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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_RAT                 Reviewed;        1382 AA.
P97523; P97579; Q63119; Q63964;
27-APR-2001, integrated into UniProtKB/Swiss-Prot.
01-MAY-1997, sequence version 1.
29-SEP-2021, entry version 183.
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;
Rattus norvegicus (Rat).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
Murinae; Rattus.
NCBI_TaxID=10116;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
STRAIN=Sprague-Dawley; TISSUE=Liver;
PubMed=9271668; DOI=10.1007/s003359900533;
Wallenius V.R., Rawet H., Skrtic S., Helou K., Qiu Y., Levan G., Ekberg S.,
Carlsson B., Isaksson O.G.P., Nakamura T., Jansson J.-O.;
"Chromosomal localization of rat hepatocyte growth factor (Hgf) and HGF
receptor (Met) and characterization of HGF receptor cDNA.";
Mamm. Genome 8:661-667(1997).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
STRAIN=Sprague-Dawley; TISSUE=Kidney;
PubMed=8853431; DOI=10.1152/ajprenal.1996.271.3.f679;
Liu Y., Tolbert E.M., Sun A.M., Dworkin L.D.;
"Primary structure of rat HGF receptor and induced expression in glomerular
mesangial cells.";
Am. J. Physiol. 271:F679-F688(1996).
[3]
NUCLEOTIDE SEQUENCE [MRNA] OF 364-495.
STRAIN=Sprague-Dawley; TISSUE=Gastric mucosa;
PubMed=8166728; DOI=10.1006/bbrc.1994.1481;
Tsujii M., Kawano S., Tsuji S., Ito T., Hayashi N., Horimoto M., Mita E.,
Nagano K., Masuda E., Hayashi N., Fusamoto H., Kamada T.;
"Increased expression of c-met messenger RNA following acute gastric injury
in rats.";
Biochem. Biophys. Res. Commun. 200:536-541(1994).
[4]
NUCLEOTIDE SEQUENCE [MRNA] OF 851-1002.
TISSUE=Intestine;
PubMed=7628535; DOI=10.1006/excr.1995.1220;
Pepper M.S., Soriano J.V., Menoud P.-A., Sappino A.-P., Orci L.,
Montesano R.;
"Modulation of hepatocyte growth factor and c-met in the rat mammary gland
during pregnancy, lactation, and involution.";
Exp. Cell Res. 219:204-210(1995).
[5]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1129-1267.
Kikuchi Y.;
Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
-!- 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). {ECO:0000250}.
-!- 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. Binds PLXNB1. Interacts when
phosphorylated with downstream effectors including STAT3, PIK3R1, SRC,
PCLG1, GRB2 and GAB1. Interacts with SPSB1, SPSB2 and SPSB4. Interacts
with INPP5D/SHIP1. When phosphorylated at Tyr-1357, interacts with
INPPL1/SHIP2. Interacts with RANBP9 and RANBP10, as well as SPSB1,
SPSB2, SPSB3 and SPSB4. SPSB1 binding occurs in the presence and in the
absence of HGF, however HGF treatment has a positive effect on this
interaction. Interacts with MUC20; prevents interaction with GRB2 and
suppresses hepatocyte growth factor-induced cell proliferation.
Interacts with GRB10. Interacts with PTPN1 and PTPN2. Interacts with
HSP90AA1 and HSP90AB1; the interaction suppresses MET kinase activity.
{ECO:0000250|UniProtKB:P08581, ECO:0000250|UniProtKB:P16056}.
-!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
-!- TISSUE SPECIFICITY: Expressed at highest levels in lung, liver and
kidney, also expressed in stomach, intestine, spleen, testis and brain.
Not expressed in heart or muscle.
-!- DEVELOPMENTAL STAGE: Expression is down-regulated during pregnancy and
is virtually undetectable during lactation. Expression progressively
increases post-lactation.
-!- INDUCTION: By interleukin-6 and acute acid-induced gastric injury.
Inhibited by prolactin.
-!- 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-1235 and
Tyr-1236 in the kinase domain leading to further phosphorylation of
Tyr-1350 and Tyr-1357 in the C-terminal multifunctional docking site.
