Uniprot ID:P08581	Protein name: Hepatocyte growth factor receptor	Gene : MET
Protein Family:"Protein kinase superfamily, Tyr protein kinase family"	Squence Length : 1390

Sequnce	>P08581 1391 MKAPAVLAPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETPIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSALGAKVLSSVKDRFINFFVGNTINSSYFPDHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYVHAFESNNFIYFLTVQRETLDAQTFHTRIIRFCSINSGLHSYMEMPLECILTEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRSAMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRTEFTTALQRVDLFMGQFSEVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHTLNQNGYTLVITGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGWCHDKCVRSEECLSGTWTQQICLPAIYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNTLKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDPVITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEFAVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHNPVFKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDLLKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISTALLLLLGFFLWLKKRKQIKDLGSELVRYDARVHTPHLDRLVSARSVSPTTEMVSNESVDYRATFPEDQFPNSSQNGSCRQVQYPLTDMSPILTSGDSDISSPLLQNTVHIDLSALNPELVQAVQHVVIGPSSLIVHFNEVIGRGHFGCVYHGTLLDNDGKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNVLSLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMKYLASKKFVHRDLAARNCMLDEKFTVKVADFGLARDMYDKEYYSVHNKTGAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVNTFDITVYLLQGRRLLQPEYCPDPLYEVMLKCWHPKAEMRPSFSELVSRISAIFSTFIGEHYVHVNATYVNVKCVAPYPSLLSSEDNADDEVDTRPASFWETS
Domains	DOMAIN 27 515 Sema DOMAIN 563 655 IPT/TIG 1 DOMAIN 657 739 IPT/TIG 2 DOMAIN 742 836 IPT/TIG 3 DOMAIN 1078 1345 Protein kinase
IPT/TIG sequence regions	563 - 655 IYKVFPNSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNTLKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDP 657 - 739 ITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEFAVKLKIDLANRETSIFSYRED 742 - 836 VYEIHPTKSFISGGSTITGVGKNLNSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHN
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. May regulate cortical bone osteogenesis (By similarity).; Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells"
Active Site	ACT_SITE 1204 1204 Proton acceptor
Binding Site	BINDING 1110 1110 ATP
Nucleotide Binding	NP_BIND 1084 1092 ATP
Mutation	"1234 1234 Y->F: Complete loss of kinase activity and of ligand-induced ubiquitination when associated with F-1235 1235 1235 Y->F: Complete loss of kinase activity when associated with F-1234 1313 1313 Y->F: No effect on ligand-induced CBL-mediated ubiquitination when associated with F-1349, F-1356 and F-1365 1349 1349 Y->F: No effect on ligand-induced CBL-mediated ubiquitination when associated with F-1313, F-1356 and F-1365 1356 1356 Y->F: No effect on ligand-induced CBL-mediated ubiquitination when associated with F-1313, F-1349 and F-1365 1365 1365 Y->F: No effect on ligand-induced CBL-mediated ubiquitination when associated with F-1313, F-1349 and F-1356"
Disease	"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 Note=The disease is caused by mutations 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 Note=The disease is caused by mutations 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 ; 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 Note=The disease is caused by mutations 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 Note=Disease susceptibility is associated with variations 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"

P08581 Proteins IPT/TIG domain Repeats