ID MET_MOUSE Reviewed; 1379 AA. AC P16056; Q62125; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 1. DT 24-JAN-2024, entry version 217. DE RecName: Full=Hepatocyte growth factor receptor; DE Short=HGF receptor; DE EC=2.7.10.1; DE AltName: Full=HGF/SF receptor; DE AltName: Full=Proto-oncogene c-Met; DE AltName: Full=Scatter factor receptor; DE Short=SF receptor; DE AltName: Full=Tyrosine-protein kinase Met; DE Flags: Precursor; GN Name=Met; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2838789; RA Chan A.M.-L., King H.W.S., Deakin E.A., Tempest P.R., Hilkens J., RA Kroezen V., Edwards D.R., Wills A.J., Brookes P., Cooper C.S.; RT "Characterization of the mouse met proto-oncogene."; RL Oncogene 2:593-599(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1199-1270. RX PubMed=2482828; DOI=10.1016/0378-1119(89)90465-4; RA Wilks A.F., Kurban R.R., Hovens C.M., Ralph S.J.; RT "The application of the polymerase chain reaction to cloning members of the RT protein tyrosine kinase family."; RL Gene 85:67-74(1989). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 924-935. RX PubMed=8384622; DOI=10.1083/jcb.121.1.145; RA Weidner K.M., Sachs M., Birchmeier W.; RT "The Met receptor tyrosine kinase transduces motility, proliferation, and RT morphogenic signals of scatter factor/hepatocyte growth factor in RT epithelial cells."; RL J. Cell Biol. 121:145-154(1993). RN [4] RP FUNCTION IN DEVELOPMENT. RX PubMed=7651534; DOI=10.1038/376768a0; RA Bladt F., Riethmacher D., Isenmann S., Aguzzi A., Birchmeier C.; RT "Essential role for the c-met receptor in the migration of myogenic RT precursor cells into the limb bud."; RL Nature 376:768-771(1995). RN [5] RP FUNCTION (MICROBIAL INFECTION), AND PHOSPHORYLATION (MICROBIAL INFECTION). RX PubMed=11081636; DOI=10.1016/s0092-8674(00)00141-0; RA Shen Y., Naujokas M., Park M., Ireton K.; RT "InIB-dependent internalization of Listeria is mediated by the Met receptor RT tyrosine kinase."; RL Cell 103:501-510(2000). RN [6] RP INTERACTION WITH INPP5D. RX PubMed=11896575; DOI=10.1038/sj.onc.1205224; RA Mancini A., Koch A., Wilms R., Tamura T.; RT "The SH2-containing inositol 5-phosphatase (SHIP)-1 is implicated in the RT control of cell-cell junction and induces dissociation and dispersion of RT MDCK cells."; RL Oncogene 21:1477-1484(2002). RN [7] RP INTERACTION WITH MUC20. RX PubMed=15314156; DOI=10.1128/mcb.24.17.7456-7468.2004; RA Higuchi T., Orita T., Katsuya K., Yamasaki Y., Akiyama K., Li H., RA Yamamoto T., Saito Y., Nakamura M.; RT "MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by RT binding to a multifunctional docking site of met."; RL Mol. Cell. Biol. 24:7456-7468(2004). RN [8] RP INTERACTION WITH SPSB1; SPSB2 AND SPSB4. RX PubMed=16369487; DOI=10.1038/nsmb1034; RA Masters S.L., Yao S., Willson T.A., Zhang J.-G., Palmer K.R., Smith B.J., RA Babon J.J., Nicola N.A., Norton R.S., Nicholson S.E.; RT "The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par- RT 4-binding residues."; RL Nat. Struct. Mol. Biol. 13:77-84(2006). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Kidney, and Liver; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [10] RP FUNCTION, AND DEVELOPMENTAL STAGE. RX PubMed=26637977; DOI=10.1016/j.ajhg.2015.11.001; RA Gray M.J., Kannu P., Sharma S., Neyt C., Zhang D., Paria N., Daniel P.B., RA Whetstone H., Sprenger H.G., Hammerschmidt P., Weng A., Dupuis L., RA Jobling R., Mendoza-Londono R., Dray M., Su P., Wilson M.J., Kapur R.P., RA McCarthy E.F., Alman B.A., Howard A., Somers G.R., Marshall C.R., RA Manners S., Flanagan A.M., Rathjen K.E., Karol L.A., Crawford H., RA Markie D.M., Rios J.J., Wise C.A., Robertson S.P.; RT "Mutations preventing regulated exon skipping in MET cause osteofibrous RT dysplasia."; RL Am. J. Hum. Genet. 