain complex I; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB. DR GO; GO:0061133; F:endopeptidase activator activity; IC:ParkinsonsUK-UCL. DR GO; GO:0009060; P:aerobic respiration; NAS:ComplexPortal. DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:ParkinsonsUK-UCL. DR GO; GO:0071300; P:cellular response to retinoic acid; IDA:ParkinsonsUK-UCL. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0032981; P:mitochondrial respiratory chain complex I assembly; IMP:UniProtKB. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IGI:ParkinsonsUK-UCL. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IGI:ParkinsonsUK-UCL. DR GO; GO:0045039; P:protein insertion into mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0042776; P:proton motive force-driven mitochondrial ATP synthesis; NAS:ComplexPortal. DR InterPro; IPR009346; GRIM-19. DR PANTHER; PTHR12966:SF0; NADH DEHYDROGENASE [UBIQUINONE] 1 ALPHA SUBCOMPLEX SUBUNIT 13; 1. DR PANTHER; PTHR12966; NADH DEHYDROGENASE UBIQUINONE 1 ALPHA SUBCOMPLEX SUBUNIT 13; 1. DR Pfam; PF06212; GRIM-19; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; KW Disease variant; Electron transport; Host-virus interaction; Membrane; KW Mitochondrion; Mitochondrion inner membrane; Nucleus; KW Primary mitochondrial disease; Proteomics identification; KW Reference proteome; Respiratory chain; Transmembrane; Transmembrane helix; KW Transport. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q95KV7" FT CHAIN 2..144 FT /note="NADH dehydrogenase [ubiquinone] 1 alpha subcomplex FT subunit 13" FT /id="PRO_0000118804" FT TRANSMEM 30..51 FT /note="Helical" FT /evidence="ECO:0000255" FT REGION 102..144 FT /note="Important for inducing cell death" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:Q95KV7" FT VAR_SEQ 143..144 FT /note="YT -> ALELQPPLADMGRAELSSNATTSLVQRRKQAWGRQSWLEQIWNAGP FT VCQRLHRGGSRPGAGAAGGLSLWAAAARGAVRSC (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056644" FT VARIANT 5 FT /note="K -> N (in a Hurthle cell variant of papillary FT carcinoma sample; dbSNP:rs137852869)" FT /evidence="ECO:0000269|PubMed:15841082" FT /id="VAR_045984" FT VARIANT 57 FT /note="R -> H (in MC1DN28; reduced NDUFA13 protein level FT resulting in complex I instability; dbSNP:rs752513525)" FT /evidence="ECO:0000269|PubMed:25901006" FT /id="VAR_078938" FT VARIANT 115 FT /note="R -> P (in a Hurthle cell variant of papillary FT carcinoma sample)" FT /evidence="ECO:0000269|PubMed:15841082" FT /id="VAR_045985" FT CONFLICT 2 FT /note="A -> P (in Ref. 3)" FT /evidence="ECO:0000305" SQ SEQUENCE 144 AA; 16698 MW; 058F608B235FF856 CRC64; MAASKVKQDM PPPGGYGPID YKRNLPRRGL SGYSMLAIGI GTLIYGHWSI MKWNRERRRL QIEDFEARIA LLPLLQAETD RRTLQMLREN LEEEAIIMKD VPDWKVGESV FHTTRWVPPL IGELYGLRTT EEALHASHGF MWYT // ID PDE8B_HUMAN Reviewed; 885 AA. AC O95263; Q5J7V7; Q86XK8; Q8IUJ7; Q8IUJ8; Q8IUJ9; Q8IUK0; Q8N3T2; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 22-AUG-2003, sequence version 2. DT 28-JAN-2026, entry version 215. DE RecName: Full=High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B; DE Short=HsPDE8B; DE EC=3.1.4.53 {ECO:0000269|PubMed:12681444}; DE AltName: Full=Cell proliferation-inducing gene 22 protein; GN Name=PDE8B; ORFNames=PIG22; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 6), AND TISSUE RP SPECIFICITY. RX PubMed=12372422; DOI=10.1016/s0006-291x(02)02371-9; RA Hayashi M., Shimada Y., Nishimura Y., Hama T., Tanaka T.; RT "Genomic organization, chromosomal localization, and alternative splicing RT of the human phosphodiesterase 8B gene."; RL Biochem. Biophys. Res. Commun. 297:1253-1258(2002). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), CATALYTIC ACTIVITY, RP ACTIVITY REGULATION, AND TISSUE SPECIFICITY. RC TISSUE=Thyroid; RX PubMed=12681444; DOI=10.1016/s0898-6568(02)00146-8; RA Gamanuma M., Yuasa K., Sasaki T., Sakurai N., Kotera J., Omori K.; RT "Comparison of enzymatic characterization and gene organization of cyclic RT nucleotide phosphodiesterase 8 family in humans."; RL Cell. Signal. 15:565-574(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RA Kim J.W.; RT "Identification of a human proliferation-inducing gene."; RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases. RN [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 227-885 (ISOFORM 1). RX PubMed=9784418; DOI=10.1006/bbrc.1998.9379; RA Hayashi M., Matsushima K., Ohashi H., Tsunoda H., Murase S., Kawarada Y., RA Tanaka T.; RT "Molecular cloning and characterization of human PDE8B, a novel thyroid- RT specific isozyme of 3',5'-cyclic nucleotide phosphodiesterase."; RL Biochem. Biophys. Res. Commun. 250:751-756(1998). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 43-885 (ISOFORM 1). RC TISSUE=Amygdala; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-517, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP INVOLVEMENT IN ADSD1. RX PubMed=20085714; DOI=10.1016/j.ajhg.2009.12.003; RA Appenzeller S., Schirmacher A., Halfter H., Baumer S., Pendziwiat M., RA Timmerman V., De Jonghe P., Fekete K., Stogbauer F., Ludemann P., Hund M., RA Quabius E.S., Ringelstein E.B., Kuhlenbaumer G.; RT "Autosomal-dominant striatal degeneration is caused by a mutation in the RT phosphodiesterase 8B gene."; RL Am. J. Hum. Genet. 86:83-87(2010). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-517, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-517, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP VARIANT PPNAD3 PRO-305, AND CHARACTERIZATION OF VARIANT PPNAD3 PRO-305. RX PubMed=18431404; DOI=10.1038/ejhg.2008.85; RA Horvath A., Giatzakis C., Tsang K., Greene E., Osorio P., Boikos S., RA Libe R., Patronas Y., Robinson-White A., Remmers E., Bertherat J., RA Nesterova M., Stratakis C.A.; RT "A cAMP-specific phosphodiesterase (PDE8B) that is mutated in adrenal RT hyperplasia is expressed widely in human and mouse tissues: a novel PDE8B RT isoform in human adrenal cortex."; RL Eur. J. Hum. Genet. 16:1245-1253(2008). CC -!- FUNCTION: Hydrolyzes the second messenger cAMP, which is a key CC regulator of many important physiological processes. May be involved in CC specific signaling in the thyroid gland. CC -!- CATALYTIC ACTIVITY: CC Reaction=3',5'-cyclic AMP + H2O = AMP + H(+); Xref=Rhea:RHEA:25277, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58165, CC ChEBI:CHEBI:456215; EC=3.1.4.53; CC Evidence={ECO:0000269|PubMed:12681444}; CC -!- COFACTOR: CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; CC Evidence={ECO:0000250}; CC Note=Binds 2 divalent metal cations per subunit. Site 1 may CC preferentially bind zinc ions, while site 2 has a preference for CC magnesium and/or manganese ions. {ECO:0000250}; CC -!- ACTIVITY REGULATION: Inhibited by dipyridimole. Insensitive to CC selective PDE inhibitors including rolipram and milrinone as well as to CC the non-selective inhibitor, IBMX. Unaffected by cGMP. CC {ECO:0000269|PubMed:12681444}. CC -!- PATHWAY: Purine metabolism; 3',5'-cyclic AMP degradation; AMP from CC 3',5'-cyclic AMP: step 1/1. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=1; Synonyms=PDE8B1; CC IsoId=O95263-1; Sequence=Displayed; CC Name=2; Synonyms=PDE8B2, PDE8B3; CC IsoId=O95263-2; Sequence=VSP_008084; CC Name=3; Synonyms=PDE8B3; CC IsoId=O95263-3; Sequence=VSP_008085; CC Name=4; Synonyms=PDE8B4; CC IsoId=O95263-4; Sequence=VSP_008082; CC Name=5; CC IsoId=O95263-5; Sequence=VSP_008081; CC Name=6; Synonyms=PDE8B2; CC IsoId=O95263-6; Sequence=VSP_008083; CC -!- TISSUE SPECIFICITY: Abundantly expressed in the thyroid. Also very CC weakly expressed in brain, spinal cord and placenta. In the thyroid CC isoform 1 predominates, and isoforms 2 and 6 are also highly expressed. CC In the placenta isoforms 1 and 2 are expressed equally. In the brain CC isoform 2 predominates. {ECO:0000269|PubMed:12372422, CC ECO:0000269|PubMed:12681444}. CC -!- DOMAIN: Composed of a C-terminal catalytic domain containing two CC putative divalent metal sites and an N-terminal regulatory domain. CC -!- DISEASE: Striatal degeneration, autosomal dominant 1 (ADSD1) CC [MIM:609161]: A movement disorder affecting the striatal part of the CC basal ganglia and characterized by bradykinesia, dysarthria and muscle CC rigidity. These symptoms resemble idiopathic Parkinson disease, but CC tremor is not present. {ECO:0000269|PubMed:20085714}. Note=The disease CC is caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Primary pigmented nodular adrenocortical disease 3 (PPNAD3) CC [MIM:614190]: A rare bilateral adrenal defect causing ACTH-independent CC Cushing syndrome. Macroscopic appearance of the adrenals is CC characteristic with small pigmented micronodules observed in the CC cortex. Adrenal glands show overall normal size and weight, and CC multiple small yellow-to-dark brown nodules surrounded by a cortex with CC a uniform appearance. Microscopically, there are moderate diffuse CC cortical hyperplasia with mostly nonpigmented nodules, multiple CC capsular deficits and massive circumscribed and infiltrating extra- CC adrenal cortical excrescences with micronodules. Clinical CC manifestations of Cushing syndrome include facial and truncal obesity, CC abdominal striae, muscular weakness, osteoporosis, arterial CC hypertension, diabetes. {ECO:0000269|PubMed:18431404}. Note=The disease CC is caused by variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 1]: Major isoform. CC -!- SIMILARITY: Belongs to the cyclic nucleotide phosphodiesterase family. CC PDE8 subfamily. {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; AY129948; AAN71723.1; -; mRNA. DR EMBL; AY129949; AAN71724.1; -; mRNA. DR EMBL; AY129950; AAN71725.1; -; Genomic_DNA. DR EMBL; AY129950; AAN71726.1; -; Genomic_DNA. DR EMBL; AY129950; AAN71727.1; -; Genomic_DNA. DR EMBL; AB085824; BAC53762.1; -; mRNA. DR EMBL; AB085825; BAC53763.1; -; mRNA. DR EMBL; AB085826; BAC53764.1; -; mRNA. DR EMBL; AB085827; BAC53765.1; -; mRNA. DR EMBL; AY423729; AAS00492.1; -; mRNA. DR EMBL; CH471084; EAW95803.1; -; Genomic_DNA. DR EMBL; BC043209; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AF079529; AAC69564.2; -; mRNA. DR EMBL; AL831924; CAD38584.1; -; mRNA. DR CCDS; CCDS34190.1; -. [O95263-3] DR CCDS; CCDS34191.1; -. [O95263-6] DR CCDS; CCDS34192.1; -. [O95263-2] DR CCDS; CCDS34193.1; -. [O95263-4] DR CCDS; CCDS4037.1; -. [O95263-1] DR PIR; JE0293; JE0293. DR RefSeq; NP_001025022.1; NM_001029851.4. [O95263-2] DR RefSeq; NP_001025023.1; NM_001029852.4. [O95263-3] DR RefSeq; NP_001025024.1; NM_001029853.4. [O95263-4] DR RefSeq; NP_001025025.1; NM_001029854.4. [O95263-6] DR RefSeq; NP_003710.1; NM_003719.5. [O95263-1] DR AlphaFoldDB; O95263; -. DR SMR; O95263; -. DR BioGRID; 114177; 12. DR CORUM; O95263; -. DR FunCoup; O95263; 217. DR IntAct; O95263; 4. DR MINT; O95263; -. DR STRING; 9606.ENSP00000264917; -. DR BindingDB; O95263; -. DR ChEMBL; CHEMBL4408; -. DR DrugBank; DB00201; Caffeine. DR DrugBank; DB09283; Trapidil. DR DrugCentral; O95263; -. DR GuidetoPHARMACOLOGY; 1308; -. DR iPTMnet; O95263; -. DR PhosphoSitePlus; O95263; -. DR BioMuta; PDE8B; -. DR jPOST; O95263; -. DR MassIVE; O95263; -. DR PaxDb; 9606-ENSP00000264917; -. DR PeptideAtlas; O95263; -. DR ProteomicsDB; 50759; -. [O95263-1] DR ProteomicsDB; 50760; -. [O95263-2] DR ProteomicsDB; 50761; -. [O95263-3] DR ProteomicsDB; 50762; -. [O95263-4] DR ProteomicsDB; 50763; -. [O95263-5] DR ProteomicsDB; 50764; -. [O95263-6] DR Pumba; O95263; -. DR Antibodypedia; 12495; 151 antibodies from 26 providers. DR DNASU; 8622; -. DR Ensembl; ENST00000264917.10; ENSP00000264917.6; ENSG00000113231.14. [O95263-1] DR Ensembl; ENST00000333194.8; ENSP00000331336.4; ENSG00000113231.14. [O95263-3] DR Ensembl; ENST00000340978.7; ENSP00000345446.3; ENSG00000113231.14. [O95263-6] DR Ensembl; ENST00000342343.8; ENSP00000345646.4; ENSG00000113231.14. [O95263-4] DR Ensembl; ENST00000346042.7; ENSP00000330428.3; ENSG00000113231.14. [O95263-2] DR Ensembl; ENST00000505283.1; ENSP00000423461.1; ENSG00000113231.14. [O95263-5] DR GeneID; 8622; -. DR KEGG; hsa:8622; -. DR MANE-Select; ENST00000264917.10; ENSP00000264917.6; NM_003719.5; NP_003710.1. DR UCSC; uc003kfa.4; human. [O95263-1] DR AGR; HGNC:8794; -. DR ClinPGx; PA33142; -. DR CTD; 8622; -. DR DisGeNET; 8622; -. DR GeneCards; PDE8B; -. DR HGNC; HGNC:8794; PDE8B. DR HPA; ENSG00000113231; Tissue enriched (thyroid). DR MalaCards; PDE8B; -. DR MIM; 603390; gene. DR MIM; 609161; phenotype. DR MIM; 614190; phenotype. DR OpenTargets; ENSG00000113231; -. DR Orphanet; 228169; Autosomal dominant striatal neurodegeneration. DR Orphanet; 647782; Isolated micronodular adrenocortical disease. DR VEuPathDB; HostDB:ENSG00000113231; -. DR eggNOG; KOG1229; Eukaryota. DR GeneTree; ENSGT00940000157817; -. DR HOGENOM; CLU_005940_4_2_1; -. DR InParanoid; O95263; -. DR OMA; RWCCGGS; -. DR OrthoDB; 189220at2759; -. DR PAN-GO; O95263; 2 GO annotations based on evolutionary models. DR PhylomeDB; O95263; -. DR BRENDA; 3.1.4.53; 2681. DR PathwayCommons; O95263; -. DR Reactome; R-HSA-418555; G alpha (s) signalling events. DR SignaLink; O95263; -. DR UniPathway; UPA00762; UER00747. DR Agora; ENSG00000113231; -. DR BioGRID-ORCS; 8622; 19 hits in 1161 CRISPR screens. DR ChiTaRS; PDE8B; human. DR GeneWiki; PDE8B; -. DR GenomeRNAi; 8622; -. DR Pharos; O95263; Tclin. DR PRO; PR:O95263; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; O95263; protein. DR Bgee; ENSG00000113231; Expressed in left lobe of thyroid gland and 104 other cell types or tissues. DR ExpressionAtlas; O95263; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0004115; F:3',5'-cyclic-AMP phosphodiesterase activity; IMP:UniProtKB. DR GO; GO:0047555; F:3',5'-cyclic-GMP phosphodiesterase activity; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl. DR GO; GO:0006198; P:cAMP catabolic process; IEA:UniProtKB-UniPathway. DR GO; GO:0141162; P:negative regulation of cAMP/PKA signal transduction; IBA:GO_Central. DR GO; GO:0061179; P:negative regulation of insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl. DR GO; GO:0090032; P:negative regulation of steroid hormone biosynthetic process; IEA:Ensembl. DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl. DR GO; GO:0035106; P:operant conditioning; IEA:Ensembl. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR GO; GO:0008542; P:visual learning; IEA:Ensembl. DR CDD; cd00077; HDc; 1. DR CDD; cd00130; PAS; 1. DR FunFam; 1.10.1300.10:FF:000002; Phosphodiesterase; 1. DR FunFam; 3.30.450.20:FF:000023; Phosphodiesterase; 1. DR Gene3D; 1.10.1300.10; 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain; 1. DR Gene3D; 3.30.450.20; PAS domain; 1. DR InterPro; IPR003607; HD/PDEase_dom. DR InterPro; IPR000014; PAS. DR InterPro; IPR035965; PAS-like_dom_sf. DR InterPro; IPR057304; PDE8-like_REC_N. DR InterPro; IPR023088; PDEase. DR InterPro; IPR002073; PDEase_catalytic_dom. DR InterPro; IPR036971; PDEase_catalytic_dom_sf. DR InterPro; IPR023174; PDEase_CS. DR NCBIfam; TIGR00229; sensory_box; 1. DR PANTHER; PTHR11347; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; 1. DR Pfam; PF13426; PAS_9; 1. DR Pfam; PF08629; PDE8; 1. DR Pfam; PF23198; PDE8A_N; 1. DR Pfam; PF00233; PDEase_I; 1. DR PRINTS; PR00387; PDIESTERASE1. DR SMART; SM00471; HDc; 1. DR SMART; SM00091; PAS; 1. DR SUPFAM; SSF109604; HD-domain/PDEase-like; 1. DR SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 1. DR PROSITE; PS50112; PAS; 1. DR PROSITE; PS00126; PDEASE_I_1; 1. DR PROSITE; PS51845; PDEASE_I_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; cAMP; Cushing syndrome; Disease variant; Hydrolase; KW Metal-binding; Phosphoprotein; Proteomics identification; KW Reference proteome. FT CHAIN 1..885 FT /note="High affinity cAMP-specific and IBMX-insensitive FT 3',5'-cyclic phosphodiesterase 8B" FT /id="PRO_0000198840" FT DOMAIN 267..338 FT /note="PAS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140" FT DOMAIN 539..875 FT /note="PDEase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01192" FT REGION 18..41 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 72..95 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 393..436 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 23..34 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 75..90 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 422..436 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 615 FT /note="Proton donor" FT /evidence="ECO:0000250|UniProtKB:O76083" FT BINDING 619 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O60658" FT BINDING 655 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O60658" FT BINDING 656 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O60658" FT BINDING 656 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:O60658" FT BINDING 781 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:O60658" FT MOD_RES 517 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 754 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:E9Q4S1" FT VAR_SEQ 1..535 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3" FT /id="VSP_008081" FT VAR_SEQ 114..133 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:12681444" FT /id="VSP_008082" FT VAR_SEQ 293..389 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12372422, FT ECO:0000303|PubMed:12681444" FT /id="VSP_008084" FT VAR_SEQ 293..339 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:12372422" FT /id="VSP_008083" FT VAR_SEQ 456..510 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12681444" FT /id="VSP_008085" FT VARIANT 305 FT /note="H -> P (in PPNAD3; shows significantly higher cyclic FT AMP levels after transfection with the mutant protein than FT after transfection with the wild-type, indicating an FT impaired ability of the mutant protein to degrade cAMP; FT dbSNP:rs121918360)" FT /evidence="ECO:0000269|PubMed:18431404" FT /id="VAR_066503" FT CONFLICT 147 FT /note="G -> R (in Ref. 7; CAD38584)" FT /evidence="ECO:0000305" SQ SEQUENCE 885 AA; 98979 MW; DB4F763E51F745A3 CRC64; MGCAPSIHVS QSGVIYCRDS DESSSPRQTT SVSQGPAAPL PGLFVQTDAA DAIPPSRASG PPSVARVRRA RTELGSGSSA GSAAPAATTS RGRRRHCCSS AEAETQTCYT SVKQVSSAEV RIGPMRLTQD PIQVLLIFAK EDSQSDGFWW ACDRAGYRCN IARTPESALE CFLDKHHEII VIDHRQTQNF DAEAVCRSIR ATNPSEHTVI LAVVSRVSDD HEEASVLPLL HAGFNRRFME NSSIIACYNE LIQIEHGEVR SQFKLRACNS VFTALDHCHE AIEITSDDHV IQYVNPAFER MMGYHKGELL GKELADLPKS DKNRADLLDT INTCIKKGKE WQGVYYARRK SGDSIQQHVK ITPVIGQGGK IRHFVSLKKL CCTTDNNKQI HKIHRDSGDN SQTEPHSFRY KNRRKESIDV KSISSRGSDA PSLQNRRYPS MARIHSMTIE APITKVINII NAAQENSPVT VAEALDRVLE ILRTTELYSP QLGTKDEDPH TSDLVGGLMT DGLRRLSGNE YVFTKNVHQS HSHLAMPITI NDVPPCISQL LDNEESWDFN IFELEAITHK RPLVYLGLKV FSRFGVCEFL NCSETTLRAW FQVIEANYHS SNAYHNSTHA ADVLHATAFF LGKERVKGSL DQLDEVAALI AATVHDVDHP GRTNSFLCNA GSELAVLYND TAVLESHHTA LAFQLTVKDT KCNIFKNIDR NHYRTLRQAI IDMVLATEMT KHFEHVNKFV NSINKPMAAE IEGSDCECNP AGKNFPENQI LIKRMMIKCA DVANPCRPLD LCIEWAGRIS EEYFAQTDEE KRQGLPVVMP VFDRNTCSIP KSQISFIDYF ITDMFDAWDA FAHLPALMQH LADNYKHWKT LDDLKCKSLR LPSDS // ID PDGFB_HUMAN Reviewed; 241 AA. AC P01127; G3XAG8; P78431; Q15354; Q6FHE7; Q9UF23; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 28-JAN-2026, entry version 261. DE RecName: Full=Platelet-derived growth factor subunit B; DE Short=PDGF subunit B; DE AltName: Full=PDGF-2; DE AltName: Full=Platelet-derived growth factor B chain; DE AltName: Full=Platelet-derived growth factor beta polypeptide; DE AltName: Full=Proto-oncogene c-Sis; DE AltName: INN=Becaplermin; DE Flags: Precursor; GN Name=PDGFB; Synonyms=PDGF2, SIS; 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=6740330; DOI=10.1126/science.6740330; RA Josephs S.F., Ratner L., Clarke M.F., Westin E.H., Reitz M.S., RA Wong-Staal F.; RT "Transforming potential of human c-sis nucleotide sequences encoding RT platelet-derived growth factor."; RL Science 225:636-639(1984). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=4033772; DOI=10.1038/316748a0; RA Collins T., Ginsburg D., Boss J.M., Orkin S.H., Pober J.S.; RT "Cultured human endothelial cells express platelet-derived growth factor B RT chain: cDNA cloning and structural analysis."; RL Nature 316:748-750(1985). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2991848; DOI=10.1093/nar/13.14.5007; RA Ratner L., Josephs S.F., Jarrett R., Reitz M.S., Wong-Staal F.; RT "Nucleotide sequence of transforming human c-sis cDNA clones with homology RT to platelet-derived growth factor."; RL Nucleic Acids Res. 13:5007-5018(1985). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=3472769; DOI=10.1101/sqb.1986.051.01.109; RA Rao C.D., Igarashi H., Pech M.W., Robbins K.C., Aaronson S.A.; RT "Oncogenic potential of the human platelet-derived growth factor RT transcriptional unit."; RL Cold Spring Harb. Symp. Quant. Biol. 51:959-966(1986). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=3517869; DOI=10.1073/pnas.83.8.2392; RA Rao C.D., Igarashi H., Chiu I.-M., Robbins K.C., Aaronson S.A.; RT "Structure and sequence of the human c-sis/platelet-derived growth factor 2 RT (SIS/PDGF2) transcriptional unit."; RL Proc. Natl. Acad. Sci. U.S.A. 83:2392-2396(1986). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [7] 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [9] 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 [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, Lung, Pancreas, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-185 (ISOFORM 2). RC TISSUE=Choriocarcinoma; RX PubMed=7659502; DOI=10.1093/nar/23.15.2815; RA Dirks R.P.H., Onnekink C., Jansen H.J., de Jong A., Bloemers H.P.J.; RT "A novel human c-sis mRNA species is transcribed from a promoter in c-sis RT intron 1 and contains the code for an alternative PDGF B-like protein."; RL Nucleic Acids Res. 23:2815-2822(1995). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-53, AND CHROMOSOMAL TRANSLOCATION RP WITH COL1A1. RX PubMed=8988177; DOI=10.1038/ng0197-95; RA Simon M.-P., Pedeutour F., Sirvent N., Grosgeorge J., Minoletti F., RA Coindre J.-M., Terrier-Lacombe M.-J., Mandahl N., Craver R.D., Blin N., RA Sozzi G., Turc-Carel C., O'Brien K.P., Kedra D., Fransson I., Guilbaud C., RA Dumanski J.P.; RT "Deregulation of the platelet-derived growth factor B-chain gene via fusion RT with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell RT fibroblastoma."; RL Nat. Genet. 15:95-98(1997). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 22-241. RX PubMed=6327048; DOI=10.1016/0092-8674(84)90307-6; RA Chiu I.-M., Reddy E.P., Givol D., Robbins K.C., Tronick S.R., RA Aaronson S.A.; RT "Nucleotide sequence analysis identifies the human c-sis proto-oncogene as RT a structural gene for platelet-derived growth factor."; RL Cell 37:123-129(1984). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-241 (ISOFORM 1). RX PubMed=3456904; DOI=10.1016/0014-5793(86)80433-1; RA Weich H.A., Sebald W., Schairer H.U., Hoppe J.; RT "The human osteosarcoma cell line U-2 OS expresses a 3.8 kilobase mRNA RT which codes for the sequence of the PDGF-B chain."; RL FEBS Lett. 198:344-348(1986). RN [15] RP PROTEIN SEQUENCE OF 82-112. RX PubMed=6306471; DOI=10.1038/304035a0; RA Waterfield M.D., Scrace G.T., Whittle N., Stroobant P., Johnsson A., RA Wasteson A., Westermark B., Heldin C.H., Huang J.S., Deuel T.F.; RT "Platelet-derived growth factor is structurally related to the putative RT transforming protein p28sis of simian sarcoma virus."; RL Nature 304:35-39(1983). RN [16] RP PROTEIN SEQUENCE OF 82-110. RX PubMed=6844921; DOI=10.1126/science.6844921; RA Antoniades H.N., Hunkapiller M.W.; RT "Human platelet-derived growth factor (PDGF): amino-terminal amino acid RT sequence."; RL Science 220:963-965(1983). RN [17] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 153-200, AND PARTIAL PROTEIN SEQUENCE. RX PubMed=6329745; DOI=10.1002/j.1460-2075.1984.tb01908.x; RA Johnsson A., Heldin C.H., Wasteson A., Westermark B., Deuel T.F., RA Huang J.S., Seeburg P.H., Gray A., Ullrich A., Scrace G., Stroobant P., RA Waterfield M.D.; RT "The c-sis gene encodes a precursor of the B chain of platelet-derived RT growth factor."; RL EMBO J. 3:921-928(1984). RN [18] RP MUTAGENESIS, AND IMPORTANCE OF ARG-108 AND ILE-111 FOR RECEPTOR BINDING. RX PubMed=1661670; DOI=10.1002/j.1460-2075.1991.tb04988.x; RA Clements J.M., Bawden L.J., Bloxidge R.E., Catlin G., Cook A.L., Craig S., RA Drummond A.H., Edwards R.M., Fallon A., Green D.R., Hellewell P.G., RA Kirwin P.M., Nayee P.D., Richardson S.J., Brown D., Chahwala S.B., RA Snarey M., Winslow D.; RT "Two PDGF-B chain residues, arginine 27 and isoleucine 30, mediate receptor RT binding and activation."; RL EMBO J. 10:4113-4120(1991). RN [19] RP INTERCHAIN DISULFIDE BONDS. RX PubMed=1317862; DOI=10.1016/s0021-9258(19)49905-5; RA Andersson M., Oestman A., Baeckstroem G., Hellman U., George-Nascimento C., RA Westermark B., Heldin C.