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hepatocyte growth factor receptor; HGF receptor; scatter factor receptor; SF receptor; HGF/SF receptor; Met proto-oncogene tyrosine kinase; c-Met (MET)

Function: - receptor for hepatocyte growth factor & scatter factor - has a tyrosine-protein kinase activity - binds PLXNB1 & GRB2 - interacts with SPSB1, SPSB2 & SPSB4 (putative) - interacts with INPP5D/SHIP1 - when phosphorylated at Tyr-1356, interacts with INPPL1/SHIP2 - interacts with RANBP9 & RANBP10, as well as SPSB1, SPSB2, SPSB3 & SPSB4 - SPSB1 binding occurs in the presence & in the absence of HGF, however HGF treatment has a positive effect on this interaction Structure: - heterodimer formed of an alpha chain (50 kD) & a beta chain (145 kD) which are disulfide linked - the kinase domain is involved in SPSB1 binding - belongs to the protein kinase superfamily, Tyr protein kinase family - contains 3 IPT/TIG domains - contains 1 protein kinase domain - contains 1 Sema domain Compartment: membrane Alternative splicing: named isoforms=2 Pathology: - activation of MET after rearrangement with the TPR gene produces an oncogenic protein - defects in MET may be associated with gastric cancer - defects in MET are a cause of a) hepatocellular carcinoma b) papillary renal cell carcinoma 2 - genetic variations in MET may be associated with susceptibility to autism type 1B - c-Met is present in greater abundance on the cell surface of colorectal hyperplastic polyps & colorectal adenomas than on normal colorectal mucosa [6] Pharmacology: - probe consisting of a peptide that binds to c-Met is attached to a fluorescent dye is used in fluorescence-guided colonoscopy [6]

Interactions

molecular events

Related

hepatocyte growth factor; hepatopoietin-A; scatter factor; SF (HGF, HPTA) met proto-oncogene

General

glycoprotein multisubunit protein proto oncogene protein tyrosine kinase receptor (RTK)

Properties

SIZE: entity length = 1390 aa MW = 156 kD COMPARTMENT: cellular membrane STATE: active state MOTIF: signal sequence {1-24} Sema {27-515} MOTIF: N-glycosylation site {N45} N-glycosylation site {N106} N-glycosylation site {N149} N-glycosylation site {N202} peptide motif {307-308} N-glycosylation site {N399} N-glycosylation site {N405} IPT/TIG 1 {563-655} MOTIF: N-glycosylation site {N607} N-glycosylation site {N635} IPT/TIG 2 {657-739} IPT/TIG 3 {742-836} MOTIF: N-glycosylation site {N785} N-glycosylation site {N879} N-glycosylation site {N930} transmembrane domain {933-955} Thr phosphorylation site {T977} Ser phosphorylation site {S988} Ser phosphorylation site {S990} Tyr phosphorylation site {Y1003} breakpoint {1009-1010} kinase domain SITE: 1078-1345 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 1084-1092 ATP-binding site NAME: ATP-binding site SITE: 1110-1110 aspartate residue {D1204} RANBP9 interaction {1212-1390} MOTIF: Tyr phosphorylation site {Y1230} Tyr phosphorylation site {Y1234} Tyr phosphorylation site {Y1235} Tyr phosphorylation site {Y1356} GENE: met proto-oncogene

Database Correlations

OMIM correlations MORBIDMAP 164860 UniProt P08581 PFAM correlations Entrez Gene 4233 Kegg hsa:4233 ENZYME 2.7.10.1

References

  1. UniProt :accession P08581
  2. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/METID131.html
  3. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=MET
  4. Wikipedia; C-MET entry http://en.wikipedia.org/wiki/C-MET
  5. Giordano S, Ponzetto C, Di Renzo MF, Cooper CS, Comoglio PM. Tyrosine kinase receptor indistinguishable from the c-met protein Nature. 1989 May 11;339(6220):155-6. PMID: 2541345
  6. Burggraaf J et al. Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met. Nat Med 2015 Aug; 21:955 PMID: 26168295

Component-of

molecular complex