Endogenous

MET

Hepatocyte growth factor receptor

MET ;
Hepatocyte growth factor receptor ;
HGF receptor ;
HGF/SF receptor ;
Proto-oncogene c-Met ;
Scatter factor receptor ;
SF receptor ;
Tyrosine-protein kinase Met

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],

Catalytic activity:ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.,Disease:Activation of MET after rearrangement with the TPR gene produces an oncogenic protein.,Disease:Defects in MET are a cause of hepatocellular carcinoma (HCC) [MIM:114550].,Disease:Defects in MET are a cause of hereditary papillary renal carcinoma (HPRC) [MIM:605074]; also known as papillary renal cell carcinoma 2 (RCCP2). HPRC is a form of inherited kidney cancer characterized by a predisposition to develop multiple, bilateral papillary renal tumors. The pattern of inheritance is consistent with autosomal dominant transmission with reduced penetrance.,Disease:Defects in MET may be associated with gastric cancer.,Disease:Genetic variations in MET may be associated with susceptibility to autism type 9 (AUTS9) [MIM:611015]. Autism is a neurodevelopmental disorder characterized by disturbance in language, perception and socialization. The disorder is classically defined by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypical, and ritualized patterns of interests and behavior.,Domain:The kinase domain is involved in SPSB1 binding.,Function:Receptor for hepatocyte growth factor and scatter factor. Has a tyrosine-protein kinase activity. Functions in cell proliferation, scattering, morphogenesis and survival.,online information:C-MET entry,similarity:Belongs to the protein kinase superfamily. Tyr protein kinase family.,similarity:Contains 1 protein kinase domain.,similarity:Contains 1 Sema domain.,similarity:Contains 3 IPT/TIG domains.,subunit:Heterodimer formed of an alpha chain (50 kDa) and a beta chain (145 kDa) which are disulfide linked. Binds PLXNB1 and GRB2. 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.,

Secreted

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. Expressed in metaphyseal bone (at protein level) (PubMed:26637977).

>>EGFR tyrosine kinase inhibitor resistance ;
>>MAPK signaling pathway ;
>>Ras signaling pathway ;
>>Rap1 signaling pathway ;
>>Calcium signaling pathway ;
>>PI3K-Akt signaling pathway ;
>>Axon guidance ;
>>Focal adhesion ;
>>Adherens junction ;
>>Bacterial invasion of epithelial cells ;
>>Epithelial cell signaling in Helicobacter pylori infection ;
>>Malaria ;
>>Pathways in cancer ;
>>Transcriptional misregulation in cancer ;
>>Proteoglycans in cancer ;
>>MicroRNAs in cancer ;
>>Chemical carcinogenesis - reactive oxygen species ;
>>Renal cell carcinoma ;
>>Melanoma ;
>>Non-small cell lung cancer ;
>>Hepatocellular carcinoma ;
>>Gastric cancer ;
>>Central carbon metabolism in cancer