MET_HUMAN
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 03-AUG-2022, entry version 266.
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 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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [53]
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 [54]
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 [55]
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 [56]
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 [57]
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 [58]
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 [59]
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 [60]
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 [61]
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).
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 muscles and neuronal
CC precursors, angiogenesis and kidney formation. In adults, participates
CC in wound healing as well as organ regeneration and tissue remodeling.
CC Promotes also differentiation and proliferation of hematopoietic cells.
CC May regulate cortical bone osteogenesis (By similarity).
CC {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). {ECO:0000250|UniProtKB:P16056,
CC ECO:0000269|PubMed:10454568, ECO:0000269|PubMed:11063574,
CC ECO:0000269|PubMed:12147692, ECO:0000269|PubMed:12198496,
CC ECO:0000269|PubMed:14559966, ECO:0000269|PubMed:14684163,
CC ECO:0000269|PubMed:15167892, ECO:0000269|PubMed:15314156,
CC ECO:0000269|PubMed:15713673, ECO:0000269|PubMed:15735664,
CC ECO:0000269|PubMed:1718989, ECO:0000269|PubMed:17662939,
CC ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:21784853,
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; Q96EY1-2: 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; 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; 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=4; 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: (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 -!- 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="http://atlasgeneticsoncology.org/Genes/METID131.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=C-MET entry;
CC URL="https://en.wikipedia.org/wiki/C-MET";
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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 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 AlphaFoldDB; P08581; -.
DR SASBDB; P08581; -.
DR SMR; P08581; -.
DR BioGRID; 110391; 200.
DR CORUM; P08581; -.
DR DIP; DIP-6023N; -.
DR ELM; P08581; -.
DR IntAct; P08581; 102.
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; DB15133; Tepotinib.
DR DrugBank; DB12200; Tivantinib.
DR DrugBank; DB11800; Tivozanib.
DR DrugCentral; P08581; -.
DR GuidetoPHARMACOLOGY; 1815; -.
DR GlyConnect; 680; 17 N-Linked glycans (6 sites).
DR GlyGen; P08581; 15 sites, 23 N-linked glycans (6 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 EPD; P08581; -.
DR jPOST; P08581; -.
DR MassIVE; P08581; -.
DR MaxQB; P08581; -.
DR PaxDb; P08581; -.
DR PeptideAtlas; P08581; -.
DR PRIDE; P08581; -.
DR ProteomicsDB; 52128; -. [P08581-1]
DR ProteomicsDB; 52129; -. [P08581-2]
DR ProteomicsDB; 52130; -. [P08581-3]
DR ABCD; P08581; 52 sequenced antibodies.
DR Antibodypedia; 3939; 2838 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; ENST00000436117.2; 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 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 neXtProt; NX_P08581; -.
DR OpenTargets; ENSG00000105976; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
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; 357191; Selection of therapeutic option in non-small cell lung carcinoma.
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; 408584at2759; -.
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 1116 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 192 other tissues.
DR ExpressionAtlas; P08581; baseline and differential.
DR Genevisible; P08581; HS.
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:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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: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:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
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:0050918; P:positive chemotaxis; IDA:UniProtKB.
DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; IMP:CAFA.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IBA:GO_Central.
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 DisProt; DP02738; -.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.60.40.10; -; 3.
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; PTHR22625; 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; SSF101912; SSF101912; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF81296; SSF81296; 3.
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.
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 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 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; the mutated receptor is still functional and can
FT sustain the transformed phenotype; somatic mutation;
FT 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; the mutated receptor is still functional and can
FT sustain the transformed phenotype; somatic mutation;
FT 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; unknown pathological significance;
FT decreased hepatocyte growth factor-activated receptor
FT activity; decreased interaction with HGF;
FT 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; the mutated receptor is still functional and can
FT sustain the transformed phenotype; somatic mutation;
FT 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; the mutated receptor is still functional and can
FT sustain the transformed phenotype; somatic mutation;
FT 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 (probable disease-associated variant found in
FT lesional sample from a patient with sporadically occurring,
FT unilateral osteofibrous dysplasia; somatic mutation;
FT 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 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; the mutated receptor is still functional and can
FT sustain the transformed phenotype; somatic mutation;
FT 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 F-
FT 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 F-
FT 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 F-
FT 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 F-
FT 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 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 1236..1238
FT /evidence="ECO:0007829|PDB:4KNB"
FT TURN 1239..1241
FT /evidence="ECO:0007829|PDB:4R1V"
FT STRAND 1243..1245
FT /evidence="ECO:0007829|PDB:4KNB"
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
