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Protein

Hepatocyte growth factor receptor

Gene

MET

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. May regulate cortical bone osteogenesis (By similarity).By similarity
Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.

Catalytic activityi

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

Enzyme regulationi

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1003Required for ligand-induced CBL-mediated ubiquitination1 Publication1
Binding sitei1110ATP1
Active sitei1204Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1084 – 1092ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • hepatocyte growth factor-activated receptor activity Source: ProtInc
  • protein phosphatase binding Source: UniProtKB
  • protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  • branching morphogenesis of an epithelial tube Source: UniProtKB
  • cell proliferation Source: ProtInc
  • cell surface receptor signaling pathway Source: UniProtKB
  • endothelial cell morphogenesis Source: UniProtKB
  • negative regulation of autophagy Source: ParkinsonsUK-UCL
  • negative regulation of hydrogen peroxide-mediated programmed cell death Source: BHF-UCL
  • positive chemotaxis Source: UniProtKB
  • positive regulation of endothelial cell chemotaxis Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • semaphorin-plexin signaling pathway Source: UniProtKB
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS02838-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-416550. Sema4D mediated inhibition of cell attachment and migration.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6806942. MET Receptor Activation.
R-HSA-6807004. Negative regulation of MET activity.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-8851805. MET activates RAS signaling.
R-HSA-8851907. MET activates PI3K/AKT signaling.
R-HSA-8865999. MET activates PTPN11.
R-HSA-8874081. MET activates PTK2 signaling.
R-HSA-8875513. MET interacts with TNS proteins.
R-HSA-8875555. MET activates RAP1 and RAC1.
R-HSA-8875656. MET receptor recycling.
R-HSA-8875791. MET activates STAT3.
SignaLinkiP08581.
SIGNORiP08581.

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatocyte growth factor receptor (EC:2.7.10.1)
Short name:
HGF receptor
Alternative name(s):
HGF/SF receptor
Proto-oncogene c-Met
Scatter factor receptor
Short name:
SF receptor
Tyrosine-protein kinase Met
Gene namesi
Name:MET
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:7029. MET.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 932ExtracellularSequence analysisAdd BLAST908
Transmembranei933 – 955HelicalSequence analysisAdd BLAST23
Topological domaini956 – 1390CytoplasmicSequence analysisAdd BLAST435

GO - Cellular componenti

  • basal plasma membrane Source: MGI
  • cell surface Source: UniProtKB
  • extracellular region Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Secreted

Pathology & Biotechi

Involvement in diseasei

Activation of MET after rearrangement with the TPR gene produces an oncogenic protein.

Defects in MET may be associated with gastric cancer.

Hepatocellular carcinoma (HCC)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes.
See also OMIM:114550
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0324901173T → I in HCC. 1 PublicationCorresponds to variant rs121913675dbSNPEnsembl.1
Natural variantiVAR_0324921244K → R in HCC. 1 PublicationCorresponds to variant rs121913677dbSNPEnsembl.1
Natural variantiVAR_0324931250M → I in HCC. 1 PublicationCorresponds to variant rs121913676dbSNPEnsembl.1
Renal cell carcinoma papillary (RCCP)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium.
See also OMIM:605074
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0324851092V → I in RCCP; constitutive autophosphorylation. 3 PublicationsCorresponds to variant rs786202724dbSNPEnsembl.1
Natural variantiVAR_0324861094H → L in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. 1 Publication1
Natural variantiVAR_0324871094H → R in RCCP; causes malignant transformation in cell lines. 2 PublicationsCorresponds to variant rs121913243dbSNPEnsembl.1
Natural variantiVAR_0324881094H → Y in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. 1 PublicationCorresponds to variant rs121913244dbSNPEnsembl.1
Natural variantiVAR_0324891106H → D in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. 2 Publications1
Natural variantiVAR_0062861131M → T in RCCP; germline mutation. 2 PublicationsCorresponds to variant rs121913668dbSNPEnsembl.1
Natural variantiVAR_0062871188V → L in RCCP; germline mutation. 2 PublicationsCorresponds to variant rs121913669dbSNPEnsembl.1
Natural variantiVAR_0062881195L → V in RCCP; somatic mutation. 1 PublicationCorresponds to variant rs121913673dbSNPEnsembl.1
Natural variantiVAR_0062891220V → I in RCCP; germline mutation. 1 PublicationCorresponds to variant rs121913670dbSNPEnsembl.1
Natural variantiVAR_0062911228D → H in RCCP; somatic mutation. 1 Publication1
Natural variantiVAR_0062901228D → N in RCCP; germline mutation. 1 PublicationCorresponds to variant rs121913671dbSNPEnsembl.1
Natural variantiVAR_0062921230Y → C in RCCP; germline mutation. 2 PublicationsCorresponds to variant rs121913246dbSNPEnsembl.1
Natural variantiVAR_0324911230Y → D in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. 2 Publications1
Natural variantiVAR_0062931230Y → H in RCCP; somatic mutation. 1 PublicationCorresponds to variant rs121913247dbSNPEnsembl.1
Natural variantiVAR_0062941250M → T in RCCP; somatic mutation. 2 PublicationsCorresponds to variant rs121913245dbSNPEnsembl.1