Dephosphorylated by PTPRJ at Tyr-1350 and Tyr-1366. Dephosphorylated by
PTPN1 and PTPN2 (By similarity). {ECO:0000250}.
-!- PTM: Ubiquitinated. Ubiquitination by CBL regulates the receptor
stability and activity through proteasomal degradation (By similarity).
{ECO:0000250}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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EMBL; X96786; CAA65582.1; -; mRNA.
EMBL; U65007; AAB19189.1; -; mRNA.
EMBL; S69881; AAB30575.1; -; mRNA.
EMBL; Z46374; CAA86508.1; -; mRNA.
EMBL; AB012281; BAA28171.1; -; Genomic_DNA.
PIR; PC2131; PC2131.
RefSeq; NP_113705.1; NM_031517.2.
SMR; P97523; -.
STRING; 10116.ENSRNOP00000009662; -.
GlyGen; P97523; 10 sites.
iPTMnet; P97523; -.
PhosphoSitePlus; P97523; -.
PaxDb; P97523; -.
PRIDE; P97523; -.
GeneID; 24553; -.
KEGG; rno:24553; -.
UCSC; RGD:3082; rat.
CTD; 4233; -.
RGD; 3082; Met.
eggNOG; KOG1095; Eukaryota.
eggNOG; KOG3610; Eukaryota.
InParanoid; P97523; -.
OrthoDB; 408584at2759; -.
PhylomeDB; P97523; -.
BRENDA; 2.7.10.1; 5301.
Reactome; R-RNO-1257604; PIP3 activates AKT signaling.
Reactome; R-RNO-416550; Sema4D mediated inhibition of cell attachment and migration.
Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
Reactome; R-RNO-6806942; MET Receptor Activation.
Reactome; R-RNO-6807004; Negative regulation of MET activity.
Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
Reactome; R-RNO-8851805; MET activates RAS signaling.
Reactome; R-RNO-8851907; MET activates PI3K/AKT signaling.
Reactome; R-RNO-8865999; MET activates PTPN11.
Reactome; R-RNO-8874081; MET activates PTK2 signaling.
Reactome; R-RNO-8875513; MET interacts with TNS proteins.
Reactome; R-RNO-8875555; MET activates RAP1 and RAC1.
Reactome; R-RNO-8875656; MET receptor recycling.
Reactome; R-RNO-8875791; MET activates STAT3.
PRO; PR:P97523; -.
Proteomes; UP000002494; Unplaced.
GO; GO:0009925; C:basal plasma membrane; ISO:RGD.
GO; GO:0005737; C:cytoplasm; IDA:RGD.
GO; GO:0030425; C:dendrite; IDA:RGD.
GO; GO:0060076; C:excitatory synapse; IDA:RGD.
GO; GO:0005615; C:extracellular space; IDA:RGD.
GO; GO:0016021; C:integral component of membrane; NAS:RGD.
GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
GO; GO:0016020; C:membrane; ISO:RGD.
GO; GO:0043005; C:neuron projection; IDA:RGD.
GO; GO:0043025; C:neuronal cell body; IDA:RGD.
GO; GO:0014069; C:postsynaptic density; IDA:RGD.
GO; GO:0045211; C:postsynaptic membrane; IDA:RGD.
GO; GO:0043235; C:receptor complex; IBA:GO_Central.
GO; GO:0036126; C:sperm flagellum; IDA:RGD.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0008013; F:beta-catenin binding; IPI:RGD.
GO; GO:0005008; F:hepatocyte growth factor-activated receptor activity; IMP:RGD.
GO; GO:0042802; F:identical protein binding; ISO:RGD.
GO; GO:0043548; F:phosphatidylinositol 3-kinase binding; IDA:RGD.
GO; GO:0043274; F:phospholipase binding; IPI:RGD.
GO; GO:0004672; F:protein kinase activity; ISO:RGD.
GO; GO:0019903; F:protein phosphatase binding; ISO:RGD.
GO; GO:0004713; F:protein tyrosine kinase activity; IDA:RGD.
GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
GO; GO:0017154; F:semaphorin receptor activity; IEA:InterPro.
GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
GO; GO:0000187; P:activation of MAPK activity; ISO:RGD.
