UniProt Accession

 MET_HUMAN; P08581; A1L467; B5A932; E7EQ94; O60366; Q12875; Q9UDX7; Q9UPL8 

Genbank Protein ID

 J02958; X54559; EU826570; AC002080; AC002543; AC004416; CH236947; CH471070; BC130420; U08818; M35074 

Genbank Nucleotide ID

 AAA59591.1; CAB56793.1; ACF47606.1; AAB54047.1; AAC60383.1; AAF66137.2; EAL24359.1; EAW83509.1; AAI30421.1; AAB60323.1; AAA59590.1 

Protein Name

 Hepatocyte growth factor receptor 

Protein Synonyms/Alias

 HGF receptor; HGF/SF receptor; Proto-oncogene c-Met; Scatter factor receptor; SF receptor; Tyrosine-protein kinase Met 

Gene Name

 MET 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
977	FLWLKKRKQIKDLGS	ubiquitination	[1]
980	LKKRKQIKDLGSELV	ubiquitination	[1, 2, 3]
1179	LVVLPYMKHGDLRNF	ubiquitination	[1]
1197	ETHNPTVKDLIGFGL	ubiquitination	[1]
1208	GFGLQVAKGMKYLAS	ubiquitination	[1]
1211	LQVAKGMKYLASKKF	ubiquitination	[1]
1237	LDEKFTVKVADFGLA	ubiquitination	[1]
1250	LARDMYDKEYYSVHN	ubiquitination	[1]
1258	EYYSVHNKTGAKLPV	ubiquitination	[1]
1266	TGAKLPVKWMALESL	ubiquitination	[1]

Reference

 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [2] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

Functional Description

 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. 

Sequence Annotation

 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.
 NP_BIND 1084 1092 ATP (By similarity).
 REGION 1212 1390 Interaction with RANBP9.
 REGION 1320 1359 Interaction with MUC20.
 ACT_SITE 1204 1204 Proton acceptor (By similarity).
 BINDING 1110 1110 ATP.
 MOD_RES 977 977 Phosphothreonine.
 MOD_RES 990 990 Phosphoserine.
 MOD_RES 997 997 Phosphoserine.
 MOD_RES 1000 1000 Phosphoserine.
 MOD_RES 1003 1003 Phosphotyrosine.
 MOD_RES 1230 1230 Phosphotyrosine.
 MOD_RES 1234 1234 Phosphotyrosine; by autocatalysis.
 MOD_RES 1235 1235 Phosphotyrosine; by autocatalysis.
 MOD_RES 1289 1289 Phosphothreonine.
 MOD_RES 1349 1349 Phosphotyrosine; by autocatalysis.
 MOD_RES 1356 1356 Phosphotyrosine; by autocatalysis.
 MOD_RES 1365 1365 Phosphotyrosine.
 CARBOHYD 45 45 N-linked (GlcNAc...) (Potential).
 CARBOHYD 106 106 N-linked (GlcNAc...).
 CARBOHYD 149 149 N-linked (GlcNAc...) (Potential).
 CARBOHYD 202 202 N-linked (GlcNAc...) (Potential).
 CARBOHYD 399 399 N-linked (GlcNAc...) (Potential).
 CARBOHYD 405 405 N-linked (GlcNAc...) (Potential).
 CARBOHYD 607 607 N-linked (GlcNAc...) (Potential).
 CARBOHYD 635 635 N-linked (GlcNAc...) (Potential).
 CARBOHYD 785 785 N-linked (GlcNAc...) (Potential).
 CARBOHYD 879 879 N-linked (GlcNAc...) (Potential).
 CARBOHYD 930 930 N-linked (GlcNAc...) (Potential).
 DISULFID 95 101
 DISULFID 98 160
 DISULFID 133 141
 DISULFID 172 175
 DISULFID 298 363
 DISULFID 385 397
 DISULFID 520 538
 DISULFID 526 561
 DISULFID 529 545
 DISULFID 541 551  

Keyword

 3D-structure; Alternative splicing; ATP-binding; Chromosomal rearrangement; Complete proteome; Disease mutation; Disulfide bond; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Proto-oncogene; Receptor; Reference proteome; Repeat; Secreted; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1390 AA 

Protein Sequence

Gene Ontology

 GO:0009925; C:basal plasma membrane; IDA:MGI.
 GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
 GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005008; F:hepatocyte growth factor-activated receptor activity; TAS:ProtInc.
 GO:0000187; P:activation of MAPK activity; IEA:Compara.
 GO:0030534; P:adult behavior; IEA:Compara.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0007420; P:brain development; IEA:Compara.
 GO:0048754; P:branching morphogenesis of an epithelial tube; IMP:UniProtKB.
 GO:0008283; P:cell proliferation; TAS:ProtInc.
 GO:0042593; P:glucose homeostasis; IEA:Compara.
 GO:0001889; P:liver development; IEA:Compara.
 GO:0014812; P:muscle cell migration; IEA:Compara.
 GO:0051450; P:myoblast proliferation; IEA:Compara.
 GO:0014902; P:myotube differentiation; IEA:Compara.
 GO:1901299; P:negative regulation of hydrogen peroxide-mediated programmed cell death; IMP:BHF-UCL.
 GO:0001890; P:placenta development; IEA:Compara.
 GO:0010828; P:positive regulation of glucose transport; IEA:Compara.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:0046777; P:protein autophosphorylation; IEA:Compara.
 GO:0060665; P:regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling; IEA:Compara. 

Interpro

 IPR013783; Ig-like_fold.
 IPR014756; Ig_E-set.
 IPR002909; IPT_TIG_rcpt.
 IPR011009; Kinase-like_dom.
 IPR003659; Plexin-like.
 IPR016201; Plexin-like_fold.
 IPR002165; Plexin_repeat.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001627; Semaphorin/CD100_Ag.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom.
 IPR016244; Tyr_kinase_HGF/MSP_rcpt.
 IPR015943; WD40/YVTN_repeat-like_dom. 

Pfam

 PF07714; Pkinase_Tyr
 PF01437; PSI
 PF01403; Sema
 PF01833; TIG 

SMART

 SM00429; IPT
 SM00423; PSI
 SM00630; Sema
 SM00219; TyrKc 

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS51004; SEMA 

PRINTS

 PR00109; TYRKINASE.