97:837-847(2015). RN [11] RP MUTAGENESIS OF TYR-1232, AND FUNCTION. RX PubMed=30777867; DOI=10.15252/emmm.201809709; RA Zhou H., Lian C., Wang T., Yang X., Xu C., Su D., Zheng S., Huang X., RA Liao Z., Zhou T., Qiu X., Chen Y., Gao B., Li Y., Wang X., You G., Fu Q., RA Gurnett C., Huang D., Su P.; RT "MET mutation causes muscular dysplasia and arthrogryposis."; RL EMBO Mol. Med. 11:0-0(2019). CC -!- FUNCTION: Receptor tyrosine kinase that transduces signals from the CC extracellular matrix into the cytoplasm by binding to hepatocyte growth CC factor/HGF ligand. Regulates many physiological processes including CC proliferation, scattering, morphogenesis and survival. Ligand binding CC at the cell surface induces autophosphorylation of MET on its CC intracellular domain that provides docking sites for downstream CC signaling molecules. Following activation by ligand, interacts with the CC PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. CC Recruitment of these downstream effectors by MET leads to the CC activation of several signaling cascades including the RAS-ERK, PI3 CC kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with CC the morphogenetic effects while PI3K/AKT coordinates prosurvival CC effects. During embryonic development, MET signaling plays a role in CC gastrulation, development and migration of neuronal precursors, CC angiogenesis and kidney formation. During skeletal muscle development, CC it is crucial for the migration of muscle progenitor cells and for the CC proliferation of secondary myoblasts (PubMed:30777867). In adults, CC participates in wound healing as well as organ regeneration and tissue CC remodeling. Promotes also differentiation and proliferation of CC hematopoietic cells (By similarity). May regulate cortical bone CC osteogenesis (PubMed:26637977). {ECO:0000250, CC ECO:0000269|PubMed:26637977, ECO:0000269|PubMed:30777867, CC ECO:0000269|PubMed:7651534}. CC -!- FUNCTION: (Microbial infection) Acts as a receptor for Listeria CC monocytogenes internalin InlB, mediating entry of the pathogen into CC cells. {ECO:0000305|PubMed:11081636}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028}; CC -!- ACTIVITY REGULATION: In its inactive state, the C-terminal tail CC interacts with the catalytic domain and inhibits the kinase activity. CC Upon ligand binding, the C-terminal tail is displaced and becomes CC phosphorylated, thus increasing the kinase activity (By similarity). CC {ECO:0000250}. CC -!- SUBUNIT: Heterodimer made of an alpha chain (50 kDa) and a beta chain CC (145 kDa) which are disulfide linked (By similarity). Binds PLXNB1 (By CC similarity). Interacts when phosphorylated with downstream effectors CC including STAT3, PIK3R1, SRC, PCLG1, GRB2 and GAB1 (By similarity). CC When phosphorylated at Tyr-1354, interacts with INPPL1/SHIP2 (By CC similarity). Interacts with RANBP9 and RANBP10 (By similarity). CC Interacts with INPP5D/SHIP1 (PubMed:11896575). Interacts with SPSB1, CC SPSB2, SPSB4 and probably SPSB3. SPSB1 binding occurs in the presence CC and in the absence of HGF, however HGF treatment has a positive effect CC on this interaction (PubMed:16369487). Interacts with MUC20; prevents CC interaction with GRB2 and suppresses hepatocyte growth factor-induced CC cell proliferation (PubMed:15314156). Interacts with GRB10 (By CC similarity). Interacts with PTPN1 and PTPN2. Interacts with HSP90AA1 CC and HSP90AB1; the interaction suppresses MET kinase activity (By CC similarity). Interacts with tensin TNS3 (By similarity). Interacts CC (when phosphorylated) with tensin TNS4 (via SH2 domain); the CC interaction increases MET protein stability by inhibiting MET CC endocytosis and subsequent lysosomal degradation (By similarity). CC {ECO:0000250|UniProtKB:P08581, ECO:0000269|PubMed:11896575, CC ECO:0000269|PubMed:15314156, ECO:0000269|PubMed:16369487}. CC -!- SUBUNIT: (Microbial infection) Interacts with L.monocytogenes InlB CC (Probable). InlB probably dimerizes upon binding to MET, which CC encourages subsequent dimerization of MET (Probable). {ECO:0000305, CC ECO:0000305|PubMed:11081636}. CC -!