GO; GO:0030534; P:adult behavior; ISO:RGD.
GO; GO:0007420; P:brain development; IEP:RGD.
GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISO:RGD.
GO; GO:0055013; P:cardiac muscle cell development; ISO:RGD.
GO; GO:0060048; P:cardiac muscle contraction; ISO:RGD.
GO; GO:0016477; P:cell migration; IBA:GO_Central.
GO; GO:0071243; P:cellular response to arsenic-containing substance; IEP:RGD.
GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
GO; GO:0071363; P:cellular response to growth factor stimulus; IEP:RGD.
GO; GO:0071241; P:cellular response to inorganic substance; IEP:RGD.
GO; GO:0071354; P:cellular response to interleukin-6; IEP:RGD.
GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEP:RGD.
GO; GO:0021953; P:central nervous system neuron differentiation; IEP:RGD.
GO; GO:0007268; P:chemical synaptic transmission; ISO:RGD.
GO; GO:0001886; P:endothelial cell morphogenesis; ISO:RGD.
GO; GO:0061436; P:establishment of skin barrier; ISO:RGD.
GO; GO:0060079; P:excitatory postsynaptic potential; ISO:RGD.
GO; GO:0030317; P:flagellated sperm motility; IMP:RGD.
GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
GO; GO:0048012; P:hepatocyte growth factor receptor signaling pathway; ISO:RGD.
GO; GO:0007595; P:lactation; IEP:RGD.
GO; GO:0001889; P:liver development; IEP:RGD.
GO; GO:0008584; P:male gonad development; IEP:RGD.
GO; GO:0050804; P:modulation of chemical synaptic transmission; ISO:RGD.
GO; GO:0014812; P:muscle cell migration; ISO:RGD.
GO; GO:0007517; P:muscle organ development; ISO:RGD.
GO; GO:0051450; P:myoblast proliferation; ISO:RGD.
GO; GO:0014902; P:myotube differentiation; ISO:RGD.
GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
GO; GO:1905098; P:negative regulation of guanyl-nucleotide exchange factor activity; ISO:RGD.
GO; GO:1901299; P:negative regulation of hydrogen peroxide-mediated programmed cell death; ISO:RGD.
GO; GO:0010801; P:negative regulation of peptidyl-threonine phosphorylation; IMP:RGD.
GO; GO:0035024; P:negative regulation of Rho protein signal transduction; ISO:RGD.
GO; GO:0051497; P:negative regulation of stress fiber assembly; ISO:RGD.
GO; GO:0070495; P:negative regulation of thrombin-activated receptor signaling pathway; ISO:RGD.
GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:RGD.
GO; GO:0071635; P:negative regulation of transforming growth factor beta production; ISO:RGD.
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; IDA:RGD.
GO; GO:0014003; P:oligodendrocyte development; IEP:RGD.
GO; GO:0031016; P:pancreas development; IEP:RGD.
GO; GO:0006909; P:phagocytosis; IBA:GO_Central.
GO; GO:0001890; P:placenta development; ISO:RGD.
GO; GO:0050918; P:positive chemotaxis; ISS:UniProtKB.
GO; GO:0050775; P:positive regulation of dendrite morphogenesis; IMP:RGD.
GO; GO:0045740; P:positive regulation of DNA replication; IMP:RGD.
GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; ISS:UniProtKB.
GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
GO; GO:0010828; P:positive regulation of glucose transmembrane transport; ISO:RGD.
GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
GO; GO:0031116; P:positive regulation of microtubule polymerization; ISO:RGD.
GO; GO:0045840; P:positive regulation of mitotic nuclear division; IMP:RGD.
GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD.
GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISO:RGD.
GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:RGD.
GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IMP:RGD.
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; IMP:RGD.
GO; GO:0046777; P:protein autophosphorylation; IDA:RGD.
GO; GO:0072593; P:reactive oxygen species metabolic process; ISO:RGD.
GO; GO:0060665; P:regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling; ISO:RGD.
GO; GO:1900407; P:regulation of cellular response to oxidative stress; ISO:RGD.
GO; GO:0032675; P:regulation of interleukin-6 production; ISO:RGD.
