ID MET_HUMAN Reviewed; 1390 AA. AC P08581; A1L467; B5A932; E7EQ94; O60366; Q12875; Q9UDX7; Q9UPL8; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 07-JUL-2009, sequence version 4. DT 27-MAR-2024, entry version 275. DE RecName: Full=Hepatocyte growth factor receptor; DE Short=HGF receptor; DE EC=2.7.10.1; DE AltName: Full=HGF/SF receptor; DE AltName: Full=Proto-oncogene c-Met; DE AltName: Full=Scatter factor receptor; DE Short=SF receptor; DE AltName: Full=Tyrosine-protein kinase Met; DE Flags: Precursor; GN Name=MET; 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 2). RX PubMed=2819873; DOI=10.1073/pnas.84.18.6379; RA Park M., Dean M., Kaul K., Braun M.J., Gonda M.A., Vande Woude G.; RT "Sequence of MET protooncogene cDNA has features characteristic of the RT tyrosine kinase family of growth-factor receptors."; RL Proc. Natl. Acad. Sci. U.S.A. 84:6379-6383(1987). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Giordano S.; RL Submitted (NOV-1990) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), 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=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D., RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., RA Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cerebellum; 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 NUCLEOTIDE SEQUENCE [MRNA] OF 1010-1390. RX PubMed=3325883; RA Chan A.M.-L., King H.W.S., Tempest P.R., Deakin E.A., Cooper C.S., RA Brookes P.; RT "Primary structure of the met protein tyrosine kinase domain."; RL Oncogene 1:229-233(1987). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1206-1264. RX PubMed=8247543; RA Lee S.-T., Strunk K.M., Spritz R.A.; RT "A survey of protein tyrosine kinase mRNAs expressed in normal human RT melanocytes."; RL Oncogene 8:3403-3410(1993). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1267-1390. RX PubMed=4069211; DOI=10.1038/318385a0; RA Dean M., Park M., le Beau M.M., Robins T.S., Diaz M.O., Rowley J.D., RA Blair D.G., Vande Woude G.F.; RT "The human met oncogene is related to the tyrosine kinase oncogenes."; RL Nature 318:385-388(1985). RN [11] RP TISSUE SPECIFICITY. RX PubMed=1917129; DOI=10.1002/ijc.2910490302; RA Prat M., Narsimhan R.P., Crepaldi T., Nicotra M.R., Natali P.G., RA Comoglio P.M.; RT "The receptor encoded by the human c-MET oncogene is expressed in RT hepatocytes, epithelial cells and solid tumors."; RL Int. J. Cancer 49:323-328(1991). RN [12] RP INTERACTION WITH PIK3R1. RX PubMed=1718989; DOI=10.1016/s0021-9258(18)54536-1; RA Graziani A., Gramaglia D., Cantley L.C., Comoglio P.M.; RT "The tyrosine-phosphorylated hepatocyte growth factor/scatter factor RT receptor associates with phosphatidylinositol 3-kinase."; RL J. Biol. Chem. 266:22087-22090(1991). RN [13] RP TISSUE SPECIFICITY. RX PubMed=1719465; RA Di Renzo M.F., Narsimhan R.P., Olivero M., Bretti S., Giordano S., RA Medico E., Gaglia P., Zara P., Comoglio P.M.; RT "Expression of the Met/HGF receptor in normal and neoplastic human RT tissues."; RL Oncogene 6:1997-2003(1991). RN [14] RP FUNCTION. RX PubMed=1846706; DOI=10.1126/science.1846706; RA Bottaro D.P., Rubin J.S., Faletto D.L., Chan A.M.-L., Kmiecik T.E., RA Vande Woude G.F., Aaronson S.A.; RT "Identification of the hepatocyte growth factor receptor as the c-met RT proto-oncogene product."; RL Science 251:802-804(1991). RN [15] RP PHOSPHORYLATION AT TYR-1235, AND ATP-BINDING SITE LYS-1110. RX PubMed=1655790; DOI=10.1016/s0021-9258(18)55031-6; RA Ferracini R., Longati P., Naldini L., Vigna E., Comoglio P.M.; RT "Identification of the major autophosphorylation site of the Met/hepatocyte RT growth factor receptor tyrosine kinase."; RL J. Biol. Chem. 266:19558-19564(1991). RN [16] RP PHOSPHORYLATION AT TYR-1349 AND TYR-1356, AND INTERACTION WITH SRC; PLCG1 RP AND GRB2. RX PubMed=7513258; DOI=10.1016/0092-8674(94)90318-2; RA Ponzetto C., Bardelli A., Zhen Z., Maina F., dalla Zonca P., Giordano S., RA Graziani A., Panayotou G., Comoglio P.M.; RT "A multifunctional docking site mediates signaling and transformation by RT the hepatocyte growth factor/scatter factor receptor family."; RL Cell 77:261-271(1994). RN [17] RP FUNCTION IN WOUND HEALING. RX PubMed=8182137; DOI=10.1172/jci117200; RA Nusrat A., Parkos C.A., Bacarra A.E., Godowski P.J., Delp-Archer C., RA Rosen E.M., Madara J.L.; RT "Hepatocyte growth factor/scatter factor effects on epithelia. Regulation RT of intercellular junctions in transformed and nontransformed cell lines, RT basolateral polarization of c-met receptor in transformed and natural RT intestinal epithelia, and induction of rapid wound repair in a transformed RT model epithelium."; RL J. Clin. Invest. 93:2056-2065(1994). RN [18] RP INTERACTION WITH STAT3. RX PubMed=9440692; DOI=10.1038/34657; RA Boccaccio C., Ando M., Tamagnone L., Bardelli A., Michieli P., RA Battistini C., Comoglio P.M.; RT "Induction of epithelial tubules by growth factor HGF depends on the STAT RT pathway."; RL Nature 391:285-288(1998). RN [19] RP INTERACTION WITH GRB10. 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 [20] RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH L.MONOCYTOGENES INLB RP (MICROBIAL INFECTION), AND PHOSPHORYLATION (MICROBIAL INFECTION). RX PubMed=11081636; DOI=10.1016/s0092-8674(00)00141-0; RA Shen Y., Naujokas M., Park M., Ireton K.; RT "InIB-dependent internalization of Listeria is mediated by the Met receptor RT tyrosine kinase."; RL Cell 103:501-510(2000). RN [21] RP INTERACTION WITH RANBP9. RX PubMed=12147692; DOI=10.1074/jbc.m205111200; RA Wang D., Li Z., Messing E.M., Wu G.; RT "Activation of Ras/Erk pathway by a novel MET-interacting protein RanBPM."; RL J. Biol. Chem. 277:36216-36222(2002). RN [22] RP UBIQUITINATION, MUTAGENESIS OF TYR-1234; TYR-1235; TYR-1313; TYR-1349; RP TYR-1356 AND TYR-1365, AND CHARACTERIZATION OF VARIANT SER-1003. RX PubMed=12244174; DOI=10.4049/jimmunol.169.7.3793; RA Taher T.E., Tjin E.P., Beuling E.A., Borst J., Spaargaren M., Pals S.T.; RT "c-Cbl is involved in Met signaling in B cells and mediates hepatocyte RT growth factor-induced receptor ubiquitination."; RL J. Immunol. 169:3793-3800(2002). RN [23] RP INTERACTION WITH PLXNB1. RX PubMed=12198496; DOI=10.1038/ncb843; RA Giordano S., Corso S., Conrotto P., Artigiani S., Gilestro G., Barberis D., RA Tamagnone L., Comoglio P.M.; RT "The semaphorin 4D receptor controls invasive growth by coupling with RT Met."; RL Nat. Cell Biol. 4:720-724(2002). RN [24] RP PHOSPHORYLATION AT TYR-1230; TYR-1234; TYR-1235; TYR-1349 AND TYR-1365, AND RP DEPHOSPHORYLATION AT TYR-1349 AND TYR-1365 BY PTPRJ. RX PubMed=12475979; DOI=10.1074/jbc.m210656200; RA Palka H.L., Park M., Tonks N.K.; RT "Hepatocyte growth factor receptor tyrosine kinase met is a substrate of RT the receptor protein-tyrosine phosphatase DEP-1."; RL J. Biol. Chem. 278:5728-5735(2003). RN [25] RP INTERACTION WITH RANBP9 AND RANBP10. RX PubMed=14684163; DOI=10.1016/j.bbrc.2003.11.124; RA Wang D., Li Z., Schoen S.R., Messing E.M., Wu G.; RT "A novel MET-interacting protein shares high sequence similarity with RT RanBPM, but fails to stimulate MET-induced Ras/Erk signaling."; RL Biochem. Biophys. Res. Commun. 313:320-326(2004). RN [26] RP FUNCTION, AND INTERACTION WITH MUC20. RX PubMed=15314156; DOI=10.1128/mcb.24.17.7456-7468.2004; RA Higuchi T., Orita T., Katsuya K., Yamasaki Y., Akiyama K., Li H., RA Yamamoto T., Saito Y., Nakamura M.; RT "MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by RT binding to a multifunctional docking site of met."; RL Mol. Cell. Biol. 24:7456-7468(2004). RN [27] RP PHOSPHORYLATION AT TYR-1356, AND INTERACTION WITH INPPL1. RX PubMed=15735664; DOI=10.1038/sj.onc.1208558; RA Koch A., Mancini A., El Bounkari O., Tamura T.; RT "The SH2-domain-containing inositol 5-phosphatase (SHIP)-2 binds to c-Met RT directly via tyrosine residue 1356 and involves hepatocyte growth factor RT (HGF)-induced lamellipodium formation, cell scattering and cell RT spreading."; RL Oncogene 24:3436-3447(2005). RN [28] RP REVIEW ON FUNCTION IN ANGIOGENESIS. RX PubMed=16862193; DOI=10.1038/nrc1912; RA Boccaccio C., Comoglio P.M.; RT "Invasive growth: a MET-driven genetic programme for cancer and stem RT cells."; RL Nat. Rev. Cancer 6:637-645(2006). RN [29] RP PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN1 AND PTPN2, INTERACTION WITH RP PTPN1 AND PTPN2, AND MUTAGENESIS OF TYR-1234 AND TYR-1235. RX PubMed=18819921; DOI=10.1074/jbc.m805916200; RA Sangwan V., Paliouras G.N., Abella J.V., Dube N., Monast A., Tremblay M.L., RA Park M.; RT "Regulation of the Met receptor-tyrosine kinase by the protein-tyrosine RT phosphatase 1B and T-cell phosphatase."; RL J. Biol. Chem. 283:34374-34383(2008). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-977 AND TYR-1003, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-990; SER-997 AND SER-1000, RP AND 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 [32] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-106. RC TISSUE=Hepatoma; RX PubMed=19196183; DOI=10.1021/pr800826u; RA Cao J., Shen C., Wang H., Shen H., Chen Y., Nie A., Yan G., Lu H., Liu Y., RA Yang P.; RT "Identification of N-glycosylation sites on secreted proteins of human RT hepatocellular carcinoma cells with a complementary proteomics approach."; RL J. Proteome Res. 8:662-672(2009). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1003 AND THR-1289, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [34] RP REVIEW ON FUNCTION. RX PubMed=20655987; DOI=10.1016/j.bbcan.2010.07.006; RA Mahtouk K., Tjin E.P., Spaargaren M., Pals S.T.; RT "The HGF/MET pathway as target for the treatment of multiple myeloma and B- RT cell lymphomas."; RL Biochim. Biophys. Acta 1806:208-219(2010). RN [35] RP FUNCTION (MICROBIAL INFECTION), AND SUBUNIT (MICROBIAL INFECTION). RX PubMed=19900460; DOI=10.1016/j.jmb.2009.10.074; RA Ferraris D.M., Gherardi E., Di Y., Heinz D.W., Niemann H.H.; RT "Ligand-mediated dimerization of the Met receptor tyrosine kinase by the RT bacterial invasion protein InlB."; RL J. Mol. Biol. 395:522-532(2010). RN [36] 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 [37] RP INTERACTION WITH GAB1. RX PubMed=21784853; DOI=10.1074/jbc.m111.239384; RA Chaudhuri A., Xie M.H., Yang B., Mahapatra K., Liu J., Marsters S., RA Bodepudi S., Ashkenazi A.; RT "Distinct involvement of the Gab1 and Grb2 adaptor proteins in signal RT transduction by the related receptor tyrosine kinases RON and MET."; RL J. Biol. Chem. 286:32762-32774(2011). RN [38] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-990, 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 [39] RP INTERACTION WITH TNS3 AND TNS4. RX PubMed=24814316; DOI=10.1016/j.devcel.2014.03.024; RA Muharram G., Sahgal P., Korpela T., De Franceschi N., Kaukonen R., RA Clark K., Tulasne D., Carpen O., Ivaska J.; RT "Tensin-4-dependent MET stabilization is essential for survival and RT proliferation in carcinoma cells."; RL Dev. Cell 29:421-436(2014). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-966, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [41] RP INVOLVEMENT IN OSFD, VARIANT OSFD 964-LEU--ASP-1010 DEL, TISSUE RP SPECIFICITY, AND UBIQUITINATION. RX PubMed=26637977; DOI=10.1016/j.ajhg.2015.11.001; RA Gray M.J., Kannu P., Sharma S., Neyt C., Zhang D., Paria N., Daniel P.B., RA Whetstone H., Sprenger H.G., Hammerschmidt P., Weng A., Dupuis L., RA Jobling R., Mendoza-Londono R., Dray M., Su P., Wilson M.J., Kapur R.P., RA McCarthy E.F., Alman B.A., Howard A., Somers G.R., Marshall C.R., RA Manners S., Flanagan A.M., Rathjen K.E., Karol L.A., Crawford H., RA Markie D.M., Rios J.J., Wise C.A., Robertson S.P.; RT "Mutations preventing regulated exon skipping in MET cause osteofibrous RT dysplasia."; RL Am. J. Hum. Genet. 97:837-847(2015). RN [42] RP INVOLVEMENT IN DFNB97, AND VARIANT DFNB97 VAL-841. RX PubMed=25941349; DOI=10.1136/jmedgenet-2015-103023; RA Mujtaba G., Schultz J.M., Imtiaz A., Morell R.J., Friedman T.B., Naz S.; RT "A mutation of MET, encoding hepatocyte growth factor receptor, is RT associated with human DFNB97 hearing loss."; RL J. Med. Genet. 52:548-552(2015). RN [43] RP INTERACTION WITH HSP90AA1 AND HSP90AB1. RX PubMed=26517842; DOI=10.1371/journal.pone.0141786; RA Prince T.L., Kijima T., Tatokoro M., Lee S., Tsutsumi S., Yim K., Rivas C., RA Alarcon S., Schwartz H., Khamit-Kush K., Scroggins B.T., Beebe K., RA Trepel J.B., Neckers L.; RT "Client proteins and small molecule inhibitors display distinct binding RT preferences for constitutive and stress-induced HSP90 isoforms and their RT conformationally restricted mutants."; RL PLoS ONE 10:E0141786-E0141786(2015). RN [44] RP INTERACTION WITH LECT2. RX PubMed=27334921; DOI=10.1074/jbc.m116.720375; RA Zheng H., Miyakawa T., Sawano Y., Asano A., Okumura A., Yamagoe S., RA Tanokura M.; RT "Crystal structure of human leukocyte cell-derived chemotaxin 2 (LECT2) RT reveals a mechanistic basis of functional evolution in a mammalian protein RT with an M23 metalloendopeptidase fold."; RL J. Biol. Chem. 291:17133-17142(2016). RN [45] RP GLYCOSYLATION AT THR-582; THR-676 AND THR-761. RX PubMed=37186866; DOI=10.1073/pnas.2302584120; RA Larsen I.S.B., Povolo L., Zhou L., Tian W., Mygind K.J., Hintze J., RA Jiang C., Hartill V., Prescott K., Johnson C.A., Mullegama S.V., RA McConkie-Rosell A., McDonald M., Hansen L., Vakhrushev S.Y., RA Schjoldager K.T., Clausen H., Worzfeld T., Joshi H.J., Halim A.; RT "The SHDRA syndrome-associated geDne TMEM260 encodes a protein-specific O- RT mannosyltransferase."; RL Proc. Natl. Acad. Sci. U.S.A. 120:e2302584120-e2302584120(2023). RN [46] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 1356-1359 IN COMPLEX WITH GRB2. RX PubMed=11063574; DOI=10.1021/bi0012336; RA Schiering N., Casale E., Caccia P., Giordano P., Battistini C.; RT "Dimer formation through domain swapping in the crystal structure of the RT Grb2-SH2-Ac-pYVNV complex."; RL Biochemistry 39:13376-13382(2000). RN [47] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1049-1360 IN COMPLEX WITH RP INHIBITOR. RX PubMed=14559966; DOI=10.1073/pnas.1734128100; RA Schiering N., Knapp S., Marconi M., Flocco M.M., Cui J., Perego R., RA Rusconi L., Cristiani C.; RT "Crystal structure of the tyrosine kinase domain of the hepatocyte growth RT factor receptor c-Met and its complex with the microbial alkaloid K-252a."; RL Proc. Natl. Acad. Sci. U.S.A. 100:12654-12659(2003). RN [48] RP STRUCTURE BY NMR OF 519-562, AND DISULFIDE BONDS. RX PubMed=15358240; DOI=10.1016/j.bbrc.2004.06.132; RA Kozlov G., Perreault A., Schrag J.D., Park M., Cygler M., Gehring K., RA Ekiel I.; RT "Insights into function of PSI domains from structure of the Met receptor RT PSI domain."; RL Biochem. Biophys. Res. Commun. 321:234-240(2004). RN [49] RP X-RAY CRYSTALLOGRAPHY (3.22 ANGSTROMS) OF 25-567 IN COMPLEX WITH HGF, AND RP DISULFIDE BONDS. RX PubMed=15167892; DOI=10.1038/sj.emboj.7600243; RA Stamos J., Lazarus R.A., Yao X., Kirchhofer D., Wiesmann C.; RT "Crystal structure of the HGF beta-chain in complex with the Sema domain of RT the Met receptor."; RL EMBO J. 23:2325-2335(2004). RN [50] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 25-740 IN COMPLEX WITH RP L.MONOCYTOGENES INLB, FUNCTION (MICROBIAL INFECTION), INTERACTION WITH RP L.MONOCYTOGENES INLB (MICROBIAL INFECTION), AND DISULFIDE BONDS. RX PubMed=17662939; DOI=10.1016/j.cell.2007.05.037; RA Niemann H.H., Jager V., Butler P.J., van den Heuvel J., Schmidt S., RA Ferraris D., Gherardi E., Heinz D.W.; RT "Structure of the human receptor tyrosine kinase Met in complex with the RT Listeria invasion protein InlB."; RL Cell 130:235-246(2007). RN [51] RP VARIANTS RCCP THR-1131; LEU-1188; VAL-1195; ILE-1220; HIS-1228; ASN-1228; RP CYS-1230; HIS-1230 AND THR-1250, AND VARIANT VAL-320. RX PubMed=9140397; DOI=10.1038/ng0597-68; RA Schmidt L., Duh F.-M., Chen F., Kishida T., Glenn G., Choyke P., RA Scherer S.W., Zhuang Z., Lubensky I., Dean M., Allikmets R., RA Chidambaram A., Bergerheim U.R., Feltis J.T., Casadevall C., Zamarron A., RA Bernues M., Richard S., Lips C.J.M., Walther M.M., Tsui L.-C., Geil L., RA Orcutt M.L., Stackhouse T., Lipan J., Slife L., Brauch H., Decker J., RA Niehans G., Hughson M.D., Moch H., Storkel S., Lerman M.I., Linehan W.M., RA Zbar B.; RT "Germline and somatic mutations in the tyrosine kinase domain of the MET RT proto-oncogene in papillary renal carcinomas."; RL Nat. Genet. 16:68-73(1997). RN [52] RP VARIANT RCCP ARG-1094, AND CHARACTERIZATION OF VARIANT RCCP ARG-1094. RX PubMed=9563489; RA Schmidt L., Junker K., Weirich G., Glenn G., Choyke P., Lubensky I., RA Zhuang Z., Jeffers M., Vande Woude G., Neumann H., Walther M., RA Linehan W.M., Zbar B.; RT "Two North American families with hereditary papillary renal carcinoma and RT identical novel mutations in the MET proto-oncogene."; RL Cancer Res. 58:1719-1722(1998). RN [53] RP VARIANTS RCCP ILE-1092; ARG-1094; ASP-1106; THR-1131; LEU-1188; ASP-1230; RP CYS-1230 AND THR-1250. RX PubMed=10433944; DOI=10.1016/s0002-9440(10)65147-4; RA Lubensky I.A., Schmidt L., Zhuang Z., Weirich G., Pack S., Zambrano N., RA Walther M.M., Choyke P., Linehan W.M., Zbar B.; RT "Hereditary and sporadic papillary renal carcinomas with c-met mutations RT share a distinct morphological phenotype."; RL Am. J. Pathol. 155:517-526(1999). RN [54] RP VARIANTS HCC ILE-1173; ARG-1244 AND ILE-1250. RX PubMed=9927037; RA Park W.S., Dong S.M., Kim S.Y., Na E.Y., Shin M.S., Pi J.H., Kim B.J., RA Bae J.H., Hong Y.K., Lee K.S., Lee S.H., Yoo N.J., Jang J.J., Pack S., RA Zhuang Z., Schmidt L., Zbar B., Lee J.Y.; RT "Somatic mutations in the kinase domain of the Met/hepatocyte growth factor RT receptor gene in childhood hepatocellular carcinomas."; RL Cancer Res. 59:307-310(1999). RN [55] RP VARIANT RCCP ILE-1092, AND CHARACTERIZATION OF VARIANT RCCP ILE-1092. RX PubMed=10417759; RX DOI=10.1002/(sici)1097-0215(19990827)82:5<640::aid-ijc4>3.0.co;2-6; RA Olivero M., Valente G., Bardelli A., Longati P., Ferrero N., Cracco C., RA Terrone C., Rocca-Rossetti S., Comoglio P.M., Di Renzo M.F.; RT "Novel mutation in the ATP-binding site of the MET oncogene tyrosine kinase RT in a HPRCC family."; RL Int. J. Cancer 82:640-643(1999). RN [56] RP VARIANTS RCCP ILE-1092; LEU-1094; TYR-1094; ASP-1106 AND ASP-1230, AND RP CHARACTERIZATION OF VARIANTS RCCP ILE-1092; LEU-1094; TYR-1094; ASP-1106 RP AND ASP-1230. RX PubMed=10327054; DOI=10.1038/sj.onc.1202547; RA Schmidt L., Junker K., Nakaigawa N., Kinjerski T., Weirich G., Miller M., RA Lubensky I., Neumann H.P.H., Brauch H., Decker J., Vocke C., Brown J.A., RA Jenkins R., Richard S., Bergerheim U., Gerrard B., Dean M., Linehan W.M., RA Zbar B.; RT "Novel mutations of the MET proto-oncogene in papillary renal carcinomas."; RL Oncogene 18:2343-2350(1999). RN [57] RP VARIANT GASTRIC CANCER SER-991, VARIANT ILE-992, CHARACTERIZATION OF RP VARIANT GASTRIC CANCER SER-991, AND CHARACTERIZATION OF VARIANT ILE-992. RX PubMed=11042681; DOI=10.1038/sj.onc.1203874; RA Lee J.