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Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)

 MET_MOUSE               Reviewed;        1379 AA.
P16056; Q62125;
01-APR-1990, integrated into UniProtKB/Swiss-Prot.
01-APR-1990, sequence version 1.
29-SEP-2021, entry version 208.
RecName: Full=Hepatocyte growth factor receptor;
Short=HGF receptor;
EC=2.7.10.1;
AltName: Full=HGF/SF receptor;
AltName: Full=Proto-oncogene c-Met;
AltName: Full=Scatter factor receptor;
Short=SF receptor;
AltName: Full=Tyrosine-protein kinase Met;
Flags: Precursor;
Name=Met;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=2838789;
Chan A.M.-L., King H.W.S., Deakin E.A., Tempest P.R., Hilkens J.,
Kroezen V., Edwards D.R., Wills A.J., Brookes P., Cooper C.S.;
"Characterization of the mouse met proto-oncogene.";
Oncogene 2:593-599(1988).
[2]
NUCLEOTIDE SEQUENCE [MRNA] OF 1199-1270.
PubMed=2482828; DOI=10.1016/0378-1119(89)90465-4;
Wilks A.F., Kurban R.R., Hovens C.M., Ralph S.J.;
"The application of the polymerase chain reaction to cloning members of the
protein tyrosine kinase family.";
Gene 85:67-74(1989).
[3]
NUCLEOTIDE SEQUENCE [MRNA] OF 924-935.
PubMed=8384622; DOI=10.1083/jcb.121.1.145;
Weidner K.M., Sachs M., Birchmeier W.;
"The Met receptor tyrosine kinase transduces motility, proliferation, and
morphogenic signals of scatter factor/hepatocyte growth factor in
epithelial cells.";
J. Cell Biol. 121:145-154(1993).
[4]
FUNCTION IN DEVELOPMENT.
PubMed=7651534; DOI=10.1038/376768a0;
Bladt F., Riethmacher D., Isenmann S., Aguzzi A., Birchmeier C.;
"Essential role for the c-met receptor in the migration of myogenic
precursor cells into the limb bud.";
Nature 376:768-771(1995).
[5]
FUNCTION (MICROBIAL INFECTION), AND PHOSPHORYLATION (MICROBIAL INFECTION).
PubMed=11081636; DOI=10.1016/s0092-8674(00)00141-0;
Shen Y., Naujokas M., Park M., Ireton K.;
"InIB-dependent internalization of Listeria is mediated by the Met receptor
tyrosine kinase.";
Cell 103:501-510(2000).
[6]
INTERACTION WITH INPP5D.
PubMed=11896575; DOI=10.1038/sj.onc.1205224;
Mancini A., Koch A., Wilms R., Tamura T.;
"The SH2-containing inositol 5-phosphatase (SHIP)-1 is implicated in the
control of cell-cell junction and induces dissociation and dispersion of
MDCK cells.";
Oncogene 21:1477-1484(2002).
[7]
INTERACTION WITH MUC20.
PubMed=15314156; DOI=10.1128/mcb.24.17.7456-7468.2004;
Higuchi T., Orita T., Katsuya K., Yamasaki Y., Akiyama K., Li H.,
Yamamoto T., Saito Y., Nakamura M.;
"MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by
binding to a multifunctional docking site of met.";
Mol. Cell. Biol. 24:7456-7468(2004).
[8]
INTERACTION WITH SPSB1; SPSB2 AND SPSB4.
PubMed=16369487; DOI=10.1038/nsmb1034;
Masters S.L., Yao S., Willson T.A., Zhang J.-G., Palmer K.R., Smith B.J.,
Babon J.J., Nicola N.A., Norton R.S., Nicholson S.E.;
"The SPRY domain of SSB-2 adopts a novel fold that presents conserved Par-
4-binding residues.";
Nat. Struct. Mol. Biol. 13:77-84(2006).
[9]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Kidney, and Liver;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and expression.";
Cell 143:1174-1189(2010).
[10]
FUNCTION, AND DEVELOPMENTAL STAGE.
PubMed=26637977; DOI=10.1016/j.ajhg.2015.11.001;
Gray M.J., Kannu P., Sharma S., Neyt C., Zhang D., Paria N., Daniel P.B.,
Whetstone H., Sprenger H.G., Hammerschmidt P., Weng A., Dupuis L.,
Jobling R., Mendoza-Londono R., Dray M., Su P., Wilson M.J., Kapur R.P.,
McCarthy E.F., Alman B.A., Howard A., Somers G.R., Marshall C.R.,
Manners S., Flanagan A.M., Rathjen K.E., Karol L.A., Crawford H.,
Markie D.M., Rios J.J., Wise C.A., Robertson S.P.;
"Mutations preventing regulated exon skipping in MET cause osteofibrous
dysplasia.";
Am. J. Hum. Genet. 97:837-847(2015).
-!- 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
(By similarity). May regulate cortical bone osteogenesis
(PubMed:26637977). {ECO:0000250, ECO:0000269|PubMed:26637977,
ECO:0000269|PubMed:7651534}.
-!- FUNCTION: (Microbial infection) Acts as a receptor for Listeria
monocytogenes internalin InlB, mediating entry of the pathogen into
cells. {ECO:0000305|PubMed:11081636}.
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
-!- 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 (By similarity).
{ECO:0000250}.
-!- SUBUNIT: Heterodimer made of an alpha chain (50 kDa) and a beta chain
(145 kDa) which are disulfide linked (By similarity). Binds PLXNB1 (By
similarity). Interacts when phosphorylated with downstream effectors
including STAT3, PIK3R1, SRC, PCLG1, GRB2 and GAB1 (By similarity).
When phosphorylated at Tyr-1354, interacts with INPPL1/SHIP2 (By
similarity). Interacts with RANBP9 and RANBP10 (By similarity).
Interacts with INPP5D/SHIP1 (PubMed:11896575). Interacts with SPSB1,
SPSB2, SPSB4 and probably SPSB3. SPSB1 binding occurs in the presence
and in the absence of HGF, however HGF treatment has a positive effect
on this interaction (PubMed:16369487). Interacts with MUC20; prevents
interaction with GRB2 and suppresses hepatocyte growth factor-induced
cell proliferation (PubMed:15314156). Interacts with GRB10 (By
similarity). Interacts with PTPN1 and PTPN2. Interacts with HSP90AA1
and HSP90AB1; the interaction suppresses MET kinase activity (By
similarity). {ECO:0000250|UniProtKB:P08581,
ECO:0000269|PubMed:11896575, ECO:0000269|PubMed:15314156,
ECO:0000269|PubMed:16369487}.
-!- SUBUNIT: (Microbial infection) Interacts with L.monocytogenes InlB
(Probable). InlB probably dimerizes upon binding to MET, which
encourages subsequent dimerization of MET (Probable). {ECO:0000305,
ECO:0000305|PubMed:11081636}.
-!- INTERACTION:
P16056; P22682: Cbl; NbExp=2; IntAct=EBI-1798780, EBI-640919;
P16056; P35918: Kdr; NbExp=3; IntAct=EBI-1798780, EBI-1555005;
P16056; P14210: HGF; Xeno; NbExp=2; IntAct=EBI-1798780, EBI-1039104;
-!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
-!- DEVELOPMENTAL STAGE: Low though detectable expression at 10 dpc. From
15 dpc at least until 17 dpc, expression strongly increases. Down-
regulated in the adult. {ECO:0000269|PubMed:26637977}.
-!- DOMAIN: The kinase domain is involved in SPSB1 binding. {ECO:0000250}.
-!- DOMAIN: The beta-propeller Sema domain mediates binding to HGF.
{ECO:0000250}.
-!- PTM: Autophosphorylated in response to ligand binding on Tyr-1232 and
Tyr-1233 in the kinase domain leading to further phosphorylation of
Tyr-1347 and Tyr-1354 in the C-terminal multifunctional docking site.
Dephosphorylated by PTPRJ at Tyr-1347 and Tyr-1363 (By similarity).
Dephosphorylated by PTPN1 and PTPN2 (By similarity). {ECO:0000250}.
-!- 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:0000250|UniProtKB:P08581}.
-!- PTM: (Microbial infection) Tyrosine phosphorylation is stimulated by
L.monocytogenes InlB. {ECO:0000269|PubMed:11081636}.
-!- DISEASE: Note=Activation of Met after rearrangement with the TPR
(translocated promoter) locus of chromosome 1 produces an oncogenic
protein.
-!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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EMBL; Y00671; CAA68680.1; -; mRNA.
EMBL; M33424; AAA40015.1; -; mRNA.
CCDS; CCDS19925.1; -.
PIR; S01254; S01254.
SMR; P16056; -.
IntAct; P16056; 4.
STRING; 10090.ENSMUSP00000111103; -.
BindingDB; P16056; -.
ChEMBL; CHEMBL5585; -.
GlyGen; P16056; 10 sites.
iPTMnet; P16056; -.
