MET
entrez
4233
canonical
uniprot
P08581
canonical
ensembl
ENSG00000105976
resolver
ensp
ENSP00000317272
resolver
ensp
ENSP00000380860
resolver
ensp
ENSP00000398776
resolver
ensp
ENSP00000781861
resolver
enst
ENST00000422097
resolver
genesymbol
MET
resolver
hgnc
HGNC:7029
resolver
uniprot
A0ACM8QMG8
resolver
uniprot
A1L467
resolver
uniprot
B4DLF5
resolver
uniprot
B5A932
resolver
uniprot
E6Y365
resolver
uniprot
E7EQ94
resolver
uniprot
H7C174
resolver
uniprot
O60366
resolver
uniprot
Q12875
resolver
uniprot
Q9UDX7
resolver
uniprot
Q9UPL8
resolver
uniprot_entry
A0ACM8QMG8_HUMAN
resolver
uniprot_entry
B4DLF5_HUMAN
resolver
uniprot_entry
E6Y365_HUMAN
resolver
uniprot_entry
MET_HUMAN
resolver
uniprot_sec
A1L467
resolver
uniprot_sec
B5A932
resolver
uniprot_sec
E7EQ94
resolver
uniprot_sec
H7C174
resolver
uniprot_sec
O60366
resolver
uniprot_sec
Q12875
resolver
uniprot_sec
Q9UDX7
resolver
uniprot_sec
Q9UPL8
resolver
activity_regulation
ACTIVITY 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.
uniprot
proteins
amino_acid_sequence
MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSALGAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYVHAFESNNFIYFLTVQRETLDAQTFHTRIIRFCSINSGLHSYMEMPLECILTEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRSAMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEFTTALQRVDLFMGQFSEVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGWCHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNTLKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDPVITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEFAVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHNPVFKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDLLKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQIKDLGSELVRYDARVHTPHLDRLVSARSVSPTTEMVSNESVDYRATFPEDQFPNSSQNGSCRQVQYPLTDMSPILTSGDSDISSPLLQNTVHIDLSALNPELVQAVQHVVIGPSSLIVHFNEVIGRGHFGCVYHGTLLDNDGKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNVLSLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMKYLASKKFVHRDLAARNCMLDEKFTVKVADFGLARDMYDKEYYSVHNKTGAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVNTFDITVYLLQGRRLLQPEYCPDPLYEVMLKCWHPKAEMRPSFSELVSRISAIFSTFIGEHYVHVNATYVNVKCVAPYPSLLSSEDNADDEVDTRPASFWETS
uniprot
proteins
disease_involvement
DISEASE: Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein.; DISEASE: Note=Defects in MET may be associated with gastric cancer.; DISEASE: 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:0000269|PubMed:9927037}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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:0000269|PubMed:10327054, ECO:0000269|PubMed:10417759, ECO:0000269|PubMed:10433944, ECO:0000269|PubMed:9140397, ECO:0000269|PubMed:9563489}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: 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.; DISEASE: 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. {ECO:0000269|PubMed:20949619}.; DISEASE: Deafness, autosomal recessive, 97 (DFNB97) [MIM:616705]: A form of non-syndromic sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:25941349}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Osteofibrous dysplasia (OSFD) [MIM:607278]: A congenital disorder of osteogenesis characterized by non-neoplastic, radiolucent lesions that affect the cortical bone immediately under the periosteum. It usually manifests as a painless swelling or anterior bowing of the long bones, most commonly the tibia and fibula. {ECO:0000269|PubMed:26637977}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Disease-associated variants identified in 4 families cause the deletion of exon 14. This results in the exclusion of an ubiquitination target site within the cytoplasmic domain, hence in protein stabilization. The persistent presence of MET at the cell surface in conditions of ligand-dependent activation retards osteoblastic differentiation. {ECO:0000269|PubMed:26637977}.; DISEASE: Arthrogryposis, distal, 11 (DA11) [MIM:620019]: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA11 is an autosomal dominant form characterized mainly by camptodactyly. Other features include absent flexion creases and limited forearm supination. {ECO:0000269|PubMed:30777867}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
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 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). {ECO:0000250|UniProtKB:P16056}.; FUNCTION: (Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells. {ECO:0000269|PubMed:11081636, ECO:0000305|PubMed:17662939, ECO:0000305|PubMed:19900460}.