-H., Han S.-U., Cho H., Jennings B., Gerrard B., Dean M., Schmidt L., RA Zbar B., Vande Woude G.F.V.; RT "A novel germ line juxtamembrane Met mutation in human gastric cancer."; RL Oncogene 19:4947-4953(2000). RN [58] RP VARIANT GASTRIC CANCER LEU-773. RX PubMed=12920089; DOI=10.1136/jmg.40.8.e97; RA Kim I.-J., Park J.-H., Kang H.C., Shin Y., Lim S.-B., Ku J.-L., Yang H.-K., RA Lee K.U., Park J.-G.; RT "A novel germline mutation in the MET extracellular domain in a Korean RT patient with the diffuse type of familial gastric cancer."; RL J. Med. Genet. 40:E97-E97(2003). RN [59] RP INTERACTION WITH SPSB1; SPSB2; SPSB3 AND SPSB4. RX PubMed=15713673; DOI=10.1074/jbc.m413897200; RA Wang D., Li Z., Messing E.M., Wu G.; RT "The SPRY domain-containing SOCS box protein 1 (SSB-1) interacts with MET RT and enhances the hepatocyte growth factor-induced Erk-Elk-1-serum response RT element pathway."; RL J. Biol. Chem. 280:16393-16401(2005). RN [60] RP POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO AUTS9, AND VARIANTS CYS-970 AND RP ILE-992. RX PubMed=17053076; DOI=10.1073/pnas.0605296103; RA Campbell D.B., Sutcliffe J.S., Ebert P.J., Militerni R., Bravaccio C., RA Trillo S., Elia M., Schneider C., Melmed R., Sacco R., Persico A.M., RA Levitt P.; RT "A genetic variant that disrupts MET transcription is associated with RT autism."; RL Proc. Natl. Acad. Sci. U.S.A. 103:16834-16839(2006). RN [61] RP VARIANTS [LARGE SCALE ANALYSIS] GLN-143; LEU-156; ASP-168; SER-375; CYS-970 RP AND ILE-992. 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 [62] RP VARIANTS TYR-150; ASP-168; TYR-385; ILE-992 AND ILE-1294, CHARACTERIZATION RP OF VARIANTS TYR-150; ASP-168; TYR-385; ILE-992 AND ILE-1294, AND POSSIBLE RP INVOLVEMENT IN CUP. RX PubMed=20949619; DOI=10.1002/humu.21374; RA Stella G.M., Benvenuti S., Gramaglia D., Scarpa A., Tomezzoli A., RA Cassoni P., Senetta R., Venesio T., Pozzi E., Bardelli A., Comoglio P.M.; RT "MET mutations in cancers of unknown primary origin (CUPs)."; RL Hum. Mutat. 32:44-50(2011). RN [63] RP VARIANT LYS-375, AND CHARACTERIZATION OF VARIANT LYS-375. RX PubMed=28294470; DOI=10.1111/cas.13233; RA Tode N., Kikuchi T., Sakakibara T., Hirano T., Inoue A., Ohkouchi S., RA Tamada T., Okazaki T., Koarai A., Sugiura H., Niihori T., Aoki Y., RA Nakayama K., Matsumoto K., Matsubara Y., Yamamoto M., Watanabe A., RA Nukiwa T., Ichinose M.; RT "Exome sequencing deciphers a germline MET mutation in familial epidermal RT growth factor receptor-mutant lung cancer."; RL Cancer Sci. 108:1263-1270(2017). RN [64] RP VARIANT DA11 CYS-1234, CHARACTERIZATION OF VARIANT DA11 CYS-1234, AND RP INVOLVEMENT IN DA11. RX PubMed=30777867; DOI=10.15252/emmm.201809709; RA Zhou H., Lian C., Wang T., Yang X., Xu C., Su D., Zheng S., Huang X., RA Liao Z., Zhou T., Qiu X., Chen Y., Gao B., Li Y., Wang X., You G., Fu Q., RA Gurnett C., Huang D., Su P.; RT "MET mutation causes muscular dysplasia and arthrogryposis."; RL EMBO Mol. Med. 11:0-0(2019). CC -!- FUNCTION: Receptor tyrosine kinase that transduces signals from the CC extracellular matrix into the cytoplasm by binding to hepatocyte growth CC factor/HGF ligand. Regulates many physiological processes including CC proliferation, scattering, morphogenesis and survival. Ligand binding CC at the cell surface induces autophosphorylation of MET on its CC intracellular domain that provides docking sites for downstream CC signaling molecules. Following activation by ligand, interacts with the CC PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. CC Recruitment of these downstream effectors by MET leads to the CC activation of several signaling cascades including the RAS-ERK, PI3 CC kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with CC the morphogenetic effects while PI3K/AKT coordinates prosurvival CC effects. During embryonic development, MET signaling plays a role in CC gastrulation, development and migration of neuronal precursors, CC angiogenesis and kidney formation. During skeletal muscle development, CC it is crucial for the migration of muscle progenitor cells and for the CC proliferation of secondary myoblasts (By similarity). In adults, CC participates in wound healing as well as organ regeneration and tissue CC remodeling. Promotes also differentiation and proliferation of CC hematopoietic cells. May regulate cortical bone osteogenesis (By CC similarity). {ECO:0000250|UniProtKB:P16056}. CC -!- FUNCTION: (Microbial infection) Acts as a receptor for Listeria CC monocytogenes internalin InlB, mediating entry of the pathogen into CC cells. {ECO:0000269|PubMed:11081636, ECO:0000305|PubMed:17662939, CC ECO:0000305|PubMed:19900460}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028}; CC -!- ACTIVITY REGULATION: In its inactive state, the C-terminal tail CC interacts with the catalytic domain and inhibits the kinase activity. CC Upon ligand binding, the C-terminal tail is displaced and becomes CC phosphorylated, thus increasing the kinase activity. CC -!- SUBUNIT: Heterodimer made of an alpha chain (50 kDa) and a beta chain CC (145 kDa) which are disulfide linked. Binds PLXNB1. Interacts when CC phosphorylated with downstream effectors including STAT3, PIK3R1, SRC, CC PCLG1, GRB2 and GAB1. Interacts with SPSB1, SPSB2 and SPSB4 (By CC similarity). Interacts with INPP5D/SHIP1. When phosphorylated at Tyr- CC 1356, interacts with INPPL1/SHIP2. Interacts with RANBP9 and RANBP10, CC as well as SPSB1, SPSB2, SPSB3 and SPSB4. SPSB1 binding occurs in the CC presence and in the absence of HGF, however HGF treatment has a CC positive effect on this interaction. Interacts with MUC20; prevents CC interaction with GRB2 and suppresses hepatocyte growth factor-induced CC cell proliferation. Interacts with GRB10. Interacts with PTPN1 and CC PTPN2. Interacts with LECT2; this interaction may have an antagonistic CC effect on receptor activation (PubMed:27334921). Interacts with CC HSP90AA1 and HSP90AB1; the interaction suppresses MET kinase activity CC (PubMed:26517842). Interacts with tensin TNS3 (PubMed:24814316). CC Interacts (when phosphorylated) with tensin TNS4 (via SH2 domain); the CC interaction increases MET protein stability by inhibiting MET CC endocytosis and subsequent lysosomal degradation (PubMed:24814316). CC {ECO:0000250|UniProtKB:P16056, ECO:0000269|PubMed:10454568, CC ECO:0000269|PubMed:11063574, ECO:0000269|PubMed:12147692, CC ECO:0000269|PubMed:12198496, ECO:0000269|PubMed:14559966, CC ECO:0000269|PubMed:14684163, ECO:0000269|PubMed:15167892, CC ECO:0000269|PubMed:15314156, ECO:0000269|PubMed:15713673, CC ECO:0000269|PubMed:15735664, ECO:0000269|PubMed:1718989, CC ECO:0000269|PubMed:17662939, ECO:0000269|PubMed:18819921, CC ECO:0000269|PubMed:21784853, ECO:0000269|PubMed:24814316, CC ECO:0000269|PubMed:26517842, ECO:0000269|PubMed:27334921, CC ECO:0000269|PubMed:7513258, ECO:0000269|PubMed:9440692}. CC -!- SUBUNIT: (Microbial infection) Interacts via extracytoplasmic residues CC 25-656 with L.monocytogenes InlB; MET can bind HGF, its endogenous CC ligand, and InlB simultaneously (PubMed:11081636, PubMed:17662939). CC InlB probably dimerizes upon binding to MET, which encourages CC subsequent dimerization of MET (Probable). CC {ECO:0000269|PubMed:11081636, ECO:0000269|PubMed:17662939, CC ECO:0000305|PubMed:19900460}. CC -!- INTERACTION: CC P08581; P22681: CBL; NbExp=15; IntAct=EBI-1039152, EBI-518228; CC P08581; Q96EY1: DNAJA3; NbExp=4; IntAct=EBI-1039152, EBI-356767; CC P08581; Q96EY1-2: DNAJA3; NbExp=2; IntAct=EBI-1039152, EBI-3952284; CC P08581; P00533: EGFR; NbExp=8; IntAct=EBI-1039152, EBI-297353; CC P08581; P09769: FGR; NbExp=2; IntAct=EBI-1039152, EBI-1383732; CC P08581; P14210: HGF; NbExp=7; IntAct=EBI-1039152, EBI-1039104; CC P08581; P14210-6: HGF; NbExp=3; IntAct=EBI-1039152, EBI-6280319; CC P08581; O15357: INPPL1; NbExp=2; IntAct=EBI-1039152, EBI-1384248; CC P08581; P35968: KDR; NbExp=3; IntAct=EBI-1039152, EBI-1005487; CC P08581; P06239: LCK; NbExp=3; IntAct=EBI-1039152, EBI-1348; CC P08581; P07948: LYN; NbExp=2; IntAct=EBI-1039152, EBI-79452; CC P08581; P08581: MET; NbExp=2; IntAct=EBI-1039152, EBI-1039152; CC P08581; P41218: MNDA; NbExp=3; IntAct=EBI-1039152, EBI-2829677; CC P08581; P15941: MUC1; NbExp=2; IntAct=EBI-1039152, EBI-2804728; CC P08581; P16333: NCK1; NbExp=2; IntAct=EBI-1039152, EBI-389883; CC P08581; O43639: NCK2; NbExp=2; IntAct=EBI-1039152, EBI-713635; CC P08581; Q16288: NTRK3; NbExp=2; IntAct=EBI-1039152, EBI-3936704; CC P08581; P27986: PIK3R1; NbExp=6; IntAct=EBI-1039152, EBI-79464; CC P08581; O00459: PIK3R2; NbExp=11; IntAct=EBI-1039152, EBI-346930; CC P08581; Q92569: PIK3R3; NbExp=11; IntAct=EBI-1039152, EBI-79893; CC P08581; P19174: PLCG1; NbExp=10; IntAct=EBI-1039152, EBI-79387; CC P08581; O43157: PLXNB1; NbExp=7; IntAct=EBI-1039152, EBI-1111488; CC P08581; O15031: PLXNB2; NbExp=2; IntAct=EBI-1039152, EBI-722004; CC P08581; Q9ULL4: PLXNB3; NbExp=2; IntAct=EBI-1039152, EBI-311073; CC P08581; Q8TCU6: PREX1; NbExp=2; IntAct=EBI-1039152, EBI-1046542; CC P08581; P18031: PTPN1; NbExp=3; IntAct=EBI-1039152, EBI-968788; CC P08581; Q06124: PTPN11; NbExp=13; IntAct=EBI-1039152, EBI-297779; CC P08581; P23467: PTPRB; NbExp=2; IntAct=EBI-1039152, EBI-1265766; CC P08581; Q12913: PTPRJ; NbExp=5; IntAct=EBI-1039152, EBI-2264500; CC P08581; Q16827: PTPRO; NbExp=2; IntAct=EBI-1039152, EBI-723739; CC P08581; P20936: RASA1; NbExp=15; IntAct=EBI-1039152, EBI-1026476; CC P08581; Q9UQQ2: SH2B3; NbExp=2; IntAct=EBI-1039152, EBI-7879749; CC P08581; O60880: SH2D1A; NbExp=3; IntAct=EBI-1039152, EBI-6983382; CC P08581; O14796: SH2D1B; NbExp=6; IntAct=EBI-1039152, EBI-3923013; CC P08581; Q9NP31: SH2D2A; NbExp=7; IntAct=EBI-1039152, EBI-490630; CC P08581; Q8N5H7: SH2D3C; NbExp=4; IntAct=EBI-1039152, EBI-745980; CC P08581; Q15464: SHB; NbExp=4; IntAct=EBI-1039152, EBI-4402156; CC P08581; P29353: SHC1; NbExp=5; IntAct=EBI-1039152, EBI-78835; CC P08581; P98077: SHC2; NbExp=2; IntAct=EBI-1039152, EBI-7256023; CC P08581; Q6S5L8: SHC4; NbExp=3; IntAct=EBI-1039152, EBI-9453524; CC P08581; Q96IW2: SHD; NbExp=2; IntAct=EBI-1039152, EBI-4402781; CC P08581; Q9H6Q3: SLA2; NbExp=4; IntAct=EBI-1039152, EBI-1222854; CC P08581; O75159: SOCS5; NbExp=2; IntAct=EBI-1039152, EBI-970130; CC P08581; O14544: SOCS6; NbExp=4; IntAct=EBI-1039152, EBI-3929549; CC P08581; P12931: SRC; NbExp=7; IntAct=EBI-1039152, EBI-621482; CC P08581; Q9ULZ2: STAP1; NbExp=3; IntAct=EBI-1039152, EBI-6083058; CC P08581; P43405: SYK; NbExp=3; IntAct=EBI-1039152, EBI-78302; CC P08581; P42680: TEC; NbExp=2; IntAct=EBI-1039152, EBI-1383480; CC P08581; Q9HBL0: TNS1; NbExp=2; IntAct=EBI-1039152, EBI-3389814; CC P08581; Q63HR2: TNS2; NbExp=2; IntAct=EBI-1039152, EBI-949753; CC P08581; Q68CZ2: TNS3; NbExp=3; IntAct=EBI-1039152, EBI-1220488; CC P08581; Q9UKW4: VAV3; NbExp=2; IntAct=EBI-1039152, EBI-297568; CC P08581; P07947: YES1; NbExp=3; IntAct=EBI-1039152, EBI-515331; CC P08581; P43403: ZAP70; NbExp=2; IntAct=EBI-1039152, EBI-1211276; CC P08581; Q08048: Hgf; Xeno; NbExp=3; IntAct=EBI-1039152, EBI-15655650; CC P08581; P0DQD2: inlB; Xeno; NbExp=4; IntAct=EBI-1039152, EBI-1379295; CC P08581; P35918: Kdr; Xeno; NbExp=3; IntAct=EBI-1039152, EBI-1555005; CC P08581; Q00944: PTK2; Xeno; NbExp=5; IntAct=EBI-1039152, EBI-2896409; CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Comment=Additional soluble isoforms seem to exist.; CC Name=1; CC IsoId=P08581-1; Sequence=Displayed; CC Name=2; CC IsoId=P08581-2; Sequence=VSP_005005; CC Name=3; Synonyms=Soluble MET variant 4; CC IsoId=P08581-3; Sequence=VSP_042447, VSP_042448; CC -!- TISSUE SPECIFICITY: Expressed in normal hepatocytes as well as in CC epithelial cells lining the stomach, the small and the large intestine. CC Found also in basal keratinocytes of esophagus and skin. High levels CC are found in liver, gastrointestinal tract, thyroid and kidney. Also CC present in the brain. Expressed in metaphyseal bone (at protein level) CC (PubMed:26637977). {ECO:0000269|PubMed:1719465, CC ECO:0000269|PubMed:1917129, ECO:0000269|PubMed:26637977}. CC -!- DOMAIN: The kinase domain is involved in SPSB1 binding. CC -!- DOMAIN: The beta-propeller Sema domain mediates binding to HGF. CC -!- PTM: Autophosphorylated in response to ligand binding on Tyr-1234 and CC Tyr-1235 in the kinase domain leading to further phosphorylation of CC Tyr-1349 and Tyr-1356 in the C-terminal multifunctional docking site. CC Dephosphorylated by PTPRJ at Tyr-1349 and Tyr-1365. Dephosphorylated by CC PTPN1 and PTPN2. {ECO:0000269|PubMed:12475979, CC ECO:0000269|PubMed:15735664, ECO:0000269|PubMed:1655790, CC ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:7513258}. CC -!- PTM: Ubiquitinated. Ubiquitination by CBL regulates MET endocytosis, CC resulting in decreasing plasma membrane receptor abundance, and in CC endosomal degradation and/or recycling of internalized receptors. CC {ECO:0000269|PubMed:12244174, ECO:0000305|PubMed:26637977}. CC -!- PTM: O-mannosylation of IPT/TIG domains by TMEM260 is required for CC protein maturation (PubMed:37186866). O-mannosylated residues are CC composed of single mannose glycans that are not elongated or modified CC (PubMed:37186866). {ECO:0000269|PubMed:37186866}. CC -!- PTM: (Microbial infection) Tyrosine phosphorylation is stimulated by CC L.monocytogenes InlB. Tyrosine phosphorylation is maximal 10-20 minutes CC after treatment with InlB and disappears by 60 minutes. The CC phosphorylated residues were not identified. CC {ECO:0000269|PubMed:11081636}. CC -!- DISEASE: Note=Activation of MET after rearrangement with the TPR gene CC produces an oncogenic protein. CC -!- DISEASE: Note=Defects in MET may be associated with gastric cancer. CC -!- DISEASE: Hepatocellular carcinoma (HCC) [MIM:114550]: A primary CC malignant neoplasm of epithelial liver cells. The major risk factors CC for HCC are chronic hepatitis B virus (HBV) infection, chronic CC hepatitis C virus (HCV) infection, prolonged dietary aflatoxin CC exposure, alcoholic cirrhosis, and cirrhosis due to other causes. CC {ECO:0000269|PubMed:9927037}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Renal cell carcinoma papillary (RCCP) [MIM:605074]: A subtype CC of renal cell carcinoma tending to show a tubulo-papillary architecture CC formed by numerous, irregular, finger-like projections of connective CC tissue. Renal cell carcinoma is a heterogeneous group of sporadic or CC hereditary carcinoma derived from cells of the proximal renal tubular CC epithelium. {ECO:0000269|PubMed:10327054, ECO:0000269|PubMed:10417759, CC ECO:0000269|PubMed:10433944, ECO:0000269|PubMed:9140397, CC ECO:0000269|PubMed:9563489}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Note=A common allele in the promoter region of the MET shows CC genetic association with susceptibility to autism in some families. CC Functional assays indicate a decrease in MET promoter activity and CC altered binding of specific transcription factor complexes. CC -!- DISEASE: Note=MET activating mutations may be involved in the CC development of a highly malignant, metastatic syndrome known as cancer CC of unknown primary origin (CUP) or primary occult malignancy. Systemic CC neoplastic spread is generally a late event in cancer progression. CC However, in some instances, distant dissemination arises at a very CC early stage, so that metastases reach clinical relevance before primary CC lesions. Sometimes, the primary lesions cannot be identified in spite CC of the progresses in the diagnosis of malignancies. CC -!- DISEASE: Deafness, autosomal recessive, 97 (DFNB97) [MIM:616705]: A CC form of non-syndromic sensorineural hearing loss with prelingual onset. CC Sensorineural deafness results from damage to the neural receptors of CC the inner ear, the nerve pathways to the brain, or the area of the CC brain that receives sound information. {ECO:0000269|PubMed:25941349}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Osteofibrous dysplasia (OSFD) [MIM:607278]: A congenital CC disorder of osteogenesis characterized by non-neoplastic, radiolucent CC lesions that affect the cortical bone immediately under the periosteum. CC It usually manifests as a painless swelling or anterior bowing of the CC long bones, most commonly the tibia and fibula. CC {ECO:0000269|PubMed:26637977}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC Disease-associated variants identified in 4 families cause the deletion CC of exon 14. This results in the exclusion of an ubiquitination target CC site within the cytoplasmic domain, hence in protein stabilization. The CC persistent presence of MET at the cell surface in conditions of ligand- CC dependent activation retards osteoblastic differentiation. CC {ECO:0000269|PubMed:26637977}. CC -!- DISEASE: Arthrogryposis, distal, 11 (DA11) [MIM:620019]: A form of CC distal arthrogryposis, a disease characterized by congenital joint CC contractures that mainly involve two or more distal parts of the limbs, CC in the absence of a primary neurological or muscle disease. DA11 is an CC autosomal dominant form characterized mainly by camptodactyly. Other CC features include absent flexion creases and limited forearm supination. CC {ECO:0000269|PubMed:30777867}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/131/MET"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=C-MET entry; CC URL="https://en.wikipedia.org/wiki/C-MET"; 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; J02958; AAA59591.1; -; mRNA. DR EMBL; X54559; CAB56793.1; -; mRNA. DR EMBL; EU826570; ACF47606.1; -; mRNA. DR EMBL; AC002080; AAB54047.1; -; Genomic_DNA. DR EMBL; AC002543; AAC60383.1; -; Genomic_DNA. DR EMBL; AC004416; AAF66137.2; -; Genomic_DNA. DR EMBL; CH236947; EAL24359.1; -; Genomic_DNA. DR EMBL; CH471070; EAW83509.1; -; Genomic_DNA. DR EMBL; BC130420; AAI30421.1; -; mRNA. DR EMBL; U08818; AAB60323.1; ALT_SEQ; mRNA. DR EMBL; M35074; AAA59590.1; -; mRNA. DR CCDS; CCDS43636.1; -. [P08581-1] DR CCDS; CCDS47689.1; -. [P08581-2] DR PIR; A40175; TVHUME. DR RefSeq; NP_000236.2; NM_000245.3. [P08581-1] DR RefSeq; NP_001120972.1; NM_001127500.2. [P08581-2] DR PDB; 1FYR; X-ray; 2.40 A; I/J/K/L=1356-1359. DR PDB; 1R0P; X-ray; 1.80 A; A=1049-1360. DR PDB; 1R1W; X-ray; 1.80 A; A=1049-1360. DR PDB; 1SHY; X-ray; 3.22 A; B=25-567. DR PDB; 1SSL; NMR; -; A=519-562. DR PDB; 2G15; X-ray; 2.15 A; A=1038-1346. DR PDB; 2RFN; X-ray; 2.50 A; A/B=1048-1351. DR PDB; 2RFS; X-ray; 2.20 A; A=1048-1351. DR PDB; 2UZX; X-ray; 2.80 A; B/D=25-740. DR PDB; 2UZY; X-ray; 4.00 A; B/D=25-740. DR PDB; 2WD1; X-ray; 2.00 A; A=1055-1346. DR PDB; 2WGJ; X-ray; 2.00 A; A=1051-1348. DR PDB; 2WKM; X-ray; 2.20 A; A=1051-1348. DR PDB; 3A4P; X-ray; 2.54 