-H.; RT "Assignment of interchain disulfide bonds in platelet-derived growth factor RT (PDGF) and evidence for agonist activity of monomeric PDGF."; RL J. Biol. Chem. 267:11260-11266(1992). RN [20] RP TISSUE SPECIFICITY. RX PubMed=11331882; DOI=10.1038/35074593; RA LaRochelle W.J., Jeffers M., McDonald W.F., Chillakuru R.A., Giese N.A., RA Lokker N.A., Sullivan C., Boldog F.L., Yang M., Vernet C., Burgess C.E., RA Fernandez E., Deegler L.L., Rittman B., Shimkets J., Shimkets R.A., RA Rothberg J.M., Lichenstein H.S.; RT "PDGF D, a novel protease-activated growth factor."; RL Nat. Cell Biol. 3:517-521(2001). RN [21] RP DISEASE, AND CHROMOSOMAL TRANSLOCATION WITH COL1A1. RX PubMed=12660034; DOI=10.1016/s0165-4608(02)00844-0; RA Sandberg A.A., Anderson W.D., Fredenberg C., Hashimoto H.; RT "Dermatofibrosarcoma protuberans of breast."; RL Cancer Genet. Cytogenet. 142:56-59(2003). RN [22] RP INTERACTION WITH LRP1 AND SORL1. RX PubMed=15053742; DOI=10.1042/bj20040149; RA Gliemann J., Hermey G., Nykjaer A., Petersen C.M., Jacobsen C., RA Andreasen P.A.; RT "The mosaic receptor sorLA/LR11 binds components of the plasminogen- RT activating system and platelet-derived growth factor-BB similarly to LRP1 RT (low-density lipoprotein receptor-related protein), but mediates slow RT internalization of bound ligand."; RL Biochem. J. 381:203-212(2004). RN [23] RP INTERACTION WITH SORL1. RX PubMed=16393139; DOI=10.1042/bj20051364; RA Hermey G., Sjoegaard S.S., Petersen C.M., Nykjaer A., Gliemann J.; RT "Tumour necrosis factor alpha-converting enzyme mediates ectodomain RT shedding of Vps10p-domain receptor family members."; RL Biochem. J. 395:285-293(2006). RN [24] RP CHARACTERIZATION OF VARIANTS IBGC5 ARG-9 AND PRO-119, AND FUNCTION. RX PubMed=26599395; DOI=10.1371/journal.pone.0143407; RA Vanlandewijck M., Lebouvier T., Andaloussi Maee M., Nahar K., Hornemann S., RA Kenkel D., Cunha S.I., Lennartsson J., Boss A., Heldin C.H., Keller A., RA Betsholtz C.; RT "Functional characterization of germline mutations in PDGFB and PDGFRB in RT primary familial brain calcification."; RL PLoS ONE 10:E0143407-E0143407(2015). RN [25] RP INTERACTION WITH CD82. RX PubMed=34530889; DOI=10.1186/s13045-021-01147-6; RA Lee J.W., Hur J., Kwon Y.W., Chae C.W., Choi J.I., Hwang I., Yun J.Y., RA Kang J.A., Choi Y.E., Kim Y.H., Lee S.E., Lee C., Jo D.H., Seok H., RA Cho B.S., Baek S.H., Kim H.S.; RT "KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic RT milieu to quiescent state."; RL J. Hematol. Oncol. 14:148-148(2021). RN [26] RP REVIEW ON FUNCTION IN DEVELOPMENT AND DISEASE. RX PubMed=18483217; DOI=10.1101/gad.1653708; RA Andrae J., Gallini R., Betsholtz C.; RT "Role of platelet-derived growth factors in physiology and medicine."; RL Genes Dev. 22:1276-1312(2008). RN [27] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS). RX PubMed=1396586; DOI=10.1002/j.1460-2075.1992.tb05485.x; RA Oefner C., D'Arcy A., Winkler F.K., Eggimann B., Hosang M.; RT "Crystal structure of human platelet-derived growth factor BB."; RL EMBO J. 11:3921-3926(1992). RN [28] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 21-185 IN COMPLEX WITH PDGFRB, RP SUBUNIT, AND DISULFIDE BONDS. RX PubMed=20534510; DOI=10.1073/pnas.1000806107; RA Shim A.H., Liu H., Focia P.J., Chen X., Lin P.C., He X.; RT "Structures of a platelet-derived growth factor/propeptide complex and a RT platelet-derived growth factor/receptor complex."; RL Proc. Natl. Acad. Sci. U.S.A. 107:11307-11312(2010). RN [29] RP VARIANTS IBGC5 ARG-9 AND PRO-119. RX PubMed=23913003; DOI=10.1038/ng.2723; RA Keller A., Westenberger A., Sobrido M.J., Garcia-Murias M., Domingo A., RA Sears R.L., Lemos R.R., Ordonez-Ugalde A., Nicolas G., da Cunha J.E., RA Rushing E.J., Hugelshofer M., Wurnig M.C., Kaech A., Reimann R., RA Lohmann K., Dobricic V., Carracedo A., Petrovic I., Miyasaki J.M., RA Abakumova I., Mae M.A., Raschperger E., Zatz M., Zschiedrich K., RA Klepper J., Spiteri E., Prieto J.M., Navas I., Preuss M., Dering C., RA Jankovic M., Paucar M., Svenningsson P., Saliminejad K., Khorshid H.R., RA Novakovic I., Aguzzi A., Boss A., Le Ber I., Defer G., Hannequin D., RA Kostic V.S., Campion D., Geschwind D.H., Coppola G., Betsholtz C., RA Klein C., Oliveira J.R.; RT "Mutations in the gene encoding PDGF-B cause brain calcifications in humans RT and mice."; RL Nat. Genet. 45:1077-1082(2013). CC -!- FUNCTION: Growth factor that plays an essential role in the regulation CC of embryonic development, cell proliferation, cell migration, survival CC and chemotaxis. Potent mitogen for cells of mesenchymal origin CC (PubMed:26599395). Required for normal proliferation and recruitment of CC pericytes and vascular smooth muscle cells in the central nervous CC system, skin, lung, heart and placenta. Required for normal blood CC vessel development, and for normal development of kidney glomeruli. CC Plays an important role in wound healing. Signaling is modulated by the CC formation of heterodimers with PDGFA (By similarity). CC {ECO:0000250|UniProtKB:P31240, ECO:0000269|PubMed:26599395}. CC -!- SUBUNIT: Antiparallel homodimer; disulfide-linked. Antiparallel CC heterodimer with PDGFA; disulfide-linked. The PDGFB homodimer interacts CC with PDGFRA and PDGFRB homodimers, and with heterodimers formed by CC PDGFRA and PDGFRB. The heterodimer composed of PDGFA and PDGFB CC interacts with PDGFRB homodimers, and with heterodimers formed by CC PDGFRA and PDGFRB. Interacts with XLKD1 (By similarity). Interacts with CC LRP1 (PubMed:15053742). Interacts with SORL1 (via the N-terminal CC ectodomain) (PubMed:15053742, PubMed:16393139). Interacts with CD82; CC this interaction inhibits PDGFB-mediated signaling pathway CC (PubMed:34530889). {ECO:0000250, ECO:0000269|PubMed:15053742, CC ECO:0000269|PubMed:16393139, ECO:0000269|PubMed:34530889}. CC -!- INTERACTION: CC P01127; Q9P287: BCCIP; NbExp=3; IntAct=EBI-1554925, EBI-711154; CC P01127; P01127: PDGFB; NbExp=3; IntAct=EBI-1554925, EBI-1554925; CC P01127; P16234: PDGFRA; NbExp=11; IntAct=EBI-1554925, EBI-2861522; CC P01127; P09619: PDGFRB; NbExp=16; IntAct=EBI-1554925, EBI-641237; CC -!- SUBCELLULAR LOCATION: Secreted. Note=Released by platelets upon CC wounding. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage; Named isoforms=2; CC Name=1; CC IsoId=P01127-1; Sequence=Displayed; CC Name=2; CC IsoId=P01127-2; Sequence=VSP_044913; CC -!- TISSUE SPECIFICITY: Expressed at high levels in the heart, brain CC (sustantia nigra), placenta and fetal kidney. Expressed at moderate CC levels in the brain (hippocampus), skeletal muscle, kidney and lung. CC {ECO:0000269|PubMed:11331882}. CC -!- DISEASE: Basal ganglia calcification, idiopathic, 5 (IBGC5) CC [MIM:615483]: A form of basal ganglia calcification, an autosomal CC dominant condition characterized by symmetric calcification in the CC basal ganglia and other brain regions. Affected individuals can either CC be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, CC including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, CC seizures, and chronic headache. Serum levels of calcium, phosphate, CC alkaline phosphatase and parathyroid hormone are normal. The CC neuropathological hallmark of the disease is vascular and pericapillary CC calcification, mainly of calcium phosphate, in the affected brain CC areas. {ECO:0000269|PubMed:23913003, ECO:0000269|PubMed:26599395}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Note=A chromosomal aberration involving PDGFB is found in CC dermatofibrosarcoma protuberans. Translocation t(17;22)(q22;q13) with CC PDGFB. {ECO:0000269|PubMed:12660034}. CC -!- PHARMACEUTICAL: Available under the name Regranex (Ortho-McNeil). Used CC to promote healing in diabetic neuropathic foot ulcers. CC -!- SIMILARITY: Belongs to the PDGF/VEGF growth factor family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/155/PDGFB"; 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; K01401; AAA60552.1; -; Genomic_DNA. DR EMBL; K01918; AAA60552.1; JOINED; Genomic_DNA. DR EMBL; J00121; AAA60552.1; JOINED; Genomic_DNA. DR EMBL; K01398; AAA60552.1; JOINED; Genomic_DNA. DR EMBL; K01399; AAA60552.1; JOINED; Genomic_DNA. DR EMBL; K01400; AAA60552.1; JOINED; Genomic_DNA. DR EMBL; X02811; CAA26579.1; -; mRNA. DR EMBL; X02744; CAA26524.1; -; mRNA. DR EMBL; M12783; AAA60553.1; -; mRNA. DR EMBL; CR456538; CAG30424.1; -; mRNA. DR EMBL; Z81010; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CR541807; CAG46606.1; -; mRNA. DR EMBL; CH471095; EAW60306.1; -; Genomic_DNA. DR EMBL; CH471095; EAW60307.1; -; Genomic_DNA. DR EMBL; BC029822; AAH29822.1; -; mRNA. DR EMBL; BC077725; AAH77725.1; -; mRNA. DR EMBL; X83705; CAA58679.1; -; mRNA. DR EMBL; X98706; CAA67262.1; -; Genomic_DNA. DR EMBL; K01917; AAA98793.1; -; Genomic_DNA. DR EMBL; K01913; AAA98793.1; JOINED; Genomic_DNA. DR EMBL; K01914; AAA98793.1; JOINED; Genomic_DNA. DR EMBL; K01915; AAA98793.1; JOINED; Genomic_DNA. DR EMBL; K01916; AAA98793.1; JOINED; Genomic_DNA. DR EMBL; X03702; CAA27333.1; -; mRNA. DR EMBL; X00561; CAA25228.1; -; Genomic_DNA. DR EMBL; X00561; CAA25229.1; -; Genomic_DNA. DR CCDS; CCDS13987.1; -. [P01127-1] DR CCDS; CCDS33650.1; -. [P01127-2] DR PIR; A94276; PFHUG2. DR RefSeq; NP_002599.1; NM_002608.4. [P01127-1] DR RefSeq; NP_148937.1; NM_033016.3. [P01127-2] DR PDB; 1PDG; X-ray; 3.00 A; A/B/C=82-190. DR PDB; 3MJG; X-ray; 2.30 A; A/B=21-185. DR PDB; 4HQU; X-ray; 2.20 A; A=82-190. DR PDB; 4HQX; X-ray; 2.30 A; A=82-183. DR PDB; 4QCI; X-ray; 2.30 A; C/D=82-190. DR PDB; 6T9E; X-ray; 2.99 A; CCC/DDD=82-190. DR PDBsum; 1PDG; -. DR PDBsum; 3MJG; -. DR PDBsum; 4HQU; -. DR PDBsum; 4HQX; -. DR PDBsum; 4QCI; -. DR PDBsum; 6T9E; -. DR AlphaFoldDB; P01127; -. DR EMDB; EMD-6426; -. DR SMR; P01127; -. DR BioGRID; 111181; 93. DR ComplexPortal; CPX-1875; Platelet-derived growth factor AB complex. DR ComplexPortal; CPX-1876; Platelet-derived growth factor BB complex. DR ComplexPortal; CPX-2882; PDGF receptor beta - PDGF-BB complex. DR ComplexPortal; CPX-2883; PDGF receptor alpha-beta - PDGF-BB complex. DR ComplexPortal; CPX-2884; PDGF receptor alpha - PDGF-BB complex. DR ComplexPortal; CPX-2885; PDGF receptor alpha - PDGF-AB complex. DR ComplexPortal; CPX-2886; PDGF receptor beta - PDGF-AB complex. DR ComplexPortal; CPX-2892; PDGF receptor alpha-beta - PDGF-AB complex. DR CORUM; P01127; -. DR DIP; DIP-5737N; -. DR FunCoup; P01127; 1104. DR IntAct; P01127; 69. DR STRING; 9606.ENSP00000330382; -. DR BindingDB; P01127; -. DR ChEMBL; CHEMBL3108633; -. DR DrugBank; DB06325; Pegpleranib. DR GlyConnect; 754; 4 N-Linked glycans (1 site). DR GlyCosmos; P01127; 1 site, 5 glycans. DR GlyGen; P01127; 3 sites, 5 N-linked glycans (1 site), 1 O-linked glycan (2 sites). DR iPTMnet; P01127; -. DR PhosphoSitePlus; P01127; -. DR BioMuta; PDGFB; -. DR DMDM; 129724; -. DR MassIVE; P01127; -. DR PaxDb; 9606-ENSP00000330382; -. DR PeptideAtlas; P01127; -. DR ProteomicsDB; 33745; -. DR ProteomicsDB; 51325; -. [P01127-1] DR TopDownProteomics; P01127-2; -. [P01127-2] DR ABCD; P01127; 9 sequenced antibodies. DR Antibodypedia; 293; 734 antibodies from 42 providers. DR DNASU; 5155; -. DR Ensembl; ENST00000331163.11; ENSP00000330382.6; ENSG00000100311.18. [P01127-1] DR Ensembl; ENST00000381551.8; ENSP00000370963.4; ENSG00000100311.18. [P01127-2] DR GeneID; 5155; -. DR KEGG; hsa:5155; -. DR MANE-Select; ENST00000331163.11; ENSP00000330382.6; NM_002608.4; NP_002599.1. DR UCSC; uc003axe.4; human. [P01127-1] DR AGR; HGNC:8800; -. DR CIViC; 5155; 3 evidence items across 1 molecular profile. DR ClinPGx; PA33145; -. DR CTD; 5155; -. DR DisGeNET; 5155; -. DR GeneCards; PDGFB; -. DR GeneReviews; PDGFB; -. DR HGNC; HGNC:8800; PDGFB. DR HPA; ENSG00000100311; Low tissue specificity. DR MalaCards; PDGFB; -. DR MIM; 190040; gene. DR MIM; 607907; phenotype. DR MIM; 615483; phenotype. DR OpenTargets; ENSG00000100311; -. DR Orphanet; 1980; Bilateral striopallidodentate calcinosis. DR Orphanet; 31112; Dermatofibrosarcoma protuberans. DR Orphanet; 263662; Familial multiple meningioma. DR Orphanet; 2495; Meningioma. DR VEuPathDB; HostDB:ENSG00000100311; -. DR eggNOG; ENOG502S2VW; Eukaryota. DR GeneTree; ENSGT00940000157367; -. DR HOGENOM; CLU_094438_0_0_1; -. DR InParanoid; P01127; -. DR OMA; KHTHDKE; -. DR OrthoDB; 8878063at2759; -. DR PAN-GO; P01127; 9 GO annotations based on evolutionary models. DR PhylomeDB; P01127; -. DR PathwayCommons; P01127; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-186763; Downstream signal transduction. DR Reactome; R-HSA-186797; Signaling by PDGF. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-3000171; Non-integrin membrane-ECM interactions. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR SignaLink; P01127; -. DR SIGNOR; P01127; -. DR Agora; ENSG00000100311; -. DR BioGRID-ORCS; 5155; 8 hits in 1145 CRISPR screens. DR ChiTaRS; PDGFB; human. DR EvolutionaryTrace; P01127; -. DR GeneWiki; PDGFB; -. DR GenomeRNAi; 5155; -. DR Pharos; P01127; Tbio. DR PRO; PR:P01127; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; P01127; protein. DR Bgee; ENSG00000100311; Expressed in olfactory bulb and 189 other cell types or tissues. DR ExpressionAtlas; P01127; baseline and differential. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0031012; C:extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:1990265; C:platelet-derived growth factor complex; IPI:ComplexPortal. DR GO; GO:0042056; F:chemoattractant activity; IDA:BHF-UCL. DR GO; GO:0005518; F:collagen binding; IDA:MGI. DR GO; GO:0008083; F:growth factor activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0048407; F:platelet-derived growth factor binding; IPI:BHF-UCL. DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; IDA:BHF-UCL. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL. DR GO; GO:0016176; F:superoxide-generating NADPH oxidase activator activity; IDA:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central. DR GO; GO:0060326; P:cell chemotaxis; IDA:UniProtKB. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:BHF-UCL. DR GO; GO:0071506; P:cellular response to mycophenolic acid; ISS:UniProtKB. DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IDA:BHF-UCL. DR GO; GO:0001892; P:embryonic placenta development; ISS:UniProtKB. DR GO; GO:0010467; P:gene expression; IDA:UniProtKB. DR GO; GO:0007507; P:heart development; ISS:UniProtKB. DR GO; GO:0035655; P:interleukin-18-mediated signaling pathway; IDA:BHF-UCL. DR GO; GO:0035556; P:intracellular signal transduction; IMP:UniProtKB. DR GO; GO:0072255; P:metanephric glomerular mesangial cell development; ISS:UniProtKB. DR GO; GO:0002548; P:monocyte chemotaxis; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB. DR GO; GO:1902894; P:negative regulation of miRNA transcription; IDA:BHF-UCL. DR GO; GO:0010512; P:negative regulation of phosphatidylinositol biosynthetic process; IDA:BHF-UCL. DR GO; GO:0010544; P:negative regulation of platelet activation; IDA:BHF-UCL. DR GO; GO:1905064; P:negative regulation of vascular associated smooth muscle cell differentiation; IDA:BHF-UCL. DR GO; GO:0038001; P:paracrine signaling; ISS:UniProtKB. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:BHF-UCL. DR GO; GO:0090280; P:positive regulation of calcium ion import; IDA:UniProtKB. DR GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IDA:BHF-UCL. DR GO; GO:0050921; P:positive regulation of chemotaxis; IDA:UniProtKB. DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0003104; P:positive regulation of glomerular filtration; ISS:UniProtKB. DR GO; GO:0072126; P:positive regulation of glomerular mesangial cell proliferation; IDA:UniProtKB. DR GO; GO:1900127; P:positive regulation of hyaluronan biosynthetic process; IDA:UniProtKB. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:BHF-UCL. DR GO; GO:2000591; P:positive regulation of metanephric mesenchymal cell migration; IDA:UniProtKB. DR GO; GO:0035793; P:positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway; IDA:UniProtKB. DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL. DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IDA:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IDA:UniProtKB. DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IDA:BHF-UCL. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:BHF-UCL. DR GO; GO:1905176; P:positive regulation of vascular associated smooth muscle cell dedifferentiation; IDA:BHF-UCL. DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IDA:UniProtKB. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:UniProtKB. DR GO; GO:0009611; P:response to wounding; IDA:BHF-UCL. DR GO; GO:0014805; P:smooth muscle adaptation; NAS:BHF-UCL. DR CDD; cd00135; PDGF; 1. DR DisProt; DP02770; -. DR FunFam; 2.10.90.10:FF:000023; Platelet-derived growth factor subunit B; 1. DR Gene3D; 2.10.90.10; Cystine-knot cytokines; 1. DR InterPro; IPR029034; Cystine-knot_cytokine. DR InterPro; IPR023581; PD_growth_factor_CS. DR InterPro; IPR000072; PDGF/VEGF_dom. DR InterPro; IPR006782; PDGF_N. DR PANTHER; PTHR11633; PLATELET-DERIVED GROWTH FACTOR; 1. DR PANTHER; PTHR11633:SF2; PLATELET-DERIVED GROWTH FACTOR SUBUNIT B; 1. DR Pfam; PF00341; PDGF; 1. DR Pfam; PF04692; PDGF_N; 1. DR SMART; SM00141; PDGF; 1. DR SUPFAM; SSF57501; Cystine-knot cytokines; 1. DR PROSITE; PS00249; PDGF_1; 1. DR PROSITE; PS50278; PDGF_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative promoter usage; Chromosomal rearrangement; KW Cleavage on pair of basic residues; Developmental protein; KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; KW Growth factor; Mitogen; Pharmaceutical; Proteomics identification; KW Proto-oncogene; Reference proteome; Secreted; Signal. FT SIGNAL 1..20 FT PROPEP 21..81 FT /note="Removed in mature form" FT /id="PRO_0000023371" FT CHAIN 82..190 FT /note="Platelet-derived growth factor subunit B" FT /id="PRO_0000023372" FT PROPEP 191..241 FT /note="Removed in mature form" FT /id="PRO_0000023373" FT REGION 216..241 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 216..230 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT SITE 108 FT /note="Involved in receptor binding" FT SITE 111 FT /note="Involved in receptor binding" FT CARBOHYD 63 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 97..141 FT /evidence="ECO:0000269|PubMed:20534510" FT DISULFID 124 FT /note="Interchain" FT /evidence="ECO:0000269|PubMed:20534510" FT DISULFID 130..178 FT /evidence="ECO:0000269|PubMed:20534510" FT DISULFID 133 FT /note="Interchain" FT /evidence="ECO:0000269|PubMed:20534510" FT DISULFID 134..180 FT /evidence="ECO:0000269|PubMed:20534510" FT VAR_SEQ 1..21 FT /note="MNRCWALFLSLCCYLRLVSAE -> MFIMGL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:7659502" FT /id="VSP_044913" FT VARIANT 9 FT /note="L -> R (in IBGC5; loss of protein expression)" FT /evidence="ECO:0000269|PubMed:23913003, FT ECO:0000269|PubMed:26599395" FT /id="VAR_070870" FT VARIANT 88 FT /note="I -> V (in dbSNP:rs17565)" FT /id="VAR_014578" FT VARIANT 119 FT /note="L -> P (in IBGC5; loss of protein expression; FT dbSNP:rs397515632)" FT /evidence="ECO:0000269|PubMed:23913003, FT ECO:0000269|PubMed:26599395" FT /id="VAR_070871" FT CONFLICT 101 FT /note="T -> E (in Ref. 16; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 105 FT /note="E -> C (in Ref. 16; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 107 FT /note="S -> C (in Ref. 16; AA sequence)" FT /evidence="ECO:0000305" FT STRAND 97..105 FT /evidence="ECO:0007829|PDB:4HQU" FT HELIX 108..111 FT /evidence="ECO:0007829|PDB:4HQU" FT STRAND 118..121 FT /evidence="ECO:0007829|PDB:4HQU" FT STRAND 123..131 FT /evidence="ECO:0007829|PDB:4HQU" FT STRAND 140..159 FT /evidence="ECO:0007829|PDB:4HQU" FT STRAND 162..181 FT /evidence="ECO:0007829|PDB:4HQU" SQ SEQUENCE 241 AA; 27283 MW; 9F9A3474CE203C0B CRC64; MNRCWALFLS LCCYLRLVSA EGDPIPEELY EMLSDHSIRS FDDLQRLLHG DPGEEDGAEL DLNMTRSHSG GELESLARGR RSLGSLTIAE PAMIAECKTR TEVFEISRRL IDRTNANFLV WPPCVEVQRC SGCCNNRNVQ CRPTQVQLRP VQVRKIEIVR KKPIFKKATV TLEDHLACKC ETVAAARPVT RSPGGSQEQR AKTPQTRVTI RTVRVRRPPK GKHRKFKHTH DKTALKETLG A // ID PGFRB_HUMAN Reviewed; 1106 AA. AC P09619; B5A957; Q8N5L4; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 28-JAN-2026, entry version 269. DE RecName: Full=Platelet-derived growth factor receptor beta; DE Short=PDGF-R-beta; DE Short=PDGFR-beta; DE EC=2.7.10.1; DE AltName: Full=Beta platelet-derived growth factor receptor; DE AltName: Full=Beta-type platelet-derived growth factor receptor; DE AltName: Full=CD140 antigen-like family member B; DE AltName: Full=Platelet-derived growth factor receptor 1; DE Short=PDGFR-1; DE AltName: CD_antigen=CD140b; DE Flags: Precursor; GN Name=PDGFRB; Synonyms=PDGFR, PDGFR1; 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), FUNCTION AS PDGFB RECEPTOR, RP SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, AND INTERACTION WITH PDGFB. RX PubMed=2835772; DOI=10.1073/pnas.85.10.3435; RA Gronwald R.G.K., Grant F.J., Haldeman B.A., Hart C.E., O'Hara P.J., RA Hagen F.S., Ross R., Bowen-Pope D.F., Murray M.J.; RT "Cloning and expression of a cDNA coding for the human platelet-derived RT growth factor receptor: evidence for more than one receptor class."; RL Proc. Natl. Acad. Sci. U.S.A. 85:3435-3439(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION AS PDGFB RECEPTOR, RP SUBCELLULAR LOCATION, GLYCOSYLATION, AUTOPHOSPHORYLATION, AND INTERACTION RP WITH PDGFA AND PDGFB. RX PubMed=2850496; DOI=10.1128/mcb.8.8.3476-3486.1988; RA Claesson-Welsh L., Eriksson A., Moren A., Severinsson L., Ek B., RA Oestman A., Betsholtz C., Heldin C.-H.; RT "cDNA cloning and expression of a human platelet-derived growth factor RT (PDGF) receptor specific for B-chain-containing PDGF molecules."; RL Mol. Cell. Biol. 8:3476-3486(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING. RX PubMed=18593464; DOI=10.1186/ar2447; RA Jin P., Zhang J., Sumariwalla P.F., Ni I., Jorgensen B., Crawford D., RA Phillips S., Feldmann M., Shepard H.M., Paleolog E.M.; RT "Novel splice variants derived from the receptor tyrosine kinase RT superfamily are potential therapeutics for rheumatoid arthritis."; RL Arthritis Res. Ther. 10:R73-R73(2008). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PHE-180. 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 [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 548-569. RX PubMed=9285559; DOI=10.1038/sj.onc.1201267; RA Chi K.D., McPhee R.A., Wagner A.S., Dietz J.J., Pantazis P., Goustin A.S.; RT "Integration of proviral DNA into the PDGF beta-receptor gene in HTLV-I- RT infected T-cells results in a novel tyrosine kinase product with RT transforming activity."; RL Oncogene 15:1051-1057(1997). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 559-1106 (ISOFORM 1), AND CHROMOSOMAL RP TRANSLOCATION WITH CEP85L. RX PubMed=21938754; DOI=10.1002/gcc.20930; RA Chmielecki J., Peifer M., Viale A., Hutchinson K., Giltnane J., Socci N.D., RA Hollis C.J., Dean R.S., Yenamandra A., Jagasia M., Kim A.S., Dave U.P., RA Thomas R.K., Pao W.; RT "Systematic screen for tyrosine kinase rearrangements identifies a novel RT C6orf204-PDGFRB fusion in a patient with recurrent T-ALL and an associated RT myeloproliferative neoplasm."; RL Genes Chromosomes Cancer 51:54-65(2012). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1046-1106. RX PubMed=2846185; DOI=10.1016/0092-8674(88)90224-3; RA Roberts W.M., Look A.T., Roussel M.F., Sherr C.J.; RT "Tandem linkage of human CSF-1 receptor (c-fms) and PDGF receptor genes."; RL Cell 55:655-661(1988). RN [9] RP PROTEIN SEQUENCE OF 33-47. