MET_MOUSE
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 03-AUG-2022, entry version 211.
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).
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 muscles and neuronal
CC precursors, angiogenesis and kidney formation. In adults, participates
CC in wound healing as well as organ regeneration and tissue remodeling.
CC Promotes also differentiation and proliferation of hematopoietic cells
CC (By similarity). May regulate cortical bone osteogenesis
CC (PubMed:26637977). {ECO:0000250, ECO:0000269|PubMed:26637977,
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). {ECO:0000250|UniProtKB:P08581,
CC ECO:0000269|PubMed:11896575, ECO:0000269|PubMed:15314156,
CC 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: (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 GlyGen; P16056; 10 sites.
DR iPTMnet; P16056; -.
DR PhosphoSitePlus; P16056; -.
DR SwissPalm; P16056; -.
DR MaxQB; P16056; -.
DR PaxDb; P16056; -.
DR PeptideAtlas; P16056; -.
DR PRIDE; P16056; -.
DR ProteomicsDB; 295888; -.
DR ABCD; P16056; 3 sequenced antibodies.
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:0005737; C:cytoplasm; 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:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0014069; C:postsynaptic density; 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: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:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
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:1905098; P:negative regulation of guanyl-nucleotide exchange factor activity; ISO: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: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:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
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:0051897; P:positive regulation of protein kinase B signaling; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; IDA: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 Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
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; PTHR22625; 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; SSF101912; SSF101912; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF81296; SSF81296; 3.
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 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 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 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
