Names & Taxonomy

Uniprot ID:
P08581
Entry Name:
MET_HUMAN
Status:
reviewed
Protein Names:
Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
Gene Names:
MET
Gene Names Primary:
MET
Organism:
Homo sapiens (Human)

Structure

Length:
1390
Sequence:
MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSALGAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYVHAFESNNFIYFLTVQRETLDAQTFHTRIIRFCSINSGLHSYMEMPLECILTEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRSAMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEFTTALQRVDLFMGQFSEVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGWCHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNTLKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDPVITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEFAVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHNPVFKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDLLKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQIKDLGSELVRYDARVHTPHLDRLVSARSVSPTTEMVSNESVDYRATFPEDQFPNSSQNGSCRQVQYPLTDMSPILTSGDSDISSPLLQNTVHIDLSALNPELVQAVQHVVIGPSSLIVHFNEVIGRGHFGCVYHGTLLDNDGKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNVLSLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMKYLASKKFVHRDLAARNCMLDEKFTVKVADFGLARDMYDKEYYSVHNKTGAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVNTFDITVYLLQGRRLLQPEYCPDPLYEVMLKCWHPKAEMRPSFSELVSRISAIFSTFIGEHYVHVNATYVNVKCVAPYPSLLSSEDNADDEVDTRPASFWETS
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Membrane; Single-pass type I membrane protein.; Isoform 3: Secreted.

Function

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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:
ENZYME REGULATION: In its inactive state, the C-terminal tail interacts with the catalytic domain and inhibits the kinase activity. Upon ligand binding, the C-terminal tail is displaced and becomes phosphorylated, thus increasing the kinase activity.
Active Site:
ACT_SITE 1204 1204 Proton acceptor.
Cross Reference Drug Bank:
DB08875 DB08865
Gene Ontology Go:
basal plasma membrane
cell surface
extracellular region
integral component of membrane
integral component of plasma membrane
plasma membrane
ATP binding
hepatocyte growth factor-activated receptor activity
protein phosphatase binding
protein tyrosine kinase activity
axon guidance
branching morphogenesis of an epithelial tube
cell proliferation
cell surface receptor signaling pathway
endothelial cell morphogenesis
hepatocyte growth factor receptor signaling pathway
negative regulation of autophagy
negative regulation of hydrogen peroxide-mediated programmed cell death
peptidyl-tyrosine phosphorylation
positive chemotaxis
positive regulation of endothelial cell chemotaxis
positive regulation of transcription from RNA polymerase II promoter
semaphorin-plexin signaling pathway
signal transduction
Gene Ontology Biological Process:
axon guidance
branching morphogenesis of an epithelial tube
cell proliferation
cell surface receptor signaling pathway
endothelial cell morphogenesis
hepatocyte growth factor receptor signaling pathway
negative regulation of autophagy
negative regulation of hydrogen peroxide-mediated programmed cell death
peptidyl-tyrosine phosphorylation
positive chemotaxis
positive regulation of endothelial cell chemotaxis
positive regulation of transcription from RNA polymerase II promoter
semaphorin-plexin signaling pathway
signal transduction
Gene Ontology Molecular Function:
ATP binding
hepatocyte growth factor-activated receptor activity
protein phosphatase binding
protein tyrosine kinase activity
Gene Ontology Cellular Component:
basal plasma membrane
cell surface
extracellular region
integral component of membrane
integral component of plasma membrane
plasma membrane
Keywords:
3D-structure
ATP-binding
Alternative splicing
Chromosomal rearrangement
Complete proteome
Deafness
Disease mutation
Disulfide bond
Glycoprotein
Kinase
Membrane
Non-syndromic deafness
Nucleotide-binding
Phosphoprotein
Polymorphism
Proto-oncogene
Receptor
Reference proteome
Repeat
Secreted
Signal
Transferase
Transmembrane
Transmembrane helix
Tyrosine-protein kinase
Ubl conjugation
Interacts With:
P22681; Q96EY1-2; P00533; P09769; P14210; P14210-6; P25147; O15357; P35968; P35918; P06239; P07948; P15941; P16333; O43639; P27986; O00459; Q92569; P19174; O43157; O15031; Q9ULL4; Q00944; P18031; Q06124; P23467; Q12913; P20936; Q9UQQ2; O60880; O14796; Q9NP31; Q8N5H7; Q15464; P29353; P98077; Q6S5L8; Q96IW2; Q9H6Q3; O75159; O14544; P12931; Q9ULZ2; P43405; P42680; Q9HBL0; Q63HR2; Q68CZ2; Q9UKW4; P07947; P43403

Publication

PubMed ID:
2819873 18593464 12853948 12690205 15489334 3325883 8247543 4069211 1917129 1718989 1719465 1846706 1655790 7513258 8182137 9440692 10454568 12147692 12244174 12198496 12475979 14684163 15314156 15735664 16862193 18819921 18691976 18669648 19196183 19369195 20655987 21269460 21784853 24275569 25941349 11063574 14559966 15358240 15167892 17662939 9140397 9563489 10433944 9927037 10417759 10327054 11042681 12920089 15713673 17053076 17344846 20949619