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [10] RP PHOSPHORYLATION AT TYR-751 AND TYR-857. RX PubMed=2550144; DOI=10.1016/0092-8674(89)90510-2; RA Kazlauskas A., Cooper J.A.; RT "Autophosphorylation of the PDGF receptor in the kinase insert region RT regulates interactions with cell proteins."; RL Cell 58:1121-1133(1989). RN [11] RP FUNCTION AS PDGFB RECEPTOR IN CELL PROLIFERATION AND CHEMOTAXIS, AND RP SUBCELLULAR LOCATION. RX PubMed=2554309; DOI=10.1073/pnas.86.21.8314; RA Matsui T., Pierce J.H., Fleming T.P., Greenberger J.S., LaRochelle W.J., RA Ruggiero M., Aaronson S.A.; RT "Independent expression of human alpha or beta platelet-derived growth RT factor receptor cDNAs in a naive hematopoietic cell leads to functional RT coupling with mitogenic and chemotactic signaling pathways."; RL Proc. Natl. Acad. Sci. U.S.A. 86:8314-8318(1989). RN [12] RP FUNCTION IN CELL PROLIFERATION; ACTIVATION OF PLCG1 AND IN PHOSPHORYLATION RP OF PLCG1 AND RASA1/GAP, AND MUTAGENESIS OF TYR-751 AND TYR-857. RX PubMed=1653029; DOI=10.1091/mbc.2.6.413; RA Kazlauskas A., Durden D.L., Cooper J.A.; RT "Functions of the major tyrosine phosphorylation site of the PDGF receptor RT beta subunit."; RL Cell Regul. 2:413-425(1991). RN [13] RP INTERACTION WITH PDGFRA; PDGFA AND PDGFB, FUNCTION AS RECEPTOR FOR PDGFA RP AND PDGFB, AND PHOSPHORYLATION AT TYR-857 AND TYR-751. RX PubMed=1709159; DOI=10.1016/s0021-9258(18)31541-2; RA Kelly J.D., Haldeman B.A., Grant F.J., Murray M.J., Seifert R.A., RA Bowen-Pope D.F., Cooper J.A., Kazlauskas A.; RT "Platelet-derived growth factor (PDGF) stimulates PDGF receptor subunit RT dimerization and intersubunit trans-phosphorylation."; RL J. Biol. Chem. 266:8987-8992(1991). RN [14] RP FUNCTION AS RECEPTOR FOR PDGFA AND PDGFB, SUBCELLULAR LOCATION, CATALYTIC RP ACTIVITY, AND MUTAGENESIS OF LYS-634. RX PubMed=1846866; DOI=10.1083/jcb.112.3.469; RA Sorkin A., Westermark B., Heldin C.H., Claesson-Welsh L.; RT "Effect of receptor kinase inactivation on the rate of internalization and RT degradation of PDGF and the PDGF beta-receptor."; RL J. Cell Biol. 112:469-478(1991). RN [15] RP FUNCTION IN ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY, RP INTERACTION WITH PIK3R1 AND RASA1, PHOSPHORYLATION AT TYR-740; TYR-751; RP TYR-771 AND TYR-857, AND MUTAGENESIS OF LYS-634; TYR-716; TYR-740; TYR-751; RP TYR-763; TYR-771; TYR-775; TYR-778 AND TYR-857. RX PubMed=1314164; DOI=10.1002/j.1460-2075.1992.tb05182.x; RA Kashishian A., Kazlauskas A., Cooper J.A.; RT "Phosphorylation sites in the PDGF receptor with different specificities RT for binding GAP and PI3 kinase in vivo."; RL EMBO J. 11:1373-1382(1992). RN [16] RP FUNCTION AS PDGFB RECEPTOR IN CELL PROLIFERATION AND PHOSPHORYLATION OF RP PLCG1, INTERACTION WITH PLCG1, PHOSPHORYLATION AT TYR-1009 AND TYR-1021, RP AND MUTAGENESIS OF TYR-1009 AND TYR-1021. RX PubMed=1396585; DOI=10.1002/j.1460-2075.1992.tb05484.x; RA Ronnstrand L., Mori S., Arridsson A.K., Eriksson A., Wernstedt C., RA Hellman U., Claesson-Welsh L., Heldin C.H.; RT "Identification of two C-terminal autophosphorylation sites in the PDGF RT beta-receptor: involvement in the interaction with phospholipase C-gamma."; RL EMBO J. 11:3911-3919(1992). RN [17] RP UBIQUITINATION, AND DEGRADATION. RX PubMed=1313434; DOI=10.1016/s0021-9258(18)42714-7; RA Mori S., Heldin C.H., Claesson-Welsh L.; RT "Ligand-induced polyubiquitination of the platelet-derived growth factor RT beta-receptor."; RL J. Biol. Chem. 267:6429-6434(1992). RN [18] RP INTERACTION WITH PIK3R1 AND RASA1, AND MUTAGENESIS OF TYR-740; TYR-751 AND RP TYR-771. RX PubMed=1375321; DOI=10.1128/mcb.12.6.2534-2544.1992; RA Kazlauskas A., Kashishian A., Cooper J.A., Valius M.; RT "GTPase-activating protein and phosphatidylinositol 3-kinase bind to RT distinct regions of the platelet-derived growth factor receptor beta RT subunit."; RL Mol. Cell. Biol. 12:2534-2544(1992). RN [19] RP FUNCTION AS PDGFB RECEPTOR IN CELL PROLIFERATION, PHOSPHORYLATION AT RP TYR-579 AND TYR-581; INTERACTION WITH SRC, CATALYTIC ACTIVITY, AND RP MUTAGENESIS OF TYR-579 AND TYR-581. RX PubMed=7685273; DOI=10.1002/j.1460-2075.1993.tb05879.x; RA Mori S., Ronnstrand L., Yokote K., Engstrom A., Courtneidge S.A., RA Claesson-Welsh L., Heldin C.H.; RT "Identification of two juxtamembrane autophosphorylation sites in the PDGF RT beta-receptor; involvement in the interaction with Src family tyrosine RT kinases."; RL EMBO J. 12:2257-2264(1993). RN [20] RP INTERACTION WITH DGFA AND PDGFB. RX PubMed=7679113; DOI=10.1016/s0021-9258(18)53739-x; RA Fretto L.J., Snape A.J., Tomlinson J.E., Seroogy J.J., Wolf D.L., RA LaRochelle W.J., Giese N.A.; RT "Mechanism of platelet-derived growth factor (PDGF) AA, AB, and BB binding RT to alpha and beta PDGF receptor."; RL J. Biol. Chem. 268:3625-3631(1993). RN [21] RP FUNCTION IN PHOSPHORYLATION AND ACTIVATION OF PTPN11, INTERACTION WITH RP PTPN11; PIK3R1; PLCG1 AND RASA1, AND MUTAGENESIS OF TYR-1009. RX PubMed=7691811; DOI=10.1016/s0021-9258(20)80562-6; RA Lechleider R.J., Sugimoto S., Bennett A.M., Kashishian A.S., Cooper J.A., RA Shoelson S.E., Walsh C.T., Neel B.G.; RT "Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by RT its binding site, phosphotyrosine 1009, on the human platelet-derived RT growth factor receptor."; RL J. Biol. Chem. 268:21478-21481(1993). RN [22] RP INTERACTION WITH NCK1 AND PIK3R1, FUNCTION IN PHOSPHORYLATION OF NCK1, AND RP MUTAGENESIS OF TYR-751. RX PubMed=7692233; DOI=10.1128/mcb.13.11.6889-6896.1993; RA Nishimura R., Li W., Kashishian A., Mondino A., Zhou M., Cooper J., RA Schlessinger J.; RT "Two signaling molecules share a phosphotyrosine-containing binding site in RT the platelet-derived growth factor receptor."; RL Mol. Cell. Biol. 13:6889-6896(1993). RN [23] RP INTERACTION WITH SHB. RX PubMed=8302579; RA Welsh M., Mares J., Karlsson T., Lavergne C., Breant B., Claesson-Welsh L.; RT "Shb is a ubiquitously expressed Src homology 2 protein."; RL Oncogene 9:19-27(1994). RN [24] RP INTERACTION WITH GRB7. RX PubMed=8940081; DOI=10.1074/jbc.271.48.30942; RA Yokote K., Margolis B., Heldin C.H., Claesson-Welsh L.; RT "Grb7 is a downstream signaling component of platelet-derived growth factor RT alpha- and beta-receptors."; RL J. Biol. Chem. 271:30942-30949(1996). RN [25] RP CHROMOSOMAL TRANSLOCATION WITH TRIP11. RX PubMed=9373237; RA Abe A., Emi N., Tanimoto M., Terasaki H., Marunouchi T., Saito H.; RT "Fusion of the platelet-derived growth factor receptor beta to a novel gene RT CEV14 in acute myelogenous leukemia after clonal evolution."; RL Blood 90:4271-4277(1997). RN [26] RP INTERACTION WITH GRB10, AND MUTAGENESIS OF TYR-579; TYR-581; TYR-716; RP TYR-740; TYR-751; TYR-771; TYR-857; TYR-1009 AND TYR-1021. RX PubMed=10454568; DOI=10.1128/mcb.19.9.6217; RA Wang J., Dai H., Yousaf N., Moussaif M., Deng Y., Boufelliga A., RA Swamy O.R., Leone M.E., Riedel H.; RT "Grb10, a positive, stimulatory signaling adapter in platelet-derived RT growth factor BB-, insulin-like growth factor I-, and insulin-mediated RT mitogenesis."; RL Mol. Cell. Biol. 19:6217-6228(1999). RN [27] RP INTERACTION WITH SH2B2/APS. RX PubMed=9989826; DOI=10.1038/sj.onc.1202326; RA Yokouchi M., Wakioka T., Sakamoto H., Yasukawa H., Ohtsuka S., Sasaki A., RA Ohtsubo M., Valius M., Inoue A., Komiya S., Yoshimura A.; RT "APS, an adaptor protein containing PH and SH2 domains, is associated with RT the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis."; RL Oncogene 18:759-767(1999). RN [28] RP PHOSPHORYLATION AT TYR-562; TYR-751; TYR-763; TYR-771; TYR-775; TYR-778; RP TYR-857; TYR-1009 AND TYR-1021, AND DEPHOSPHORYLATION AT TYR-751; TYR-857; RP TYR-1009 AND TYR-1021 BY PTPRJ. RX PubMed=10821867; DOI=10.1074/jbc.275.21.16219; RA Kovalenko M., Denner K., Sandstrom J., Persson C., Gross S., Jandt E., RA Vilella R., Bohmer F., Ostman A.; RT "Site-selective dephosphorylation of the platelet-derived growth factor RT beta-receptor by the receptor-like protein-tyrosine phosphatase DEP-1."; RL J. Biol. Chem. 275:16219-16226(2000). RN [29] RP INTERACTION WITH PIK3C2B. RX PubMed=10805725; DOI=10.1128/mcb.20.11.3817-3830.2000; RA Arcaro A., Zvelebil M.J., Wallasch C., Ullrich A., Waterfield M.D., RA Domin J.; RT "Class II phosphoinositide 3-kinases are downstream targets of activated RT polypeptide growth factor receptors."; RL Mol. Cell. Biol. 20:3817-3830(2000). RN [30] RP FUNCTION AS A RECEPTOR FOR PDGFC, AND INTERACTION WITH PDGFC. RX PubMed=11297552; DOI=10.1074/jbc.m101056200; RA Gilbertson D.G., Duff M.E., West J.W., Kelly J.D., Sheppard P.O., RA Hofstrand P.D., Gao Z., Shoemaker K., Bukowski T.R., Moore M., RA Feldhaus A.L., Humes J.M., Palmer T.E., Hart C.E.; RT "Platelet-derived growth factor C (PDGF-C), a novel growth factor that RT binds to PDGF alpha and beta receptor."; RL J. Biol. Chem. 276:27406-27414(2001). RN [31] RP FUNCTION AS A RECEPTOR FOR PDGFD. RX PubMed=11331881; DOI=10.1038/35074588; RA Bergsten E., Uutela M., Li X., Pietras K., Oestman A., Heldin C.-H., RA Alitalo K., Eriksson U.; RT "PDGF-D is a specific, protease-activated ligand for the PDGF beta- RT receptor."; RL Nat. Cell Biol. 3:512-516(2001). RN [32] RP CHROMOSOMAL TRANSLOCATION WITH ETV6. RX PubMed=12181402; DOI=10.1056/nejmoa020150; RA Apperley J.F., Gardembas M., Melo J.V., Russell-Jones R., Bain B.J., RA Baxter E.J., Chase A., Chessells J.M., Colombat M., Dearden C.E., RA Dimitrijevic S., Mahon F.-X., Marin D., Nikolova Z., Olavarria E., RA Silberman S., Schultheis B., Cross N.C.P., Goldman J.M.; RT "Response to imatinib mesylate in patients with chronic myeloproliferative RT diseases with rearrangements of the platelet-derived growth factor receptor RT beta."; RL N. Engl. J. Med. 347:481-487(2002). RN [33] RP CHROMOSOMAL TRANSLOCATION WITH PDE4DIP. RX PubMed=12907457; DOI=10.1182/blood-2003-04-1150; RA Wilkinson K., Velloso E.R.P., Lopes L.F., Lee C., Aster J.C., Shipp M.A., RA Aguiar R.C.T.; RT "Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated RT with eosinophilia: involvement of PDGFRB and response to imatinib."; RL Blood 102:4187-4190(2003). RN [34] RP CHROMOSOMAL TRANSLOCATION WITH SPECC1. RX PubMed=15087372; DOI=10.1158/0008-5472.can-03-4026; RA Morerio C., Acquila M., Rosanda C., Rapella A., Dufour C., Locatelli F., RA Maserati E., Pasquali F., Panarello C.; RT "HCMOGT-1 is a novel fusion partner to PDGFRB in juvenile myelomonocytic RT leukemia with t(5;17)(q33;p11.2)."; RL Cancer Res. 64:2649-2651(2004). RN [35] RP CHROMOSOMAL TRANSLOCATION WITH TP53BP1, AND ACTIVITY REGULATION. RX PubMed=15492236; DOI=10.1158/0008-5472.can-04-2005; RA Grand F.H., Burgstaller S., Kuhr T., Baxter E.J., Webersinke G., Thaler J., RA Chase A.J., Cross N.C.; RT "p53-Binding protein 1 is fused to the platelet-derived growth factor RT receptor beta in a patient with a t(5;15)(q33;q22) and an imatinib- RT responsive eosinophilic myeloproliferative disorder."; RL Cancer Res. 64:7216-7219(2004). RN [36] RP PHOSPHORYLATION AT TYR-579; TYR-751; TYR-771 AND TYR-1021, AND RP DEPHOSPHORYLATION AT TYR-579 AND TYR-1021 BY PTPN2. RX PubMed=14966296; DOI=10.1128/mcb.24.5.2190-2201.2004; RA Persson C., Saevenhed C., Bourdeau A., Tremblay M.L., Markova B., RA Boehmer F.D., Haj F.G., Neel B.G., Elson A., Heldin C.H., Roennstrand L., RA Ostman A., Hellberg C.; RT "Site-selective regulation of platelet-derived growth factor beta receptor RT tyrosine phosphorylation by T-cell protein tyrosine phosphatase."; RL Mol. Cell. Biol. 24:2190-2201(2004). RN [37] RP PHOSPHORYLATION AT TYR-579; TYR-581; TYR-716; TYR-740; TYR-771; TYR-857; RP TYR-1009 AND TYR-1021. RX PubMed=15902258; DOI=10.1038/nature03587; RA Choi M.H., Lee I.K., Kim G.W., Kim B.U., Han Y.H., Yu D.Y., Park H.S., RA Kim K.Y., Lee J.S., Choi C., Bae Y.S., Lee B.I., Rhee S.G., Kang S.W.; RT "Regulation of PDGF signalling and vascular remodelling by peroxiredoxin RT II."; RL Nature 435:347-353(2005). RN [38] RP INTERACTION WITH CBL, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-1021, AND RP UBIQUITINATION. RX PubMed=17620338; DOI=10.1074/jbc.m701797200; RA Reddi A.L., Ying G., Duan L., Chen G., Dimri M., Douillard P., Druker B.J., RA Naramura M., Band V., Band H.; RT "Binding of Cbl to a phospholipase Cgamma1-docking site on platelet-derived RT growth factor receptor beta provides a dual mechanism of negative RT regulation."; RL J. Biol. Chem. 282:29336-29347(2007). RN [39] RP FUNCTION AS PDGFD RECEPTOR. RX PubMed=21098708; DOI=10.1158/0008-5472.can-10-0511; RA Ustach C.V., Huang W., Conley-LaComb M.K., Lin C.Y., Che M., Abrams J., RA Kim H.R.; RT "A novel signaling axis of matriptase/PDGF-D/ss-PDGFR in human prostate RT cancer."; RL Cancer Res. 70:9631-9640(2010). RN [40] RP FUNCTION IN PHOSPHORYLATION OF CBL; STAM; PDCD6IP/ALIX; PLCG1 AND PTPN11, RP CATALYTIC ACTIVITY, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF LYS-634 AND TYR-857. RX PubMed=20494825; DOI=10.1016/j.cellsig.2010.05.004; RA Wardega P., Heldin C.H., Lennartsson J.; RT "Mutation of tyrosine residue 857 in the PDGF beta-receptor affects cell RT proliferation but not migration."; RL Cell. Signal. 22:1363-1368(2010). RN [41] RP FUNCTION. RX PubMed=20529858; DOI=10.1074/jbc.m110.102566; RA Mendelson K., Swendeman S., Saftig P., Blobel C.P.; RT "Stimulation of platelet-derived growth factor receptor beta (PDGFRbeta) RT activates ADAM17 and promotes metalloproteinase-dependent cross-talk RT between the PDGFRbeta and epidermal growth factor receptor (EGFR) signaling RT pathways."; RL J. Biol. Chem. 285:25024-25032(2010). RN [42] RP FUNCTION IN SMOOTH MUSCLE CELL PROLIFERATION AND MIGRATION. RX PubMed=21733313; DOI=10.1017/s0007114511002571; RA Kim H.J., Cha B.Y., Choi B., Lim J.S., Woo J.T., Kim J.S.; RT "Glyceollins inhibit platelet-derived growth factor-mediated human arterial RT smooth muscle cell proliferation and migration."; RL Br. J. Nutr. 107:24-35(2012). RN [43] RP INTERACTION WITH SHC1 AND GRB2, AND FUNCTION IN PHOSPHORYLATION OF SHC1. RX PubMed=8195171; DOI=10.1016/s0021-9258(17)36611-5; RA Yokote K., Mori S., Hansen K., McGlade J., Pawson T., Heldin C.H., RA Claesson-Welsh L.; RT "Direct interaction between Shc and the platelet-derived growth factor RT beta-receptor."; RL J. Biol. Chem. 269:15337-15343(1994). RN [44] RP FUNCTION IN SMOOTH MUSCLE CELL MIGRATION AND NEOINTIMA FORMATION AFTER RP BLOOD VESSEL INJURY, AND MUTAGENESIS OF TYR-740; TYR-751 AND TYR-1021. RX PubMed=21679854; DOI=10.1016/j.jacc.2011.02.037; RA Caglayan E., Vantler M., Leppanen O., Gerhardt F., Mustafov L., RA Ten Freyhaus H., Kappert K., Odenthal M., Zimmermann W.H., Tallquist M.D., RA Rosenkranz S.; RT "Disruption of platelet-derived growth factor-dependent RT phosphatidylinositol 3-kinase and phospholipase Cgamma 1 activity abolishes RT vascular smooth muscle cell proliferation and migration and attenuates RT neointima formation in vivo."; RL J. Am. Coll. Cardiol. 57:2527-2538(2011). RN [45] RP INVOLVEMENT IN PENTT, VARIANT PENTT ALA-665, AND CHARACTERIZATION OF RP VARIANT PENTT ALA-665. RX PubMed=26279204; DOI=10.1016/j.ajhg.2015.07.009; RA Johnston J.J., Sanchez-Contreras M.Y., Keppler-Noreuil K.M., Sapp J., RA Crenshaw M., Finch N.A., Cormier-Daire V., Rademakers R., Sybert V.P., RA Biesecker L.G.; RT "A point mutation in PDGFRB causes autosomal-dominant Penttinen syndrome."; RL Am. J. Hum. Genet. 97:465-474(2015). RN [46] RP INVOLVEMENT IN KOGS, AND VARIANT KOGS ARG-584. RX PubMed=25454926; DOI=10.1016/j.jpeds.2014.10.015; RA Takenouchi T., Yamaguchi Y., Tanikawa A., Kosaki R., Okano H., Kosaki K.; RT "Novel overgrowth syndrome phenotype due to recurrent de novo PDGFRB RT mutation."; RL J. Pediatr. 166:483-486(2015). RN [47] RP CHARACTERIZATION OF VARIANTS IBGC4 PRO-658; TRP-987 AND VAL-1071, AND RP FUNCTION. RX PubMed=26599395; DOI=10.1371/journal.pone.0143407; RA Vanlandewijck M., Lebouvier T., Andaloussi Maee M., Nahar K., Hornemann S., RA Kenkel D., Cunha S.I., Lennartsson J., Boss A., Heldin C.H., Keller A., RA Betsholtz C.; RT "Functional characterization of germline mutations in PDGFB and PDGFRB in RT primary familial brain calcification."; RL PLoS ONE 10:E0143407-E0143407(2015). RN [48] RP REVIEW ON SIGNALING AND AUTOPHOSPHORYLATION. RX PubMed=9739761; DOI=10.1016/s0304-419x(98)00015-8; RA Heldin C.H., Ostman A., Ronnstrand L.; RT "Signal transduction via platelet-derived growth factor receptors."; RL Biochim. Biophys. Acta 1378:F79-113(1998). RN [49] RP REVIEW. RX PubMed=15207817; DOI=10.1016/j.cytogfr.2004.03.002; RA Ostman A.; RT "PDGF receptors-mediators of autocrine tumor growth and regulators of tumor RT vasculature and stroma."; RL Cytokine Growth Factor Rev. 15:275-286(2004). RN [50] RP REVIEW. RX PubMed=17419949; DOI=10.1016/s0065-230x(06)97011-0; RA Ostman A., Heldin C.H.; RT "PDGF receptors as targets in tumor treatment."; RL Adv. Cancer Res. 97:247-274(2007). RN [51] RP REVIEW ON FUNCTION; LIGANDS; ROLE IN DEVELOPMENT AND DISEASE AND ACTIVATION RP OF SIGNALING PATHWAYS. RX PubMed=18483217; DOI=10.1101/gad.1653708; RA Andrae J., Gallini R., Betsholtz C.; RT "Role of platelet-derived growth factors in physiology and medicine."; RL Genes Dev. 22:1276-1312(2008). RN [52] RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 751-755 IN COMPLEX WITH PIK3R1, RP AND COMPARISON WITH NMR ANALYSIS. RX PubMed=11567151; DOI=10.1107/s0907444901012434; RA Pauptit R.A., Dennis C.A., Derbyshire D.J., Breeze A.L., Weston S.A., RA Rowsell S., Murshudov G.N.; RT "NMR trial models: experiences with the colicin immunity protein Im7 and RT the p85alpha C-terminal SH2-peptide complex."; RL Acta Crystallogr. D 57:1397-1404(2001). RN [53] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1102-1106 IN COMPLEX WITH NHERF1, RP AND INTERACTION WITH NHERF1. RX PubMed=11882663; DOI=10.1074/jbc.m201507200; RA Karthikeyan S., Leung T., Ladias J.A.A.; RT "Structural determinants of the Na+/H+ exchanger regulatory factor RT interaction with the beta 2 adrenergic and platelet-derived growth factor RT receptors."; RL J. Biol. Chem. 277:18973-18978(2002). RN [54] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 33-314 IN COMPLEX WITH PDGFB, RP SUBUNIT, GLYCOSYLATION AT ASN-45; ASN-89; ASN-103; ASN-215; ASN-230; RP ASN-292 AND ASN-307, AND DISULFIDE BONDS. RX PubMed=20534510; DOI=10.1073/pnas.1000806107; RA Shim A.H., Liu H., Focia P.J., Chen X., Lin P.C., He X.; RT "Structures of a platelet-derived growth factor/propeptide complex and a RT platelet-derived growth factor/receptor complex."; RL Proc. Natl. Acad. Sci. U.S.A. 107:11307-11312(2010). RN [55] RP VARIANTS [LARGE SCALE ANALYSIS] PHE-29; LYS-282; LYS-485; HIS-589; TYR-718 RP AND ILE-882. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [56] RP VARIANT IMF1 THR-660, AND INVOLVEMENT IN IMF1. RX PubMed=23731542; DOI=10.1016/j.ajhg.2013.04.024; RA Martignetti J.A., Tian L., Li D., Ramirez M.C., Camacho-Vanegas O., RA Camacho S.C., Guo Y., Zand D.J., Bernstein A.M., Masur S.K., Kim C.E., RA Otieno F.G., Hou C., Abdel-Magid N., Tweddale B., Metry D., Fournet J.C., RA Papp E., McPherson E.W., Zabel C., Vaksmann G., Morisot C., Keating B., RA Sleiman P.M., Cleveland J.A., Everman D.B., Zackai E., Hakonarson H.; RT "Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis."; RL Am. J. Hum. Genet. 92:1001-1007(2013). RN [57] RP VARIANT IMF1 CYS-561, AND INVOLVEMENT IN IMF1. RX PubMed=23731537; DOI=10.1016/j.ajhg.2013.04.026; RA Cheung Y.H., Gayden T., Campeau P.M., Leduc C.A., Russo D., Nguyen V.H., RA Guo J., Qi M., Guan Y., Albrecht S., Moroz B., Eldin K.W., Lu J.T., RA Schwartzentruber J., Malkin D., Berghuis A.M., Emil S., Gibbs R.A., RA Burk D.L., Vanstone M., Lee B.H., Orchard D., Boycott K.M., Chung W.K., RA Jabado N.; RT "A recurrent PDGFRB mutation causes familial infantile myofibromatosis."; RL Am. J. Hum. Genet. 92:996-1000(2013). RN [58] RP VARIANTS IBGC4 PRO-658; TRP-987 AND VAL-1071, AND INVOLVEMENT IN IBGC4. RX PubMed=24065723; DOI=10.1093/brain/awt255; RG French IBGC Study Group; RA Nicolas G., Pottier C., Charbonnier C., Guyant-Marechal L., Le Ber I., RA Pariente J., Labauge P., Ayrignac X., Defebvre L., Maltete D., RA Martinaud O., Lefaucheur R., Guillin O., Wallon D., Chaumette B., RA Rondepierre P., Derache N., Fromager G., Schaeffer S., Krystkowiak P., RA Verny C., Jurici S., Sauvee M., Verin M., Lebouvier T., Rouaud O., RA Thauvin-Robinet C., Rousseau S., Rovelet-Lecrux A., Frebourg T., RA Campion D., Hannequin D.; RT "Phenotypic spectrum of probable and genetically-confirmed idiopathic basal RT ganglia calcification."; RL Brain 136:3395-3407(2013). RN [59] RP VARIANTS IBGC4 PRO-658 AND TRP-987, AND INVOLVEMENT IN IBGC4. RX PubMed=23255827; DOI=10.1212/wnl.0b013e31827ccf34; RA Nicolas G., Pottier C., Maltete D., Coutant S., Rovelet-Lecrux A., RA Legallic S., Rousseau S., Vaschalde Y., Guyant-Marechal L., Augustin J., RA Martinaud O., Defebvre L., Krystkowiak P., Pariente J., Clanet M., RA Labauge P., Ayrignac X., Lefaucheur R., Le Ber I., Frebourg T., RA Hannequin D., Campion D.; RT "Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia RT calcification."; RL Neurology 80:181-187(2013). RN [60] RP VARIANT PENTT SER-666, CHARACTERIZATION OF VARIANT PENTT SER-666, AND RP INVOLVEMENT IN PENTT. RX PubMed=30573803; DOI=10.1038/s41431-018-0323-z; RA Bredrup C., Stokowy T., McGaughran J., Lee S., Sapkota D., Cristea I., RA Xu L., Tveit K.S., Hoevding G., Steen V.M., Roedahl E., Bruland O., RA Houge G.; RT "A tyrosine kinase-activating variant Asn666Ser in PDGFRB causes a RT progeria-like condition in the severe end of Penttinen syndrome."; RL Eur. J. Hum. Genet. 27:574-581(2019). RN [61] RP VARIANT OPDKD TYR-666, CHARACTERIZATION OF VARIANT OPDKD TYR-666, AND RP INVOLVEMENT IN OPDKD. RX PubMed=33450762; DOI=10.1093/hmg/ddab014; RA Bredrup C., Cristea I., Safieh L.A., Di Maria E., Gjertsen B.T., RA Tveit K.S., Thu F., Bull N., Edward D.P., Hennekam R.C.M., Hoevding G., RA Haugen O.H., Houge G., Roedahl E., Bruland O.; RT "Temperature-dependent autoactivation associated with clinical variability RT of PDGFRB Asn666 substitutions."; RL Hum. Mol. Genet. 30:72-77(2021). CC -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor CC for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA CC and PDGFB, and plays an essential role in the regulation of embryonic CC development, cell proliferation, survival, differentiation, chemotaxis CC and migration. Plays an essential role in blood vessel development by CC promoting proliferation, migration and recruitment of pericytes and CC smooth muscle cells to endothelial cells. Plays a role in the migration CC of vascular smooth muscle cells and the formation of neointima at CC vascular injury sites. Required for normal development of the CC cardiovascular system. Required for normal recruitment of pericytes CC (mesangial cells) in the kidney glomerulus, and for normal formation of CC a branched network of capillaries in kidney glomeruli. Promotes CC rearrangement of the actin cytoskeleton and the formation of membrane CC ruffles. Binding of its cognate ligands - homodimeric PDGFB, CC heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD -leads to CC the activation of several signaling cascades; the response depends on CC the nature of the bound ligand and is modulated by the formation of CC heterodimers between PDGFRA and PDGFRB. Phosphorylates PLCG1, PIK3R1, CC PTPN11, RASA1/GAP, CBL, SHC1 and NCK1. Activation of PLCG1 leads to the CC production of the cellular signaling molecules diacylglycerol and CC inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the CC activation of protein kinase C. Phosphorylation of PIK3R1, the CC regulatory subunit of phosphatidylinositol 3-kinase, leads to the CC activation of the AKT1 signaling pathway. Phosphorylation of SHC1, or CC of the C-terminus of PTPN11, creates a binding site for GRB2, resulting CC in the activation of HRAS, RAF1 and down-stream MAP kinases, including CC MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation and activation CC of SRC family kinases. Promotes phosphorylation of PDCD6IP/ALIX and CC STAM. Receptor signaling is down-regulated by protein phosphatases that CC dephosphorylate the receptor and its down-stream effectors, and by CC rapid internalization of the activated receptor. CC {ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:11331881, CC ECO:0000269|PubMed:1314164, ECO:0000269|PubMed:1396585, CC ECO:0000269|PubMed:1653029, ECO:0000269|PubMed:1709159, CC ECO:0000269|PubMed:1846866, ECO:0000269|PubMed:20494825, CC ECO:0000269|PubMed:20529858, ECO:0000269|PubMed:21098708, CC ECO:0000269|PubMed:21679854, ECO:0000269|PubMed:21733313, CC ECO:0000269|PubMed:2554309, ECO:0000269|PubMed:26599395, CC ECO:0000269|PubMed:2835772, ECO:0000269|PubMed:2850496, CC ECO:0000269|PubMed:7685273, ECO:0000269|PubMed:7691811, CC ECO:0000269|PubMed:7692233, ECO:0000269|PubMed:8195171}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.10.1; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, CC ECO:0000269|PubMed:1846866, ECO:0000269|PubMed:20494825, CC ECO:0000269|PubMed:7685273}; CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence CC of bound ligand. Binding of PDGFB and/or PDGFD leads to dimerization CC and activation by autophosphorylation on tyrosine residues. Inhibited CC by imatinib. {ECO:0000269|PubMed:15492236}. CC -!