uniprot
proteins
mass_dalton
155541
uniprot
proteins
mutagenesis
MUTAGEN 1234; /note="Y->F: Complete loss of kinase activity and of ligand-induced ubiquitination. Alters interaction with PTPN1 and PTPN2. Loss of interaction with PTPN1 and PTPN2; when associated with F-1235."; /evidence="ECO:0000269|PubMed:12244174, ECO:0000269|PubMed:18819921"; MUTAGEN 1235; /note="Y->F: Complete loss of kinase activity. Alters interaction with PTPN1 and PTPN2. Loss of interaction with PTPN1 and PTPN2; when associated with F-1234."; /evidence="ECO:0000269|PubMed:12244174, ECO:0000269|PubMed:18819921"; MUTAGEN 1313; /note="Y->F: No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1349, F-1356 and F-1365."; /evidence="ECO:0000269|PubMed:12244174"; MUTAGEN 1349; /note="Y->F: No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1313, F-1356 and F-1365."; /evidence="ECO:0000269|PubMed:12244174"; MUTAGEN 1356; /note="Y->F: No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1313, F-1349 and F-1365."; /evidence="ECO:0000269|PubMed:12244174"; MUTAGEN 1365; /note="Y->F: No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1313, F-1349 and F-1356."; /evidence="ECO:0000269|PubMed:12244174
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated in response to ligand binding on Tyr-1234 and Tyr-1235 in the kinase domain leading to further phosphorylation of Tyr-1349 and Tyr-1356 in the C-terminal multifunctional docking site. Dephosphorylated by PTPRJ at Tyr-1349 and Tyr-1365. Dephosphorylated by PTPN1 and PTPN2. {ECO:0000269|PubMed:12475979, ECO:0000269|PubMed:15735664, ECO:0000269|PubMed:1655790, ECO:0000269|PubMed:18819921, ECO:0000269|PubMed:7513258}.; PTM: Ubiquitinated. Ubiquitination by CBL regulates MET endocytosis, resulting in decreasing plasma membrane receptor abundance, and in endosomal degradation and/or recycling of internalized receptors. {ECO:0000269|PubMed:12244174, ECO:0000305|PubMed:26637977}.; PTM: O-mannosylation of IPT/TIG domains by TMEM260 is required for protein maturation (PubMed:37186866). O-mannosylated residues are composed of single mannose glycans that are not elongated or modified (PubMed:37186866). {ECO:0000269|PubMed:37186866}.; PTM: (Microbial infection) Tyrosine phosphorylation is stimulated by L.monocytogenes InlB. Tyrosine phosphorylation is maximal 10-20 minutes after treatment with InlB and disappears by 60 minutes. The phosphorylated residues were not identified. {ECO:0000269|PubMed:11081636}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10327054
uniprot
proteins
pubmed
10417759
uniprot
proteins
pubmed
10433944
uniprot
proteins
pubmed
10454568
uniprot
proteins
pubmed
11042681
uniprot
proteins
pubmed
11063574
uniprot
proteins
pubmed
11081636
uniprot
proteins
pubmed
12147692
uniprot
proteins
pubmed
12198496
uniprot
proteins
pubmed
12244174
uniprot
proteins
pubmed
12475979
uniprot
proteins
pubmed
12690205
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
12920089
uniprot
proteins
pubmed
14559966
uniprot
proteins
pubmed
14684163
uniprot
proteins
pubmed
15167892
uniprot
proteins
pubmed
15314156
uniprot
proteins
pubmed
15358240
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15713673
uniprot
proteins
pubmed
15735664
uniprot
proteins
pubmed
1655790
uniprot
proteins
pubmed
16862193
uniprot
proteins
pubmed
17053076
uniprot
proteins
pubmed
1718989
uniprot
proteins
pubmed
1719465
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17662939
uniprot
proteins
pubmed
1846706
uniprot
proteins
pubmed
18593464
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18819921
uniprot
proteins
pubmed
1917129
uniprot
proteins
pubmed
19196183
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19900460
uniprot
proteins
pubmed
20655987
uniprot
proteins
pubmed
20949619
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21784853
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24814316
uniprot
proteins
pubmed
25941349
uniprot
proteins
pubmed
26517842
uniprot
proteins
pubmed
26637977
uniprot
proteins
pubmed
27334921
uniprot
proteins
pubmed
2819873
uniprot
proteins
pubmed
28294470
uniprot
proteins
pubmed
30777867
uniprot
proteins
pubmed
3325883
uniprot
proteins
pubmed
37186866
uniprot
proteins
pubmed
4069211
uniprot
proteins
pubmed
7513258
uniprot
proteins
pubmed
8182137
uniprot
proteins
pubmed
8247543
uniprot
proteins
pubmed
9140397
uniprot
proteins
pubmed
9440692
uniprot
proteins
pubmed
9563489
uniprot
proteins
pubmed
9927037
uniprot
proteins
sequence_length
1390
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: [Isoform 3]: Secreted.
uniprot
proteins
transmembrane_region
TRANSMEM 933..955; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins