Tclin MET Hepatocyte growth factor receptor

Protein Summary

Description

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. May regulate cortical bone osteogenesis (By similarity). Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells. This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that are linked via disulfide bonds to form the mature receptor. Further processing of the beta subunit results in the formation of the M10 peptide, which has been shown to reduce lung fibrosis. Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. Mutations in this gene are associated with papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers. Amplification and overexpression of this gene are also associated with multiple human cancers. [provided by RefSeq, May 2016]

Uniprot Accession IDs

• P08581
• A1L467
• B5A932
• E7EQ94
• O60366
• Q12875
• Q9UDX7
• Q9UPL8
• HGF receptor

Gene Name

• MET

Ensembl ID

• ENST00000318493
• ENSP00000317272
• ENSG00000105976
• ENST00000397752
• ENSP00000380860
• ENST00000436117
• ENSP00000410980

Symbol

• HGFR
• AUTS9
• RCCP2
• c-Met
• DFNB97

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	1
protein domain	1
biological process	0.99
hub protein	0.99
molecular function	0.99

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tk Group / Met Family / Hepatocyte Growth Factor Receptor

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2866.8   (req: < 5)

Gene RIFs: 1243   (req: <= 3)

Antibodies: 2650   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2866.8   (req: >= 5)

Gene RIFs: 1243   (req: > 3)

Antibodies: 2650   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 37

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 1746

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 6