- SUBUNIT: Interacts with homodimeric PDGFB and PDGFD, and with CC heterodimers formed by PDGFA and PDGFB. May also interact with CC homodimeric PDGFC. Monomer in the absence of bound ligand. Interaction CC with homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or CC homodimeric PDGFD, leads to receptor dimerization, where both PDGFRA CC homodimers and heterodimers with PDGFRB are observed. Interacts with CC SH2B2/APS. Interacts directly (tyrosine phosphorylated) with SHB. CC Interacts (tyrosine phosphorylated) with PIK3R1 and RASA1. Interacts CC (tyrosine phosphorylated) with CBL. Interacts (tyrosine phosphorylated) CC with SRC and SRC family kinases. Interacts (tyrosine phosphorylated) CC with PIK3C2B, maybe indirectly. Interacts (tyrosine phosphorylated) CC with SHC1, GRB7, GRB10 and NCK1. Interaction with GRB2 is mediated by CC SHC1. Interacts (via C-terminus) with NHERF1. CC {ECO:0000269|PubMed:10454568, ECO:0000269|PubMed:10805725, CC ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:11567151, CC ECO:0000269|PubMed:11882663, ECO:0000269|PubMed:1314164, CC ECO:0000269|PubMed:1375321, ECO:0000269|PubMed:1396585, CC ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:17620338, CC ECO:0000269|PubMed:20534510, ECO:0000269|PubMed:2835772, CC ECO:0000269|PubMed:2850496, ECO:0000269|PubMed:7679113, CC ECO:0000269|PubMed:7691811, ECO:0000269|PubMed:7692233, CC ECO:0000269|PubMed:8195171, ECO:0000269|PubMed:8302579, CC ECO:0000269|PubMed:8940081, ECO:0000269|PubMed:9989826}. CC -!- INTERACTION: CC P09619; P05067: APP; NbExp=3; IntAct=EBI-641237, EBI-77613; CC P09619; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-641237, EBI-742887; CC P09619; P06241: FYN; NbExp=3; IntAct=EBI-641237, EBI-515315; CC P09619; Q14451: GRB7; NbExp=4; IntAct=EBI-641237, EBI-970191; CC P09619; P14778: IL1R1; NbExp=2; IntAct=EBI-641237, EBI-525905; CC P09619; P35968: KDR; NbExp=2; IntAct=EBI-641237, EBI-1005487; CC P09619; Q53G59: KLHL12; NbExp=6; IntAct=EBI-641237, EBI-740929; CC P09619; Q5T749: KPRP; NbExp=3; IntAct=EBI-641237, EBI-10981970; CC P09619; Q15323: KRT31; NbExp=3; IntAct=EBI-641237, EBI-948001; CC P09619; O76011: KRT34; NbExp=3; IntAct=EBI-641237, EBI-1047093; CC P09619; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-641237, EBI-10172052; CC P09619; P60328: KRTAP12-3; NbExp=3; IntAct=EBI-641237, EBI-11953334; CC P09619; O94898: LRIG2; NbExp=3; IntAct=EBI-641237, EBI-2830372; CC P09619; O75581: LRP6; NbExp=3; IntAct=EBI-641237, EBI-910915; CC P09619; O14745: NHERF1; NbExp=5; IntAct=EBI-641237, EBI-349787; CC P09619; Q15599: NHERF2; NbExp=2; IntAct=EBI-641237, EBI-1149760; CC P09619; P01127: PDGFB; NbExp=16; IntAct=EBI-641237, EBI-1554925; CC P09619; P27986: PIK3R1; NbExp=21; IntAct=EBI-641237, EBI-79464; CC P09619; O00459: PIK3R2; NbExp=3; IntAct=EBI-641237, EBI-346930; CC P09619; P19174: PLCG1; NbExp=7; IntAct=EBI-641237, EBI-79387; CC P09619; P60484: PTEN; NbExp=3; IntAct=EBI-641237, EBI-696162; CC P09619; P18031: PTPN1; NbExp=3; IntAct=EBI-641237, EBI-968788; CC P09619; Q06124: PTPN11; NbExp=8; IntAct=EBI-641237, EBI-297779; CC P09619; Q05209: PTPN12; NbExp=3; IntAct=EBI-641237, EBI-2266035; CC P09619; P23470: PTPRG; NbExp=2; IntAct=EBI-641237, EBI-2258115; CC P09619; Q12913: PTPRJ; NbExp=4; IntAct=EBI-641237, EBI-2264500; CC P09619; P20936: RASA1; NbExp=3; IntAct=EBI-641237, EBI-1026476; CC P09619; Q13239: SLA; NbExp=4; IntAct=EBI-641237, EBI-726214; CC P09619; Q15654: TRIP6; NbExp=3; IntAct=EBI-641237, EBI-742327; CC P09619; P07947: YES1; NbExp=3; IntAct=EBI-641237, EBI-515331; CC P09619; P0CK45: E5; Xeno; NbExp=2; IntAct=EBI-641237, EBI-7015490; CC P09619; P35918: Kdr; Xeno; NbExp=4; IntAct=EBI-641237, EBI-1555005; CC P09619; Q28619: NHERF1; Xeno; NbExp=3; IntAct=EBI-641237, EBI-7073613; CC P09619; P23727: PIK3R1; Xeno; NbExp=6; IntAct=EBI-641237, EBI-520244; CC P09619; P08487: PLCG1; Xeno; NbExp=3; IntAct=EBI-641237, EBI-8013886; CC P09619; P41499: Ptpn11; Xeno; NbExp=4; IntAct=EBI-641237, EBI-7180604; CC P09619; P25020: V-SRC; Xeno; NbExp=4; IntAct=EBI-641237, EBI-8636140; CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane CC protein. Cytoplasmic vesicle. Lysosome lumen. Note=After ligand CC binding, the autophosphorylated receptor is ubiquitinated and CC internalized, leading to its degradation. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P09619-1; Sequence=Displayed; CC Name=2; CC IsoId=P09619-2; Sequence=VSP_056008, VSP_056009; CC -!- PTM: Autophosphorylated on tyrosine residues upon ligand binding. CC Autophosphorylation occurs in trans, i.e. one subunit of the dimeric CC receptor phosphorylates tyrosine residues on the other subunit. CC Phosphorylation at Tyr-579, and to a lesser degree, at Tyr-581, is CC important for interaction with SRC family kinases. Phosphorylation at CC Tyr-740 and Tyr-751 is important for interaction with PIK3R1. CC Phosphorylation at Tyr-751 is important for interaction with NCK1. CC Phosphorylation at Tyr-771 and Tyr-857 is important for interaction CC with RASA1/GAP. Phosphorylation at Tyr-857 is important for efficient CC phosphorylation of PLCG1 and PTPN11, resulting in increased CC phosphorylation of AKT1, MAPK1/ERK2 and/or MAPK3/ERK1, PDCD6IP/ALIX and CC STAM, and in increased cell proliferation. Phosphorylation at Tyr-1009 CC is important for interaction with PTPN11. Phosphorylation at Tyr-1009 CC and Tyr-1021 is important for interaction with PLCG1. Phosphorylation CC at Tyr-1021 is important for interaction with CBL; PLCG1 and CBL CC compete for the same binding site. Dephosphorylated by PTPRJ at Tyr- CC 751, Tyr-857, Tyr-1009 and Tyr-1021. Dephosphorylated by PTPN2 at Tyr- CC 579 and Tyr-1021. {ECO:0000269|PubMed:10821867, CC ECO:0000269|PubMed:1314164, ECO:0000269|PubMed:1396585, CC ECO:0000269|PubMed:14966296, ECO:0000269|PubMed:15902258, CC ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:2550144, CC ECO:0000269|PubMed:7685273}. CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:20534510, CC ECO:0000269|PubMed:2850496}. CC -!- PTM: Ubiquitinated. After autophosphorylation, the receptor is CC polyubiquitinated, leading to its degradation. CC {ECO:0000269|PubMed:1313434, ECO:0000269|PubMed:17620338}. CC -!- DISEASE: Note=A chromosomal aberration involving PDGFRB is found in a CC form of chronic myelomonocytic leukemia (CMML). Translocation CC t(5;12)(q33;p13) with EVT6/TEL. It is characterized by abnormal clonal CC myeloid proliferation and by progression to acute myelogenous leukemia CC (AML). CC -!- DISEASE: Myeloproliferative disorder chronic with eosinophilia (MPE) CC [MIM:131440]: A hematologic disorder characterized by malignant CC eosinophils proliferation. Note=The gene represented in this entry may CC be involved in disease pathogenesis. Chromosomal aberrations involving CC PDGFRB have been found in many instances of chronic myeloproliferative CC disorder with eosinophilia. Translocation t(5;12) with ETV6 on CC chromosome 12 creating an PDGFRB-ETV6 fusion protein (PubMed:12181402). CC Translocation t(5;15)(q33;q22) with TP53BP1 creating a PDGFRB-TP53BP1 CC fusion protein (PubMed:15492236). Translocation t(1;5)(q23;q33) that CC forms a PDE4DIP-PDGFRB fusion protein (PubMed:12907457). Translocation CC t(5;6)(q33-34;q23) with CEP85L that fuses the 5'-end of CEP85L (isoform CC 4) to the 3'-end of PDGFRB (PubMed:21938754). CC {ECO:0000269|PubMed:12181402, ECO:0000269|PubMed:12907457, CC ECO:0000269|PubMed:15492236, ECO:0000269|PubMed:21938754}. CC -!- DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of CC acute leukemia, a cancer of the white blood cells. AML is a malignant CC disease of bone marrow characterized by maturational arrest of CC hematopoietic precursors at an early stage of development. Clonal CC expansion of myeloid blasts occurs in bone marrow, blood, and other CC tissue. Myelogenous leukemias develop from changes in cells that CC normally produce neutrophils, basophils, eosinophils and monocytes. CC Note=The gene represented in this entry may be involved in disease CC pathogenesis. A chromosomal aberration involving PDGFRB has been found CC in a patient with AML. Translocation t(5;14)(q33;q32) with TRIP11 CC (PubMed:9373237). {ECO:0000269|PubMed:9373237}. CC -!- DISEASE: Leukemia, juvenile myelomonocytic (JMML) [MIM:607785]: An CC aggressive pediatric myelodysplastic syndrome/myeloproliferative CC disorder characterized by malignant transformation in the hematopoietic CC stem cell compartment with proliferation of differentiated progeny. CC Patients have splenomegaly, enlarged lymph nodes, rashes, and CC hemorrhages. Note=The gene represented in this entry may be involved in CC disease pathogenesis. A chromosomal aberration involving PDGFRB has CC been found in a patient with JMML. Translocation t(5;17)(q33;p11.2) CC with SPECC1 (PubMed:15087372). {ECO:0000269|PubMed:15087372}. CC -!- DISEASE: Basal ganglia calcification, idiopathic, 4 (IBGC4) CC [MIM:615007]: A form of basal ganglia calcification, an autosomal CC dominant condition characterized by symmetric calcification in the CC basal ganglia and other brain regions. Affected individuals can either CC be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, CC including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, CC seizures, and chronic headache. Serum levels of calcium, phosphate, CC alkaline phosphatase and parathyroid hormone are normal. The CC neuropathological hallmark of the disease is vascular and pericapillary CC calcification, mainly of calcium phosphate, in the affected brain CC areas. {ECO:0000269|PubMed:23255827, ECO:0000269|PubMed:24065723, CC ECO:0000269|PubMed:26599395}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Myofibromatosis, infantile 1 (IMF1) [MIM:228550]: A rare CC mesenchymal disorder characterized by the development of benign tumors CC in the skin, striated muscles, bones, and, more rarely, visceral CC organs. Subcutaneous or soft tissue nodules commonly involve the skin CC of the head, neck, and trunk. Skeletal and muscular lesions occur in CC about half of the patients. Lesions may be solitary or multicentric, CC and they may be present at birth or become apparent in early infancy or CC occasionally in adult life. Visceral lesions are associated with high CC morbidity and mortality. {ECO:0000269|PubMed:23731537, CC ECO:0000269|PubMed:23731542}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Kosaki overgrowth syndrome (KOGS) [MIM:616592]: A syndrome CC characterized by somatic overgrowth, distinctive facial features, CC hyperelastic and fragile skin, and progressive neurologic deterioration CC with white matter lesions on brain imaging. CC {ECO:0000269|PubMed:25454926}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Premature aging syndrome, Penttinen type (PENTT) [MIM:601812]: CC An autosomal dominant syndrome characterized by a prematurely aged CC appearance with lipoatrophy, epidermal and dermal atrophy along with CC hypertrophic lesions that resemble scars, thin hair, proptosis, CC underdeveloped cheekbones, and marked acro-osteolysis. CC {ECO:0000269|PubMed:26279204, ECO:0000269|PubMed:30573803}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Ocular pterygium-digital keloid dysplasia syndrome (OPDKD) CC [MIM:621091]: An autosomal dominant disorder that presents in childhood CC with aggressive ingrowth of vascularized connective tissue on the CC cornea, ultimately leading to loss of vision. Later, affected CC individuals develop keloids on digits after minor trauma, but are CC otherwise healthy. {ECO:0000269|PubMed:33450762}. Note=The disease may CC be caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/21/PDGFRB"; 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; J03278; AAA60049.1; -; mRNA. DR EMBL; M21616; AAA36427.1; -; mRNA. DR EMBL; EU826595; ACF47631.1; -; mRNA. DR EMBL; AC005895; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC011382; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC032224; AAH32224.1; -; mRNA. DR EMBL; U33172; AAC51675.1; -; Genomic_DNA. DR CCDS; CCDS4303.1; -. [P09619-1] DR PIR; A28206; PFHUGB. DR RefSeq; NP_002600.1; NM_002609.4. [P09619-1] DR PDB; 1GQ5; X-ray; 2.20 A; A=1102-1106. DR PDB; 1H9O; X-ray; 1.79 A; B=751-755. DR PDB; 1SHA; X-ray; 1.50 A; B=751-755. DR PDB; 2IUI; X-ray; 2.40 A; C/D=748-758. DR PDB; 2L6W; NMR; -; A/B=526-563. DR PDB; 2PLD; NMR; -; B=1018-1029. DR PDB; 2PLE; NMR; -; B=1018-1029. DR PDB; 3MJG; X-ray; 2.30 A; X/Y=33-314. DR PDBsum; 1GQ5; -. DR PDBsum; 1H9O; -. DR PDBsum; 1SHA; -. DR PDBsum; 2IUI; -. DR PDBsum; 2L6W; -. DR PDBsum; 2PLD; -. DR PDBsum; 2PLE; -. DR PDBsum; 3MJG; -. DR AlphaFoldDB; P09619; -. DR BMRB; P09619; -. DR EMDB; EMD-6426; -. DR SMR; P09619; -. DR BioGRID; 111185; 211. DR ComplexPortal; CPX-2882; PDGF receptor beta - PDGF-BB complex. DR ComplexPortal; CPX-2883; PDGF receptor alpha-beta - PDGF-BB complex. DR ComplexPortal; CPX-2886; PDGF receptor beta - PDGF-AB complex. DR ComplexPortal; CPX-2888; PDGF receptor alpha-beta - PDGF-CC complex. DR ComplexPortal; CPX-2889; PDGF receptor beta - PDGF-DD complex. DR ComplexPortal; CPX-2890; PDGF receptor alpha-beta - PDGF-DD complex. DR ComplexPortal; CPX-2891; PDGF receptor beta - PDGF-CC complex. DR ComplexPortal; CPX-2892; PDGF receptor alpha-beta - PDGF-AB complex. DR CORUM; P09619; -. DR DIP; DIP-558N; -. DR FunCoup; P09619; 1764. DR IntAct; P09619; 390. DR MINT; P09619; -. DR STRING; 9606.ENSP00000261799; -. DR BindingDB; P09619; -. DR ChEMBL; CHEMBL1913; -. DR DrugBank; DB00102; Becaplermin. DR DrugBank; DB01254; Dasatinib. DR DrugBank; DB12147; Erdafitinib. DR DrugBank; DB11741; Famitinib. DR DrugBank; DB10770; Foreskin fibroblast (neonatal). DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB11845; Lucitanib. DR DrugBank; DB06595; Midostaurin. DR DrugBank; DB09079; Nintedanib. DR DrugBank; DB06589; Pazopanib. DR DrugBank; DB08339; PD-166326. DR DrugBank; DB17041; PD-173952. DR DrugBank; DB02567; PD173955. DR DrugBank; DB12978; Pexidartinib. DR DrugBank; DB09221; Polaprezinc. DR DrugBank; DB15822; Pralsetinib. DR DrugBank; DB08896; Regorafenib. DR DrugBank; DB14840; Ripretinib. DR DrugBank; DB06436; Semaxanib. DR DrugBank; DB00398; Sorafenib. DR DrugBank; DB08009; SU-11652. DR DrugBank; DB01268; Sunitinib. DR DrugBank; DB13093; TAK-593. DR DrugBank; DB11800; Tivozanib. DR DrugBank; DB09283; Trapidil. DR DrugBank; DB05146; XL820. DR DrugBank; DB05014; XL999. DR DrugCentral; P09619; -. DR GuidetoPHARMACOLOGY; 1804; -. DR TCDB; 8.A.23.1.37; the basigin (basigin) family. DR GlyConnect; 1967; 4 N-Linked glycans (3 sites). DR GlyCosmos; P09619; 11 sites, 4 glycans. DR GlyGen; P09619; 13 sites, 4 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; P09619; -. DR PhosphoSitePlus; P09619; -. DR BioMuta; PDGFRB; -. DR DMDM; 129890; -. DR CPTAC; CPTAC-1630; -. DR CPTAC; CPTAC-3063; -. DR jPOST; P09619; -. DR MassIVE; P09619; -. DR PaxDb; 9606-ENSP00000261799; -. DR PeptideAtlas; P09619; -. DR ProteomicsDB; 52253; -. [P09619-1] DR Pumba; P09619; -. DR ABCD; P09619; 7 sequenced antibodies. DR Antibodypedia; 3424; 2244 antibodies from 49 providers. DR DNASU; 5159; -. DR Ensembl; ENST00000261799.9; ENSP00000261799.4; ENSG00000113721.15. [P09619-1] DR GeneID; 5159; -. DR KEGG; hsa:5159; -. DR MANE-Select; ENST00000261799.9; ENSP00000261799.4; NM_002609.4; NP_002600.1. DR UCSC; uc003lro.4; human. [P09619-1] DR AGR; HGNC:8804; -. DR CIViC; 5159; 2 evidence items across 3 molecular profiles. DR ClinPGx; PA33148; -. DR CTD; 5159; -. DR DisGeNET; 5159; -. DR GeneCards; PDGFRB; -. DR GeneReviews; PDGFRB; -. DR HGNC; HGNC:8804; PDGFRB. DR HPA; ENSG00000113721; Low tissue specificity. DR MalaCards; PDGFRB; -. DR MIM; 131440; phenotype. DR MIM; 173410; gene. DR MIM; 228550; phenotype. DR MIM; 601626; phenotype. DR MIM; 601812; phenotype. DR MIM; 607785; phenotype. DR MIM; 615007; phenotype. DR MIM; 616592; phenotype. DR MIM; 621091; phenotype. DR OpenTargets; ENSG00000113721; -. DR Orphanet; 363665; Acroosteolysis-keloid-like lesions-premature aging syndrome. DR Orphanet; 1980; Bilateral striopallidodentate calcinosis. DR Orphanet; 86830; Chronic myeloproliferative disease, unclassifiable. DR Orphanet; 2591; Infantile myofibromatosis. DR Orphanet; 477831; Kosaki overgrowth syndrome. DR Orphanet; 168950; Myeloid/lymphoid neoplasm associated with PDGFRB rearrangement. DR Orphanet; 314950; Primary hypereosinophilic syndrome. DR VEuPathDB; HostDB:ENSG00000113721; -. DR eggNOG; KOG0200; Eukaryota. DR GeneTree; ENSGT00940000157138; -. DR HOGENOM; CLU_000288_49_0_1; -. DR InParanoid; P09619; -. DR OMA; WPEDQEF; -. DR OrthoDB; 9936425at2759; -. DR PAN-GO; P09619; 10 GO annotations based on evolutionary models. DR PhylomeDB; P09619; -. DR BRENDA; 2.7.10.1; 2681. DR PathwayCommons; P09619; -. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-186763; Downstream signal transduction. DR Reactome; R-HSA-186797; Signaling by PDGF. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR SignaLink; P09619; -. DR SIGNOR; P09619; -. DR Agora; ENSG00000113721; -. DR BioGRID-ORCS; 5159; 18 hits in 1194 CRISPR screens. DR CD-CODE; 91857CE7; Nucleolus. DR ChiTaRS; PDGFRB; human. DR EvolutionaryTrace; P09619; -. DR GeneWiki; PDGFRB; -. DR GenomeRNAi; 5159; -. DR Pharos; P09619; Tclin. DR PRO; PR:P09619; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P09619; protein. DR Bgee; ENSG00000113721; Expressed in stromal cell of endometrium and 182 other cell types or tissues. DR ExpressionAtlas; P09619; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-SubCell. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0043202; C:lysosomal lumen; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; IDA:BHF-UCL. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0005096; F:GTPase activator activity; IMP:UniProtKB. DR GO; GO:0160185; F:phospholipase C activator activity; IMP:UniProtKB. DR GO; GO:0004992; F:platelet activating factor receptor activity; TAS:ProtInc. DR GO; GO:0005019; F:platelet-derived growth factor beta-receptor activity; IDA:UniProtKB. DR GO; GO:0048407; F:platelet-derived growth factor binding; IDA:UniProtKB. DR GO; GO:0005017; F:platelet-derived growth factor receptor activity; TAS:ProtInc. DR GO; GO:0005161; F:platelet-derived growth factor receptor binding; IPI:BHF-UCL. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; IDA:UniProtKB. DR GO; GO:0005102; F:signaling receptor binding; IPI:UniProtKB. DR GO; GO:0038085; F:vascular endothelial growth factor binding; IPI:BHF-UCL. DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central. DR GO; GO:0035909; P:aorta morphogenesis; ISS:BHF-UCL. DR GO; GO:0055003; P:cardiac myofibril assembly; ISS:UniProtKB. DR GO; GO:0060326; P:cell chemotaxis; IDA:UniProtKB. DR GO; GO:0060981; P:cell migration involved in coronary angiogenesis; ISS:UniProtKB. DR GO; GO:0035441; P:cell migration involved in vasculogenesis; ISS:UniProtKB. DR GO; GO:0007169; P:cell surface receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR GO; GO:0072277; P:metanephric glomerular capillary formation; ISS:UniProtKB. DR GO; GO:0072262; P:metanephric glomerular mesangial cell proliferation involved in metanephros development; ISS:UniProtKB. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IDA:UniProtKB. DR GO; GO:0048008; P:platelet-derived growth factor receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0035791; P:platelet-derived growth factor receptor-beta signaling pathway; IMP:UniProtKB. DR GO; GO:0090280; P:positive regulation of calcium ion import; ISS:UniProtKB. DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IMP:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0038091; P:positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0050921; P:positive regulation of chemotaxis; ISS:UniProtKB. DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISS:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:UniProtKB. DR GO; GO:0035793; P:positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway; ISS:UniProtKB. DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISS:UniProtKB. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:UniProtKB. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISS:UniProtKB. DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:UniProtKB. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:BHF-UCL. DR GO; GO:0061298; P:retina vasculature development in camera-type eye; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; IDA:UniProtKB. DR GO; GO:0014805; P:smooth muscle adaptation; NAS:BHF-UCL. DR GO; GO:0071670; P:smooth muscle cell chemotaxis; ISS:BHF-UCL. DR CDD; cd00096; Ig; 1. DR CDD; cd05859; Ig4_PDGFR; 1. DR CDD; cd05861; IgI_PDGFR-alphabeta; 1. DR CDD; cd05107; PTKc_PDGFR_beta; 1. DR FunFam; 3.30.200.20:FF:000025; Platelet-derived growth factor receptor alpha; 1. DR FunFam; 1.10.510.10:FF:000140; Platelet-derived growth factor receptor beta; 1. DR FunFam; 2.60.40.10:FF:000223; Platelet-derived growth factor receptor beta; 1. DR FunFam; 2.60.40.10:FF:000572; Platelet-derived growth factor receptor beta; 1. DR FunFam; 2.60.40.10:FF:000715; Platelet-derived growth factor receptor beta; 1. DR FunFam; 2.60.40.10:FF:000814; Platelet-derived growth factor receptor beta; 1. DR FunFam; 2.60.40.10:FF:000982; Platelet-derived growth factor receptor beta; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 5. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR007110; Ig-like_dom. DR InterPro; IPR036179; Ig-like_dom_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR003599; Ig_sub. DR InterPro; IPR003598; Ig_sub2. DR InterPro; IPR013151; Immunoglobulin_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR027288; PGFRB. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR050122; RTK. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS. DR PANTHER; PTHR24416:SF53; PLATELET-DERIVED GROWTH FACTOR RECEPTOR BETA; 1. DR PANTHER; PTHR24416; TYROSINE-PROTEIN KINASE RECEPTOR; 1. DR Pfam; PF00047; ig; 1. DR Pfam; PF13927; Ig_3; 1. DR Pfam; PF25305; Ig_PDGFR_d4; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR PIRSF; PIRSF500948; Beta-PDGF_receptor; 1. DR PIRSF; PIRSF000615; TyrPK_CSF1-R; 1. DR PRINTS; PR01832; VEGFRECEPTOR. DR SMART; SM00409; IG; 3. DR SMART; SM00408; IGc2; 3. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF48726; Immunoglobulin; 3. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50835; IG_LIKE; 2. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Chemotaxis; KW Chromosomal rearrangement; Cytoplasmic vesicle; Developmental protein; KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; KW Immunoglobulin domain; Kinase; Lysosome; Membrane; Nucleotide-binding; KW Phosphoprotein; Proteomics identification; Proto-oncogene; Receptor; KW Reference proteome; Repeat; Signal; Transferase; Transmembrane; KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. FT SIGNAL 1..32 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 33..1106 FT /note="Platelet-derived growth factor receptor beta" FT /id="PRO_0000016757" FT TOPO_DOM 33..532 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 533..553 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 554..1106 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 33..120 FT /note="Ig-like C2-type 1" FT DOMAIN 129..210 FT /note="Ig-like C2-type 2" FT DOMAIN 214..309 FT /note="Ig-like C2-type 3" FT DOMAIN 331..403 FT /note="Ig-like C2-type 4" FT DOMAIN 416..524 FT /note="Ig-like C2-type 5" FT DOMAIN 600..962 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1019..1106 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1043..1060 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1066..1088 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 826 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 606..614 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 634 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000305" FT SITE 527..528 FT /note="Breakpoint for insertion to form PDE4DIP-PDGFRB FT fusion protein" FT SITE 527..528 FT /note="Breakpoint for translocation to form TRIP11-PDGFRB" FT SITE 558..559 FT /note="Breakpoint for translocation to form the CEP85L- FT PDGFRB fusion protein" FT MOD_RES 562 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10821867" FT MOD_RES 579 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:14966296, FT ECO:0000269|PubMed:15902258, ECO:0000269|PubMed:7685273" FT MOD_RES 581 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:15902258, FT ECO:0000269|PubMed:7685273" FT MOD_RES 686 FT /note="Phosphotyrosine; by ABL1 and ABL2" FT /evidence="ECO:0000250|UniProtKB:P05622" FT MOD_RES 716 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:15902258" FT MOD_RES 740 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:1314164, FT ECO:0000269|PubMed:15902258" FT MOD_RES 751 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10821867, FT ECO:0000269|PubMed:1314164, ECO:0000269|PubMed:14966296, FT ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:2550144" FT MOD_RES 763 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10821867" FT MOD_RES 771 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10821867, FT ECO:0000269|PubMed:1314164, ECO:0000269|PubMed:14966296, FT ECO:0000269|PubMed:15902258" FT MOD_RES 775 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10821867" FT MOD_RES 778 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10821867" FT MOD_RES 857 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10821867, FT ECO:0000269|PubMed:1314164, ECO:0000269|PubMed:15902258, FT ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:2550144" FT MOD_RES 934 FT /note="Phosphotyrosine; by ABL1 and ABL2" FT /evidence="ECO:0000250|UniProtKB:P05622" FT MOD_RES 970 FT /note="Phosphotyrosine; by ABL1 and ABL2" FT /evidence="ECO:0000250|UniProtKB:P05622" FT MOD_RES 1009 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10821867, FT ECO:0000269|PubMed:1396585, ECO:0000269|PubMed:15902258" FT MOD_RES 1021 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:10821867, FT ECO:0000269|PubMed:1396585, ECO:0000269|PubMed:14966296, FT ECO:0000269|PubMed:15902258" FT CARBOHYD 45 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 89 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20534510" FT CARBOHYD 103 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20534510" FT CARBOHYD 215 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20534510" FT CARBOHYD 230 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20534510" FT CARBOHYD 292 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20534510" FT CARBOHYD 307 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:20534510" FT CARBOHYD 354 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 371 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 468 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 479 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 54..100 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:20534510" FT DISULFID 149..190 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:20534510" FT DISULFID 235..291 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114, FT ECO:0000269|PubMed:20534510" FT DISULFID 436..508 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114" FT VAR_SEQ 311..336 FT /note="VESGYVRLLGEVGTLQFAELHRSRTL -> RAATCGSWERWAHYNLLSCIGA FT GHCR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:18593464" FT /id="VSP_056008" FT VAR_SEQ 337..1106 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:18593464" FT /id="VSP_056009" FT VARIANT 29 FT /note="I -> F (in dbSNP:rs17110944)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_034377" FT VARIANT 180 FT /note="S -> F (in dbSNP:rs17853027)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_035125" FT VARIANT 282 FT /note="E -> K (in dbSNP:rs34586048)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042027" FT VARIANT 345 FT /note="P -> S (in dbSNP:rs2229558)" FT /id="VAR_049717" FT VARIANT 485 FT /note="E -> K (in dbSNP:rs41287110)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042028" FT VARIANT 561 FT /note="R -> C (in IMF1; dbSNP:rs367543286)" FT /evidence="ECO:0000269|PubMed:23731537" FT /id="VAR_069925" FT VARIANT 584 FT /note="P -> R (in KOGS; dbSNP:rs863224946)" FT /evidence="ECO:0000269|PubMed:25454926" FT /id="VAR_075865" FT VARIANT 589 FT /note="Y -> H (in a gastric adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042029" FT VARIANT 658 FT /note="L -> P (in IBGC4; no effect on protein abundance; FT loss of PDGF beta receptor activity; dbSNP:rs397509381)" FT /evidence="ECO:0000269|PubMed:23255827, FT ECO:0000269|PubMed:24065723, ECO:0000269|PubMed:26599395" FT /id="VAR_069320" FT VARIANT 660 FT /note="P -> T (in IMF1; dbSNP:rs144050370)" FT /evidence="ECO:0000269|PubMed:23731542" FT /id="VAR_069926" FT VARIANT 665 FT /note="V -> A (in PENTT; gain of function in protein FT tyrosine kinase activity; shows ligand-independent FT constitutive signaling; dbSNP:rs1554108211)" FT /evidence="ECO:0000269|PubMed:26279204" FT /id="VAR_075866" FT VARIANT 666 FT /note="N -> S (in PENTT; likely pathogenic; gain-of- FT function variant resulting in constitutive FT autophosphorylation and increased phosphorylation of FT downstream signaling proteins; levels of protein FT phosphorylation are similar at 32 and 37 degrees Celsius; FT dbSNP:rs2113894766)" FT /evidence="ECO:0000269|PubMed:30573803" FT /id="VAR_090402" FT VARIANT 666 FT /note="N -> Y (in OPDKD; likely pathogenic; gain-of- FT function variant resulting in temperature-dependent FT constitutive autophosphorylation and increased FT phosphorylation of downstream signaling proteins; levels of FT protein phosphorylation at 32 degrees Celsius are higher FT than at 37 degrees; dbSNP:rs797044887)" FT /evidence="ECO:0000269|PubMed:33450762" FT /id="VAR_090403" FT VARIANT 718 FT /note="N -> Y (in dbSNP:rs35322465)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042030" FT VARIANT 882 FT /note="T -> I (in a breast infiltrating ductal carcinoma FT sample; somatic mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042031" FT VARIANT 987 FT /note="R -> W (in IBGC4; decreased protein abundance; no FT effect on receptor activity; decreased PDGF signaling FT pathway; dbSNP:rs397509382)" FT /evidence="ECO:0000269|PubMed:23255827, FT ECO:0000269|PubMed:24065723, ECO:0000269|PubMed:26599395" FT /id="VAR_069321" FT VARIANT 1071 FT /note="E -> V (in IBGC4; no effect on protein abundance; no FT effect on receptor activity; decreased PDGF signaling FT pathway)" FT /evidence="ECO:0000269|PubMed:24065723, FT ECO:0000269|PubMed:26599395" FT /id="VAR_075395" FT MUTAGEN 579 FT /note="Y->F: Loss of kinase activity; when associated with FT F-581. Strongly reduces interaction with SRC family FT kinases. No effect on interaction with GRB10." FT /evidence="ECO:0000269|PubMed:10454568, FT ECO:0000269|PubMed:7685273" FT MUTAGEN 581 FT /note="Y->F: Loss of kinase activity; when associated with FT F-579. No effect on interaction with GRB10." FT /evidence="ECO:0000269|PubMed:10454568, FT ECO:0000269|PubMed:7685273" FT MUTAGEN 634 FT /note="K->A,R: Loss of kinase activity. Abolishes FT interaction with RASA1. No effect on phosphatidylinositol FT 3-kinase activity." FT /evidence="ECO:0000269|PubMed:1314164, FT ECO:0000269|PubMed:1846866, ECO:0000269|PubMed:20494825" FT MUTAGEN 716 FT /note="Y->F: No effect neither on interaction with GRB10 FT and RASA1 nor on phosphatidylinositol 3-kinase activity." FT /evidence="ECO:0000269|PubMed:10454568, FT ECO:0000269|PubMed:1314164" FT MUTAGEN 740 FT /note="Y->F: Strongly reduces up-regulation of cell FT proliferation; when associated with F-751. Strongly FT decreases phosphatidylinositol 3-kinase activity. No effect FT on interaction with GRB10 and RASA1." FT /evidence="ECO:0000269|PubMed:10454568, FT ECO:0000269|PubMed:1314164, ECO:0000269|PubMed:1375321, FT ECO:0000269|PubMed:21679854" FT MUTAGEN 751 FT /note="Y->F: Strongly reduces up-regulation of cell FT proliferation; when associated with F-740. Abolishes FT phosphatidylinositol 3-kinase activity and interaction with FT NCK1, and slightly reduces interaction with RASA1. No FT effect on interaction with GRB10." FT /evidence="ECO:0000269|PubMed:10454568, FT ECO:0000269|PubMed:1314164, ECO:0000269|PubMed:1375321, FT ECO:0000269|PubMed:1653029, ECO:0000269|PubMed:21679854, FT ECO:0000269|PubMed:7692233" FT MUTAGEN 763 FT /note="Y->F: No effect on interaction with RASA1 and on FT phosphatidylinositol 3-kinase activity." FT /evidence="ECO:0000269|PubMed:1314164" FT MUTAGEN 771 FT /note="Y->F: Loss of interaction with GRB10. Abolishes FT interaction with RASA1. No effect on phosphatidylinositol FT 3-kinase activity." FT /evidence="ECO:0000269|PubMed:10454568, FT ECO:0000269|PubMed:1314164, ECO:0000269|PubMed:1375321" FT MUTAGEN 775 FT /note="Y->F: No effect on interaction with RASA1 and on FT phosphatidylinositol 3-kinase activity." FT /evidence="ECO:0000269|PubMed:1314164" FT MUTAGEN 778 FT /note="Y->F: Strongly reduces expression levels." FT /evidence="ECO:0000269|PubMed:1314164" FT MUTAGEN 857 FT /note="Y->F: Reduces kinase activity. No effect on FT interaction with GRB10. Abolishes interaction with RASA1. FT No effect on phosphatidylinositol 3-kinase activity." FT /evidence="ECO:0000269|PubMed:10454568, FT ECO:0000269|PubMed:1314164, ECO:0000269|PubMed:1653029, FT ECO:0000269|PubMed:20494825" FT MUTAGEN 1009 FT /note="Y->F: No effect on interaction with GRB10. Abolishes FT interaction with PLCG1; when associated with F-1021." FT /evidence="ECO:0000269|PubMed:10454568, FT ECO:0000269|PubMed:1396585, ECO:0000269|PubMed:7691811" FT MUTAGEN 1021 FT /note="Y->F: Strongly reduces up-regulation of cell FT proliferation. Abolishes interaction with PLCG1; when FT associated with F-1009. No effect on interaction with FT GRB10." FT /evidence="ECO:0000269|PubMed:10454568, FT ECO:0000269|PubMed:1396585, ECO:0000269|PubMed:17620338, FT ECO:0000269|PubMed:21679854" FT CONFLICT 241 FT /note="E -> D (in Ref. 2; AAA36427)" FT /evidence="ECO:0000305" FT STRAND 40..43 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 50..58 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 61..64 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 70..75 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 81..87 FT /evidence="ECO:0007829|PDB:3MJG" FT HELIX 92..94 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 96..101 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 114..119 FT /evidence="ECO:0007829|PDB:3MJG" FT HELIX 132..135 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 136..141 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 145..147 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 158..164 FT /evidence="ECO:0007829|PDB:3MJG" FT TURN 175..177 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 178..181 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 185..194 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 197..200 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 204..208 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 217..221 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 223..226 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 231..239 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 241..248 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 252..255 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 261..265 FT /evidence="ECO:0007829|PDB:3MJG" FT TURN 267..270 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 271..280 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 287..295 FT /evidence="ECO:0007829|PDB:3MJG" FT TURN 296..299 FT /evidence="ECO:0007829|PDB:3MJG" FT STRAND 300..311 FT /evidence="ECO:0007829|PDB:3MJG" FT HELIX 530..556 FT /evidence="ECO:0007829|PDB:2L6W" SQ SEQUENCE 1106 AA; 123968 MW; 038C15E531D6E89D CRC64; MRLPGAMPAL ALKGELLLLS LLLLLEPQIS QGLVVTPPGP ELVLNVSSTF VLTCSGSAPV VWERMSQEPP QEMAKAQDGT FSSVLTLTNL TGLDTGEYFC THNDSRGLET DERKRLYIFV PDPTVGFLPN DAEELFIFLT EITEITIPCR VTDPQLVVTL HEKKGDVALP VPYDHQRGFS GIFEDRSYIC KTTIGDREVD SDAYYVYRLQ VSSINVSVNA VQTVVRQGEN ITLMCIVIGN EVVNFEWTYP RKESGRLVEP VTDFLLDMPY HIRSILHIPS AELEDSGTYT CNVTESVNDH QDEKAINITV VESGYVRLLG EVGTLQFAEL HRSRTLQVVF EAYPPPTVLW FKDNRTLGDS SAGEIALSTR NVSETRYVSE LTLVRVKVAE AGHYTMRAFH EDAEVQLSFQ LQINVPVRVL ELSESHPDSG EQTVRCRGRG MPQPNIIWSA CRDLKRCPRE LPPTLLGNSS EEESQLETNV TYWEEEQEFE VVSTLRLQHV DRPLSVRCTL RNAVGQDTQE VIVVPHSLPF KVVVISAILA LVVLTIISLI ILIMLWQKKP RYEIRWKVIE SVSSDGHEYI YVDPMQLPYD STWELPRDQL VLGRTLGSGA FGQVVEATAH GLSHSQATMK VAVKMLKSTA RSSEKQALMS ELKIMSHLGP HLNVVNLLGA CTKGGPIYII TEYCRYGDLV DYLHRNKHTF LQHHSDKRRP PSAELYSNAL PVGLPLPSHV SLTGESDGGY MDMSKDESVD YVPMLDMKGD VKYADIESSN YMAPYDNYVP SAPERTCRAT LINESPVLSY MDLVGFSYQV ANGMEFLASK NCVHRDLAAR NVLICEGKLV KICDFGLARD IMRDSNYISK GSTFLPLKWM APESIFNSLY TTLSDVWSFG ILLWEIFTLG GTPYPELPMN EQFYNAIKRG YRMAQPAHAS DEIYEIMQKC WEEKFEIRPP FSQLVLLLER LLGEGYKKKY QQVDEEFLRS DHPAILRSQA RLPGFHGLRS PLDTSSVLYT AVQPNEGDND YIIPLPDPKP EVADEGPLEG SPSLASSTLN EVNTSSTISC DSPLEPQDEP EPEPQLELQV EPEPELEQLP DSGCPAPRAE AEDSFL // ID S20A2_HUMAN Reviewed; 652 AA. AC Q08357; DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 28-JAN-2026, entry version 184. DE RecName: Full=Sodium-dependent phosphate transporter 2; DE AltName: Full=Gibbon ape leukemia virus receptor 2; DE Short=GLVR-2; DE AltName: Full=Phosphate transporter 2; DE Short=PiT-2; DE Short=Pit2; DE Short=hPit2; DE AltName: Full=Solute carrier family 20 member 2; GN Name=SLC20A2; Synonyms=GLVR2, PIT2; 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 FUNCTION AS RETROVIRAL RECEPTOR (MICROBIAL RP FUNCTION). RC TISSUE=Placenta; RX PubMed=8302848; DOI=10.1073/pnas.91.3.1168; RA van Zeijl M., Johann S.V., Closs E., Cunningham J., Eddy R., Shows T.B., RA O'Hara B.; RT "A human amphotropic retrovirus receptor is a second member of the gibbon RT ape leukemia virus receptor family."; RL Proc. Natl. Acad. Sci. U.S.A. 91:1168-1172(1994). RN [2] 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP TOPOLOGY, GLYCOSYLATION AT ASN-81, AND MUTAGENESIS OF ASN-81. RX PubMed=11356966; DOI=10.1128/jvi.75.12.5584-5592.2001; RA Salauen C., Rodrigues P., Heard J.M.; RT "Transmembrane topology of PiT-2, a phosphate transporter-retrovirus RT receptor."; RL J. Virol. 75:5584-5592(2001). RN [5] RP TOPOLOGY, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=9151850; DOI=10.1128/jvi.71.6.4564-4570.1997; RA Chien M.L., Foster J.L., Douglas J.L., Garcia J.V.; RT "The amphotropic murine leukemia virus receptor gene encodes a 71- RT kilodalton protein that is induced by phosphate depletion."; RL J. Virol. 71:4564-4570(1997). RN [6] RP FUNCTION AS RETROVIRAL RECEPTOR (MICROBIAL FUNCTION). RX PubMed=11435563; DOI=10.1128/jvi.75.15.6841-6849.2001; RA Sugai J., Eiden M., Anderson M.M., Van Hoeven N., Meiering C.D., RA Overbaugh J.; RT "Identification of envelope determinants of feline leukemia virus subgroup RT B that permit infection and gene transfer to cells expressing human Pit1 or RT Pit2."; RL J. Virol. 75:6841-6849(2001). RN [7] RP FUNCTION AS SODIUM-PHOSPHATE SYMPORTER, FUNCTION AS RETROVIRAL RECEPTOR RP (MICROBIAL FUNCTION), SUBUNIT, MUTAGENESIS OF GLU-55 AND GLU-575, AND RP TRANSPORTER ACTIVITY. RX PubMed=12205090; DOI=10.1074/jbc.m207096200; RA Boettger P., Pedersen L.; RT "Two highly conserved glutamate residues critical for type III sodium- RT dependent phosphate transport revealed by uncoupling transport function RT from retroviral receptor function."; RL J. Biol. Chem. 277:42741-42747(2002). RN [8] RP FUNCTION AS SODIUM-PHOSPHATE SYMPORTER, FUNCTION AS RETROVIRAL RECEPTOR RP (MICROBIAL FUNCTION), SUBUNIT, MUTAGENESIS OF ASP-506, CHARACTERIZATION OF RP VARIANT IBGC1 ASN-28, AND TRANSPORTER ACTIVITY. RX PubMed=15955065; DOI=10.1111/j.1742-4658.2005.04720.x; RA Boettger P., Pedersen L.; RT "Evolutionary and experimental analyses of inorganic phosphate transporter RT PiT family reveals two related signature sequences harboring highly RT conserved aspartic acids critical for sodium-dependent phosphate transport RT function of human PiT2."; RL FEBS J. 272:3060-3074(2005). RN [9] RP FUNCTION AS SODIUM-PHOSPHATE SYMPORTER, BIOPHYSICOCHEMICAL PROPERTIES, RP MUTAGENESIS OF GLU-55; GLU-91 AND GLU-575, AND TRANSPORTER ACTIVITY. RX PubMed=16790504; DOI=10.1152/ajpcell.00015.2006; RA Boettger P., Hede S.E., Grunnet M., Hoyer B., Klaerke D.A., Pedersen L.; RT "Characterization of transport mechanisms and determinants critical for RT Na+-dependent Pi symport of the PiT family paralogs human PiT1 and PiT2."; RL Am. J. Physiol. 291:C1377-C1387(2006). RN [10] RP FUNCTION AS SODIUM-PHOSPHATE SYMPORTER, TRANSPORTER ACTIVITY, AND RP STOICHIOMETRY. RX PubMed=17494632; DOI=10.1152/ajpcell.00064.2007; RA Ravera S., Virkki L.V., Murer H., Forster I.C.; RT "Deciphering PiT transport kinetics and substrate specificity using RT electrophysiology and flux measurements."; RL Am. J. Physiol. 293:C606-C620(2007). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-256; SER-259; SER-268; RP SER-316 AND SER-385, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259 AND SER-316, AND 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 [15] RP VARIANTS IBGC1 VAL-42 DEL; ARG-498; LYS-575; MET-595; TRP-601 AND LEU-601, RP CHARACTERIZATION OF VARIANTS IBGC1 VAL-42 DEL; ARG-498; LYS-575; MET-595; RP TRP-601 AND LEU-601, FUNCTION AS SODIUM-PHOSPHATE SYMPORTER, AND RP TRANSPORTER ACTIVITY. RX PubMed=22327515; DOI=10.1038/ng.1077; RA Wang C., Li Y., Shi L., Ren J., Patti M., Wang T., de Oliveira J.R., RA Sobrido M.J., Quintans B., Baquero M., Cui X., Zhang X.Y., Wang L., Xu H., RA Wang J., Yao J., Dai X., Liu J., Zhang L., Ma H., Gao Y., Ma X., Feng S., RA Liu M., Wang Q.K., Forster I.C., Zhang X., Liu J.Y.; RT "Mutations in SLC20A2 link familial idiopathic basal ganglia calcification RT with phosphate homeostasis."; RL Nat. Genet. 44:254-256(2012). RN [16] RP INVOLVEMENT IN IBGC1. RX PubMed=23406454; DOI=10.1111/ene.12044; RA Lemos R.R., Oliveira M.F., Oliveira J.R.; RT "Reporting a new mutation at the SLC20A2 gene in familial idiopathic basal RT ganglia calcification."; RL Eur. J. Neurol. 20:E43-43(2013). RN [17] RP VARIANTS IBGC1 LEU-11; ASN-28 AND PRO-62. RX PubMed=23939468; DOI=10.1016/j.gene.2013.07.071; RA Chen W.J., Yao X.P., Zhang Q.J., Ni W., He J., Li H.F., Liu X.Y., RA Zhao G.X., Murong S.X., Wang N., Wu Z.Y.; RT "Novel SLC20A2 mutations identified in southern Chinese patients with RT idiopathic basal ganglia calcification."; RL Gene 529:159-162(2013). RN [18] RP VARIANTS IBGC1 GLN-382; GLN-502; LEU-568 AND LEU-601. RX PubMed=23334463; DOI=10.1007/s10048-012-0349-2; RA Hsu S.C., Sears R.L., Lemos R.R., Quintans B., Huang A., Spiteri E., RA Nevarez L., Mamah C., Zatz M., Pierce K.D., Fullerton J.M., Adair J.C., RA Berner J.E., Bower M., Brodaty H., Carmona O., Dobricic V., Fogel B.L., RA Garcia-Estevez D., Goldman J., Goudreau J.L., Hopfer S., Jankovic M., RA Jauma S., Jen J.C., Kirdlarp S., Klepper J., Kostic V., Lang A.E., RA Linglart A., Maisenbacher M.K., Manyam B.V., Mazzoni P., Miedzybrodzka Z., RA Mitarnun W., Mitchell P.B., Mueller J., Novakovic I., Paucar M., RA Paulson H., Simpson S.A., Svenningsson P., Tuite P., Vitek J., RA Wetchaphanphesat S., Williams C., Yang M., Schofield P.R., RA de Oliveira J.R., Sobrido M.J., Geschwind D.H., Coppola G.; RT "Mutations in SLC20A2 are a major cause of familial idiopathic basal RT ganglia calcification."; RL Neurogenetics 14:11-22(2013). RN [19] RP VARIANTS IBGC1 ASN-28; LEU-184; SER-194 AND SER-571. RX PubMed=24065723; DOI=10.1093/brain/awt255; RG French IBGC Study Group; RA Nicolas G., Pottier C., Charbonnier C., Guyant-Marechal L., Le Ber I., RA Pariente J., Labauge P., Ayrignac X., Defebvre L., Maltete D., RA Martinaud O., Lefaucheur R., Guillin O., Wallon D., Chaumette B., RA Rondepierre P., Derache N., Fromager G., Schaeffer S., Krystkowiak P., RA Verny C., Jurici S., Sauvee M., Verin M., Lebouvier T., Rouaud O., RA Thauvin-Robinet C., Rousseau S., Rovelet-Lecrux A., Frebourg T., RA Campion D., Hannequin D.; RT "Phenotypic spectrum of probable and genetically-confirmed idiopathic basal RT ganglia calcification."; RL Brain 136:3395-3407(2013). RN [20] RP VARIANTS IBGC1 TRP-434 AND MET-595. RX PubMed=25284758; DOI=10.1002/mds.26053; RA Taglia I., Mignarri A., Olgiati S., Menci E., Petrocelli P.L., RA Breedveld G.J., Scaglione C., Martinelli P., Federico A., Bonifati V., RA Dotti M.T.; RT "Primary familial brain calcification: Genetic analysis and clinical RT spectrum."; RL Mov. Disord. 29:1691-1695(2014). RN [21] RP VARIANTS IBGC1 VAL-51; HIS-71; MET-115 AND ARG-637. RX PubMed=24463626; DOI=10.1212/wnl.0000000000000143; RA Yamada M., Tanaka M., Takagi M., Kobayashi S., Taguchi Y., Takashima S., RA Tanaka K., Touge T., Hatsuta H., Murayama S., Hayashi Y., Kaneko M., RA Ishiura H., Mitsui J., Atsuta N., Sobue G., Shimozawa N., Inuzuka T., RA Tsuji S., Hozumi I.; RT "Evaluation of SLC20A2 mutations that cause idiopathic basal ganglia RT calcification in Japan."; RL Neurology 82:705-712(2014). RN [22] RP CHARACTERIZATION OF VARIANT IBGC1 GLN-PHE-VAL-THR-629 INS, FUNCTION AS RP SODIUM-PHOSPHATE SYMPORTER, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=28722801; DOI=10.1002/jcp.26104; RA Taglia I., Formichi P., Battisti C., Peppoloni G., Barghigiani M., RA Tessa A., Federico A.; RT "Primary familial brain calcification with a novel SLC20A2 mutation: RT Analysis of PiT-2 expression and localization."; RL J. Cell. Physiol. 233:2324-2331(2018). RN [23] RP CHARACTERIZATION OF VARIANTS IBGC1 MET-115 AND ARG-637, FUNCTION AS RP SODIUM-PHOSPHATE SYMPORTER, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=30704756; DOI=10.1016/j.bbrc.2019.01.096; RA Sekine S.I., Nishii K., Masaka T., Kurita H., Inden M., Hozumi I.; RT "SLC20A2 variants cause dysfunctional phosphate transport activity in RT endothelial cells induced from Idiopathic Basal Ganglia Calcification RT patients-derived iPSCs."; RL Biochem. Biophys. Res. Commun. 510:303-308(2019). CC -!- FUNCTION: Sodium-phosphate symporter which preferentially transports CC the monovalent form of phosphate with a stoichiometry of two sodium CC ions per phosphate ion (PubMed:12205090, PubMed:15955065, CC PubMed:16790504, PubMed:17494632, PubMed:22327515, PubMed:28722801, CC PubMed:30704756). Plays a critical role in the determination of bone CC quality and strength by providing phosphate for bone mineralization (By CC similarity). Required to maintain normal cerebrospinal fluid phosphate CC levels (By similarity). Mediates phosphate-induced calcification of CC vascular smooth muscle cells (VCMCs) and can functionally compensate CC for loss of SLC20A1 in VCMCs (By similarity). CC {ECO:0000250|UniProtKB:Q80UP8, ECO:0000269|PubMed:12205090, CC ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:16790504, CC ECO:0000269|PubMed:17494632, ECO:0000269|PubMed:22327515, CC ECO:0000269|PubMed:28722801, ECO:0000269|PubMed:30704756}. CC -!