Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

MET (P08581) - Overview - Molecular Target Synopsis


MET, Hepatocyte growth factor receptor
Enzyme Classification
UniProt P08581

Also Known as MET_HUMAN, MET

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)., (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells. 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. Interacts with LECT2; this interaction may have an antagonistic effect on receptor activation (PubMed:27334921). Interacts with HSP90AA1 and HSP90AB1; the interaction suppresses MET kinase activity (PubMed:26517842).

Inspect Structure
See all 3D Structures for MET

Isoforms / Transcripts (Protein Coding)


MET is targeted by Approved Drugs Cabozantinib, Crizotinib. (see details)

Sub-cellular localization

UniProt: MET is active in the following subcellular-locations: membrane, secreted.
GO terms: MET is active in the following subcellular-locations: basal plasma membrane, cell surface, extracellular region, integral component of membrane, integral component of plasma membrane, plasma membrane, receptor complex.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project MET has gain in 19 cell-lines, loss in 1 cell-lines and no signal in 983 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: SK_MEL_5, HS578T, CAKI_1

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H920, HCC4011, Detroit 562

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HSMM, HMEC, NHLF

(see details)

RNA Interference

MET was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: JIMT1, HCC1954. (see details)

3D Structures

For MET there are:
84 structures (106 chains) solved
72 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

MET is solved in complex with the approved drug(s):


(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

MET has been screened with 5211 compounds (7785 bioactivities), 2335 compounds have bioactivities that show binding affinity of <= 500nM (3369 bioactivities). (see details)