A; A=1049-1360. DR PDB; 3BUX; X-ray; 1.35 A; A/C=997-1009. DR PDB; 3C1X; X-ray; 2.17 A; A=1049-1360. DR PDB; 3CCN; X-ray; 1.90 A; A=1048-1350. DR PDB; 3CD8; X-ray; 2.00 A; A=1048-1350. DR PDB; 3CE3; X-ray; 2.40 A; A=1049-1360. DR PDB; 3CTH; X-ray; 2.30 A; A=1049-1360. DR PDB; 3CTJ; X-ray; 2.50 A; A=1049-1360. DR PDB; 3DKC; X-ray; 1.52 A; A=1049-1360. DR PDB; 3DKF; X-ray; 1.80 A; A=1049-1360. DR PDB; 3DKG; X-ray; 1.91 A; A=1049-1360. DR PDB; 3EFJ; X-ray; 2.60 A; A/B=1048-1351. DR PDB; 3EFK; X-ray; 2.20 A; A/B=1048-1351. DR PDB; 3F66; X-ray; 1.40 A; A/B=1052-1349. DR PDB; 3F82; X-ray; 2.50 A; A=1049-1360. DR PDB; 3I5N; X-ray; 2.00 A; A=1048-1350. DR PDB; 3L8V; X-ray; 2.40 A; A=1049-1360. DR PDB; 3LQ8; X-ray; 2.02 A; A=1051-1348. DR PDB; 3Q6U; X-ray; 1.60 A; A=1048-1348. DR PDB; 3Q6W; X-ray; 1.75 A; A=1048-1348. DR PDB; 3QTI; X-ray; 2.00 A; A/B=1050-1360. DR PDB; 3R7O; X-ray; 2.30 A; A=1048-1348. DR PDB; 3RHK; X-ray; 1.94 A; A/B=1038-1346. DR PDB; 3U6H; X-ray; 2.00 A; A=1048-1351. DR PDB; 3U6I; X-ray; 2.10 A; A=1048-1351. DR PDB; 3VW8; X-ray; 2.10 A; A=1024-1352. DR PDB; 3ZBX; X-ray; 2.20 A; A=1051-1348. DR PDB; 3ZC5; X-ray; 2.20 A; A=1051-1348. DR PDB; 3ZCL; X-ray; 1.40 A; A=1051-1348. DR PDB; 3ZXZ; X-ray; 1.80 A; A=1051-1348. DR PDB; 3ZZE; X-ray; 1.87 A; A=1051-1348. DR PDB; 4AOI; X-ray; 1.90 A; A=1051-1348. DR PDB; 4AP7; X-ray; 1.80 A; A=1051-1348. DR PDB; 4DEG; X-ray; 2.00 A; A=1048-1351. DR PDB; 4DEH; X-ray; 2.00 A; A=1048-1351. DR PDB; 4DEI; X-ray; 2.05 A; A=1048-1351. DR PDB; 4EEV; X-ray; 1.80 A; A=1038-1346. DR PDB; 4GG5; X-ray; 2.42 A; A=1038-1346. DR PDB; 4GG7; X-ray; 2.27 A; A=1038-1346. DR PDB; 4IWD; X-ray; 1.99 A; A=1048-1348. DR PDB; 4K3J; X-ray; 2.80 A; B=39-564. DR PDB; 4KNB; X-ray; 2.40 A; A/B/C/D=1060-1346. DR PDB; 4MXC; X-ray; 1.63 A; A=1038-1346. DR PDB; 4O3T; X-ray; 2.99 A; B=25-567. DR PDB; 4O3U; X-ray; 3.04 A; B=25-567. DR PDB; 4R1V; X-ray; 1.20 A; A=1055-1345. DR PDB; 4R1Y; X-ray; 2.00 A; A=1055-1346. DR PDB; 4XMO; X-ray; 1.75 A; A=1048-1350. DR PDB; 4XYF; X-ray; 1.85 A; A=1048-1351. DR PDB; 5DG5; X-ray; 2.60 A; A/B=1038-1346. DR PDB; 5EOB; X-ray; 1.75 A; A=1038-1346. DR PDB; 5EYC; X-ray; 1.80 A; A=1048-1351. DR PDB; 5EYD; X-ray; 1.85 A; A=1048-1351. DR PDB; 5HLW; X-ray; 1.97 A; A=1057-1355. DR PDB; 5HNI; X-ray; 1.71 A; X/Y=1049-1360. DR PDB; 5HO6; X-ray; 1.97 A; A=1049-1360. DR PDB; 5HOA; X-ray; 2.14 A; A=1049-1360. DR PDB; 5HOR; X-ray; 2.20 A; A=1049-1360. DR PDB; 5HTI; X-ray; 1.66 A; A=1038-1346. DR PDB; 5LSP; X-ray; 2.60 A; A/P=519-743, X/Y=25-35. DR PDB; 5T3Q; X-ray; 2.00 A; A=1048-1350. DR PDB; 5UAB; X-ray; 1.90 A; A=1023-1360. DR PDB; 5UAD; X-ray; 2.25 A; A=1023-1360. DR PDB; 5YA5; X-ray; 1.89 A; A=1038-1346. DR PDB; 6GCU; X-ray; 6.00 A; A/D=25-741. DR PDB; 6I04; X-ray; 3.10 A; A/B=25-564. DR PDB; 6SD9; X-ray; 2.35 A; A=1038-1346. DR PDB; 6SDC; X-ray; 1.67 A; A=1038-1346. DR PDB; 6SDD; X-ray; 1.93 A; A=1038-1346. DR PDB; 6SDE; X-ray; 2.49 A; A=1038-1346. DR PDB; 6UBW; X-ray; 2.00 A; A=1023-1360. DR PDB; 6WVZ; X-ray; 3.10 A; M=39-564. DR PDB; 7B3Q; X-ray; 1.75 A; A=1049-1346. DR PDB; 7B3T; X-ray; 2.23 A; A=1049-1346. DR PDB; 7B3V; X-ray; 1.93 A; A=1049-1346. DR PDB; 7B3W; X-ray; 2.02 A; A=1049-1346. DR PDB; 7B3Z; X-ray; 1.80 A; A=1049-1346. DR PDB; 7B40; X-ray; 1.76 A; A=1049-1346. DR PDB; 7B41; X-ray; 1.97 A; A=1049-1346. DR PDB; 7B42; X-ray; 1.80 A; A=1049-1346. DR PDB; 7B43; X-ray; 1.87 A; A/B=1049-1346. DR PDB; 7B44; X-ray; 1.76 A; A=1049-1346. DR PDB; 7MO7; EM; 4.80 A; B/E=1-1390. DR PDB; 7MO8; EM; 4.50 A; B=1-1390. DR PDB; 7MO9; EM; 4.00 A; E=1-1390. DR PDB; 7MOA; EM; 4.90 A; E=1-1390. DR PDB; 7MOB; EM; 5.00 A; C/D=1-1390. DR PDB; 7V3R; X-ray; 1.70 A; A=1038-1346. DR PDB; 7V3S; X-ray; 1.90 A; A=1038-1346. DR PDB; 7Y4T; X-ray; 2.16 A; A=1038-1346. DR PDB; 7Y4U; X-ray; 2.26 A; A=1038-1346. DR PDB; 8AN8; X-ray; 2.39 A; A/B=1052-1346. DR PDB; 8ANS; X-ray; 2.01 A; A=1052-1346. DR PDB; 8AU3; X-ray; 2.26 A; A/B=1051-1349. DR PDB; 8AU5; X-ray; 2.72 A; A=1051-1349. DR PDB; 8AW1; X-ray; 2.14 A; A/B=1051-1349. DR PDB; 8GVJ; X-ray; 2.71 A; A=1038-1346. DR PDB; 8OUU; X-ray; 1.77 A; A/B=1038-1346. DR PDB; 8OUV; X-ray; 1.78 A; A/B=1038-1346. DR PDB; 8OV7; X-ray; 1.95 A; A=1038-1346. DR PDB; 8OVZ; X-ray; 2.21 A; A/B=1038-1346. DR PDB; 8OW3; X-ray; 2.27 A; A=1038-1346. DR PDB; 8OWG; X-ray; 2.63 A; A/B/C=1038-1346. DR PDBsum; 1FYR; -. DR PDBsum; 1R0P; -. DR PDBsum; 1R1W; -. DR PDBsum; 1SHY; -. DR PDBsum; 1SSL; -. DR PDBsum; 2G15; -. DR PDBsum; 2RFN; -. DR PDBsum; 2RFS; -. DR PDBsum; 2UZX; -. DR PDBsum; 2UZY; -. DR PDBsum; 2WD1; -. DR PDBsum; 2WGJ; -. DR PDBsum; 2WKM; -. DR PDBsum; 3A4P; -. DR PDBsum; 3BUX; -. DR PDBsum; 3C1X; -. DR PDBsum; 3CCN; -. DR PDBsum; 3CD8; -. DR PDBsum; 3CE3; -. DR PDBsum; 3CTH; -. DR PDBsum; 3CTJ; -. DR PDBsum; 3DKC; -. DR PDBsum; 3DKF; -. DR PDBsum; 3DKG; -. DR PDBsum; 3EFJ; -. DR PDBsum; 3EFK; -. DR PDBsum; 3F66; -. DR PDBsum; 3F82; -. DR PDBsum; 3I5N; -. DR PDBsum; 3L8V; -. DR PDBsum; 3LQ8; -. DR PDBsum; 3Q6U; -. DR PDBsum; 3Q6W; -. DR PDBsum; 3QTI; -. DR PDBsum; 3R7O; -. DR PDBsum; 3RHK; -. DR PDBsum; 3U6H; -. DR PDBsum; 3U6I; -. DR PDBsum; 3VW8; -. DR PDBsum; 3ZBX; -. DR PDBsum; 3ZC5; -. DR PDBsum; 3ZCL; -. DR PDBsum; 3ZXZ; -. DR PDBsum; 3ZZE; -. DR PDBsum; 4AOI; -. DR PDBsum; 4AP7; -. DR PDBsum; 4DEG; -. DR PDBsum; 4DEH; -. DR PDBsum; 4DEI; -. DR PDBsum; 4EEV; -. DR PDBsum; 4GG5; -. DR PDBsum; 4GG7; -. DR PDBsum; 4IWD; -. DR PDBsum; 4K3J; -. DR PDBsum; 4KNB; -. DR PDBsum; 4MXC; -. DR PDBsum; 4O3T; -. DR PDBsum; 4O3U; -. DR PDBsum; 4R1V; -. DR PDBsum; 4R1Y; -. DR PDBsum; 4XMO; -. DR PDBsum; 4XYF; -. DR PDBsum; 5DG5; -. DR PDBsum; 5EOB; -. DR PDBsum; 5EYC; -. DR PDBsum; 5EYD; -. DR PDBsum; 5HLW; -. DR PDBsum; 5HNI; -. DR PDBsum; 5HO6; -. DR PDBsum; 5HOA; -. DR PDBsum; 5HOR; -. DR PDBsum; 5HTI; -. DR PDBsum; 5LSP; -. DR PDBsum; 5T3Q; -. DR PDBsum; 5UAB; -. DR PDBsum; 5UAD; -. DR PDBsum; 5YA5; -. DR PDBsum; 6GCU; -. DR PDBsum; 6I04; -. DR PDBsum; 6SD9; -. DR PDBsum; 6SDC; -. DR PDBsum; 6SDD; -. DR PDBsum; 6SDE; -. DR PDBsum; 6UBW; -. DR PDBsum; 6WVZ; -. DR PDBsum; 7B3Q; -. DR PDBsum; 7B3T; -. DR PDBsum; 7B3V; -. DR PDBsum; 7B3W; -. DR PDBsum; 7B3Z; -. DR PDBsum; 7B40; -. DR PDBsum; 7B41; -. DR PDBsum; 7B42; -. DR PDBsum; 7B43; -. DR PDBsum; 7B44; -. DR PDBsum; 7MO7; -. DR PDBsum; 7MO8; -. DR PDBsum; 7MO9; -. DR PDBsum; 7MOA; -. DR PDBsum; 7MOB; -. DR PDBsum; 7V3R; -. DR PDBsum; 7V3S; -. DR PDBsum; 7Y4T; -. DR PDBsum; 7Y4U; -. DR PDBsum; 8AN8; -. DR PDBsum; 8ANS; -. DR PDBsum; 8AU3; -. DR PDBsum; 8AU5; -. DR PDBsum; 8AW1; -. DR PDBsum; 8GVJ; -. DR PDBsum; 8OUU; -. DR PDBsum; 8OUV; -. DR PDBsum; 8OV7; -. DR PDBsum; 8OVZ; -. DR PDBsum; 8OW3; -. DR PDBsum; 8OWG; -. DR AlphaFoldDB; P08581; -. DR EMDB; EMD-23919; -. DR EMDB; EMD-23920; -. DR EMDB; EMD-23921; -. DR EMDB; EMD-23922; -. DR EMDB; EMD-23923; -. DR SASBDB; P08581; -. DR SMR; P08581; -. DR BioGRID; 110391; 272. DR CORUM; P08581; -. DR DIP; DIP-6023N; -. DR ELM; P08581; -. DR IntAct; P08581; 170. DR MINT; P08581; -. DR STRING; 9606.ENSP00000317272; -. DR BindingDB; P08581; -. DR ChEMBL; CHEMBL3717; -. DR DrugBank; DB06896; 1-(4-fluorophenyl)-N-[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxamide. DR DrugBank; DB08791; 1-[(2-NITROPHENYL)SULFONYL]-1H-PYRROLO[3,2-B]PYRIDINE-6-CARBOXAMIDE. DR DrugBank; DB06997; 2-(4-fluorophenyl)-N-{[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]carbamoyl}acetamide. DR DrugBank; DB07969; 3-[3-(4-methylpiperazin-1-yl)-7-(trifluoromethyl)quinoxalin-5-yl]phenol. DR DrugBank; DB08079; AMG-208. DR DrugBank; DB16695; Amivantamab. DR DrugBank; DB12742; Amuvatinib. DR DrugBank; DB12267; Brigatinib. DR DrugBank; DB08875; Cabozantinib. DR DrugBank; DB11791; Capmatinib. DR DrugBank; DB08865; Crizotinib. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB02152; K-252a. DR DrugBank; DB07369; N-(3-chlorophenyl)-N-methyl-2-oxo-3-[(3,4,5-trimethyl-1H-pyrrol-2-yl)methyl]-2H-indole-5-sulfonamide. DR DrugBank; DB06995; N-({4-[(2-aminopyridin-4-yl)oxy]-3-fluorophenyl}carbamoyl)-2-(4-fluorophenyl)acetamide. DR DrugBank; DB06314; SGX-523. DR DrugBank; DB01268; Sunitinib. DR DrugBank; DB15133; Tepotinib. DR DrugBank; DB12200; Tivantinib. DR DrugBank; DB11800; Tivozanib. DR DrugCentral; P08581; -. DR GuidetoPHARMACOLOGY; 1815; -. DR TCDB; 8.A.23.1.45; the basigin (basigin) family. DR GlyConnect; 680; 17 N-Linked glycans (6 sites). DR GlyCosmos; P08581; 13 sites, 23 glycans. DR GlyGen; P08581; 18 sites, 23 N-linked glycans (6 sites), 2 O-linked glycans (3 sites). DR iPTMnet; P08581; -. DR PhosphoSitePlus; P08581; -. DR SwissPalm; P08581; -. DR BioMuta; MET; -. DR DMDM; 251757497; -. DR OGP; P08581; -. DR CPTAC; CPTAC-1496; -. DR CPTAC; CPTAC-2784; -. DR CPTAC; CPTAC-2816; -. DR EPD; P08581; -. DR jPOST; P08581; -. DR MassIVE; P08581; -. DR MaxQB; P08581; -. DR PaxDb; 9606-ENSP00000317272; -. DR PeptideAtlas; P08581; -. DR ProteomicsDB; 52128; -. [P08581-1] DR ProteomicsDB; 52129; -. [P08581-2] DR ProteomicsDB; 52130; -. [P08581-3] DR Pumba; P08581; -. DR ABCD; P08581; 52 sequenced antibodies. DR Antibodypedia; 3939; 3521 antibodies from 50 providers. DR CPTC; P08581; 1 antibody. DR DNASU; 4233; -. DR Ensembl; ENST00000318493.11; ENSP00000317272.6; ENSG00000105976.16. [P08581-2] DR Ensembl; ENST00000397752.8; ENSP00000380860.3; ENSG00000105976.16. [P08581-1] DR Ensembl; ENST00000436117.3; ENSP00000410980.2; ENSG00000105976.16. [P08581-3] DR GeneID; 4233; -. DR KEGG; hsa:4233; -. DR MANE-Select; ENST00000397752.8; ENSP00000380860.3; NM_000245.4; NP_000236.2. DR UCSC; uc003vij.4; human. [P08581-1] DR AGR; HGNC:7029; -. DR CTD; 4233; -. DR DisGeNET; 4233; -. DR GeneCards; MET; -. DR HGNC; HGNC:7029; MET. DR HPA; ENSG00000105976; Tissue enhanced (liver). DR MalaCards; MET; -. DR MIM; 114550; phenotype. DR MIM; 164860; gene. DR MIM; 605074; phenotype. DR MIM; 607278; phenotype. DR MIM; 616705; phenotype. DR MIM; 620019; phenotype. DR neXtProt; NX_P08581; -. DR OpenTargets; ENSG00000105976; -. DR Orphanet; 47044; Hereditary papillary renal cell carcinoma. DR Orphanet; 106; NON RARE IN EUROPE: Autism. DR Orphanet; 488265; Osteofibrous dysplasia. DR Orphanet; 319298; Papillary renal cell carcinoma. DR Orphanet; 33402; Pediatric hepatocellular carcinoma. DR Orphanet; 90636; Rare autosomal recessive non-syndromic sensorineural deafness type DFNB. DR PharmGKB; PA30763; -. DR VEuPathDB; HostDB:ENSG00000105976; -. DR eggNOG; KOG1095; Eukaryota. DR eggNOG; KOG3610; Eukaryota. DR GeneTree; ENSGT00940000158022; -. DR HOGENOM; CLU_005158_0_0_1; -. DR InParanoid; P08581; -. DR OMA; DEEPGQC; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; P08581; -. DR TreeFam; TF317402; -. DR BRENDA; 2.7.10.1; 2681. DR PathwayCommons; P08581; -. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-416550; Sema4D mediated inhibition of cell attachment and migration. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6806942; MET Receptor Activation. DR Reactome; R-HSA-6807004; Negative regulation of MET activity. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-HSA-8851805; MET activates RAS signaling. DR Reactome; R-HSA-8851907; MET activates PI3K/AKT signaling. DR Reactome; R-HSA-8865999; MET activates PTPN11. DR Reactome; R-HSA-8874081; MET activates PTK2 signaling. DR Reactome; R-HSA-8875360; InlB-mediated entry of Listeria monocytogenes into host cell. DR Reactome; R-HSA-8875513; MET interacts with TNS proteins. DR Reactome; R-HSA-8875555; MET activates RAP1 and RAC1. DR Reactome; R-HSA-8875656; MET receptor recycling. DR Reactome; R-HSA-8875791; MET activates STAT3. DR Reactome; R-HSA-9022699; MECP2 regulates neuronal receptors and channels. DR Reactome; R-HSA-9734091; Drug-mediated inhibition of MET activation. DR SignaLink; P08581; -. DR SIGNOR; P08581; -. DR BioGRID-ORCS; 4233; 32 hits in 1202 CRISPR screens. DR ChiTaRS; MET; human. DR EvolutionaryTrace; P08581; -. DR GeneWiki; C-Met; -. DR GenomeRNAi; 4233; -. DR Pharos; P08581; Tclin. DR PRO; PR:P08581; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P08581; Protein. DR Bgee; ENSG00000105976; Expressed in pigmented layer of retina and 193 other cell types or tissues. DR ExpressionAtlas; P08581; baseline and differential. DR GO; GO:0009925; C:basal plasma membrane; IDA:MGI. DR GO; GO:0009986; C:cell surface; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0005008; F:hepatocyte growth factor receptor activity; IBA:GO_Central. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0140677; F:molecular function activator activity; EXP:DisProt. DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; TAS:Reactome. DR GO; GO:0017154; F:semaphorin receptor activity; IEA:InterPro. DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:UniProtKB. DR GO; GO:0016477; P:cell migration; IBA:GO_Central. DR GO; GO:0007166; P:cell surface receptor signaling pathway; NAS:UniProtKB. DR GO; GO:0001886; P:endothelial cell morphogenesis; IDA:UniProtKB. DR GO; GO:0061436; P:establishment of skin barrier; IMP:CAFA. DR GO; GO:0001889; P:liver development; IBA:GO_Central. DR GO; GO:0010507; P:negative regulation of autophagy; NAS:ParkinsonsUK-UCL. DR GO; GO:1905098; P:negative regulation of guanyl-nucleotide exchange factor activity; IDA:CAFA. DR GO; GO:1901299; P:negative regulation of hydrogen peroxide-mediated programmed cell death; IMP:BHF-UCL. DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; IDA:CAFA. DR GO; GO:0051497; P:negative regulation of stress fiber assembly; IDA:CAFA. DR GO; GO:0070495; P:negative regulation of thrombin-activated receptor signaling pathway; IDA:CAFA. DR GO; GO:0007399; P:nervous system development; IBA:GO_Central. DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central. DR GO; GO:0031016; P:pancreas development; IBA:GO_Central. DR GO; GO:0006909; P:phagocytosis; IBA:GO_Central. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0050918; P:positive chemotaxis; IDA:UniProtKB. DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; IMP:UniProtKB. DR GO; GO:0031116; P:positive regulation of microtubule polymerization; IMP:CAFA. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; IDA:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR CDD; cd00603; IPT_PCSR; 1. DR CDD; cd01180; IPT_plexin_repeat1; 1. DR CDD; cd01179; IPT_plexin_repeat2; 1. DR CDD; cd01181; IPT_plexin_repeat3; 1. DR CDD; cd05058; PTKc_Met_Ron; 1. DR CDD; cd11278; Sema_MET; 1. DR DisProt; DP02738; -. DR Gene3D; 2.60.40.10; Immunoglobulins; 3. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR IDEAL; IID00704; -. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR002909; IPT_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR031148; Plexin. DR InterPro; IPR002165; Plexin_repeat. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR016201; PSI. DR InterPro; IPR001627; Semap_dom. DR InterPro; IPR036352; Semap_dom_sf. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR016244; Tyr_kinase_HGF/MSP_rcpt. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR PANTHER; PTHR22625:SF61; HEPATOCYTE GROWTH FACTOR RECEPTOR; 1. DR PANTHER; PTHR22625; PLEXIN; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF01437; PSI; 1. DR Pfam; PF01403; Sema; 1. DR Pfam; PF01833; TIG; 3. DR PIRSF; PIRSF000617; TyrPK_HGF-R; 1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00429; IPT; 4. DR SMART; SM00423; PSI; 1. DR SMART; SM00630; Sema; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF81296; E set domains; 3. DR SUPFAM; SSF103575; Plexin repeat; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF101912; Sema domain; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS51004; SEMA; 1. DR Genevisible; P08581; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Chromosomal rearrangement; KW Deafness; Disease variant; Disulfide bond; Glycoprotein; Kinase; Membrane; KW Non-syndromic deafness; Nucleotide-binding; Phosphoprotein; Proto-oncogene; KW Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase; KW Ubl conjugation. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT CHAIN 25..1390 FT /note="Hepatocyte growth factor receptor" FT /id="PRO_0000024440" FT TOPO_DOM 25..932 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 933..955 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 956..1390 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 27..515 FT /note="Sema" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT DOMAIN 563..655 FT /note="IPT/TIG 1" FT DOMAIN 657..739 FT /note="IPT/TIG 2" FT DOMAIN 742..836 FT /note="IPT/TIG 3" FT DOMAIN 1078..1345 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1212..1390 FT /note="Interaction with RANBP9" FT REGION 1320..1359 FT /note="Interaction with MUC20" FT /evidence="ECO:0000269|PubMed:15314156" FT ACT_SITE 1204 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 1084..1092 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 1110 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT SITE 307..308 FT /note="Cleavage" FT /evidence="ECO:0000255" FT SITE 1003 FT /note="Required for ligand-induced CBL-mediated FT ubiquitination" FT /evidence="ECO:0000269|PubMed:12244174" FT SITE 1009..1010 FT /note="Breakpoint for translocation to form TPR-MET FT oncogene" FT MOD_RES 966 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 977 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976" FT MOD_RES 990 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 997 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1000 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1003 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195" FT MOD_RES 1230 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:12475979" FT MOD_RES 1234 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12475979" FT MOD_RES 1235 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12475979, FT ECO:0000269|PubMed:1655790" FT MOD_RES 1289 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 1349 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:12475979, FT ECO:0000269|PubMed:7513258" FT MOD_RES 1356 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:15735664, FT ECO:0000269|PubMed:7513258" FT MOD_RES 1365 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:12475979" FT CARBOHYD 45 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 106 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19196183" FT CARBOHYD 149 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 202 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 399 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 405 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 582 FT /note="O-linked (Man) threonine" FT /evidence="ECO:0000269|PubMed:37186866" FT CARBOHYD 607 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 635 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 676 FT /note="O-linked (Man) threonine" FT /evidence="ECO:0000269|PubMed:37186866" FT CARBOHYD 761 FT /note="O-linked (Man) threonine" FT /evidence="ECO:0000269|PubMed:37186866" FT CARBOHYD 785 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 879 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 930 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 95..101 FT DISULFID 98..160 FT DISULFID 133..141 FT /evidence="ECO:0000269|PubMed:17662939, FT ECO:0007744|PDB:2UZX, ECO:0007744|PDB:2UZY" FT DISULFID 172..175 FT /evidence="ECO:0000269|PubMed:17662939, FT ECO:0007744|PDB:2UZX, ECO:0007744|PDB:2UZY" FT DISULFID 298..363 FT /evidence="ECO:0000269|PubMed:17662939, FT ECO:0007744|PDB:2UZX, ECO:0007744|PDB:2UZY" FT DISULFID 385..397 FT /evidence="ECO:0000269|PubMed:17662939, FT ECO:0007744|PDB:2UZY" FT DISULFID 520..538 FT /evidence="ECO:0000269|PubMed:17662939, FT ECO:0007744|PDB:2UZX, ECO:0007744|PDB:2UZY" FT DISULFID 526..561 FT /evidence="ECO:0000269|PubMed:17662939, FT ECO:0007744|PDB:2UZX, ECO:0007744|PDB:2UZY" FT DISULFID 529..545 FT /evidence="ECO:0000269|PubMed:17662939, FT ECO:0007744|PDB:2UZX, ECO:0007744|PDB:2UZY" FT DISULFID 541..551 FT /evidence="ECO:0000269|PubMed:17662939, FT ECO:0007744|PDB:2UZX, ECO:0007744|PDB:2UZY" FT DISULFID 610..624 FT /evidence="ECO:0000269|PubMed:17662939, FT ECO:0007744|PDB:2UZX, ECO:0007744|PDB:2UZY" FT DISULFID 697..709 FT /evidence="ECO:0000269|PubMed:17662939, FT ECO:0007744|PDB:2UZY" FT VAR_SEQ 755..764 FT /note="SGGSTITGVG -> RHVNIALIQR (in isoform 3)" FT /evidence="ECO:0000303|PubMed:18593464" FT /id="VSP_042447" FT VAR_SEQ 755 FT /note="S -> STWWKEPLNIVSFLFCFAS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:2819873" FT /id="VSP_005005" FT VAR_SEQ 765..1390 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:18593464" FT /id="VSP_042448" FT VARIANT 143 FT /note="R -> Q (in dbSNP:rs35469582)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041738" FT VARIANT 150 FT /note="H -> Y (found in a case of cancer of unknown primary FT origin; uncertain significance; somatic mutation; the FT mutated receptor is still functional and can sustain the FT transformed phenotype; dbSNP:rs1436957498)" FT /evidence="ECO:0000269|PubMed:20949619" FT /id="VAR_064855" FT VARIANT 156 FT /note="S -> L (in dbSNP:rs56311081)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_041739" FT VARIANT 168 FT /note="E -> D (found in a case of cancer of unknown primary FT origin; uncertain significance; somatic mutation; the FT mutated receptor is still functional and can sustain the FT transformed phenotype; dbSNP:rs55985569)" FT /evidence="ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:20949619" FT /id="VAR_041740" FT VARIANT 238 FT /note="L -> S (in dbSNP:rs34349517)" FT /id="VAR_032478" FT VARIANT 316 FT /note="I -> M (in dbSNP:rs35225896)" FT /id="VAR_032479" FT VARIANT 320 FT /note="A -> V (in dbSNP:rs35776110)" FT /evidence="ECO:0000269|PubMed:9140397" FT /id="VAR_006285" FT VARIANT 375 FT /note="N -> K (found in lung cancer also including cases FT carrying EGFR mutations; uncertain significance; decreased FT hepatocyte growth factor-activated receptor activity; FT decreased interaction with HGF; dbSNP:rs776693512)" FT /evidence="ECO:0000269|PubMed:28294470" FT /id="VAR_079370" FT VARIANT 375 FT /note="N -> S (in dbSNP:rs33917957)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_032480" FT VARIANT 385 FT /note="C -> Y (found in a case of cancer of unknown primary FT origin; uncertain significance; somatic mutation; the FT mutated receptor is still functional and can sustain the FT transformed phenotype; dbSNP:rs752055485)" FT /evidence="ECO:0000269|PubMed:20949619" FT /id="VAR_064856" FT VARIANT 773 FT /note="P -> L (in gastric cancer; dbSNP:rs771333219)" FT /evidence="ECO:0000269|PubMed:12920089" FT /id="VAR_032481" FT VARIANT 841 FT /note="F -> V (in DFNB97; dbSNP:rs794728016)" FT /evidence="ECO:0000269|PubMed:25941349" FT /id="VAR_075757" FT VARIANT 964..1010 FT /note="Missing (in OSFD; loss of CBL-mediated FT destabilization)" FT /evidence="ECO:0000269|PubMed:26637977" FT /id="VAR_076584" FT VARIANT 970 FT /note="R -> C (in dbSNP:rs34589476)" FT /evidence="ECO:0000269|PubMed:17053076, FT ECO:0000269|PubMed:17344846" FT /id="VAR_032482" FT VARIANT 991 FT /note="P -> S (in gastric cancer; prolonged tyrosine FT phosphorylation in response to HGF/SF; transforming FT activity in athymic nude mice; dbSNP:rs768678989)" FT /evidence="ECO:0000269|PubMed:11042681" FT /id="VAR_032483" FT VARIANT 992 FT /note="T -> I (found in a case of cancer of unknown primary FT origin; uncertain significance; somatic mutation; the FT mutated receptor is still functional and can sustain the FT transformed phenotype; dbSNP:rs56391007)" FT /evidence="ECO:0000269|PubMed:11042681, FT ECO:0000269|PubMed:17053076, ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:20949619" FT /id="VAR_032484" FT VARIANT 1003 FT /note="Y -> S (found in a patient with sporadic unilateral FT osteofibrous dysplasia; uncertain significance; somatic FT mutation; complete loss of ligand-induced CBL-mediated FT ubiquitination, resulting in protein stabilization)" FT /evidence="ECO:0000269|PubMed:12244174" FT /id="VAR_076585" FT VARIANT 1092 FT /note="V -> I (in RCCP; constitutive autophosphorylation; FT dbSNP:rs786202724)" FT /evidence="ECO:0000269|PubMed:10327054, FT ECO:0000269|PubMed:10417759, ECO:0000269|PubMed:10433944" FT /id="VAR_032485" FT VARIANT 1094 FT /note="H -> L (in RCCP; constitutive autophosphorylation; FT causes malignant transformation in cell lines)" FT /evidence="ECO:0000269|PubMed:10327054" FT /id="VAR_032486" FT VARIANT 1094 FT /note="H -> R (in RCCP; causes malignant transformation in FT cell lines; dbSNP:rs121913243)" FT /evidence="ECO:0000269|PubMed:10433944, FT ECO:0000269|PubMed:9563489" FT /id="VAR_032487" FT VARIANT 1094 FT /note="H -> Y (in RCCP; constitutive autophosphorylation; FT causes malignant transformation in cell lines; FT dbSNP:rs121913244)" FT /evidence="ECO:0000269|PubMed:10327054" FT /id="VAR_032488" FT VARIANT 1106 FT /note="H -> D (in RCCP; constitutive autophosphorylation; FT causes malignant transformation in cell lines)" FT /evidence="ECO:0000269|PubMed:10327054, FT ECO:0000269|PubMed:10433944" FT /id="VAR_032489" FT VARIANT 1131 FT /note="M -> T (in RCCP; germline mutation; FT dbSNP:rs121913668)" FT /evidence="ECO:0000269|PubMed:10433944, FT ECO:0000269|PubMed:9140397" FT /id="VAR_006286" FT VARIANT 1173 FT /note="T -> I (in HCC; dbSNP:rs121913675)" FT /evidence="ECO:0000269|PubMed:9927037" FT /id="VAR_032490" FT VARIANT 1188 FT /note="V -> L (in RCCP; germline mutation; FT dbSNP:rs121913669)" FT /evidence="ECO:0000269|PubMed:10433944, FT ECO:0000269|PubMed:9140397" FT /id="VAR_006287" FT VARIANT 1195 FT /note="L -> V (in RCCP; somatic mutation; FT dbSNP:rs121913673)" FT /evidence="ECO:0000269|PubMed:9140397" FT /id="VAR_006288" FT VARIANT 1220 FT /note="V -> I (in RCCP; germline mutation; FT dbSNP:rs121913670)" FT /evidence="ECO:0000269|PubMed:9140397" FT /id="VAR_006289" FT VARIANT 1228 FT /note="D -> H (in RCCP; somatic mutation; FT dbSNP:rs121913671)" FT /evidence="ECO:0000269|PubMed:9140397" FT /id="VAR_006291" FT VARIANT 1228 FT /note="D -> N (in RCCP; germline mutation; FT dbSNP:rs121913671)" FT /evidence="ECO:0000269|PubMed:9140397" FT /id="VAR_006290" FT VARIANT 1230 FT /note="Y -> C (in RCCP; germline mutation; FT dbSNP:rs121913246)" FT /evidence="ECO:0000269|PubMed:10433944, FT ECO:0000269|PubMed:9140397" FT /id="VAR_006292" FT VARIANT 1230 FT /note="Y -> D (in RCCP; constitutive autophosphorylation; FT causes malignant transformation in cell lines)" FT /evidence="ECO:0000269|PubMed:10327054, FT ECO:0000269|PubMed:10433944" FT /id="VAR_032491" FT VARIANT 1230 FT /note="Y -> H (in RCCP; somatic mutation; FT dbSNP:rs121913247)" FT /evidence="ECO:0000269|PubMed:9140397" FT /id="VAR_006293" FT VARIANT 1234 FT /note="Y -> C (in DA11; not phosphorylated in response to FT HGF; severely decreased tyrosin kinase activity; FT dbSNP:rs1554400286)" FT /evidence="ECO:0000269|PubMed:30777867" FT /id="VAR_087543" FT VARIANT 1244 FT /note="K -> R (in HCC; dbSNP:rs121913677)" FT /evidence="ECO:0000269|PubMed:9927037" FT /id="VAR_032492" FT VARIANT 1250 FT /note="M -> I (in HCC; dbSNP:rs121913676)" FT /evidence="ECO:0000269|PubMed:9927037" FT /id="VAR_032493" FT VARIANT 1250 FT /note="M -> T (in RCCP; somatic mutation; FT dbSNP:rs121913245)" FT /evidence="ECO:0000269|PubMed:10433944, FT ECO:0000269|PubMed:9140397" FT /id="VAR_006294" FT VARIANT 1294 FT /note="V -> I (found in a case of cancer of unknown primary FT origin; uncertain significance; somatic mutation; the FT mutated receptor is still functional and can sustain the FT transformed phenotype; dbSNP:rs1263785859)" FT /evidence="ECO:0000269|PubMed:20949619" FT /id="VAR_064857" FT MUTAGEN 1234 FT /note="Y->F: Complete loss of kinase activity and of FT ligand-induced ubiquitination. Alters interaction with FT PTPN1 and PTPN2. Loss of interaction with PTPN1 and PTPN2; FT when associated with F-1235." FT /evidence="ECO:0000269|PubMed:12244174, FT ECO:0000269|PubMed:18819921" FT MUTAGEN 1235 FT /note="Y->F: Complete loss of kinase activity. Alters FT interaction with PTPN1 and PTPN2. Loss of interaction with FT PTPN1 and PTPN2; when associated with F-1234." FT /evidence="ECO:0000269|PubMed:12244174, FT ECO:0000269|PubMed:18819921" FT MUTAGEN 1313 FT /note="Y->F: No effect on ligand-induced CBL-mediated FT ubiquitination; when associated with F-1349, F-1356 