GO; GO:0010447; P:response to acidic pH; IEP:RGD.
GO; GO:0042493; P:response to drug; IEP:RGD.
GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
GO; GO:0009611; P:response to wounding; IEP:RGD.
GO; GO:0071526; P:semaphorin-plexin signaling pathway; ISS:UniProtKB.
GO; GO:0007519; P:skeletal muscle tissue development; ISO:RGD.
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; -; 3.
InterPro; IPR013783; Ig-like_fold.
InterPro; IPR014756; Ig_E-set.
InterPro; IPR002909; IPT_dom.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR031148; Plexin.
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; 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..1382
/note="Hepatocyte growth factor receptor"
/id="PRO_0000024442"
TOPO_DOM 25..935
/note="Extracellular"
/evidence="ECO:0000255"
TRANSMEM 936..956
/note="Helical"
/evidence="ECO:0000255"
TOPO_DOM 957..1379
/note="Cytoplasmic"
/evidence="ECO:0000255"
DOMAIN 27..516
/note="Sema"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DOMAIN 564..656
/note="IPT/TIG 1"
DOMAIN 658..740
/note="IPT/TIG 2"
DOMAIN 743..837
/note="IPT/TIG 3"
DOMAIN 1079..1346
/note="Protein kinase"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
NP_BIND 1085..1093
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
REGION 1213..1382
/note="Interaction with RANBP9"
/evidence="ECO:0000250"
REGION 1321..1360
/note="Interaction with MUC20"
/evidence="ECO:0000250"
ACT_SITE 1205
/note="Proton acceptor"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
ECO:0000255|PROSITE-ProRule:PRU10028"
BINDING 1111
/note="ATP"
/evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
SITE 308..309
/note="Cleavage"
/evidence="ECO:0000255"
MOD_RES 967
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 978
/note="Phosphothreonine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 991
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 998
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1001
/note="Phosphoserine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1004
/note="Phosphotyrosine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1231
/note="Phosphotyrosine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1235
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1236
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1290
/note="Phosphothreonine"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1350
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1357
/note="Phosphotyrosine; by autocatalysis"
/evidence="ECO:0000250|UniProtKB:P08581"
MOD_RES 1366
/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 203
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 359
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 400
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 406
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 608
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 636
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 786
/note="N-linked (GlcNAc...) asparagine"
/evidence="ECO:0000255"
CARBOHYD 880
/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 173..176
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 299..364
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 386..398
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 521..539