- INTERACTION: CC P16056; P22682: Cbl; NbExp=2; IntAct=EBI-1798780, EBI-640919; CC P16056; Q3UVX5: Grm5; NbExp=3; IntAct=EBI-1798780, EBI-8795045; CC P16056; P35918: Kdr; NbExp=3; IntAct=EBI-1798780, EBI-1555005; CC P16056; Q6VNS1: Ntrk3; NbExp=5; IntAct=EBI-1798780, EBI-16744951; CC P16056; F6SEU4: Syngap1; NbExp=3; IntAct=EBI-1798780, EBI-5797569; CC P16056; P14210: HGF; Xeno; NbExp=2; IntAct=EBI-1798780, EBI-1039104; CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. CC -!- DEVELOPMENTAL STAGE: Low though detectable expression at 10 dpc. From CC 15 dpc at least until 17 dpc, expression strongly increases. Down- CC regulated in the adult. {ECO:0000269|PubMed:26637977}. CC -!- DOMAIN: The kinase domain is involved in SPSB1 binding. {ECO:0000250}. CC -!- DOMAIN: The beta-propeller Sema domain mediates binding to HGF. CC {ECO:0000250}. CC -!- PTM: Autophosphorylated in response to ligand binding on Tyr-1232 and CC Tyr-1233 in the kinase domain leading to further phosphorylation of CC Tyr-1347 and Tyr-1354 in the C-terminal multifunctional docking site. CC Dephosphorylated by PTPRJ at Tyr-1347 and Tyr-1363 (By similarity). CC Dephosphorylated by PTPN1 and PTPN2 (By similarity). {ECO:0000250}. CC -!- PTM: Ubiquitinated. Ubiquitination by CBL regulates MET endocytosis, CC resulting in decreasing plasma membrane receptor abundance, and in CC endosomal degradation and/or recycling of internalized receptors. CC {ECO:0000250|UniProtKB:P08581}. CC -!- PTM: O-mannosylation of IPT/TIG domains by TMEM260 is required for CC protein maturation. O-mannosylated residues are composed of single CC mannose glycans that are not elongated or modified. CC {ECO:0000250|UniProtKB:P08581}. CC -!- PTM: (Microbial infection) Tyrosine phosphorylation is stimulated by CC L.monocytogenes InlB. {ECO:0000269|PubMed:11081636}. CC -!- DISEASE: Note=Activation of Met after rearrangement with the TPR CC (translocated promoter) locus of chromosome 1 produces an oncogenic CC protein. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Y00671; CAA68680.1; -; mRNA. DR EMBL; M33424; AAA40015.1; -; mRNA. DR CCDS; CCDS19925.1; -. DR PIR; S01254; S01254. DR AlphaFoldDB; P16056; -. DR SASBDB; P16056; -. DR SMR; P16056; -. DR IntAct; P16056; 146. DR MINT; P16056; -. DR STRING; 10090.ENSMUSP00000111103; -. DR BindingDB; P16056; -. DR ChEMBL; CHEMBL5585; -. DR GlyCosmos; P16056; 10 sites, No reported glycans. DR GlyGen; P16056; 10 sites. DR iPTMnet; P16056; -. DR PhosphoSitePlus; P16056; -. DR SwissPalm; P16056; -. DR MaxQB; P16056; -. DR PaxDb; 10090-ENSMUSP00000111103; -. DR PeptideAtlas; P16056; -. DR ProteomicsDB; 295888; -. DR Pumba; P16056; -. DR ABCD; P16056; 3 sequenced antibodies. DR AGR; MGI:96969; -. DR MGI; MGI:96969; Met. DR eggNOG; KOG1095; Eukaryota. DR eggNOG; KOG3610; Eukaryota. DR InParanoid; P16056; -. DR PhylomeDB; P16056; -. DR BRENDA; 2.7.10.1; 3474. DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling. DR Reactome; R-MMU-416550; Sema4D mediated inhibition of cell attachment and migration. DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade. DR Reactome; R-MMU-6806942; MET Receptor Activation. DR Reactome; R-MMU-6807004; Negative regulation of MET activity. DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR Reactome; R-MMU-8851805; MET activates RAS signaling. DR Reactome; R-MMU-8851907; MET activates PI3K/AKT signaling. DR Reactome; R-MMU-8865999; MET activates PTPN11. DR Reactome; R-MMU-8874081; MET activates PTK2 signaling. DR Reactome; R-MMU-8875513; MET interacts with TNS proteins. DR Reactome; R-MMU-8875555; MET activates RAP1 and RAC1. DR Reactome; R-MMU-8875656; MET receptor recycling. DR Reactome; R-MMU-8875791; MET activates STAT3. DR Reactome; R-MMU-9734091; Drug-mediated inhibition of MET activation. DR ChiTaRS; Met; mouse. DR PRO; PR:P16056; -. DR Proteomes; UP000000589; Unplaced. DR RNAct; P16056; Protein. DR GO; GO:0009925; C:basal plasma membrane; ISO:MGI. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0060076; C:excitatory synapse; ISO:MGI. DR GO; GO:0005615; C:extracellular space; ISO:MGI. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0043025; C:neuronal cell body; ISO:MGI. DR GO; GO:0045211; C:postsynaptic membrane; ISO:MGI. DR GO; GO:0043235; C:receptor complex; IBA:GO_Central. DR GO; GO:0036126; C:sperm flagellum; ISO:MGI. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI. DR GO; GO:0005008; F:hepatocyte growth factor receptor activity; IDA:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0140677; F:molecular function activator activity; ISO:MGI. DR GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISO:MGI. DR GO; GO:0043274; F:phospholipase binding; ISO:MGI. DR GO; GO:0004672; F:protein kinase activity; IDA:MGI. DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI. DR GO; GO:0004713; F:protein tyrosine kinase activity; ISO:MGI. DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI. DR GO; GO:0017154; F:semaphorin receptor activity; IEA:InterPro. DR GO; GO:0030534; P:adult behavior; IMP:MGI. DR GO; GO:0007420; P:brain development; IMP:MGI. DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISO:MGI. DR GO; GO:0055013; P:cardiac muscle cell development; IMP:MGI. DR GO; GO:0060048; P:cardiac muscle contraction; IMP:MGI. DR GO; GO:0016477; P:cell migration; IBA:GO_Central. DR GO; GO:0007268; P:chemical synaptic transmission; IMP:CACAO. DR GO; GO:0001886; P:endothelial cell morphogenesis; ISO:MGI. DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI. DR GO; GO:0061436; P:establishment of skin barrier; ISO:MGI. DR GO; GO:0060079; P:excitatory postsynaptic potential; IMP:BHF-UCL. DR GO; GO:0030317; P:flagellated sperm motility; ISO:MGI. DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI. DR GO; GO:1904659; P:glucose transmembrane transport; IMP:MGI. DR GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; IDA:MGI. DR GO; GO:0001889; P:liver development; IMP:MGI. DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IMP:BHF-UCL. DR GO; GO:0014812; P:muscle cell migration; IMP:MGI. DR GO; GO:0007517; P:muscle organ development; IMP:MGI. DR GO; GO:0051450; P:myoblast proliferation; IMP:MGI. DR GO; GO:0014902; P:myotube differentiation; IMP:MGI. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI. DR GO; GO:1901299; P:negative regulation of hydrogen peroxide-mediated programmed cell death; ISO:MGI. DR GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISO:MGI. DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; ISO:MGI. DR GO; GO:0051497; P:negative regulation of stress fiber assembly; ISO:MGI. DR GO; GO:0070495; P:negative regulation of thrombin-activated receptor signaling pathway; ISO:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0071635; P:negative regulation of transforming growth factor beta production; IMP:MGI. DR GO; GO:0007399; P:nervous system development; IBA:GO_Central. DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central. DR GO; GO:0001764; P:neuron migration; ISO:MGI. DR GO; GO:0031016; P:pancreas development; IBA:GO_Central. DR GO; GO:0006909; P:phagocytosis; IBA:GO_Central. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0001890; P:placenta development; IMP:MGI. DR GO; GO:0050918; P:positive chemotaxis; IMP:UniProtKB. DR GO; GO:0050775; P:positive regulation of dendrite morphogenesis; ISO:MGI. DR GO; GO:0045740; P:positive regulation of DNA replication; ISO:MGI. DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; ISS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:0010828; P:positive regulation of glucose transmembrane transport; IMP:MGI. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IPI:MGI. DR GO; GO:0031116; P:positive regulation of microtubule polymerization; ISO:MGI. DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISO:MGI. DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI. DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IMP:MGI. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI. DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:MGI. DR GO; GO:0060665; P:regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling; IMP:MGI. DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; IMP:MGI. DR GO; GO:0032675; P:regulation of interleukin-6 production; IMP:MGI. DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; IMP:UniProtKB. DR GO; GO:0007519; P:skeletal muscle tissue development; IMP:MGI. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR CDD; cd00603; IPT_PCSR; 1. DR CDD; cd01180; IPT_plexin_repeat1; 1. DR CDD; cd01179; IPT_plexin_repeat2; 1. DR CDD; cd05058; PTKc_Met_Ron; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR014756; Ig_E-set. DR InterPro; IPR002909; IPT_dom. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR031148; Plexin. DR InterPro; IPR002165; Plexin_repeat. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR016201; PSI. DR InterPro; IPR001627; Semap_dom. DR InterPro; IPR036352; Semap_dom_sf. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR016244; Tyr_kinase_HGF/MSP_rcpt. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR PANTHER; PTHR22625:SF61; HEPATOCYTE GROWTH FACTOR RECEPTOR; 1. DR PANTHER; PTHR22625; PLEXIN; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF01437; PSI; 1. DR Pfam; PF01403; Sema; 1. DR Pfam; PF01833; TIG; 3. DR PIRSF; PIRSF000617; TyrPK_HGF-R; 1. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00429; IPT; 4. DR SMART; SM00423; PSI; 1. DR SMART; SM00630; Sema; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF81296; E set domains; 3. DR SUPFAM; SSF103575; Plexin repeat; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF101912; Sema domain; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS51004; SEMA; 1. PE 1: Evidence at protein level; KW ATP-binding; Disulfide bond; Glycoprotein; Kinase; Membrane; KW Nucleotide-binding; Phosphoprotein; Proto-oncogene; Receptor; KW Reference proteome; Repeat; Signal; Transferase; Transmembrane; KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT CHAIN 25..1379 FT /note="Hepatocyte growth factor receptor" FT /id="PRO_0000024441" FT TOPO_DOM 25..931 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 932..954 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 955..1379 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 27..514 FT /note="Sema" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT DOMAIN 562..654 FT /note="IPT/TIG 1" FT DOMAIN 656..738 FT /note="IPT/TIG 2" FT DOMAIN 741..835 FT /note="IPT/TIG 3" FT DOMAIN 1076..1343 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1210..1379 FT /note="Interaction with RANBP9" FT /evidence="ECO:0000250" FT REGION 1318..1357 FT /note="Interaction with MUC20" FT /evidence="ECO:0000250" FT ACT_SITE 1202 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 1082..1090 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 1108 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT SITE 306..307 FT /note="Cleavage" FT /evidence="ECO:0000255" FT SITE 1001 FT /note="Required for ligand-induced CBL-mediated FT ubiquitination" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 964 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 975 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 988 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 995 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 998 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 1001 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 1228 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 1232 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 1233 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 1287 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 1347 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 1354 