- FUNCTION: (Microbial infection) Functions as a retroviral receptor and CC confers human cells susceptibility to infection to amphotropic murine CC leukemia virus (A-MuLV), 10A1 murine leukemia virus (10A1 MLV) and some CC feline leukemia virus subgroup B (FeLV-B) variants. CC {ECO:0000269|PubMed:11435563, ECO:0000269|PubMed:12205090, CC ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:8302848}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 Na(+)(out) + phosphate(out) = 2 Na(+)(in) + phosphate(in); CC Xref=Rhea:RHEA:71259, ChEBI:CHEBI:29101, ChEBI:CHEBI:43474; CC Evidence={ECO:0000269|PubMed:12205090, ECO:0000269|PubMed:15955065, CC ECO:0000269|PubMed:16790504, ECO:0000269|PubMed:17494632, CC ECO:0000269|PubMed:22327515, ECO:0000269|PubMed:28722801, CC ECO:0000269|PubMed:30704756}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=163.5 uM for phosphate {ECO:0000269|PubMed:16790504}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12205090, CC ECO:0000269|PubMed:15955065}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28722801, CC ECO:0000269|PubMed:30704756, ECO:0000269|PubMed:9151850}; Multi-pass CC membrane protein {ECO:0000269|PubMed:9151850}. Apical cell membrane CC {ECO:0000250|UniProtKB:Q63488}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC -!- INDUCTION: Increased by phosphate depletion in osteosarcoma cell lines. CC {ECO:0000269|PubMed:9151850}. CC -!- DISEASE: Basal ganglia calcification, idiopathic, 1 (IBGC1) CC [MIM:213600]: A form of basal ganglia calcification, an autosomal CC dominant condition characterized by symmetric calcification in the CC basal ganglia and other brain regions. Affected individuals can either CC be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, CC including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, CC seizures, and chronic headache. Serum levels of calcium, phosphate, CC alkaline phosphatase and parathyroid hormone are normal. The CC neuropathological hallmark of the disease is vascular and pericapillary CC calcification, mainly of calcium phosphate, in the affected brain CC areas. {ECO:0000269|PubMed:15955065, ECO:0000269|PubMed:22327515, CC ECO:0000269|PubMed:23334463, ECO:0000269|PubMed:23406454, CC ECO:0000269|PubMed:23939468, ECO:0000269|PubMed:24065723, CC ECO:0000269|PubMed:24463626, ECO:0000269|PubMed:25284758, CC ECO:0000269|PubMed:28722801, ECO:0000269|PubMed:30704756}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the inorganic phosphate transporter (PiT) (TC CC 2.A.20) family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L20852; AAA18018.1; -; mRNA. DR EMBL; AK291202; BAF83891.1; -; mRNA. DR EMBL; BC028600; AAH28600.1; -; mRNA. DR CCDS; CCDS6132.1; -. DR PIR; A37000; A37000. DR RefSeq; NP_001244109.1; NM_001257180.2. DR RefSeq; NP_001244110.1; NM_001257181.2. DR RefSeq; NP_006740.1; NM_006749.5. DR RefSeq; XP_005273670.1; XM_005273613.4. DR RefSeq; XP_016869237.1; XM_017013748.2. DR RefSeq; XP_024303003.1; XM_024447235.2. DR RefSeq; XP_024303004.1; XM_024447236.2. DR RefSeq; XP_047278076.1; XM_047422120.1. DR RefSeq; XP_047278077.1; XM_047422121.1. DR RefSeq; XP_047278078.1; XM_047422122.1. DR RefSeq; XP_054217019.1; XM_054361044.1. DR RefSeq; XP_054217020.1; XM_054361045.1. DR RefSeq; XP_054217021.1; XM_054361046.1. DR RefSeq; XP_054217022.1; XM_054361047.1. DR RefSeq; XP_054217023.1; XM_054361048.1. DR RefSeq; XP_054217024.1; XM_054361049.1. DR RefSeq; XP_054217025.1; XM_054361050.1. DR AlphaFoldDB; Q08357; -. DR SMR; Q08357; -. DR BioGRID; 112463; 130. DR FunCoup; Q08357; 652. DR IntAct; Q08357; 80. DR MINT; Q08357; -. DR STRING; 9606.ENSP00000429754; -. DR BindingDB; Q08357; -. DR ChEMBL; CHEMBL4295806; -. DR DrugBank; DB11348; Calcium Phosphate. DR DrugBank; DB14481; Calcium phosphate dihydrate. DR DrugBank; DB14502; Sodium phosphate, dibasic. DR DrugBank; DB09449; Sodium phosphate, monobasic. DR DrugBank; DB14503; Sodium phosphate, monobasic, unspecified form. DR DrugBank; DB09436; Technetium Tc-99m succimer. DR TCDB; 2.A.20.2.3; the inorganic phosphate transporter (pit) family. DR GlyCosmos; Q08357; 1 site, No reported glycans. DR GlyGen; Q08357; 3 sites, 1 N-linked glycan (1 site). DR iPTMnet; Q08357; -. DR PhosphoSitePlus; Q08357; -. DR BioMuta; SLC20A2; -. DR DMDM; 74735615; -. DR jPOST; Q08357; -. DR MassIVE; Q08357; -. DR PaxDb; 9606-ENSP00000340465; -. DR PeptideAtlas; Q08357; -. DR ProteomicsDB; 58600; -. DR Pumba; Q08357; -. DR Antibodypedia; 11470; 154 antibodies from 27 providers. DR DNASU; 6575; -. DR Ensembl; ENST00000342228.7; ENSP00000340465.3; ENSG00000168575.12. DR Ensembl; ENST00000517366.2; ENSP00000427756.2; ENSG00000168575.12. DR Ensembl; ENST00000518384.2; ENSP00000430462.2; ENSG00000168575.12. DR Ensembl; ENST00000518717.2; ENSP00000430166.2; ENSG00000168575.12. DR Ensembl; ENST00000520179.5; ENSP00000429712.1; ENSG00000168575.12. DR Ensembl; ENST00000520262.6; ENSP00000429754.1; ENSG00000168575.12. DR Ensembl; ENST00000713988.1; ENSP00000519279.1; ENSG00000168575.12. DR GeneID; 6575; -. DR KEGG; hsa:6575; -. DR MANE-Select; ENST00000520262.6; ENSP00000429754.1; NM_001257180.2; NP_001244109.1. DR UCSC; uc003xpe.5; human. DR AGR; HGNC:10947; -. DR ClinPGx; PA35834; -. DR CTD; 6575; -. DR DisGeNET; 6575; -. DR GeneCards; SLC20A2; -. DR GeneReviews; SLC20A2; -. DR HGNC; HGNC:10947; SLC20A2. DR HPA; ENSG00000168575; Tissue enhanced (choroid plexus, skeletal muscle). DR MalaCards; SLC20A2; -. DR MIM; 158378; gene. DR MIM; 213600; phenotype. DR OpenTargets; ENSG00000168575; -. DR Orphanet; 1980; Bilateral striopallidodentate calcinosis. DR VEuPathDB; HostDB:ENSG00000168575; -. DR eggNOG; KOG2493; Eukaryota. DR GeneTree; ENSGT00390000014879; -. DR HOGENOM; CLU_015355_3_1_1; -. DR InParanoid; Q08357; -. DR OMA; MQAFCIA; -. DR OrthoDB; 260807at2759; -. DR PAN-GO; Q08357; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q08357; -. DR BioCyc; MetaCyc:ENSG00000168575-MONOMER; -. DR PathwayCommons; Q08357; -. DR Reactome; R-HSA-427652; Sodium-coupled phosphate cotransporters. DR Reactome; R-HSA-5619111; Defective SLC20A2 causes idiopathic basal ganglia calcification 1 (IBGC1). DR SignaLink; Q08357; -. DR SIGNOR; Q08357; -. DR Agora; ENSG00000168575; -. DR BioGRID-ORCS; 6575; 14 hits in 1159 CRISPR screens. DR ChiTaRS; SLC20A2; human. DR GeneWiki; SLC20A2; -. DR GenomeRNAi; 6575; -. DR Pharos; Q08357; Tbio. DR PRO; PR:Q08357; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q08357; protein. DR Bgee; ENSG00000168575; Expressed in left lobe of thyroid gland and 198 other cell types or tissues. DR ExpressionAtlas; Q08357; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB. DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IMP:UniProtKB. DR GO; GO:0005315; F:phosphate transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc. DR GO; GO:0005436; F:sodium:phosphate symporter activity; IDA:UniProtKB. DR GO; GO:0001618; F:virus receptor activity; IMP:UniProtKB. DR GO; GO:0006811; P:monoatomic ion transport; TAS:Reactome. DR GO; GO:0035435; P:phosphate ion transmembrane transport; IBA:GO_Central. DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB. DR InterPro; IPR001204; Phos_transporter. DR PANTHER; PTHR11101; PHOSPHATE TRANSPORTER; 1. DR PANTHER; PTHR11101:SF83; SODIUM-DEPENDENT PHOSPHATE TRANSPORTER 2; 1. DR Pfam; PF01384; PHO4; 1. PE 1: Evidence at protein level; KW Cell membrane; Disease variant; Glycoprotein; KW Host cell receptor for virus entry; Host-virus interaction; Ion transport; KW Membrane; Phosphate transport; Phosphoprotein; Proteomics identification; KW Receptor; Reference proteome; Sodium; Sodium transport; Symport; KW Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..652 FT /note="Sodium-dependent phosphate transporter 2" FT /id="PRO_0000341268" FT TOPO_DOM 1..5 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 6..26 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 27..46 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 47..67 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 68..86 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 87..107 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 108..109 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 110..130 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 131..142 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 143..163 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 164..190 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 191..211 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 212..213 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 214..234 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 235..482 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 483..503 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 504..530 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 531..551 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 552..571 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 572..586 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 587..593 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 594..609 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 610..621 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 622..642 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 643..652 FT /note="Extracellular" FT /evidence="ECO:0000255" FT REGION 273..307 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 458..477 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 295..304 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 253 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q63488" FT MOD_RES 256 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 259 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 268 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 316 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 385 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT CARBOHYD 81 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:11356966" FT VARIANT 11 FT /note="I -> L (in IBGC1; dbSNP:rs201836672)" FT /evidence="ECO:0000269|PubMed:23939468" FT /id="VAR_072255" FT VARIANT 28 FT /note="D -> N (in IBGC1; Impairs phosphate transport; no FT effect on retroviral receptor function; FT dbSNP:rs1554561099)" FT /evidence="ECO:0000269|PubMed:15955065, FT ECO:0000269|PubMed:23939468, ECO:0000269|PubMed:24065723" FT /id="VAR_072256" FT VARIANT 42 FT /note="Missing (in IBGC1; substantially impaired phosphate FT transport)" FT /evidence="ECO:0000269|PubMed:22327515" FT /id="VAR_067545" FT VARIANT 51 FT /note="A -> V (in IBGC1)" FT /evidence="ECO:0000269|PubMed:24463626" FT /id="VAR_072257" FT VARIANT 62 FT /note="L -> P (in IBGC1)" FT /evidence="ECO:0000269|PubMed:23939468" FT /id="VAR_072258" FT VARIANT 71 FT /note="R -> H (in IBGC1)" FT /evidence="ECO:0000269|PubMed:24463626" FT /id="VAR_072259" FT VARIANT 115 FT /note="T -> M (in IBGC1; loss of sodium-dependent phosphate FT transport but no effect on cell membrane localization; FT dbSNP:rs775911275)" FT /evidence="ECO:0000269|PubMed:24463626, FT ECO:0000269|PubMed:30704756" FT /id="VAR_072260" FT VARIANT 184 FT /note="P -> L (in IBGC1; uncertain significance)" FT /evidence="ECO:0000269|PubMed:24065723" FT /id="VAR_075396" FT VARIANT 194 FT /note="N -> S (in IBGC1; uncertain significance; FT dbSNP:rs748252183)" FT /evidence="ECO:0000269|PubMed:24065723" FT /id="VAR_075397" FT VARIANT 382 FT /note="R -> Q (in IBGC1; dbSNP:rs200010919)" FT /evidence="ECO:0000269|PubMed:23334463" FT /id="VAR_072261" FT VARIANT 434 FT /note="S -> W (in IBGC1; dbSNP:rs1357615935)" FT /evidence="ECO:0000269|PubMed:25284758" FT /id="VAR_072262" FT VARIANT 498 FT /note="G -> R (in IBGC1; substantially impaired phosphate FT transport)" FT /evidence="ECO:0000269|PubMed:22327515" FT /id="VAR_067546" FT VARIANT 502 FT /note="H -> Q (in IBGC1)" FT /evidence="ECO:0000269|PubMed:23334463" FT /id="VAR_072263" FT VARIANT 568 FT /note="P -> L (in IBGC1; dbSNP:rs763252801)" FT /evidence="ECO:0000269|PubMed:23334463" FT /id="VAR_072264" FT VARIANT 571 FT /note="G -> S (in IBGC1; dbSNP:rs1388992742)" FT /evidence="ECO:0000269|PubMed:24065723" FT /id="VAR_075398" FT VARIANT 575 FT /note="E -> K (in IBGC1; substantially impaired phosphate FT transport; dbSNP:rs387906653)" FT /evidence="ECO:0000269|PubMed:22327515" FT /id="VAR_067547" FT VARIANT 595 FT /note="T -> M (in IBGC1; substantially impaired phosphate FT transport; dbSNP:rs387906654)" FT /evidence="ECO:0000269|PubMed:22327515, FT ECO:0000269|PubMed:25284758" FT /id="VAR_067548" FT VARIANT 601 FT /note="S -> L (in IBGC1; substantially impaired phosphate FT transport; dbSNP:rs387906652)" FT /evidence="ECO:0000269|PubMed:22327515, FT ECO:0000269|PubMed:23334463" FT /id="VAR_067549" FT VARIANT 601 FT /note="S -> W (in IBGC1; substantially impaired phosphate FT transport; dbSNP:rs387906652)" FT /evidence="ECO:0000269|PubMed:22327515" FT /id="VAR_067550" FT VARIANT 629 FT /note="T -> TWFVT (in IBGC1; uncertain significance; FT reduced sodium-dependent phosphate transport and cell FT membrane localization)" FT /evidence="ECO:0000269|PubMed:28722801" FT /id="VAR_088078" FT VARIANT 637 FT /note="S -> R (in IBGC1; loss of sodium-dependent phosphate FT transport but no effect on cell membrane localization)" FT /evidence="ECO:0000269|PubMed:24463626, FT ECO:0000269|PubMed:30704756" FT /id="VAR_072265" FT MUTAGEN 55 FT /note="E->D,K: Abolishes sodium-dependent phosphate FT transport; no effect on retroviral receptor function." FT /evidence="ECO:0000269|PubMed:12205090, FT ECO:0000269|PubMed:16790504" FT MUTAGEN 55 FT /note="E->Q: Abolishes phosphate but not sodium uptake; FT when associated with Q-91 and Q-575." FT /evidence="ECO:0000269|PubMed:12205090, FT ECO:0000269|PubMed:16790504" FT MUTAGEN 81 FT /note="N->V: Abolishes N-glycosylation." FT /evidence="ECO:0000269|PubMed:11356966" FT MUTAGEN 91 FT /note="E->Q: Abolishes phosphate but not sodium uptake; FT when associated with Q-55 and Q-575." FT /evidence="ECO:0000269|PubMed:16790504" FT MUTAGEN 506 FT /note="D->N: Impairs phosphate transport; no effect on FT retroviral receptor function." FT /evidence="ECO:0000269|PubMed:15955065" FT MUTAGEN 575 FT /note="E->D,K: Abolishes sodium-dependent phosphate FT transport; no effect on retroviral receptor function." FT /evidence="ECO:0000269|PubMed:12205090, FT ECO:0000269|PubMed:16790504" FT MUTAGEN 575 FT /note="E->Q: Abolishes phosphate but not sodium uptake; FT when associated with Q-55 and Q-91." FT /evidence="ECO:0000269|PubMed:12205090, FT ECO:0000269|PubMed:16790504" SQ SEQUENCE 652 AA; 70392 MW; A0A870C7927DE39C CRC64; MAMDEYLWMV ILGFIIAFIL AFSVGANDVA NSFGTAVGSG VVTLRQACIL ASIFETTGSV LLGAKVGETI RKGIIDVNLY NETVETLMAG EVSAMVGSAV WQLIASFLRL PISGTHCIVG STIGFSLVAI GTKGVQWMEL VKIVASWFIS PLLSGFMSGL LFVLIRIFIL KKEDPVPNGL RALPVFYAAT IAINVFSIMY TGAPVLGLVL PMWAIALISF GVALLFAFFV WLFVCPWMRR KITGKLQKEG ALSRVSDESL SKVQEAESPV FKELPGAKAN DDSTIPLTGA AGETLGTSEG TSAGSHPRAA YGRALSMTHG SVKSPISNGT FGFDGHTRSD GHVYHTVHKD SGLYKDLLHK IHIDRGPEEK PAQESNYRLL RRNNSYTCYT AAICGLPVHA TFRAADSSAP EDSEKLVGDT VSYSKKRLRY DSYSSYCNAV AEAEIEAEEG GVEMKLASEL ADPDQPREDP AEEEKEEKDA PEVHLLFHFL QVLTACFGSF AHGGNDVSNA IGPLVALWLI YKQGGVTQEA ATPVWLLFYG GVGICTGLWV WGRRVIQTMG KDLTPITPSS GFTIELASAF TVVIASNIGL PVSTTHCKVG SVVAVGWIRS RKAVDWRLFR NIFVAWFVTV PVAGLFSAAV MALLMYGILP YV // ID S39AE_HUMAN Reviewed; 492 AA. AC Q15043; A6NH98; B4DIW3; B6EU88; D3DSR4; Q6ZME8; Q96BB3; DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 3. DT 28-JAN-2026, entry version 178. DE RecName: Full=Metal cation symporter ZIP14 {ECO:0000305|PubMed:18270315}; DE AltName: Full=LIV-1 subfamily of ZIP zinc transporter 4 {ECO:0000303|PubMed:12659941}; DE Short=LZT-Hs4 {ECO:0000303|PubMed:12659941}; DE AltName: Full=Solute carrier family 39 member 14 {ECO:0000312|HGNC:HGNC:20858}; DE AltName: Full=Zrt- and Irt-like protein 14 {ECO:0000303|PubMed:15642354}; DE Short=ZIP-14 {ECO:0000303|PubMed:15642354}; DE Flags: Precursor; GN Name=SLC39A14 {ECO:0000312|HGNC:HGNC:20858}; GN Synonyms=KIAA0062 {ECO:0000312|EMBL:BAA06685.1}, GN ZIP14 {ECO:0000303|PubMed:15642354}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Bone marrow; RX PubMed=7584044; DOI=10.1093/dnares/1.5.223; RA Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., RA Kawarabayasi Y., Ishikawa K., Tabata S.; RT "Prediction of the coding sequences of unidentified human genes. II. The RT coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of RT cDNA clones from human cell line KG-1."; RL DNA Res. 1:223-229(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT PRO-33. RC TISSUE=Colon; 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 SUBUNIT, AND MOTIF. RX PubMed=12659941; DOI=10.1016/s0005-2736(03)00048-8; RA Taylor K.M., Nicholson R.I.; RT "The LZT proteins; the LIV-1 subfamily of zinc transporters."; RL Biochim. Biophys. Acta 1611:16-30(2003). RN [7] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=15642354; DOI=10.1016/j.febslet.2004.12.006; RA Taylor K.M., Morgan H.E., Johnson A., Nicholson R.I.; RT "Structure-function analysis of a novel member of the LIV-1 subfamily of RT zinc transporters, ZIP14."; RL FEBS Lett. 579:427-432(2005). RN [8] RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2). RX PubMed=18270315; DOI=10.1124/mol.107.043588; RA Girijashanker K., He L., Soleimani M., Reed J.M., Li H., Liu Z., Wang B., RA Dalton T.P., Nebert D.W.; RT "Slc39a14 gene encodes ZIP14, a metal/bicarbonate symporter: similarities RT to the ZIP8 transporter."; RL Mol. Pharmacol. 73:1413-1423(2008). RN [9] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-77. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [10] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-77 AND ASN-102. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N-linked RT cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=20682781; DOI=10.1074/jbc.m110.143248; RA Zhao N., Gao J., Enns C.A., Knutson M.D.; RT "ZRT/IRT-like protein 14 (ZIP14) promotes the cellular assimilation of iron RT from transferrin."; RL J. Biol. Chem. 285:32141-32150(2010). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY. RX PubMed=23052185; DOI=10.1007/s00011-012-0559-y; RA Sayadi A., Nguyen A.T., Bard F.A., Bard-Chapeau E.A.; RT "Zip14 expression induced by lipopolysaccharides in macrophages attenuates RT inflammatory response."; RL Inflamm. Res. 62:133-143(2013). RN [14] 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 [15] RP INDUCTION BY IRON, UBIQUITINATION, MUTAGENESIS OF ASN-77; ASN-87 AND RP ASN-102, AND GLYCOSYLATION AT ASN-77; ASN-87 AND ASN-102. RX PubMed=24927598; DOI=10.1073/pnas.1405355111; RA Zhao N., Zhang A.S., Worthen C., Knutson M.D., Enns C.A.; RT "An iron-regulated and glycosylation-dependent proteasomal degradation RT pathway for the plasma membrane metal transporter ZIP14."; RL Proc. Natl. Acad. Sci. U.S.A. 111:9175-9180(2014). RN [16] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=27703010; DOI=10.1074/jbc.m116.748632; RA Aydemir T.B., Troche C., Kim M.H., Cousins R.J.; RT "Hepatic ZIP14-mediated Zinc Transport Contributes to Endosomal Insulin RT Receptor Trafficking and Glucose Metabolism."; RL J. Biol. Chem. 291:23939-23951(2016). RN [17] RP INDUCTION. RX PubMed=28673968; DOI=10.1073/pnas.1704012114; RA Kim M.H., Aydemir T.B., Kim J., Cousins R.J.; RT "Hepatic ZIP14-mediated zinc transport is required for adaptation to RT endoplasmic reticulum stress."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E5805-E5814(2017). RN [18] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=31028174; DOI=10.1074/jbc.ra119.008762; RA Scheiber I.F., Wu Y., Morgan S.E., Zhao N.; RT "The intestinal metal transporter ZIP14 maintains systemic manganese RT homeostasis."; RL J. Biol. Chem. 294:9147-9160(2019). RN [19] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=31699897; DOI=10.1074/jbc.ra119.009371; RA Steimle B.L., Smith F.M., Kosman D.J.; RT "The solute carriers ZIP8 and ZIP14 regulate manganese accumulation in RT brain microvascular endothelial cells and control brain manganese levels."; RL J. Biol. Chem. 294:19197-19208(2019). RN [20] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY (ISOFORM 2), INVOLVEMENT RP IN HMNDYT2, MOTIF, VARIANTS HMNDYT2 VAL-98; ARG-383 AND LYS-469, AND RP CHARACTERIZATION OF VARIANTS HMNDYT2 VAL-98; ARG-383 AND LYS-469. RX PubMed=27231142; DOI=10.1038/ncomms11601; RA Tuschl K., Meyer E., Valdivia L.E., Zhao N., Dadswell C., Abdul-Sada A., RA Hung C.Y., Simpson M.A., Chong W.K., Jacques T.S., Woltjer R.L., Eaton S., RA Gregory A., Sanford L., Kara E., Houlden H., Cuno S.M., Prokisch H., RA Valletta L., Tiranti V., Younis R., Maher E.R., Spencer J., RA Straatman-Iwanowska A., Gissen P., Selim L.A., Pintos-Morell G., RA Coroleu-Lletget W., Mohammad S.S., Yoganathan S., Dale R.C., Thomas M., RA Rihel J., Bodamer O.A., Enns C.A., Hayflick S.J., Clayton P.T., Mills P.B., RA Kurian M.A., Wilson S.W.; RT "Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood- RT onset parkinsonism-dystonia."; RL Nat. Commun. 7:11601-11601(2016). RN [21] RP INVOLVEMENT IN HCIN, VARIANT HCIN ARG-441, CHARACTERIZATION OF VARIANT HCIN RP ARG-441, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=29621230; DOI=10.1371/journal.pgen.1007321; RA Hendrickx G., Borra V.M., Steenackers E., Yorgan T.A., Hermans C., RA Boudin E., Waterval J.J., Jansen I.D.C., Aydemir T.B., Kamerling N., RA Behets G.J., Plumeyer C., D'Haese P.C., Busse B., Everts V., Lammens M., RA Mortier G., Cousins R.J., Schinke T., Stokroos R.J., Manni J.J., RA Van Hul W.; RT "Conditional mouse models support the role of SLC39A14 (ZIP14) in RT Hyperostosis Cranialis Interna and in bone homeostasis."; RL PLoS Genet. 14:E1007321-E1007321(2018). CC -!- FUNCTION: Electroneutral transporter of the plasma membrane mediating CC the cellular uptake of the divalent metal cations zinc, manganese and CC iron that are important for tissue homeostasis, metabolism, development CC and immunity (PubMed:15642354, PubMed:27231142, PubMed:29621230). CC Functions as an energy-dependent symporter, transporting through the CC membranes an electroneutral complex composed of a divalent metal cation CC and two bicarbonate anions (By similarity). Beside these endogenous CC cellular substrates, can also import cadmium a non-essential metal CC which is cytotoxic and carcinogenic (By similarity). Controls the CC cellular uptake by the intestinal epithelium of systemic zinc, which is CC in turn required to maintain tight junctions and the intestinal CC permeability (By similarity). Modifies the activity of zinc-dependent CC phosphodiesterases, thereby indirectly regulating G protein-coupled CC receptor signaling pathways important for gluconeogenesis and CC chondrocyte differentiation (By similarity). Regulates insulin receptor CC signaling, glucose uptake, glycogen synthesis and gluconeogenesis in CC hepatocytes through the zinc-dependent intracellular catabolism of CC insulin (PubMed:27703010). Through zinc cellular uptake also plays a CC role in the adaptation of cells to endoplasmic reticulum stress (By CC similarity). Major manganese transporter of the basolateral membrane of CC intestinal epithelial cells, it plays a central role in manganese CC systemic homeostasis through intestinal manganese uptake CC (PubMed:31028174). Also involved in manganese extracellular uptake by CC cells of the blood-brain barrier (PubMed:31699897). May also play a CC role in manganese and zinc homeostasis participating in their CC elimination from the blood through the hepatobiliary excretion (By CC similarity). Also functions in the extracellular uptake of free iron. CC May also function intracellularly and mediate the transport from CC endosomes to cytosol of iron endocytosed by transferrin CC (PubMed:20682781). Plays a role in innate immunity by regulating the CC expression of cytokines by activated macrophages (PubMed:23052185). CC {ECO:0000250|UniProtKB:Q75N73, ECO:0000269|PubMed:15642354, CC ECO:0000269|PubMed:20682781, ECO:0000269|PubMed:23052185, CC ECO:0000269|PubMed:27231142, ECO:0000269|PubMed:27703010, CC ECO:0000269|PubMed:29621230, ECO:0000269|PubMed:31028174, CC ECO:0000269|PubMed:31699897}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Zn(2+)(out) + 2 hydrogencarbonate(out) = Zn(2+)(in) + 2 CC hydrogencarbonate(in); Xref=Rhea:RHEA:62252, ChEBI:CHEBI:17544, CC ChEBI:CHEBI:29105; Evidence={ECO:0000305|PubMed:15642354}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62253; CC Evidence={ECO:0000269|PubMed:15642354}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Mn(2+)(out) + 2 hydrogencarbonate(out) = Mn(2+)(in) + 2 CC hydrogencarbonate(in); Xref=Rhea:RHEA:62260, ChEBI:CHEBI:17544, CC ChEBI:CHEBI:29035; Evidence={ECO:0000305|PubMed:31699897}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62261; CC Evidence={ECO:0000269|PubMed:31699897}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Fe(2+)(out) + 2 hydrogencarbonate(out) = Fe(2+)(in) + 2 CC hydrogencarbonate(in); Xref=Rhea:RHEA:62368, ChEBI:CHEBI:17544, CC ChEBI:CHEBI:29033; Evidence={ECO:0000250|UniProtKB:Q75N73}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62369; CC Evidence={ECO:0000250|UniProtKB:Q75N73}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Cd(2+)(out) + 2 hydrogencarbonate(out) = Cd(2+)(in) + 2 CC hydrogencarbonate(in); Xref=Rhea:RHEA:62256, ChEBI:CHEBI:17544, CC ChEBI:CHEBI:48775; Evidence={ECO:0000250|UniProtKB:Q75N73}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62257; CC Evidence={ECO:0000250|UniProtKB:Q75N73}; CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:12659941}. CC -!