PhosphoSitePlus; P16056; -.
SwissPalm; P16056; -.
MaxQB; P16056; -.
PaxDb; P16056; -.
PeptideAtlas; P16056; -.
PRIDE; P16056; -.
ProteomicsDB; 295888; -.
MGI; MGI:96969; Met.
eggNOG; KOG1095; Eukaryota.
eggNOG; KOG3610; Eukaryota.
InParanoid; P16056; -.
PhylomeDB; P16056; -.
BRENDA; 2.7.10.1; 3474.
Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
Reactome; R-MMU-416550; Sema4D mediated inhibition of cell attachment and migration.
Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
Reactome; R-MMU-6806942; MET Receptor Activation.
Reactome; R-MMU-6807004; Negative regulation of MET activity.
Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
Reactome; R-MMU-8851805; MET activates RAS signaling.
Reactome; R-MMU-8851907; MET activates PI3K/AKT signaling.
Reactome; R-MMU-8865999; MET activates PTPN11.
Reactome; R-MMU-8874081; MET activates PTK2 signaling.
Reactome; R-MMU-8875513; MET interacts with TNS proteins.
Reactome; R-MMU-8875555; MET activates RAP1 and RAC1.
Reactome; R-MMU-8875656; MET receptor recycling.
Reactome; R-MMU-8875791; MET activates STAT3.
ChiTaRS; Met; mouse.
PRO; PR:P16056; -.
Proteomes; UP000000589; Unplaced.
RNAct; P16056; protein.
GO; GO:0009925; C:basal plasma membrane; ISO:MGI.
GO; GO:0005737; C:cytoplasm; ISO:MGI.
GO; GO:0030425; C:dendrite; ISO:MGI.
GO; GO:0060076; C:excitatory synapse; ISO:MGI.
GO; GO:0005615; C:extracellular space; ISO:MGI.
GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
GO; GO:0016020; C:membrane; IDA:MGI.
GO; GO:0043005; C:neuron projection; ISO:MGI.
GO; GO:0043025; C:neuronal cell body; ISO:MGI.
GO; GO:0005886; C:plasma membrane; ISO:MGI.
GO; GO:0014069; C:postsynaptic density; ISO:MGI.
GO; GO:0045211; C:postsynaptic membrane; ISO:MGI.
GO; GO:0043235; C:receptor complex; IBA:GO_Central.
GO; GO:0036126; C:sperm flagellum; ISO:MGI.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
GO; GO:0005008; F:hepatocyte growth factor-activated receptor activity; IDA:MGI.
GO; GO:0042802; F:identical protein binding; ISO:MGI.
GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; ISO:MGI.
GO; GO:0043274; F:phospholipase binding; ISO:MGI.
GO; GO:0004672; F:protein kinase activity; IDA:MGI.
GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
GO; GO:0004713; F:protein tyrosine kinase activity; ISO:MGI.
GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
GO; GO:0017154; F:semaphorin receptor activity; IEA:InterPro.
GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
GO; GO:0030534; P:adult behavior; IMP:MGI.
GO; GO:0007420; P:brain development; IMP:MGI.
GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISO:MGI.
GO; GO:0055013; P:cardiac muscle cell development; IMP:MGI.
GO; GO:0060048; P:cardiac muscle contraction; IMP:MGI.
GO; GO:0016477; P:cell migration; IBA:GO_Central.
GO; GO:0007268; P:chemical synaptic transmission; IMP:CACAO.
GO; GO:0001886; P:endothelial cell morphogenesis; ISO:MGI.
GO; GO:0061436; P:establishment of skin barrier; ISO:MGI.
GO; GO:0060079; P:excitatory postsynaptic potential; IMP:BHF-UCL.
GO; GO:0030317; P:flagellated sperm motility; ISO:MGI.
GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; IDA:MGI.
GO; GO:0001889; P:liver development; IMP:MGI.
GO; GO:0050804; P:modulation of chemical synaptic transmission; IMP:BHF-UCL.
GO; GO:0014812; P:muscle cell migration; IMP:MGI.
GO; GO:0007517; P:muscle organ development; IMP:MGI.
GO; GO:0051450; P:myoblast proliferation; IMP:MGI.
GO; GO:0014902; P:myotube differentiation; IMP:MGI.
GO; GO:0010629; P:negative regulation of gene expression; IMP:MGI.
GO; GO:1905098; P:negative regulation of guanyl-nucleotide exchange factor activity; ISO:MGI.
GO; GO:1901299; P:negative regulation of hydrogen peroxide-mediated programmed cell death; ISO:MGI.
GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; ISO:MGI.
GO; GO:0035024; P:negative regulation of Rho protein signal transduction; ISO:MGI.
GO; GO:0051497; P:negative regulation of stress fiber assembly; ISO:MGI.
GO; GO:0070495; P:negative regulation of thrombin-activated receptor signaling pathway; ISO:MGI.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
GO; GO:0071635; P:negative regulation of transforming growth factor beta production; IMP:MGI.
GO; GO:0007399; P:nervous system development; IBA:GO_Central.
GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
GO; GO:0001764; P:neuron migration; ISO:MGI.
GO; GO:0031016; P:pancreas development; IBA:GO_Central.
GO; GO:0006909; P:phagocytosis; IBA:GO_Central.
GO; GO:0001890; P:placenta development; IMP:MGI.
GO; GO:0050918; P:positive chemotaxis; IMP:UniProtKB.
GO; GO:0050775; P:positive regulation of dendrite morphogenesis; ISO:MGI.
GO; GO:0045740; P:positive regulation of DNA replication; ISO:MGI.
GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; ISS:UniProtKB.
GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
GO; GO:0010828; P:positive regulation of glucose transmembrane transport; IMP:MGI.
GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
GO; GO:0043410; P:positive regulation of MAPK cascade; IPI:MGI.
GO; GO:0031116; P:positive regulation of microtubule polymerization; ISO:MGI.
GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISO:MGI.
GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
GO; GO:1900745; P:positive regulation of p38MAPK cascade; IMP:MGI.
GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; ISO:MGI.
GO; GO:0051897; P:positive regulation of protein kinase B signaling; IBA:GO_Central.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:MGI.
GO; GO:0060665; P:regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling; IMP:MGI.
GO; GO:1900407; P:regulation of cellular response to oxidative stress; IMP:MGI.
GO; GO:0032675; P:regulation of interleukin-6 production; IMP:MGI.
GO; GO:0071526; P:semaphorin-plexin signaling pathway; IMP:UniProtKB.
GO; GO:0007519; P:skeletal muscle tissue development; IMP:MGI.
GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
Gene3D; 2.130.10.10; -; 1.
Gene3D; 2.60.40.10; -; 2.
InterPro; IPR013783; Ig-like_fold.
InterPro; IPR014756; Ig_E-set.
InterPro; IPR002909; IPT_dom.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR031148; Plexin.
InterPro; IPR002165; Plexin_repeat.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR016201; PSI.
InterPro; IPR001627; Semap_dom.
InterPro; IPR036352; Semap_dom_sf.
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
InterPro; IPR008266; Tyr_kinase_AS.
InterPro; IPR020635; Tyr_kinase_cat_dom.
InterPro; IPR016244; Tyr_kinase_HGF/MSP_rcpt.
InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
PANTHER; PTHR22625; PTHR22625; 1.
Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
Pfam; PF01437; PSI; 1.
Pfam; PF01403; Sema; 1.
Pfam; PF01833; TIG; 3.
PIRSF; PIRSF000617; TyrPK_HGF-R; 1.
PRINTS; PR00109; TYRKINASE.
SMART; SM00429; IPT; 4.
SMART; SM00423; PSI; 1.
SMART; SM00630; Sema; 1.
SMART; SM00219; TyrKc; 1.
SUPFAM; SSF101912; SSF101912; 1.
SUPFAM; SSF56112; SSF56112; 1.
SUPFAM; SSF81296; SSF81296; 3.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PROSITE; PS51004; SEMA; 1.