and FT F-1365." FT /evidence="ECO:0000269|PubMed:12244174" FT MUTAGEN 1349 FT /note="Y->F: No effect on ligand-induced CBL-mediated FT ubiquitination; when associated with F-1313, F-1356 and FT F-1365." FT /evidence="ECO:0000269|PubMed:12244174" FT MUTAGEN 1356 FT /note="Y->F: No effect on ligand-induced CBL-mediated FT ubiquitination; when associated with F-1313, F-1349 and FT F-1365." FT /evidence="ECO:0000269|PubMed:12244174" FT MUTAGEN 1365 FT /note="Y->F: No effect on ligand-induced CBL-mediated FT ubiquitination; when associated with F-1313, F-1349 and FT F-1356." FT /evidence="ECO:0000269|PubMed:12244174" FT CONFLICT 237 FT /note="V -> A (in Ref. 3; ACF47606)" FT /evidence="ECO:0000305" FT CONFLICT 508 FT /note="K -> R (in Ref. 3; ACF47606)" FT /evidence="ECO:0000305" FT CONFLICT 720 FT /note="F -> S (in Ref. 3; ACF47606)" FT /evidence="ECO:0000305" FT CONFLICT 1191 FT /note="G -> A (in Ref. 1; AAA59591)" FT /evidence="ECO:0000305" FT CONFLICT 1272 FT /note="L -> V (in Ref. 1; AAA59591, 2; CAB56793 and 6; FT AAA59590)" FT /evidence="ECO:0000305" FT HELIX 25..30 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 45..47 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 52..58 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 61..66 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 69..74 FT /evidence="ECO:0007829|PDB:2UZX" FT TURN 75..77 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 80..84 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 89..91 FT /evidence="ECO:0007829|PDB:4K3J" FT STRAND 93..95 FT /evidence="ECO:0007829|PDB:4K3J" FT STRAND 97..99 FT /evidence="ECO:0007829|PDB:1SHY" FT HELIX 103..105 FT /evidence="ECO:0007829|PDB:4O3T" FT STRAND 111..113 FT /evidence="ECO:0007829|PDB:4K3J" FT STRAND 119..123 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 125..133 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 135..139 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 141..145 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 155..160 FT /evidence="ECO:0007829|PDB:4K3J" FT STRAND 166..168 FT /evidence="ECO:0007829|PDB:6WVZ" FT STRAND 173..175 FT /evidence="ECO:0007829|PDB:6I04" FT STRAND 182..189 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 192..199 FT /evidence="ECO:0007829|PDB:2UZX" FT HELIX 205..208 FT /evidence="ECO:0007829|PDB:6WVZ" FT STRAND 213..219 FT /evidence="ECO:0007829|PDB:2UZX" FT HELIX 231..233 FT /evidence="ECO:0007829|PDB:2UZX" FT HELIX 239..241 FT /evidence="ECO:0007829|PDB:2UZX" FT TURN 242..244 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 247..255 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 258..268 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 272..274 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 277..281 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 284..286 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 292..300 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 312..314 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 316..323 FT /evidence="ECO:0007829|PDB:2UZX" FT HELIX 327..333 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 341..349 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 356..366 FT /evidence="ECO:0007829|PDB:2UZX" FT HELIX 367..374 FT /evidence="ECO:0007829|PDB:2UZX" FT HELIX 380..382 FT /evidence="ECO:0007829|PDB:4K3J" FT STRAND 383..385 FT /evidence="ECO:0007829|PDB:4K3J" FT HELIX 387..390 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 392..394 FT /evidence="ECO:0007829|PDB:1SHY" FT TURN 395..397 FT /evidence="ECO:0007829|PDB:4O3T" FT STRAND 418..422 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 424..427 FT /evidence="ECO:0007829|PDB:2UZX" FT TURN 429..436 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 439..447 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 450..457 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 462..466 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 469..471 FT /evidence="ECO:0007829|PDB:4K3J" FT STRAND 476..480 FT /evidence="ECO:0007829|PDB:4K3J" FT STRAND 490..493 FT /evidence="ECO:0007829|PDB:2UZX" FT TURN 496..498 FT /evidence="ECO:0007829|PDB:4O3T" FT STRAND 501..506 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 509..514 FT /evidence="ECO:0007829|PDB:2UZX" FT HELIX 520..522 FT /evidence="ECO:0007829|PDB:5LSP" FT HELIX 526..529 FT /evidence="ECO:0007829|PDB:5LSP" FT HELIX 534..536 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 539..541 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 544..546 FT /evidence="ECO:0007829|PDB:5LSP" FT HELIX 548..550 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 552..554 FT /evidence="ECO:0007829|PDB:2UZX" FT STRAND 557..559 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 564..574 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 580..586 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 589..592 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 595..598 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 602..605 FT /evidence="ECO:0007829|PDB:5LSP" FT HELIX 614..616 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 619..625 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 633..641 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 646..655 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 658..663 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 665..668 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 674..681 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 688..692 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 698..702 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 704..710 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 718..726 FT /evidence="ECO:0007829|PDB:5LSP" FT STRAND 729..739 FT /evidence="ECO:0007829|PDB:5LSP" FT HELIX 1048..1050 FT /evidence="ECO:0007829|PDB:4EEV" FT HELIX 1055..1057 FT /evidence="ECO:0007829|PDB:3F66" FT HELIX 1060..1066 FT /evidence="ECO:0007829|PDB:4R1V" FT HELIX 1067..1069 FT /evidence="ECO:0007829|PDB:4R1V" FT HELIX 1073..1075 FT /evidence="ECO:0007829|PDB:4R1V" FT STRAND 1076..1087 FT /evidence="ECO:0007829|PDB:4R1V" FT STRAND 1090..1098 FT /evidence="ECO:0007829|PDB:4R1V" FT STRAND 1100..1102 FT /evidence="ECO:0007829|PDB:4EEV" FT STRAND 1104..1111 FT /evidence="ECO:0007829|PDB:4R1V" FT HELIX 1118..1132 FT /evidence="ECO:0007829|PDB:4R1V" FT STRAND 1144..1146 FT /evidence="ECO:0007829|PDB:4R1V" FT STRAND 1149..1151 FT /evidence="ECO:0007829|PDB:3F66" FT STRAND 1154..1158 FT /evidence="ECO:0007829|PDB:4R1V" FT STRAND 1161..1163 FT /evidence="ECO:0007829|PDB:8AN8" FT HELIX 1165..1170 FT /evidence="ECO:0007829|PDB:4R1V" FT TURN 1172..1174 FT /evidence="ECO:0007829|PDB:3ZCL" FT HELIX 1178..1197 FT /evidence="ECO:0007829|PDB:4R1V" FT HELIX 1207..1209 FT /evidence="ECO:0007829|PDB:4R1V" FT STRAND 1210..1212 FT /evidence="ECO:0007829|PDB:4R1V" FT STRAND 1218..1220 FT /evidence="ECO:0007829|PDB:4R1V" FT HELIX 1224..1226 FT /evidence="ECO:0007829|PDB:4R1V" FT TURN 1227..1230 FT /evidence="ECO:0007829|PDB:7B43" FT HELIX 1232..1234 FT /evidence="ECO:0007829|PDB:4R1V" FT STRAND 1235..1237 FT /evidence="ECO:0007829|PDB:7Y4T" FT TURN 1239..1241 FT /evidence="ECO:0007829|PDB:4R1V" FT STRAND 1244..1246 FT /evidence="ECO:0007829|PDB:7Y4T" FT HELIX 1247..1249 FT /evidence="ECO:0007829|PDB:4R1V" FT HELIX 1252..1257 FT /evidence="ECO:0007829|PDB:4R1V" FT HELIX 1262..1277 FT /evidence="ECO:0007829|PDB:4R1V" FT STRAND 1283..1287 FT /evidence="ECO:0007829|PDB:4EEV" FT HELIX 1289..1291 FT /evidence="ECO:0007829|PDB:4R1V" FT HELIX 1292..1297 FT /evidence="ECO:0007829|PDB:4R1V" FT HELIX 1310..1319 FT /evidence="ECO:0007829|PDB:4R1V" FT HELIX 1324..1326 FT /evidence="ECO:0007829|PDB:4R1V" FT HELIX 1330..1342 FT /evidence="ECO:0007829|PDB:4R1V" FT TURN 1354..1358 FT /evidence="ECO:0007829|PDB:1R0P" SQ SEQUENCE 1390 AA; 155541 MW; 9CF896D1273905C3 CRC64; MKAPAVLAPG ILVLLFTLVQ RSNGECKEAL AKSEMNVNMK YQLPNFTAET PIQNVILHEH HIFLGATNYI YVLNEEDLQK VAEYKTGPVL EHPDCFPCQD CSSKANLSGG VWKDNINMAL VVDTYYDDQL ISCGSVNRGT CQRHVFPHNH TADIQSEVHC IFSPQIEEPS QCPDCVVSAL GAKVLSSVKD RFINFFVGNT INSSYFPDHP LHSISVRRLK ETKDGFMFLT DQSYIDVLPE FRDSYPIKYV HAFESNNFIY FLTVQRETLD AQTFHTRIIR FCSINSGLHS YMEMPLECIL TEKRKKRSTK KEVFNILQAA YVSKPGAQLA RQIGASLNDD ILFGVFAQSK PDSAEPMDRS AMCAFPIKYV NDFFNKIVNK NNVRCLQHFY GPNHEHCFNR TLLRNSSGCE ARRDEYRTEF TTALQRVDLF MGQFSEVLLT SISTFIKGDL TIANLGTSEG RFMQVVVSRS GPSTPHVNFL LDSHPVSPEV IVEHTLNQNG YTLVITGKKI TKIPLNGLGC RHFQSCSQCL SAPPFVQCGW CHDKCVRSEE CLSGTWTQQI CLPAIYKVFP NSAPLEGGTR LTICGWDFGF RRNNKFDLKK TRVLLGNESC TLTLSESTMN TLKCTVGPAM NKHFNMSIII SNGHGTTQYS TFSYVDPVIT SISPKYGPMA GGTLLTLTGN YLNSGNSRHI SIGGKTCTLK SVSNSILECY TPAQTISTEF AVKLKIDLAN RETSIFSYRE DPIVYEIHPT KSFISGGSTI TGVGKNLNSV SVPRMVINVH EAGRNFTVAC QHRSNSEIIC CTTPSLQQLN LQLPLKTKAF FMLDGILSKY FDLIYVHNPV FKPFEKPVMI SMGNENVLEI KGNDIDPEAV KGEVLKVGNK SCENIHLHSE AVLCTVPNDL LKLNSELNIE WKQAISSTVL GKVIVQPDQN FTGLIAGVVS ISTALLLLLG FFLWLKKRKQ IKDLGSELVR YDARVHTPHL DRLVSARSVS PTTEMVSNES VDYRATFPED QFPNSSQNGS CRQVQYPLTD MSPILTSGDS DISSPLLQNT VHIDLSALNP ELVQAVQHVV IGPSSLIVHF NEVIGRGHFG CVYHGTLLDN DGKKIHCAVK SLNRITDIGE VSQFLTEGII MKDFSHPNVL SLLGICLRSE GSPLVVLPYM KHGDLRNFIR NETHNPTVKD LIGFGLQVAK GMKYLASKKF VHRDLAARNC MLDEKFTVKV ADFGLARDMY DKEYYSVHNK TGAKLPVKWM ALESLQTQKF TTKSDVWSFG VLLWELMTRG APPYPDVNTF DITVYLLQGR RLLQPEYCPD PLYEVMLKCW HPKAEMRPSF SELVSRISAI FSTFIGEHYV HVNATYVNVK CVAPYPSLLS SEDNADDEVD TRPASFWETS //