- INTERACTION: CC Q15043-2; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-12176399, EBI-741037; CC Q15043-2; Q9UH03: SEPTIN3; NbExp=3; IntAct=EBI-12176399, EBI-727037; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15642354, CC ECO:0000269|PubMed:27231142, ECO:0000269|PubMed:27703010, CC ECO:0000269|PubMed:29621230}; Multi-pass membrane protein CC {ECO:0000255}. Apical cell membrane {ECO:0000269|PubMed:31699897}; CC Multi-pass membrane protein {ECO:0000255}. Basolateral cell membrane CC {ECO:0000269|PubMed:31028174, ECO:0000269|PubMed:31699897}; Multi-pass CC membrane protein {ECO:0000255}. Early endosome membrane CC {ECO:0000269|PubMed:20682781, ECO:0000269|PubMed:27703010}; Multi-pass CC membrane protein {ECO:0000255}. Late endosome membrane CC {ECO:0000269|PubMed:27703010}; Multi-pass membrane protein CC {ECO:0000255}. Lysosome membrane {ECO:0000269|PubMed:20682781}; Multi- CC pass membrane protein {ECO:0000255}. Note=Localized and functional at CC both apical and basolateral membranes of microvascular capillary CC endothelial cells that constitute the blood-brain barrier CC (PubMed:31699897). Localized at the basolateral membrane of enterocytes CC (PubMed:31028174). Enriched at the plasma membrane upon glucose uptake CC (PubMed:27703010). {ECO:0000269|PubMed:27703010, CC ECO:0000269|PubMed:31028174, ECO:0000269|PubMed:31699897}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1 {ECO:0000303|PubMed:27231142}; Synonyms=ZIP14B CC {ECO:0000303|PubMed:18270315}; CC IsoId=Q15043-1; Sequence=Displayed; CC Name=3; CC IsoId=Q15043-2; Sequence=VSP_029728; CC Name=2 {ECO:0000303|PubMed:27231142}; Synonyms=ZIP14A CC {ECO:0000303|PubMed:18270315}; CC IsoId=Q15043-3; Sequence=VSP_040139; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with higher expression in CC liver, pancreas, fetal liver, thyroid gland, left and right ventricle, CC right atrium and fetal heart (PubMed:15642354, PubMed:20682781, CC PubMed:7584044). Weakly expressed in spleen, thymus, and peripheral CC blood leukocytes (PubMed:7584044). Expressed in liver and in brain by CC large neurons in the globus pallidus, the insular cortex and the CC dentate nucleus and to a lower extent in the putamen and the caudate CC nucleus (at protein level) (PubMed:27231142). Expressed in osteoblasts CC and giant osteoclast-like cells, but not in osteocytes found CC osteoblastoma and giant cell tumors (at protein level) CC (PubMed:29621230). Expressed by microvascular capillary endothelial CC cells that constitute the blood-brain barrier (at protein level) CC (PubMed:31699897). Expressed by macrophages (PubMed:23052185). CC {ECO:0000269|PubMed:15642354, ECO:0000269|PubMed:20682781, CC ECO:0000269|PubMed:23052185, ECO:0000269|PubMed:31699897, CC ECO:0000269|PubMed:7584044}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Widely expressed but not detected in CC brain, heart, skeletal muscle, placenta and fetal skin. CC {ECO:0000269|PubMed:27231142}. CC -!- INDUCTION: Up-regulated by iron (at protein level) (PubMed:24927598). CC Down-regulation upon iron depletion occurs through proteasomal CC degradation of the intracellular pool (PubMed:24927598). Up-regulated CC by tunicamycin, a drug inducing endoplasmic reticulum stress (at CC protein level) (PubMed:28673968). Up-regulated by CC lipopolysaccharide/LPS (PubMed:23052185). {ECO:0000269|PubMed:23052185, CC ECO:0000269|PubMed:24927598, ECO:0000269|PubMed:28673968}. CC -!- PTM: Ubiquitinated. Ubiquitination occurs upon iron depletion. The CC ubiquitinated form undergoes proteasomal degradation. CC {ECO:0000269|PubMed:24927598}. CC -!- PTM: N-glycosylated. N-glycosylation at Asn-102 is required for iron- CC regulated extraction of the transporter from membranes and subsequent CC proteasomal degradation. {ECO:0000269|PubMed:24927598}. CC -!- DISEASE: Hypermanganesemia with dystonia 2 (HMNDYT2) [MIM:617013]: A CC metabolic autosomal recessive disorder characterized by increased blood CC manganese levels, neurodegeneration, and rapidly progressive CC parkinsonism and dystonia. Affected individuals present with loss of CC developmental milestones, progressive dystonia and bulbar dysfunction CC in infancy or early childhood. Towards the end of the first decade, CC they manifest severe generalized pharmacoresistant dystonia, CC spasticity, limb contractures and scoliosis, and loss of independent CC ambulation. Cognition may be impaired, but is better preserved than CC motor function. {ECO:0000269|PubMed:27231142}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Hyperostosis cranialis interna (HCIN) [MIM:144755]: An CC autosomal dominant bone disorder characterized by endosteal CC hyperostosis and osteosclerosis of the calvaria and the skull base. The CC progressive bone overgrowth causes entrapment and dysfunction of CC cranial nerves I, II, V, VII, and VIII, its first symptoms often CC presenting during the second decade of life. CC {ECO:0000269|PubMed:29621230}. Note=The disease is caused by variants CC affecting the gene represented in this entry. Conditional knockin mice CC overexpressing Arg-438 variant, which is the mouse equivalent of human CC variant Leu-441, in osteoblasts have a severe skeletal phenotype marked CC by a drastic increase in cortical thickness due to an enhanced CC endosteal bone formation, resembling the underlying pathology in HCI CC patients. {ECO:0000269|PubMed:29621230}. CC -!- SIMILARITY: Belongs to the ZIP transporter (TC 2.A.5) family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA06685.1; 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; D31887; BAA06685.1; ALT_INIT; mRNA. DR EMBL; AK172810; BAD18780.1; -; mRNA. DR EMBL; AK295807; BAG58625.1; -; mRNA. DR EMBL; AC087854; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC105910; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471080; EAW63681.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63682.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63683.1; -; Genomic_DNA. DR EMBL; BC015770; AAH15770.1; -; mRNA. DR CCDS; CCDS47822.1; -. [Q15043-2] DR CCDS; CCDS47823.1; -. [Q15043-1] DR CCDS; CCDS6030.1; -. [Q15043-3] DR RefSeq; NP_001121903.1; NM_001128431.4. [Q15043-1] DR RefSeq; NP_001128625.1; NM_001135153.3. [Q15043-1] DR RefSeq; NP_001128626.1; NM_001135154.3. [Q15043-2] DR RefSeq; NP_001338584.1; NM_001351655.2. [Q15043-1] DR RefSeq; NP_001338585.1; NM_001351656.2. [Q15043-1] DR RefSeq; NP_001338589.1; NM_001351660.2. [Q15043-1] DR RefSeq; NP_056174.2; NM_015359.6. [Q15043-3] DR RefSeq; XP_006716387.1; XM_006716324.4. [Q15043-1] DR RefSeq; XP_047277610.1; XM_047421654.1. [Q15043-1] DR RefSeq; XP_047277611.1; XM_047421655.1. [Q15043-1] DR AlphaFoldDB; Q15043; -. DR SMR; Q15043; -. DR BioGRID; 117063; 343. DR FunCoup; Q15043; 631. DR IntAct; Q15043; 255. DR MINT; Q15043; -. DR STRING; 9606.ENSP00000370635; -. DR DrugBank; DB06757; Manganese cation. DR DrugBank; DB14533; Zinc chloride. DR DrugBank; DB14548; Zinc sulfate, unspecified form. DR TCDB; 2.A.5.4.5; the zinc (zn(2+))-iron (fe(2+)) permease (zip) family. DR GlyCosmos; Q15043; 3 sites, No reported glycans. DR GlyGen; Q15043; 4 sites, 21 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; Q15043; -. DR PhosphoSitePlus; Q15043; -. DR SwissPalm; Q15043; -. DR BioMuta; SLC39A14; -. DR DMDM; 313104191; -. DR jPOST; Q15043; -. DR MassIVE; Q15043; -. DR PaxDb; 9606-ENSP00000352779; -. DR PeptideAtlas; Q15043; -. DR ProteomicsDB; 60392; -. [Q15043-1] DR ProteomicsDB; 60393; -. [Q15043-2] DR ProteomicsDB; 60394; -. [Q15043-3] DR Pumba; Q15043; -. DR Antibodypedia; 9517; 193 antibodies from 27 providers. DR DNASU; 23516; -. DR Ensembl; ENST00000240095.10; ENSP00000240095.6; ENSG00000104635.16. [Q15043-2] DR Ensembl; ENST00000289952.9; ENSP00000289952.5; ENSG00000104635.16. [Q15043-1] DR Ensembl; ENST00000359741.10; ENSP00000352779.5; ENSG00000104635.16. [Q15043-3] DR Ensembl; ENST00000381237.6; ENSP00000370635.1; ENSG00000104635.16. [Q15043-1] DR GeneID; 23516; -. DR KEGG; hsa:23516; -. DR MANE-Select; ENST00000381237.6; ENSP00000370635.1; NM_001128431.4; NP_001121903.1. DR UCSC; uc003xbp.5; human. [Q15043-1] DR AGR; HGNC:20858; -. DR ClinPGx; PA134863701; -. DR CTD; 23516; -. DR DisGeNET; 23516; -. DR GeneCards; SLC39A14; -. DR GeneReviews; SLC39A14; -. DR HGNC; HGNC:20858; SLC39A14. DR HPA; ENSG00000104635; Tissue enhanced (liver, pancreas). DR MalaCards; SLC39A14; -. DR MIM; 144755; phenotype. DR MIM; 608736; gene. DR MIM; 617013; phenotype. DR OpenTargets; ENSG00000104635; -. DR Orphanet; 521406; Dystonia-parkinsonism-hypermanganesemia syndrome. DR VEuPathDB; HostDB:ENSG00000104635; -. DR eggNOG; KOG2693; Eukaryota. DR GeneTree; ENSGT00940000157986; -. DR InParanoid; Q15043; -. DR OMA; ADHYSTP; -. DR OrthoDB; 200954at2759; -. DR PAN-GO; Q15043; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q15043; -. DR PathwayCommons; Q15043; -. DR Reactome; R-HSA-442380; Zinc influx into cells by the SLC39 gene family. DR SignaLink; Q15043; -. DR Agora; ENSG00000104635; -. DR BioGRID-ORCS; 23516; 16 hits in 1166 CRISPR screens. DR ChiTaRS; SLC39A14; human. DR GenomeRNAi; 23516; -. DR Pharos; Q15043; Tbio. DR PRO; PR:Q15043; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q15043; protein. DR Bgee; ENSG00000104635; Expressed in cartilage tissue and 199 other cell types or tissues. DR ExpressionAtlas; Q15043; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB. DR GO; GO:0031902; C:late endosome membrane; IDA:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0015086; F:cadmium ion transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0015093; F:ferrous iron transmembrane transporter activity; IEA:Ensembl. DR GO; GO:0005381; F:iron ion transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0005384; F:manganese ion transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015296; F:monoatomic anion:monoatomic cation symporter activity; ISS:UniProtKB. DR GO; GO:0140410; F:monoatomic cation:bicarbonate symporter activity; IDA:UniProtKB. DR GO; GO:0005385; F:zinc ion transmembrane transporter activity; IDA:BHF-UCL. DR GO; GO:0071333; P:cellular response to glucose stimulus; ISS:UniProtKB. DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB. DR GO; GO:0002062; P:chondrocyte differentiation; ISS:UniProtKB. DR GO; GO:0006094; P:gluconeogenesis; ISS:UniProtKB. DR GO; GO:0098739; P:import across plasma membrane; IMP:UniProtKB. DR GO; GO:0098662; P:inorganic cation transmembrane transport; ISS:UniProtKB. DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0030003; P:intracellular monoatomic cation homeostasis; IBA:GO_Central. DR GO; GO:0006882; P:intracellular zinc ion homeostasis; IDA:BHF-UCL. DR GO; GO:0033212; P:iron import into cell; IMP:UniProtKB. DR GO; GO:0034755; P:iron ion transmembrane transport; IMP:UniProtKB. DR GO; GO:0055071; P:manganese ion homeostasis; ISS:UniProtKB. DR GO; GO:0071421; P:manganese ion transmembrane transport; IMP:UniProtKB. DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0010817; P:regulation of hormone levels; ISS:UniProtKB. DR GO; GO:0071578; P:zinc ion import across plasma membrane; IDA:UniProtKB. DR GO; GO:0071577; P:zinc ion transmembrane transport; IDA:BHF-UCL. DR InterPro; IPR003689; ZIP. DR InterPro; IPR050799; ZIP_Transporter. DR PANTHER; PTHR12191:SF5; METAL CATION SYMPORTER ZIP14; 1. DR PANTHER; PTHR12191; SOLUTE CARRIER FAMILY 39; 1. DR Pfam; PF02535; Zip; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Disease variant; Dystonia; Endosome; KW Glycoprotein; Ion transport; Lysosome; Membrane; Neurodegeneration; KW Parkinsonism; Proteomics identification; Reference proteome; Signal; KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation; Zinc; KW Zinc transport. FT SIGNAL 1..30 FT /evidence="ECO:0000255" FT CHAIN 31..492 FT /note="Metal cation symporter ZIP14" FT /id="PRO_0000312194" FT TOPO_DOM 31..157 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 158..178 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 179..186 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 187..207 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 208..224 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 225..245 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 246..397 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 398..418 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 419..424 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 425..445 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 446..460 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 461..481 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 482..492 FT /note="Extracellular" FT /evidence="ECO:0000255" FT MOTIF 251..258 FT /note="HHHGHXHX-motif" FT /evidence="ECO:0000305|PubMed:27231142" FT MOTIF 376..381 FT /note="XEXPHE-motif" FT /evidence="ECO:0000305|PubMed:12659941" FT CARBOHYD 77 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19349973, ECO:0000269|PubMed:24927598" FT CARBOHYD 87 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:24927598" FT CARBOHYD 102 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973, FT ECO:0000269|PubMed:24927598" FT VAR_SEQ 156..199 FT /note="YGLLCVTVISLCSLLGASVVPFMKKTFYKRLLLYFIALAIGTLY -> FGFL FT SVSLINLASLLGVLVLPCTEKAFFSRVLTYFIALSIGTLL (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_040139" FT VAR_SEQ 445..492 FT /note="FPEMNEVCQEDERKGSILIPFIIQNLGLLTGFTIMVVLTMYSGQIQIG -> FT MEFCSVAQAGVQWCHLSSLQPLPLGLKRLSCLSLPSN (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_029728" FT VARIANT 33 FT /note="L -> P (in dbSNP:rs896378)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_037450" FT VARIANT 98 FT /note="F -> V (in HMNDYT2; no effect on protein abundance; FT no effect on subcellular localization at the plasma FT membrane and within the cytoplasm; decreased manganese ion FT transmembrane transporter activity; dbSNP:rs879253763)" FT /evidence="ECO:0000269|PubMed:27231142" FT /id="VAR_077004" FT VARIANT 383 FT /note="G -> R (in HMNDYT2; no effect on protein abundance; FT no effect on subcellular localization at the plasma FT membrane and within the cytoplasm; decreased manganese ion FT transmembrane transporter activity; dbSNP:rs879253766)" FT /evidence="ECO:0000269|PubMed:27231142" FT /id="VAR_077005" FT VARIANT 441 FT /note="L -> R (in HCIN; loss of localization at the plasma FT membrane; loss of Zn uptake activity; dbSNP:rs1554520924)" FT /evidence="ECO:0000269|PubMed:29621230" FT /id="VAR_080794" FT VARIANT 469 FT /note="N -> K (in HMNDYT2; no effect on protein abundance; FT no effect on subcellular localization at the plasma FT membrane and within the cytoplasm; decreased manganese ion FT transmembrane transporter activity; dbSNP:rs750281602)" FT /evidence="ECO:0000269|PubMed:27231142" FT /id="VAR_077006" FT MUTAGEN 77 FT /note="N->A: Decreased N-glycosylation." FT /evidence="ECO:0000269|PubMed:24927598" FT MUTAGEN 87 FT /note="N->A: Decreased N-glycosylation." FT /evidence="ECO:0000269|PubMed:24927598" FT MUTAGEN 102 FT /note="N->A: Decreased N-glycosylation." FT /evidence="ECO:0000269|PubMed:24927598" FT CONFLICT 57 FT /note="L -> P (in Ref. 2; BAD18780)" FT /evidence="ECO:0000305" FT CONFLICT 314 FT /note="D -> G (in Ref. 2; BAG58625)" FT /evidence="ECO:0000305" FT CONFLICT 380 FT /note="H -> R (in Ref. 2; BAD18780)" FT /evidence="ECO:0000305" SQ SEQUENCE 492 AA; 54212 MW; F2ACE1DA4656A5F0 CRC64; MKLLLLHPAF QSCLLLTLLG LWRTTPEAHA SSLGAPAISA ASFLQDLIHR YGEGDSLTLQ QLKALLNHLD VGVGRGNVTQ HVQGHRNLST CFSSGDLFTA HNFSEQSRIG SSELQEFCPT ILQQLDSRAC TSENQENEEN EQTEEGRPSA VEVWGYGLLC VTVISLCSLL GASVVPFMKK TFYKRLLLYF IALAIGTLYS NALFQLIPEA FGFNPLEDYY VSKSAVVFGG FYLFFFTEKI LKILLKQKNE HHHGHSHYAS ESLPSKKDQE EGVMEKLQNG DLDHMIPQHC SSELDGKAPM VDEKVIVGSL SVQDLQASQS ACYWLKGVRY SDIGTLAWMI TLSDGLHNFI DGLAIGASFT VSVFQGISTS VAILCEEFPH ELGDFVILLN AGMSIQQALF FNFLSACCCY LGLAFGILAG SHFSANWIFA LAGGMFLYIS LADMFPEMNE VCQEDERKGS ILIPFIIQNL GLLTGFTIMV VLTMYSGQIQ IG // ID S53A1_HUMAN Reviewed; 696 AA. AC Q9UBH6; O95719; Q7L8K9; Q8IW20; Q9NT19; Q9UFB9; DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 28-JAN-2026, entry version 172. DE RecName: Full=Solute carrier family 53 member 1 {ECO:0000303|PubMed:31043717}; DE AltName: Full=Phosphate exporter SLC53A1 {ECO:0000305|PubMed:31043717}; DE AltName: Full=Protein SYG1 homolog; DE AltName: Full=Xenotropic and polytropic murine leukemia virus receptor X3; DE Short=X-receptor; DE AltName: Full=Xenotropic and polytropic retrovirus receptor 1; GN Name=XPR1 {ECO:0000303|PubMed:31043717}; GN Synonyms=SLC53A1 {ECO:0000303|PubMed:31043717}, SYG1, X3; 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=9988277; DOI=10.1038/6005; RA Yang Y.-L., Guo L., Xu S., Holland C.A., Kitamura T., Hunter K., RA Cunningham J.M.; RT "Receptors for polytropic and xenotropic mouse leukaemia viruses encoded by RT a single gene at Rmc1."; RL Nat. Genet. 21:216-219(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND RP DEVELOPMENTAL STAGE. RC TISSUE=Lymphocyte; RX PubMed=9927670; DOI=10.1073/pnas.96.3.927; RA Tailor C.S., Nouri A., Lee C.G., Kozak C., Kabat D.; RT "Cloning and characterization of a cell surface receptor for xenotropic and RT polytropic murine leukemia viruses."; RL Proc. Natl. Acad. Sci. U.S.A. 96:927-932(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, DEVELOPMENTAL RP STAGE, AND VARIANT ALA-491. RC TISSUE=Cervix carcinoma; RX PubMed=9990033; DOI=10.1073/pnas.96.4.1385; RA Battini J.-L., Rasko J.E.J., Miller A.D.; RT "A human cell-surface receptor for xenotropic and polytropic murine RT leukemia viruses: possible role in G protein-coupled signal transduction."; RL Proc. Natl. Acad. Sci. U.S.A. 96:1385-1390(1999). 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 (JUL-2007) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 103-696 (ISOFORM 1). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-690, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-668 AND THR-690, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-690, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [12] RP FUNCTION, TRANSPORTER ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=23791524; DOI=10.1016/j.celrep.2013.05.035; RA Giovannini D., Touhami J., Charnet P., Sitbon M., Battini J.L.; RT "Inorganic phosphate export by the retrovirus receptor XPR1 in metazoans."; RL Cell Rep. 3:1866-1873(2013). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-668, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [14] RP FUNCTION, TRANSPORTER ACTIVITY, INVOLVEMENT IN IBGC6, VARIANTS IBGC6 RP ASN-136; PRO-140; PRO-145 AND SER-218, AND CHARACTERIZATION OF VARIANTS RP IBGC6 ASN-136; PRO-140; PRO-145 AND SER-218. RX PubMed=25938945; DOI=10.1038/ng.3289; RA Legati A., Giovannini D., Nicolas G., Lopez-Sanchez U., Quintans B., RA Oliveira J.R., Sears R.L., Ramos E.M., Spiteri E., Sobrido M.J., RA Carracedo A., Castro-Fernandez C., Cubizolle S., Fogel B.L., Goizet C., RA Jen J.C., Kirdlarp S., Lang A.E., Miedzybrodzka Z., Mitarnun W., Paucar M., RA Paulson H., Pariente J., Richard A.C., Salins N.S., Simpson S.A., RA Striano P., Svenningsson P., Tison F., Unni V.K., Vanakker O., RA Wessels M.W., Wetchaphanphesat S., Yang M., Boller F., Campion D., RA Hannequin D., Sitbon M., Geschwind D.H., Battini J.L., Coppola G.; RT "Mutations in XPR1 cause primary familial brain calcification associated RT with altered phosphate export."; RL Nat. Genet. 47:579-581(2015). RN [15] RP FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, INVOLVEMENT IN IBGC6, RP VARIANTS IBGC6 CYS-459; ASP-619 AND SER-629, CHARACTERIZATION OF VARIANTS RP IBGC6 CYS-459; ASP-619 AND SER-629, AND MUTAGENESIS OF 612-LEU--THR-696. RX PubMed=31043717; DOI=10.1038/s41598-019-43255-x; RA Lopez-Sanchez U., Nicolas G., Richard A.C., Maltete D., Charif M., RA Ayrignac X., Goizet C., Touhami J., Labesse G., Battini J.L., Sitbon M.; RT "Characterization of XPR1/SLC53A1 variants located outside of the SPX RT domain in patients with primary familial brain calcification."; RL Sci. Rep. 9:6776-6776(2019). RN [16] {ECO:0007744|PDB:5IJH} RP X-RAY CRYSTALLOGRAPHY (2.43 ANGSTROMS) OF 1-207, DOMAIN, AND FUNCTION. RX PubMed=27080106; DOI=10.1126/science.aad9858; RA Wild R., Gerasimaite R., Jung J.Y., Truffault V., Pavlovic I., Schmidt A., RA Saiardi A., Jessen H.J., Poirier Y., Hothorn M., Mayer A.; RT "Control of eukaryotic phosphate homeostasis by inositol polyphosphate RT sensor domains."; RL Science 352:986-990(2016). RN [17] {ECO:0007744|PDB:8X5B, ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F} RP STRUCTURE BY ELECTRON MICROSCOPY (2.84 ANGSTROMS) IN COMPLEXES WITH RP PHOSPHATE AND INOSITOL HEXAKISPHOSPHATE, FUNCTION, TRANSPORTER ACTIVITY, RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, SUBUNIT, DOMAIN, TOPOLOGY, AND RP MUTAGENESIS OF TYR-22; LYS-158; GLY-238; GLY-242; ARG-270; ARG-273; RP PHE-394; ASP-398; ARG-459; ARG-466; SER-497; ASP-533; ARG-570; TRP-573; RP THR-582; ARG-603; ARG-604; ARG-611 AND PHE-623. RX PubMed=39169184; DOI=10.1038/s41586-024-07852-9; RA Yan R., Chen H., Liu C., Zhao J., Wu D., Jiang J., Gong J., Jiang D.; RT "Human XPR1 structures reveal phosphate export mechanism."; RL Nature 633:960-967(2024). RN [18] {ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IWS} RP STRUCTURE BY ELECTRON MICROSCOPY (2.86 ANGSTROMS) OF 1-631 IN COMPLEX WITH RP INOSITOL HEXAKISPHOSPHATE, FUNCTION, TRANSPORTER ACTIVITY, ACTIVITY RP REGULATION, SUBCELLULAR LOCATION, SUBUNIT, DOMAIN, TOPOLOGY, AND RP MUTAGENESIS OF ARG-211; ARG-219; LYS-482; ARG-570; TRP-573; ARG-603 AND RP ARG-604. RX PubMed=39325866; DOI=10.1126/science.adp3252; RA Lu Y., Yue C.X., Zhang L., Yao D., Xia Y., Zhang Q., Zhang X., Li S., RA Shen Y., Cao M., Guo C.R., Qin A., Zhao J., Zhou L., Yu Y., Cao Y.; RT "Structural basis for inositol pyrophosphate gating of the phosphate RT channel XPR1."; RL Science 386:eadp3252-eadp3252(2024). RN [19] {ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) IN COMPLEX WITH RP PHOSPHATE, FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, SUBUNIT, RP TOPOLOGY, AND MUTAGENESIS OF ARG-270; ASN-401; ARG-448; GLN-452; ARG-459; RP TYR-483; ARG-570; TRP-573; GLN-576; GLU-600 AND ARG-603. RX PubMed=39747008; DOI=10.1038/s41467-024-55471-9; RA Zhang W., Chen Y., Guan Z., Wang Y., Tang M., Du Z., Zhang J., Cheng M., RA Zuo J., Liu Y., Wang Q., Liu Y., Zhang D., Yin P., Ma L., Liu Z.; RT "Structural insights into the mechanism of phosphate recognition and RT transport by XPR1."; RL Nat. Commun. 16:18-18(2025). RN [20] {ECO:0007744|PDB:9IJY, ECO:0007744|PDB:9IJZ} RP STRUCTURE BY ELECTRON MICROSCOPY (2.64 ANGSTROMS) IN COMPLEX WITH RP PHOSPHATE, FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, SUBUNIT, RP DOMAIN, TOPOLOGY, AND MUTAGENESIS OF LYS-158; LYS-161; LYS-165; PHE-235; RP LEU-239; LYS-482; ARG-570; TRP-573; ARG-603 AND ARG-604. RX PubMed=39814721; DOI=10.1038/s41467-025-55995-8; RA He Q., Zhang R., Tury S., Courgnaud V., Liu F., Battini J.L., Li B., RA Chen Q.; RT "Structural basis of phosphate export by human XPR1."; RL Nat. Commun. 16:683-683(2025). CC -!