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 527..562
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 530..546
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
DISULFID 542..552
/evidence="ECO:0000255|PROSITE-ProRule:PRU00352"
CONFLICT 53
/note="H -> Q (in Ref. 2; AAB19189)"
/evidence="ECO:0000305"
CONFLICT 58
/note="P -> H (in Ref. 2; AAB19189)"
/evidence="ECO:0000305"
CONFLICT 240
/note="P -> G (in Ref. 2; AAB19189)"
/evidence="ECO:0000305"
CONFLICT 427
/note="R -> A (in Ref. 2; AAB19189)"
/evidence="ECO:0000305"
CONFLICT 485
/note="Y -> H (in Ref. 2; AAB19189)"
/evidence="ECO:0000305"
CONFLICT 490..495
/note="EVIVEH -> GAAGIR (in Ref. 3)"
/evidence="ECO:0000305"
CONFLICT 533
/note="P -> A (in Ref. 2; AAB19189)"
/evidence="ECO:0000305"
CONFLICT 740
/note="R -> G (in Ref. 2; AAB19189)"
/evidence="ECO:0000305"
CONFLICT 744
/note="V -> F (in Ref. 2; AAB19189)"
/evidence="ECO:0000305"
CONFLICT 808
/note="R -> Q (in Ref. 2; AAB19189)"
/evidence="ECO:0000305"
CONFLICT 890..893
/note="SEAL -> TASV (in Ref. 4; CAA86508)"
/evidence="ECO:0000305"
CONFLICT 907
/note="Missing (in Ref. 4; CAA86508)"
/evidence="ECO:0000305"
CONFLICT 924
/note="K -> E (in Ref. 4; CAA86508)"
/evidence="ECO:0000305"
CONFLICT 934
/note="A -> R (in Ref. 4; CAA86508)"
/evidence="ECO:0000305"
CONFLICT 1028
/note="L -> P (in Ref. 2; AAB19189)"
/evidence="ECO:0000305"
CONFLICT 1068
/note="P -> Q (in Ref. 2; AAB19189)"
/evidence="ECO:0000305"
CONFLICT 1197
/note="V -> A (in Ref. 2 and 5)"
/evidence="ECO:0000305"
CONFLICT 1331
/note="V -> F (in Ref. 2; AAB19189)"
/evidence="ECO:0000305"
SEQUENCE 1382 AA; 153941 MW; 66B8F2C88FE34427 CRC64;
MKAPTALAPG ILLLLLTLAQ RSHGECKEAL VKSEMNVNMK YQLPNFTAET PIHNVVLPGH
HIYLGATNYI YVLNDKDLQK VSEFKTGPVV EHPDCFPCQD CSSKANVSGG VWKDNVNMAL
LVDTYYDDQL ISCGSVNRGT CQRHVLPPDN AADIQSEVHC MFSPLAEEES GQCPDCVVSA
LGAKVLLSEK DRFINFFVGN TINSSYPPDY SLHSISVRRL KETQDGFKFL TDQSYIDVLP
EFRDSYPIKY IHAFESNHFI YFLTVQKETL DAQTFHTRII RFCSVDSGLH SYMEMPLECI
LTEKRRKRST REEVFNILQA AYVSKPGANL AKQIGASPYD DILYGVFAQS KPDSAEPMNR
SAVCAFPIKY VNDFFNKIVN KNNVRCLQHF YGPNHEHCFN RTLLRNSSGC EVRSDEYRTE
FTTALQRVDL FMGRLNHVLL TSISTFIKGD LTIANLGTSE GRFMQVVLSR TAHFTPHVNF
LLDSYPVSPE VIVEHPSNQN GYTLVVTGKK ITKIPLNGLG CGHFQSCSQC LSPPYFIQCG
WCHNRCVHSN ECPSGTWTQE ICLPAVYKVF PTSAPLEGGT MLTICGWDFG FKKNNKFDLR
KTKVLLGNES CTLTLSESTT NTLKCTVGPA MSEHFNVSVI VSNSRETTQY SAFSYVDPVI
TSISPRYGPH AGGTLLTLTG KYLNSGNSRH ISIGGKTCTL KSVSDSILEC YTPGHTVSAE
FPVKLKIDLA DRVTSSFSYR EDPVVSEIHP TKSFISGGST ITGIGKNLNS VSTPKLVIEV
HDVGVNYTVA CQHRSSSEII CCTTPSLRQL DLQLPLKTKA FFLLDGILSK HFDLTYVHDP
MFKPFEKPVM ISMGNENVVE IKGDDIDPEA VKGEVLKVGN KSCENLHWHS EALLCTVPSD
LLKLNGGELN IEWKQAVSST VLGKVIVQPD QNFAGLIIGA VSISVVVLLV SGLFLWLRKR
KHKDLGSELV RYDARVHTPH LDRLVSARSV SPTTEMVSNE SVDYRATFPE DQFPNSSQNG
ACRQVQYLLT DLSPILTSGD SDISSPLLQN TVHIDLSALN PELVQAVPHV VIGPSSLIVH
FNEVIGRGHF GCVYHGTLLD SDGKKIHCAV KSLNRITDIE EVSQFLTEGI IMKDFSHPNV
LSLLGICLRS EGSPLVVLPY MKHGDLRNFI RNETHNPTVK DLIGFGLQVA KGMKYLVSKK
FVHRDLAARN CMLDEKFTVK VADFGLARDM YDKEYYSVHN KTGAKLPVKW MALESLQTQK
FTTKSDVWSF GVLLWELMTR GAPPYPDVNT FDITIYLLQG RRLLQPEYCP DALYEVMLKC
WHPKAEMRPS VSELVSRISS IFSTFIGEHY VHVNATYVNV KCVAPYPSLL PSQDNIDGEA
NT


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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.