Homo sapiens Protein: MET | |||||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||||
InnateDB Protein | IDBP-234643.6 | ||||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||
Gene Symbol | MET | ||||||||||||||||||||||||||||
Protein Name | met proto-oncogene (hepatocyte growth factor receptor) | ||||||||||||||||||||||||||||
Synonyms | AUTS9; c-Met; HGFR; RCCP2; | ||||||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||||||
Ensembl Protein | ENSP00000380860 | ||||||||||||||||||||||||||||
InnateDB Gene | IDBG-37371 (MET) | ||||||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||||||
Function | 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.Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells. | ||||||||||||||||||||||||||||
Subcellular Localization | Membrane; Single-pass type I membrane protein.Isoform 3: Secreted. | ||||||||||||||||||||||||||||
Disease Associations | Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein.Note=Defects in MET may be associated with gastric cancer.Hepatocellular 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. {ECO:0000269PubMed:9927037}. Note=The disease is caused by mutations affecting the gene represented in this entry.Renal 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. {ECO:0000269PubMed:10327054, ECO:0000269PubMed:10417759, ECO:0000269PubMed:10433944, ECO:0000269PubMed:9140397, ECO:0000269PubMed:9563489}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=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.Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies. | ||||||||||||||||||||||||||||
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 present in the brain. {ECO:0000269PubMed:1719465, ECO:0000269PubMed:1917129}. | ||||||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 144 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||||||
InterPro |
IPR000719
Protein kinase domain IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain IPR001627 Sema domain IPR002165 Plexin IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain IPR002909 IPT domain IPR011009 Protein kinase-like domain IPR014756 Immunoglobulin E-set IPR016201 Plexin-like fold IPR016244 Tyrosine-protein kinase, HGF/MSP receptor IPR020635 Tyrosine-protein kinase, catalytic domain |
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PFAM |
PF00069
PF07714 PF01403 PF01437 PF01833 |
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PRINTS |
PR00109
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PIRSF |
PIRSF000617
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SMART |
SM00630
SM00220 SM00429 SM00423 SM00219 |
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TIGRFAMs | |||||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||||
SwissProt | P08581 | ||||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-P08581 | ||||||||||||||||||||||||||||
TrEMBL | Q9UEJ3 | ||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||
Entrez Gene | 4233 | ||||||||||||||||||||||||||||
UniGene | Hs.619431 | ||||||||||||||||||||||||||||
RefSeq | NP_000236 | ||||||||||||||||||||||||||||
HUGO | HGNC:7029 | ||||||||||||||||||||||||||||
OMIM | 164860 | ||||||||||||||||||||||||||||
CCDS | CCDS43636 | ||||||||||||||||||||||||||||
HPRD | 01280 | ||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||
EMBL | AC002080 AC002543 AC004416 AK296974 AK298552 BC130420 CH236947 CH471070 EU826570 J02958 M15325 M35074 U08818 X54559 | ||||||||||||||||||||||||||||
GenPept | AAA59585 AAA59590 AAA59591 AAB54047 AAB60323 AAC60383 AAF66137 AAI30421 ACF47606 BAG59517 BAG60748 CAB56793 EAL24359 EAW83509 EAW83510 | ||||||||||||||||||||||||||||