Hepatocyte growth factor receptor
Also known as: MET
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 neuronal precursors, angiogenesis and kidney formation. During skeletal muscle development, it is crucial for the migration of muscle progenitor cells and for the proliferation of secondary myoblasts (By similarity). In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Also promotes differentiation and proliferation of hematopoietic cells. May regulate cortical bone osteogenesis (By similarity).
Classification
- Family (Pfam)
- PF07714 PK_Tyr_Ser-Thr, PF01437 PSI, PF01403 Sema, PF01833 TIG
- InterPro
- Ig-like_fold, Ig_E-set, IPT_dom, Kinase-like_dom_sf, Plexin, Plexin_repeat, Prot_kinase_dom, Protein_kinase_ATP_BS, PSI, Semap_dom, Semap_dom_sf, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_AS, Tyr_kinase_cat_dom, Tyr_kinase_HGF/MSP_rcpt, WD40/YVTN_repeat-like_dom_sf
- Functional cluster
- Immunoglobulin-Domain Cell Adhesion Proteins
Experimental structures · PDB · 120
- 1FYR X-ray 2.40A
- 1R0P X-ray 1.80A
- 1R1W X-ray 1.80A
- 1SHY X-ray 3.22A
- 1SSL NMR
- 2G15 X-ray 2.15A
- 2RFN X-ray 2.50A
- 2RFS X-ray 2.20A
- 2UZX X-ray 2.80A
- 2UZY X-ray 4.00A
- 2WD1 X-ray 2.00A
- 2WGJ X-ray 2.00A
- … and 108 more
A predicted model is available from AlphaFold.
Gene Ontology · 29
- GO:0009925 basal plasma membrane
- GO:0009986 cell surface
- GO:0005576 extracellular region
- GO:0016020 membrane
- GO:0005886 plasma membrane
- GO:0098794 postsynapse
- GO:0043235 receptor complex
- GO:0005524 ATP binding
- GO:0005008 hepatocyte growth factor receptor activity
- GO:0042802 identical protein binding
- GO:0140677 molecular function activator activity
- GO:0019903 protein phosphatase binding
- GO:0004713 protein tyrosine kinase activity
- GO:0017154 semaphorin receptor activity
- GO:0048754 branching morphogenesis of an epithelial tube
- GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
- GO:0007166 cell surface receptor signaling pathway
- GO:0001886 endothelial cell morphogenesis
- GO:0060079 excitatory postsynaptic potential
- GO:0048012 hepatocyte growth factor receptor signaling pathway
- GO:0001889 liver development
- GO:0010507 negative regulation of autophagy
- GO:1901299 negative regulation of hydrogen peroxide-mediated programmed cell death
- GO:0030182 neuron differentiation
- GO:0031016 pancreas development
- GO:0050918 positive chemotaxis
- GO:2001028 positive regulation of endothelial cell chemotaxis
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0071526 semaphorin-plexin signaling pathway
Disease associations
- hepatocellular carcinoma MONDO:0007256
- hereditary papillary renal cell carcinoma MONDO:0003789
- osteofibrous dysplasia MONDO:0011806
- autosomal recessive nonsyndromic hearing loss 97 MONDO:0014739
- arthrogryposis, distal, IIa 11 MONDO:0031045
Drugs targeting this protein · 28
- FORETINIB inhibitor
- SGX-523 inhibitor
- MK-2461 inhibitor
- PF-04217903 inhibitor
- AMUVATINIB inhibitor
- CABOZANTINIB S-MALATE inhibitor
- TIVANTINIB inhibitor
- JNJ-38877605 inhibitor
- BMS-794833 inhibitor
- MK-8033 inhibitor
- GOLVATINIB inhibitor
- CAPMATINIB inhibitor
- SAVOLITINIB inhibitor
- TEPOTINIB inhibitor
- MERESTINIB inhibitor
- ALTIRATINIB inhibitor
- TAS-115 inhibitor
- AMG-337 inhibitor
- EMD-1204831 inhibitor
- NINGETINIB inhibitor
- GLESATINIB inhibitor
- CAPMATINIB HYDROCHLORIDE inhibitor
- SAR-125844 inhibitor
- TEPOTINIB HYDROCHLORIDE inhibitor
- BMS-777607 inhibitor
- TEREVALEFIM agonist
- AMG-208 inhibitor
- CRIZOTINIB inhibitor
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Hepatocyte growth factor receptor 1.00
- Hepatocyte growth factor receptor 1.00
- Hepatocyte growth factor receptor 1.00
- Hepatocyte growth factor receptor 1.00
- Hepatocyte growth factor receptor 1.00
- Hepatocyte growth factor receptor 1.00
- Hepatocyte growth factor receptor 1.00
- Hepatocyte growth factor receptor 1.00
- Hepatocyte growth factor receptor 1.00
- Hepatocyte growth factor receptor 1.00
- Hepatocyte growth factor receptor 1.00
- Hepatocyte growth factor receptor 1.00
Co-cited proteins · studied together in the literature
- Internalin B 2 shared papers
- Hepatocyte growth factor receptor 4 shared papers
- Macrophage-stimulating protein receptor 3 shared papers
- Leukocyte cell-derived chemotaxin-2 1 shared papers
- Disks large-associated protein 3 1 shared papers
- Hepatocyte growth factor 1 shared papers
- Protein O-mannosyl-transferase TMEM260 1 shared papers
- Protein O-mannosyl-transferase TMEM260 1 shared papers
- Plexin-B1 1 shared papers
- Mitochondrial glutathione transporter SLC25A40 1 shared papers
- Ran-binding protein 9 2 shared papers
- Hepatocyte growth factor receptor 1 shared papers
Literature · 62 cited papers
- The SHDRA syndrome-associated geDne TMEM260 encodes a protein-specific O-mannosyltransferase. Proc. Natl. Acad. Sci. U.S.A. · 2023
- MET mutation causes muscular dysplasia and arthrogryposis. EMBO Mol. Med. · 2019
- Exome sequencing deciphers a germline MET mutation in familial epidermal growth factor receptor-mutant lung cancer. Cancer Sci. · 2017
- Crystal structure of human leukocyte cell-derived chemotaxin 2 (LECT2) reveals a mechanistic basis of functional evolution in a mammalian protein with an M23 metalloendopeptidase fold. J. Biol. Chem. · 2016
- Mutations preventing regulated exon skipping in MET cause osteofibrous dysplasia. Am. J. Hum. Genet. · 2015
- Client proteins and small molecule inhibitors display distinct binding preferences for constitutive and stress-induced HSP90 isoforms and their conformationally restricted mutants. PLoS ONE · 2015
- A mutation of MET, encoding hepatocyte growth factor receptor, is associated with human DFNB97 hearing loss. J. Med. Genet. · 2015
- Tensin-4-dependent MET stabilization is essential for survival and proliferation in carcinoma cells. Dev. Cell · 2014
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- Distinct involvement of the Gab1 and Grb2 adaptor proteins in signal transduction by the related receptor tyrosine kinases RON and MET. J. Biol. Chem. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- … and 50 more in the literature graph