- FUNCTION: Inorganic ion transporter that mediates phosphate ion export CC across the plasma membrane (PubMed:23791524, PubMed:25938945, CC PubMed:27080106, PubMed:31043717, PubMed:39169184, PubMed:39325866, CC PubMed:39747008, PubMed:39814721). Plays a major role in phosphate CC homeostasis, preventing intracellular phosphate accumulation and CC possible calcium phosphate precipitation, ultimately preserving calcium CC signaling (PubMed:27080106). Binds inositol hexakisphosphate (Ins6P) CC and similar inositol polyphosphates, such as 5-diphospho-inositol CC pentakisphosphate (5-InsP7), which are important intracellular CC signaling molecules involved in regulation of phosphate flux CC (PubMed:27080106, PubMed:39169184, PubMed:39325866). CC {ECO:0000269|PubMed:23791524, ECO:0000269|PubMed:25938945, CC ECO:0000269|PubMed:27080106, ECO:0000269|PubMed:31043717, CC ECO:0000269|PubMed:39169184, ECO:0000269|PubMed:39325866, CC ECO:0000269|PubMed:39747008, ECO:0000269|PubMed:39814721}. CC -!- CATALYTIC ACTIVITY: CC Reaction=phosphate(in) = phosphate(out); Xref=Rhea:RHEA:32823, CC ChEBI:CHEBI:43474; Evidence={ECO:0000269|PubMed:23791524, CC ECO:0000269|PubMed:25938945, ECO:0000269|PubMed:31043717, CC ECO:0000269|PubMed:39169184, ECO:0000269|PubMed:39325866, CC ECO:0000269|PubMed:39747008, ECO:0000269|PubMed:39814721}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32824; CC Evidence={ECO:0000305|PubMed:23791524, ECO:0000305|PubMed:25938945, CC ECO:0000305|PubMed:31043717}; CC -!- ACTIVITY REGULATION: Allosterically activated by inositol CC hexakisphosphate (Ins6P). {ECO:0000269|PubMed:39169184, CC ECO:0000269|PubMed:39325866}. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:39169184, CC ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, CC ECO:0000269|PubMed:39814721}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23791524, CC ECO:0000269|PubMed:31043717}; Multi-pass membrane protein CC {ECO:0000269|PubMed:39169184, ECO:0000269|PubMed:39325866, CC ECO:0000269|PubMed:39747008, ECO:0000269|PubMed:39814721}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UBH6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UBH6-2; Sequence=VSP_030748; CC -!- TISSUE SPECIFICITY: Widely expressed. Detected in spleen, lymph node, CC thymus, leukocytes, bone marrow, heart, kidney, pancreas and skeletal CC muscle. {ECO:0000269|PubMed:9927670, ECO:0000269|PubMed:9990033}. CC -!- DEVELOPMENTAL STAGE: Expressed in fetal liver. CC {ECO:0000269|PubMed:9927670, ECO:0000269|PubMed:9990033}. CC -!- DOMAIN: The SPX domain plays a role in the regulation of phosphate flux CC (PubMed:39169184, PubMed:39325866, PubMed:39814721). Inositol CC hexakisphosphate (Ins6P) is bound between two SPX domains of the CC homodimer (PubMed:39169184, PubMed:39325866). The SPX domain has high CC affinity for inositol polyphosphates and its affinity for inorganic CC phosphate is two to three orders of magnitude lower (PubMed:27080106). CC {ECO:0000269|PubMed:27080106, ECO:0000269|PubMed:39169184, CC ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39814721}. CC -!- DISEASE: Basal ganglia calcification, idiopathic, 6 (IBGC6) CC [MIM:616413]: A form of basal ganglia calcification, an autosomal CC dominant condition characterized by symmetric calcification in the CC basal ganglia and other brain regions. Affected individuals can either CC be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, CC including parkinsonism, dystonia, tremor, ataxia, dementia, psychosis, CC seizures, and chronic headache. Serum levels of calcium, phosphate, CC alkaline phosphatase and parathyroid hormone are normal. The CC neuropathological hallmark of the disease is vascular and pericapillary CC calcification, mainly of calcium phosphate, in the affected brain CC areas. {ECO:0000269|PubMed:25938945, ECO:0000269|PubMed:31043717}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the SYG1 (TC 2.A.94) family. {ECO:0000305}. CC -!- CAUTION: Confers susceptibility to xenotropic murine leukemia CC retrovirus (X-MLV) infection in vitro, but it is unclear whether its CC ability to act as a receptor for xenotropic and polytropic murine CC leukemia retroviruses is relevant in vivo and whether such viruses can CC infect human. {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; AF115389; AAD17211.1; -; mRNA. DR EMBL; AF089744; AAD10196.1; -; mRNA. DR EMBL; AF099082; AAD08928.1; -; mRNA. DR EMBL; AL590085; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL162431; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL358434; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471067; EAW91086.1; -; Genomic_DNA. DR EMBL; BC041142; AAH41142.1; -; mRNA. DR EMBL; AL133058; CAB61383.1; -; mRNA. DR EMBL; AL137583; CAB70825.1; -; mRNA. DR CCDS; CCDS1340.1; -. [Q9UBH6-1] DR CCDS; CCDS44284.1; -. [Q9UBH6-2] DR PIR; T42660; T42660. DR RefSeq; NP_001129141.1; NM_001135669.2. [Q9UBH6-2] DR RefSeq; NP_004727.2; NM_004736.3. [Q9UBH6-1] DR PDB; 5IJH; X-ray; 2.43 A; A/B=1-207. DR PDB; 8TYU; X-ray; 1.40 A; A/B=1-94, A/B=130-207. DR PDB; 8TYV; X-ray; 1.85 A; A/B=1-94, A/B=130-207. DR PDB; 8X5B; EM; 2.84 A; A/F=229-696. DR PDB; 8X5E; EM; 3.61 A; A=229-696. DR PDB; 8X5F; EM; 2.96 A; A/B=1-696. DR PDB; 8YET; EM; 4.16 A; A/B=1-620. DR PDB; 8YEX; EM; 3.68 A; A/B=228-619. DR PDB; 8YF4; EM; 3.41 A; A/B=227-619. DR PDB; 8YFD; EM; 3.57 A; A/B=227-622. DR PDB; 8YFU; EM; 4.59 A; A/B=21-620. DR PDB; 8YFW; EM; 3.65 A; A/B=21-620. DR PDB; 8YFX; EM; 3.56 A; A/B=227-622. DR PDB; 8ZTO; EM; 3.55 A; A/B=1-696. DR PDB; 9DVJ; EM; 2.52 A; A/B=1-696. DR PDB; 9DVK; EM; 3.06 A; A/B=1-696. DR PDB; 9DVL; EM; 2.97 A; A/B=1-696. DR PDB; 9DVM; EM; 2.92 A; A/B=1-696. DR PDB; 9DVN; EM; 2.75 A; A/B=1-696. DR PDB; 9DVO; EM; 3.10 A; A/B=1-696. DR PDB; 9DVP; EM; 2.81 A; A/B=1-696. DR PDB; 9IJY; EM; 2.64 A; A/B=1-696. DR PDB; 9IJZ; EM; 2.91 A; A/B=1-696. DR PDB; 9INE; EM; 3.32 A; A/B=1-696. DR PDB; 9INF; EM; 3.36 A; A/B=1-696. DR PDB; 9INH; EM; 3.68 A; A/D=1-696. DR PDB; 9ITG; EM; 3.03 A; A/B=1-696. DR PDB; 9IUC; EM; 3.80 A; A/B=1-696. DR PDB; 9IWS; EM; 2.86 A; A/B=1-631. DR PDB; 9J4X; EM; 2.90 A; A/B=1-696. DR PDB; 9J51; EM; 3.10 A; A/B=1-696. DR PDB; 9J52; EM; 3.10 A; A/B=1-696. DR PDB; 9J53; EM; 3.30 A; A/B=1-696. DR PDB; 9J97; EM; 3.30 A; A/B=1-696. DR PDB; 9J98; EM; 3.33 A; A/B=1-696. DR PDBsum; 5IJH; -. DR PDBsum; 8TYU; -. DR PDBsum; 8TYV; -. DR PDBsum; 8X5B; -. DR PDBsum; 8X5E; -. DR PDBsum; 8X5F; -. DR PDBsum; 8YET; -. DR PDBsum; 8YEX; -. DR PDBsum; 8YF4; -. DR PDBsum; 8YFD; -. DR PDBsum; 8YFU; -. DR PDBsum; 8YFW; -. DR PDBsum; 8YFX; -. DR PDBsum; 8ZTO; -. DR PDBsum; 9DVJ; -. DR PDBsum; 9DVK; -. DR PDBsum; 9DVL; -. DR PDBsum; 9DVM; -. DR PDBsum; 9DVN; -. DR PDBsum; 9DVO; -. DR PDBsum; 9DVP; -. DR PDBsum; 9IJY; -. DR PDBsum; 9IJZ; -. DR PDBsum; 9INE; -. DR PDBsum; 9INF; -. DR PDBsum; 9INH; -. DR PDBsum; 9ITG; -. DR PDBsum; 9IUC; -. DR PDBsum; 9IWS; -. DR PDBsum; 9J4X; -. DR PDBsum; 9J51; -. DR PDBsum; 9J52; -. DR PDBsum; 9J53; -. DR PDBsum; 9J97; -. DR PDBsum; 9J98; -. DR AlphaFoldDB; Q9UBH6; -. DR EMDB; EMD-38065; -. DR EMDB; EMD-38067; -. DR EMDB; EMD-38068; -. DR EMDB; EMD-39203; -. DR EMDB; EMD-39204; -. DR EMDB; EMD-39210; -. DR EMDB; EMD-39220; -. DR EMDB; EMD-39230; -. DR EMDB; EMD-39231; -. DR EMDB; EMD-39232; -. DR EMDB; EMD-45656; -. DR EMDB; EMD-45657; -. DR EMDB; EMD-47208; -. DR EMDB; EMD-47209; -. DR EMDB; EMD-47210; -. DR EMDB; EMD-47211; -. DR EMDB; EMD-47212; -. DR EMDB; EMD-47213; -. DR EMDB; EMD-47214; -. DR EMDB; EMD-60469; -. DR EMDB; EMD-60645; -. DR EMDB; EMD-60646; -. DR EMDB; EMD-60704; -. DR EMDB; EMD-60705; -. DR EMDB; EMD-60707; -. DR EMDB; EMD-60861; -. DR EMDB; EMD-60897; -. DR EMDB; EMD-60962; -. DR EMDB; EMD-61138; -. DR EMDB; EMD-61139; -. DR EMDB; EMD-61140; -. DR EMDB; EMD-61141; -. DR EMDB; EMD-61859; -. DR EMDB; EMD-61860; -. DR EMDB; EMD-61861; -. DR EMDB; EMD-61862; -. DR EMDB; EMD-61863; -. DR EMDB; EMD-61864; -. DR EMDB; EMD-61865; -. DR EMDB; EMD-61866; -. DR EMDB; EMD-61867; -. DR EMDB; EMD-61868; -. DR EMDB; EMD-61869; -. DR EMDB; EMD-61870; -. DR EMDB; EMD-61871; -. DR EMDB; EMD-61875; -. DR SMR; Q9UBH6; -. DR BioGRID; 114647; 230. DR FunCoup; Q9UBH6; 2397. DR IntAct; Q9UBH6; 181. DR MINT; Q9UBH6; -. DR STRING; 9606.ENSP00000356562; -. DR TCDB; 2.A.94.1.6; the phosphate permease (pho1) family. DR iPTMnet; Q9UBH6; -. DR PhosphoSitePlus; Q9UBH6; -. DR SwissPalm; Q9UBH6; -. DR BioMuta; XPR1; -. DR DMDM; 74753221; -. DR jPOST; Q9UBH6; -. DR MassIVE; Q9UBH6; -. DR PaxDb; 9606-ENSP00000356562; -. DR PeptideAtlas; Q9UBH6; -. DR ProteomicsDB; 83970; -. [Q9UBH6-1] DR ProteomicsDB; 83971; -. [Q9UBH6-2] DR Pumba; Q9UBH6; -. DR Antibodypedia; 20589; 190 antibodies from 29 providers. DR DNASU; 9213; -. DR Ensembl; ENST00000367589.3; ENSP00000356561.3; ENSG00000143324.15. [Q9UBH6-2] DR Ensembl; ENST00000367590.9; ENSP00000356562.4; ENSG00000143324.15. [Q9UBH6-1] DR GeneID; 9213; -. DR KEGG; hsa:9213; -. DR MANE-Select; ENST00000367590.9; ENSP00000356562.4; NM_004736.4; NP_004727.2. DR UCSC; uc001goi.4; human. [Q9UBH6-1] DR AGR; HGNC:12827; -. DR ClinPGx; PA37420; -. DR CTD; 9213; -. DR DisGeNET; 9213; -. DR GeneCards; XPR1; -. DR GeneReviews; XPR1; -. DR HGNC; HGNC:12827; XPR1. DR HPA; ENSG00000143324; Low tissue specificity. DR MalaCards; XPR1; -. DR MIM; 605237; gene. DR MIM; 616413; phenotype. DR OpenTargets; ENSG00000143324; -. DR Orphanet; 1980; Bilateral striopallidodentate calcinosis. DR VEuPathDB; HostDB:ENSG00000143324; -. DR eggNOG; KOG1162; Eukaryota. DR GeneTree; ENSGT00500000044895; -. DR HOGENOM; CLU_006116_3_0_1; -. DR InParanoid; Q9UBH6; -. DR OMA; ETSHFYT; -. DR OrthoDB; 9970435at2759; -. DR PAN-GO; Q9UBH6; 7 GO annotations based on evolutionary models. DR PhylomeDB; Q9UBH6; -. DR PathwayCommons; Q9UBH6; -. DR SignaLink; Q9UBH6; -. DR Agora; ENSG00000143324; -. DR BioGRID-ORCS; 9213; 63 hits in 1164 CRISPR screens. DR ChiTaRS; XPR1; human. DR GenomeRNAi; 9213; -. DR Pharos; Q9UBH6; Tbio. DR PRO; PR:Q9UBH6; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9UBH6; protein. DR Bgee; ENSG00000143324; Expressed in cortical plate and 192 other cell types or tissues. DR ExpressionAtlas; Q9UBH6; baseline and differential. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0015562; F:efflux transmembrane transporter activity; IMP:UniProtKB. DR GO; GO:0000822; F:inositol hexakisphosphate binding; IDA:UniProtKB. DR GO; GO:0005315; F:phosphate transmembrane transporter activity; IMP:UniProtKB. DR GO; GO:0001618; F:virus receptor activity; IEA:Ensembl. DR GO; GO:0016036; P:cellular response to phosphate starvation; IBA:GO_Central. DR GO; GO:0030643; P:intracellular phosphate ion homeostasis; IMP:UniProtKB. DR GO; GO:0035435; P:phosphate ion transmembrane transport; IMP:UniProtKB. DR GO; GO:0006817; P:phosphate ion transport; IBA:GO_Central. DR GO; GO:0009615; P:response to virus; IEA:Ensembl. DR CDD; cd14477; SPX_XPR1_like; 1. DR InterPro; IPR004342; EXS_C. DR InterPro; IPR004331; SPX_dom. DR PANTHER; PTHR10783:SF103; SOLUTE CARRIER FAMILY 53 MEMBER 1; 1. DR PANTHER; PTHR10783; XENOTROPIC AND POLYTROPIC RETROVIRUS RECEPTOR 1-RELATED; 1. DR Pfam; PF03124; EXS; 1. DR Pfam; PF03105; SPX; 3. DR PROSITE; PS51380; EXS; 1. DR PROSITE; PS51382; SPX; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Membrane; Phosphate transport; Phosphoprotein; Proteomics identification; KW Reference proteome; Transmembrane; Transmembrane helix; Transport. FT CHAIN 1..696 FT /note="Solute carrier family 53 member 1" FT /id="PRO_0000315853" FT TOPO_DOM 1..228 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TRANSMEM 229..259 FT /note="Helical; Name=1" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TOPO_DOM 260..264 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TRANSMEM 265..296 FT /note="Helical; Name=2" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TOPO_DOM 297..309 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TRANSMEM 310..337 FT /note="Helical; Name=3" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TOPO_DOM 338..343 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TRANSMEM 344..365 FT /note="Helical; Name=4" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT INTRAMEM 366..383 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TOPO_DOM 384..388 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TRANSMEM 389..422 FT /note="Discontinuously helical; Name=5" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TOPO_DOM 423..429 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TRANSMEM 430..471 FT /note="Discontinuously helical; Name=6" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TOPO_DOM 472 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TRANSMEM 473..503 FT /note="Helical; Name=7" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TOPO_DOM 504..506 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TRANSMEM 507..534 FT /note="Helical; Name=8" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TOPO_DOM 535..553 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TRANSMEM 554..585 FT /note="Discontinuously helical; Name=9" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TOPO_DOM 586..587 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TRANSMEM 588..626 FT /note="Helical; Name=10" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT TOPO_DOM 627..696 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5E, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:8YET, ECO:0007744|PDB:8YEX, FT ECO:0007744|PDB:8YF4, ECO:0007744|PDB:8YFD, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:8YFX, ECO:0007744|PDB:9IJY, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9IWS, FT ECO:0007744|PDB:9J4X, ECO:0007744|PDB:9J51, FT ECO:0007744|PDB:9J52, ECO:0007744|PDB:9J53" FT DOMAIN 2..224 FT /note="SPX" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0007744|PDB:8X5B, FT ECO:0007744|PDB:8X5F, ECO:0007744|PDB:8YET, FT ECO:0007744|PDB:8YFU, ECO:0007744|PDB:8YFW, FT ECO:0007744|PDB:9IWS" FT DOMAIN 439..643 FT /note="EXS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00712" FT REGION 158..165 FT /note="Important for inositol polyphosphate binding" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866" FT REGION 673..696 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 398 FT /ligand="phosphate" FT /ligand_id="ChEBI:CHEBI:43474" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39747008, ECO:0000269|PubMed:39814721, FT ECO:0007744|PDB:8X5B, ECO:0007744|PDB:9IJZ, FT ECO:0007744|PDB:9J52" FT BINDING 401 FT /ligand="phosphate" FT /ligand_id="ChEBI:CHEBI:43474" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39747008, ECO:0000269|PubMed:39814721, FT ECO:0007744|PDB:8X5B, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:9IJY, ECO:0007744|PDB:9IJZ, FT ECO:0007744|PDB:9J52" FT BINDING 482 FT /ligand="phosphate" FT /ligand_id="ChEBI:CHEBI:43474" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39747008, ECO:0000269|PubMed:39814721, FT ECO:0007744|PDB:8X5B, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:9IJY, ECO:0007744|PDB:9IJZ, FT ECO:0007744|PDB:9J52" FT BINDING 483 FT /ligand="phosphate" FT /ligand_id="ChEBI:CHEBI:43474" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39747008, ECO:0000269|PubMed:39814721, FT ECO:0007744|PDB:8X5B, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:9IJY, ECO:0007744|PDB:9IJZ, FT ECO:0007744|PDB:9J52" FT BINDING 570 FT /ligand="phosphate" FT /ligand_id="ChEBI:CHEBI:43474" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39747008, ECO:0000269|PubMed:39814721, FT ECO:0007744|PDB:8X5B, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:9IJY, ECO:0007744|PDB:9IJZ, FT ECO:0007744|PDB:9J52" FT BINDING 603 FT /ligand="phosphate" FT /ligand_id="ChEBI:CHEBI:43474" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39747008, ECO:0000269|PubMed:39814721, FT ECO:0007744|PDB:8X5B, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:9IJZ, ECO:0007744|PDB:9J52" FT BINDING 604 FT /ligand="phosphate" FT /ligand_id="ChEBI:CHEBI:43474" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39747008, ECO:0000269|PubMed:39814721, FT ECO:0007744|PDB:8X5B, ECO:0007744|PDB:8X5F, FT ECO:0007744|PDB:9IJY, ECO:0007744|PDB:9IJZ, FT ECO:0007744|PDB:9J52" FT SITE 573 FT /note="Gating residue for phosphate transport" FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721" FT MOD_RES 668 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 690 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231" FT VAR_SEQ 437..501 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_030748" FT VARIANT 136 FT /note="S -> N (in IBGC6; phosphate efflux is impaired; FT present at the plasma membrane; dbSNP:rs786205902)" FT /evidence="ECO:0000269|PubMed:25938945" FT /id="VAR_073840" FT VARIANT 140 FT /note="L -> P (in IBGC6; phosphate efflux is impaired; FT present at the plasma membrane; dbSNP:rs786205903)" FT /evidence="ECO:0000269|PubMed:25938945" FT /id="VAR_073841" FT VARIANT 145 FT /note="L -> P (in IBGC6; dominant negative; phosphate FT efflux is impaired; loss of localization to the plasma FT membrane; dbSNP:rs786205901)" FT /evidence="ECO:0000269|PubMed:25938945" FT /id="VAR_073842" FT VARIANT 218 FT /note="L -> S (in IBGC6; phosphate efflux is impaired; FT present at the plasma membrane; dbSNP:rs786205904)" FT /evidence="ECO:0000269|PubMed:25938945" FT /id="VAR_073843" FT VARIANT 459 FT /note="R -> C (in IBGC6; phosphate efflux is decreased; FT present at the plasma membrane)" FT /evidence="ECO:0000269|PubMed:31043717" FT /id="VAR_087987" FT VARIANT 491 FT /note="T -> A (in dbSNP:rs1061012)" FT /evidence="ECO:0000269|PubMed:9990033" FT /id="VAR_038350" FT VARIANT 619 FT /note="N -> D (in IBGC6; phosphate efflux is impaired; FT present at the plasma membrane)" FT /evidence="ECO:0000269|PubMed:31043717" FT /id="VAR_087988" FT VARIANT 629 FT /note="I -> S (in IBGC6; phosphate efflux is decreased; FT present at the plasma membrane)" FT /evidence="ECO:0000269|PubMed:31043717" FT /id="VAR_087989" FT MUTAGEN 22 FT /note="Y->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184" FT MUTAGEN 158 FT /note="K->A: Decreases phosphate efflux. Decreases FT phosphate efflux; when associated with A-161 and A-165." FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39814721" FT MUTAGEN 161 FT /note="K->A: Decreases phosphate efflux; when associated FT with A-158 and A-165." FT /evidence="ECO:0000269|PubMed:39814721" FT MUTAGEN 165 FT /note="K->A: Decreases phosphate efflux; when associated FT with A-158 and A-161." FT /evidence="ECO:0000269|PubMed:39814721" FT MUTAGEN 211 FT /note="R->E: Increases phosphate efflux; when associated FT with E-219." FT /evidence="ECO:0000269|PubMed:39325866" FT MUTAGEN 219 FT /note="R->E: Increases phosphate efflux; when associated FT with E-211." FT /evidence="ECO:0000269|PubMed:39325866" FT MUTAGEN 235 FT /note="F->G: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39814721" FT MUTAGEN 238 FT /note="G->F: Monomeric; decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184" FT MUTAGEN 239 FT /note="L->G: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39814721" FT MUTAGEN 242 FT /note="G->F: Monomeric; decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184" FT MUTAGEN 270 FT /note="R->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39747008" FT MUTAGEN 273 FT /note="R->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184" FT MUTAGEN 394 FT /note="F->A: Increases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184" FT MUTAGEN 398 FT /note="D->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184" FT MUTAGEN 401 FT /note="N->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39747008" FT MUTAGEN 448 FT /note="R->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39747008" FT MUTAGEN 452 FT /note="Q->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39747008" FT MUTAGEN 459 FT /note="R->A,C: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39747008" FT MUTAGEN 466 FT /note="R->A: Increases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184" FT MUTAGEN 482 FT /note="K->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39325866, FT ECO:0000269|PubMed:39814721" FT MUTAGEN 483 FT /note="Y->F: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39747008" FT MUTAGEN 497 FT /note="S->C: Decreases phosphate efflux. Decreases FT phosphate efflux; when associated with C-582." FT /evidence="ECO:0000269|PubMed:39169184" FT MUTAGEN 533 FT /note="D->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184" FT MUTAGEN 570 FT /note="R->A,C,L: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721" FT MUTAGEN 573 FT /note="W->A,F,G,L,N,Y: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721" FT MUTAGEN 576 FT /note="Q->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39747008" FT MUTAGEN 582 FT /note="T->C: Decreases phosphate efflux. Decreases FT phosphate efflux; when associated with C-497." FT /evidence="ECO:0000269|PubMed:39169184" FT MUTAGEN 600 FT /note="E->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39747008" FT MUTAGEN 603 FT /note="R->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39747008, FT ECO:0000269|PubMed:39814721" FT MUTAGEN 604 FT /note="R->A: Decreases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184, FT ECO:0000269|PubMed:39325866, ECO:0000269|PubMed:39814721" FT MUTAGEN 611 FT /note="R->A: Increases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184" FT MUTAGEN 612..696 FT /note="Missing: Loss of localization to the plasma FT membrane." FT /evidence="ECO:0000269|PubMed:31043717" FT MUTAGEN 623 FT /note="F->A: Increases phosphate efflux." FT /evidence="ECO:0000269|PubMed:39169184" FT HELIX 4..10 FT /evidence="ECO:0007829|PDB:8TYU" FT HELIX 13..18 FT /evidence="ECO:0007829|PDB:8TYU" FT HELIX 22..34 FT /evidence="ECO:0007829|PDB:8TYU" FT TURN 39..41 FT /evidence="ECO:0007829|PDB:8TYU" FT HELIX 44..94 FT /evidence="ECO:0007829|PDB:8TYU" FT HELIX 119..122 FT /evidence="ECO:0007829|PDB:5IJH" FT HELIX 130..167 FT /evidence="ECO:0007829|PDB:8TYU" FT HELIX 171..178 FT /evidence="ECO:0007829|PDB:8TYU" FT TURN 179..182 FT /evidence="ECO:0007829|PDB:8TYU" FT HELIX 184..187 FT /evidence="ECO:0007829|PDB:8TYU" FT HELIX 190..199 FT /evidence="ECO:0007829|PDB:8TYU" FT TURN 206..209 FT /evidence="ECO:0007829|PDB:8X5F" FT HELIX 211..218 FT /evidence="ECO:0007829|PDB:9IWS" FT HELIX 231..256 FT /evidence="ECO:0007829|PDB:9IJY" FT STRAND 261..263 FT /evidence="ECO:0007829|PDB:9IJY" FT HELIX 266..293 FT /evidence="ECO:0007829|PDB:9IJY" FT TURN 294..296 FT /evidence="ECO:0007829|PDB:9IJY" FT HELIX 299..302 FT /evidence="ECO:0007829|PDB:9IJY" FT STRAND 307..309 FT /evidence="ECO:0007829|PDB:8X5B" FT HELIX 313..335 FT /evidence="ECO:0007829|PDB:9IJY" FT HELIX 337..339 FT /evidence="ECO:0007829|PDB:9J4X" FT STRAND 340..342 FT /evidence="ECO:0007829|PDB:9IJY" FT HELIX 346..360 FT /evidence="ECO:0007829|PDB:9IJY" FT HELIX 368..382 FT /evidence="ECO:0007829|PDB:9IJY" FT TURN 383..386 FT /evidence="ECO:0007829|PDB:9IWS" FT HELIX 391..402 FT /evidence="ECO:0007829|PDB:9IJY" FT HELIX 404..418 FT /evidence="ECO:0007829|PDB:9IJY" FT STRAND 423..425 FT /evidence="ECO:0007829|PDB:8X5B" FT TURN 426..429 FT /evidence="ECO:0007829|PDB:9J98" FT HELIX 439..441 FT /evidence="ECO:0007829|PDB:9IJY" FT STRAND 444..446 FT /evidence="ECO:0007829|PDB:8X5F" FT HELIX 447..469 FT /evidence="ECO:0007829|PDB:9IJY" FT HELIX 476..502 FT /evidence="ECO:0007829|PDB:9IJY" FT HELIX 506..531 FT /evidence="ECO:0007829|PDB:9IJY" FT TURN 532..534 FT /evidence="ECO:0007829|PDB:9J97" FT STRAND 544..547 FT /evidence="ECO:0007829|PDB:9J4X" FT STRAND 552..554 FT /evidence="ECO:0007829|PDB:9IWS" FT HELIX 556..581 FT /evidence="ECO:0007829|PDB:9IJY" FT TURN 586..588 FT /evidence="ECO:0007829|PDB:9IJY" FT HELIX 589..617 FT /evidence="ECO:0007829|PDB:9IJY" FT TURN 620..623 FT /evidence="ECO:0007829|PDB:9IWS" SQ SEQUENCE 696 AA; 81535 MW; B5B4BABF5CA2503A CRC64; MKFAEHLSAH ITPEWRKQYI QYEAFKDMLY SAQDQAPSVE VTDEDTVKRY FAKFEEKFFQ TCEKELAKIN TFYSEKLAEA QRRFATLQNE LQSSLDAQKE STGVTTLRQR RKPVFHLSHE ERVQHRNIKD LKLAFSEFYL SLILLQNYQN LNFTGFRKIL KKHDKILETS RGADWRVAHV EVAPFYTCKK INQLISETEA VVTNELEDGD RQKAMKRLRV PPLGAAQPAP AWTTFRVGLF CGIFIVLNIT LVLAAVFKLE TDRSIWPLIR IYRGGFLLIE FLFLLGINTY GWRQAGVNHV LIFELNPRSN LSHQHLFEIA GFLGILWCLS LLACFFAPIS VIPTYVYPLA LYGFMVFFLI NPTKTFYYKS RFWLLKLLFR VFTAPFHKVG FADFWLADQL NSLSVILMDL EYMICFYSLE LKWDESKGLL PNNSEESGIC HKYTYGVRAI VQCIPAWLRF IQCLRRYRDT KRAFPHLVNA GKYSTTFFMV TFAALYSTHK ERGHSDTMVF FYLWIVFYII SSCYTLIWDL KMDWGLFDKN AGENTFLREE IVYPQKAYYY CAIIEDVILR FAWTIQISIT STTLLPHSGD IIATVFAPLE VFRRFVWNFF RLENEHLNNC GEFRAVRDIS VAPLNADDQT LLEQMMDQDD GVRNRQKNRS WKYNQSISLR RPRLASQSKA RDTKVLIEDT DDEANT //