1: Evidence at protein level;
ATP-binding; Disulfide bond; Glycoprotein; Kinase; Membrane;
Nucleotide-binding; Phosphoprotein; Proto-oncogene; Receptor;
Reference proteome; Repeat; Signal; Transferase; Transmembrane;
Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
SIGNAL 1..24
/evidence="ECO:0000255"
CHAIN 25..1379
/note="Hepatocyte growth factor receptor"
/id="PRO_0000024441"
TOPO_DOM 25..931
/note="Extracellular"
/evidence="ECO:0000255"
TRANSMEM 932..954
/note="Helical"
/evidence="ECO:0000255"
TOPO_DOM 955..1379
/note="Cytoplasmic"
/evidence="ECO:0000255"
DOMAIN 27..514
/note="Sema"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DOMAIN 562..654
/note="IPT/TIG 1"
DOMAIN 656..738
/note="IPT/TIG 2"
DOMAIN 741..835
/note="IPT/TIG 3"
DOMAIN 1076..1343
/note="Protein kinase"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
NP_BIND 1082..1090
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
REGION 1210..1379
/note="Interaction with RANBP9"
/evidence="ECO:0000250"
REGION 1318..1357
/note="Interaction with MUC20"
/evidence="ECO:0000250"
ACT_SITE 1202
/note="Proton acceptor"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
ECO:0000255|PROSITE-ProRule:PRU10028"
BINDING 1108
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SITE 306..307
/note="Cleavage"
/evidence="ECO:0000255"
SITE 1001
/note="Required for ligand-induced CBL-mediated
ubiquitination"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 964
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 975
/note="Phosphothreonine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 988
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 995
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 998
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1001
/note="Phosphotyrosine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1228
/note="Phosphotyrosine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1232
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1233
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1287
/note="Phosphothreonine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1347
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1354
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1363
/note="Phosphotyrosine"
/evidence="ECO:0000250|UniProtKB:P08581"
CARBOHYD 45
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 106
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 201
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 357
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 398
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 404
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 606
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 634
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 784
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 878
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
DISULFID 95..101
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 98..160
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 133..141
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 171..174
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 297..362
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 384..396
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 519..537
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 525..560
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 528..544
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 540..550
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
CONFLICT 1199
/note="V -> I (in Ref. 2; AAA40015)"
/evidence="ECO:0000305"
CONFLICT 1255
/note="T -> R (in Ref. 2; AAA40015)"
/evidence="ECO:0000305"
CONFLICT 1261
/note="K -> T (in Ref. 2; AAA40015)"
/evidence="ECO:0000305"
CONFLICT 1269..1270
/note="VL -> IP (in Ref. 2; AAA40015)"
/evidence="ECO:0000305"
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


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Pathways :
WP444: Signaling of Hepatocyte Growth Factor Receptor
WP94: Signaling of Hepatocyte Growth Factor Receptor
WP193: Signaling of Hepatocyte Growth Factor Receptor
WP810: Signaling of Hepatocyte Growth Factor Receptor
WP313: Signaling of Hepatocyte Growth Factor Receptor
WP1162: Signaling of Hepatocyte Growth Factor Receptor
WP1046: Signaling of Hepatocyte Growth Factor Receptor
WP1235: Signaling of Hepatocyte Growth Factor Receptor
WP1206: Signaling of Hepatocyte Growth Factor Receptor
WP927: Signaling of Hepatocyte Growth Factor Receptor
WP2292: Chemokine signaling pathway
WP2272: Pathogenic Escherichia coli infection
WP474: Endochondral Ossification
WP2328: Allograft rejection
WP1004: Kit Receptor Signaling Pathway
WP1354: B Cell Receptor Signaling Pathway
WP2079: Serotonin Receptor 2 and STAT3 Signaling
WP878: EPO Receptor Signaling
WP2118: Arrhythmogenic right ventricular cardiomyopathy
WP352: T Cell Receptor Signaling Pathway
WP894: T Cell Receptor Signaling Pathway
WP2355: Corticotropin-releasing hormone
WP733: Serotonin Receptor 2 and STAT3 Signaling
WP1025: B Cell Receptor Signaling Pathway
WP138: Androgen receptor signaling pathway

Related Genes :
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[Met] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[Met] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[MET] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)

Bibliography :
[31819003] Aberrant activation of hepatocyte growth factor/MET signaling promotes β-catenin-mediated prostatic tumorigenesis.
[30930049] Inhibition of the MET Kinase Activity and Cell Growth in MET-Addicted Cancer Cells by Bi-Paratopic Linking.
[30670153] Proteolytic cleavages of MET: the divide-and-conquer strategy of a receptor tyrosine kinase.
[30401749] Activation of hepatocyte growth factor/MET signaling initiates oncogenic transformation and enhances tumor aggressiveness in the murine prostate.
[28827556] Characterization and structural determination of a new anti-MET function-blocking antibody with binding epitope distinct from the ligand binding domain.
[28212658] c-Met expression and activity in urogenital cancers - novel aspects of signal transduction and medical implications.
[28107696] A mini-review of c-Met as a potential therapeutic target in melanoma.
[28061464] MET receptor variant R970C favors calpain-dependent generation of a fragment promoting epithelial cell scattering.
[27864331] Role of Sphingosine Kinase 1 and S1P Transporter Spns2 in HGF-mediated Lamellipodia Formation in Lung Endothelium.
[26712116] Developing Antagonists for the Met-HGF/SF Protein-Protein Interaction Using a Fragment-Based Approach.