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P08581" FT MOD_RES 1363 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P08581" FT CARBOHYD 45 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 106 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 201 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 357 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 398 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 404 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 581 FT /note="O-linked (Man) threonine" FT /evidence="ECO:0000250|UniProtKB:P08581" FT CARBOHYD 606 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 634 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 675 FT /note="O-linked (Man) threonine" FT /evidence="ECO:0000250|UniProtKB:P08581" FT CARBOHYD 760 FT /note="O-linked (Man) threonine" FT /evidence="ECO:0000250|UniProtKB:P08581" FT CARBOHYD 784 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 878 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 95..101 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT DISULFID 98..160 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT DISULFID 133..141 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT DISULFID 171..174 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT DISULFID 297..362 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT DISULFID 384..396 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT DISULFID 519..537 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT DISULFID 525..560 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT DISULFID 528..544 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT DISULFID 540..550 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00352" FT MUTAGEN 1232 FT /note="Y->C: Mice heterozygous for the mutation show FT reduced number of myofibers in appendicular and axial FT muscles, defective migration of muscle progenitor cells and FT impaired proliferation of secondary myoblasts." FT /evidence="ECO:0000269|PubMed:30777867" FT CONFLICT 1199 FT /note="V -> I (in Ref. 2; AAA40015)" FT /evidence="ECO:0000305" FT CONFLICT 1255 FT /note="T -> R (in Ref. 2; AAA40015)" FT /evidence="ECO:0000305" FT CONFLICT 1261 FT /note="K -> T (in Ref. 2; AAA40015)" FT /evidence="ECO:0000305" FT CONFLICT 1269..1270 FT /note="VL -> IP (in Ref. 2; AAA40015)" FT /evidence="ECO:0000305" SQ SEQUENCE 1379 AA; 153549 MW; FC5CC87FDD8ADED8 CRC64; MKAPTVLAPG ILVLLLSLVQ RSHGECKEAL VKSEMNVNMK YQLPNFTAET PIQNVVLHGH HIYLGATNYI YVLNDKDLQK VSEFKTGPVL EHPDCLPCRD CSSKANSSGG VWKDNINMAL LVDTYYDDQL ISCGSVNRGT CQRHVLPPDN SADIQSEVHC MFSPEEESGQ CPDCVVSALG AKVLLSEKDR FINFFVGNTI NSSYPPGYSL HSISVRRLKE TQDGFKFLTD QSYIDVLPEF LDSYPIKYIH AFESNHFIYF LTVQKETLDA QTFHTRIIRF CSVDSGLHSY MEMPLECILT EKRRKRSTRE EVFNILQAAY VSKPGANLAK QIGASPSDDI LFGVFAQSKP DSAEPVNRSA VCAFPIKYVN DFFNKIVNKN NVRCLQHFYG PNHEHCFNRT LLRNSSGCEA RSDEYRTEFT TALQRVDLFM GRLNQVLLTS ISTFIKGDLT IANLGTSEGR FMQVVLSRTA HLTPHVNFLL DSHPVSPEVI VEHPSNQNGY TLVVTGKKIT KIPLNGLGCG HFQSCSQCLS APYFIQCGWC HNQCVRFDEC PSGTWTQEIC LPAVYKVFPT SAPLEGGTVL TICGWDFGFR KNNKFDLRKT KVLLGNESCT LTLSESTTNT LKCTVGPAMS EHFNVSVIIS NSRETTQYSA FSYVDPVITS ISPRYGPQAG GTLLTLTGKY LNSGNSRHIS IGGKTCTLKS VSDSILECYT PAQTTSDEFP VKLKIDLANR ETSSFSYRED PVVYEIHPTK SFISGGSTIT GIGKTLNSVS LPKLVIDVHE VGVNYTVACQ HRSNSEIICC TTPSLKQLGL QLPLKTKAFF LLDGILSKHF DLTYVHNPVF EPFEKPVMIS MGNENVVEIK GNNIDPEAVK GEVLKVGNQS CESLHWHSGA VLCTVPSDLL KLNSELNIEW KQAVSSTVLG KVIVQPDQNF AGLIIGAVSI SVVVLLLSGL FLWMRKRKHK DLGSELVRYD ARVHTPHLDR LVSARSVSPT TEMVSNESVD YRATFPEDQF PNSSQNGACR QVQYPLTDLS PILTSGDSDI SSPLLQNTVH IDLSALNPEL VQAVQHVVIG PSSLIVHFNE VIGRGHFGCV YHGTLLDNDG KKIHCAVKSL NRITDIEEVS QFLTEGIIMK DFSHPNVLSL LGICLRSEGS PLVVLPYMKH GDLRNFIRNE THNPTVKDLI GFGLQVAKGM KYLASKKFVH RDLAARNCML DEKFTVKVAD FGLARDMYDK EYYSVHNKTG AKLPVKWMAL ESLQTQKFTT KSDVWSFGVL LWELMTRGAP PYPDVNTFDI TIYLLQGRRL LQPEYCPDAL YEVMLKCWHP KAEMRPSFSE LVSRISSIFS TFIGEHYVHV NATYVNVKCV APYPSLLPSQ DNIDGEGNT //