InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MET

Summary

InnateDB Protein

IDBP-385605.5

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

ENSP00000410980

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.

Experimentally validated
Total	144 [view]
Protein-Protein	138 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004713	protein tyrosine kinase activity
GO:0004872	receptor activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0019903	protein phosphatase binding

Biological Process

GO:0007165	signal transduction
GO:0007166	cell surface receptor signaling pathway
GO:0007275	multicellular organismal development
GO:0007411	axon guidance
GO:0008283	cell proliferation
GO:0018108	peptidyl-tyrosine phosphorylation
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0048754	branching morphogenesis of an epithelial tube
GO:0050918	positive chemotaxis
GO:0071526	semaphorin-plexin signaling pathway
GO:1901299	negative regulation of hydrogen peroxide-mediated programmed cell death
GO:2001028	positive regulation of endothelial cell chemotaxis

Cellular Component

GO:0005576	extracellular region
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009925	basal plasma membrane
GO:0016020	membrane
GO:0016021	integral component of membrane