Gene content    
MET ( by HUGO)
Met Proto-Oncogene
Oncogene
Met Proto-Oncogene
Hepatocyte Growth Factor Receptor
Proto-Oncogene C-Met
Scatter Factor Receptor
Tyrosine-Protein Kinase Met
HGF Receptor
HGF/SF Receptor
SF Receptor
EC 2.7.10.1
AUTS9
HGFR
RCCP2
c-Met
Met Proto-Oncogene Tyrosine Kinase
EC 2.7.10
NCBI: 7q31    Ensembl: 7q31.2
MET_HUMANSize: 1390 amino acidsMass: 155541 Da

  • Subunit: Heterodimer made of an alpha chain (50 kDa) and a beta chain (145 kDa) which are disulfide linked. Binds PLXNB1. Interacts when phosphorylated with downstream effectors including STAT3, PIK3R1, SRC, PCLG1, GRB2 and GAB1. Interacts with SPSB1, SPSB2 and SPSB4 (By similarity). Interacts with INPP5D/SHIP1. When phosphorylated at Tyr-1356, interacts with INPPL1/SHIP2. Interacts with RANBP9 and RANBP10, as well as SPSB1, SPSB2, SPSB3 and SPSB4. SPSB1 binding occurs in the presence and in the absence of HGF, however HGF treatment has a positive effect on this interaction. Interacts with MUC20; prevents interaction with GRB2 and suppresses hepatocyte growth factor-induced cell proliferation. Interacts with GRB10. Interacts with PTPN1 and PTPN2 Selected PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] for MET (see all 55): 1FYR (3D) [IMAGE] 1R0P (3D) [IMAGE] 1R1W (3D) [IMAGE] 1SHY (3D) [IMAGE] 1SSL (3D) [IMAGE] 1UX3 (3D) [IMAGE]
  • Tissue specificity: Expressed in normal hepatocytes as well as in epithelial cells lining the stomach, the small and the large intestine. Found also in basal keratinocytes of esophagus and skin. High levels are found in liver, gastrointestinal tract, thyroid and kidney. Also
  • Function:
    Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells
                          
    Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells Function: Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells
  • Catalytic activity:
    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
  • Similarity:
    Belongs to the protein kinase superfamily. Tyr protein kinase family
                          
    Contains 3 IPT/TIG domains
                          
    Contains 1 protein kinase domain
                          
    Contains 1 Sema domain [IMAGE]
  • Protein Domain/Family    
    Source ID Domain Name Type
    InterProIPR000719Prot_kinase_domProtein kinaseDomain
    IPR001245Ser-Thr/Tyr_kinase_cat_domTyrosine protein kinaseDomain
    IPR001627Semap_domSemaphorin/CD100 antigenDomain
    IPR002165Plexin_repeatPlexinRepeat
    IPR002909IPTCell surface receptor IPT/TIGDomain
    IPR008266Tyr_kinase_ASTyrosine protein kinase, active siteActive Sites
    IPR011009Kinase-like_domProtein kinase-likeDomain
    BlocksIPB002909Cell surface receptor IPT/TIGCell surface receptor IPT/TIG
    IPB008266Tyrosine protein kinaseTyrosine protein kinase, active site

    Gene Ontology    
    Type Term Evidence Source Pub
    Biological Process branching morphogenesis of an epithelial tube IMP GOA 16153003
    cell proliferation TAS GOA 10871856
    cell surface receptor signaling pathway NAS GOA 2819873
    endothelial cell morphogenesis IDA GOA 14500721
    peptidyl-tyrosine phosphorylation NAS GOA 3325883
    positive chemotaxis IDA GOA 15218527
    semaphorin-plexin signaling pathway IDA GOA 15218527
    signal transduction TAS GOA 1846706
    Cellular Component basal plasma membrane IDA GOA 15314156
    cell surface IDA GOA 19581412
    integral component of membrane NAS GOA 2819873
    integral component of plasma membrane TAS GOA 1846706
    Molecular Function protein binding IPI GOA 11571281
    protein phosphatase binding IPI GOA 18819921
    protein tyrosine kinase activity NAS GOA 3325883

    Disorder & Mutation    
    Source Disease
    SWISS-PROTRenal cell carcinoma papillary (RCCP) [MIM:605074]: A subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. Note=The disease is caused by mutations affecting the gene represented in this entry
    SWISS-PROTNote=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein
    SWISS-PROTNote=Defects in MET may be associated with gastric cancer
    SWISS-PROTHepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Note=The disease is caused by mutations affecting the gene represented in this entry
    SWISS-PROTNote=A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes

    MET cross reference    
    PubMed OMIM Entrez Gene NCKU SNP Nucleotide UniProt Genome Data Viewer HomoloGene