A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes.

MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.

Deafness, autosomal recessive, 97 (DFNB97)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of non-syndromic sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
See also OMIM:616705
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_075757841F → V in DFNB97. 1 PublicationCorresponds to variant rs794728016dbSNPEnsembl.1
Osteofibrous dysplasia (OSFD)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry. Disease-associated variants identified in 4 families cause the deletion of exon 14. This results in the exclusion of an ubiquitination target site within the cytoplasmic domain, hence in protein stabilization. The persistent presence of MET at the cell surface in conditions of ligand-dependent activation retards osteoblastic differentiation.1 Publication
Disease descriptionA congenital disorder of osteogenesis characterized by non-neoplastic, radiolucent lesions that affect the cortical bone immediately under the periosteum. It usually manifests as a painless swelling or anterior bowing of the long bones, most commonly the tibia and fibula.
See also OMIM:607278
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_076584964 – 1010Missing in OSFD; loss of CBL-mediated destabilization. 1 PublicationAdd BLAST47

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1234Y → F: Complete loss of kinase activity and of ligand-induced ubiquitination. Alters interaction with PTPN1 and PTPN2. Loss of interaction with PTPN1 and PTPN2; when associated with F-1235. 2 Publications1
Mutagenesisi1235Y → F: Complete loss of kinase activity. Alters interaction with PTPN1 and PTPN2. Loss of interaction with PTPN1 and PTPN2; when associated with F-1234. 2 Publications1
Mutagenesisi1313Y → F: No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1349, F-1356 and F-1365. 1 Publication1
Mutagenesisi1349Y → F: No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1313, F-1356 and F-1365. 1 Publication1
Mutagenesisi1356Y → F: No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1313, F-1349 and F-1365. 1 Publication1
Mutagenesisi1365Y → F: No effect on ligand-induced CBL-mediated ubiquitination; when associated with F-1313, F-1349 and F-1356. 1 Publication1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei1009 – 1010Breakpoint for translocation to form TPR-MET oncogene2

Keywords - Diseasei

Deafness, Disease mutation, Non-syndromic deafness, Proto-oncogene

Organism-specific databases

DisGeNETi4233.
MalaCardsiMET.
MIMi114550. phenotype.
605074. phenotype.
607278. phenotype.
616705. phenotype.
OpenTargetsiENSG00000105976.
Orphaneti106. Autism.
47044. Familial papillary renal cell carcinoma.
PharmGKBiPA30763.

Chemistry databases

ChEMBLiCHEMBL3717.
DrugBankiDB08875. Cabozantinib.
DB08865. Crizotinib.
GuidetoPHARMACOLOGYi1815.

Polymorphism and mutation databases

BioMutaiMET.
DMDMi251757497.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Sequence analysisAdd BLAST24
ChainiPRO_000002444025 – 1390Hepatocyte growth factor receptorAdd BLAST1366

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi45N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi95 ↔ 101
Disulfide bondi98 ↔ 160
Glycosylationi106N-linked (GlcNAc...)1 Publication1
Disulfide bondi133 ↔ 141
Glycosylationi149N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi172 ↔ 175
Glycosylationi202N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi298 ↔ 363
Disulfide bondi385 ↔ 397
Glycosylationi399N-linked (GlcNAc...)Sequence analysis1
Glycosylationi405N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi520 ↔ 538
Disulfide bondi526 ↔ 561
Disulfide bondi529 ↔ 545
Disulfide bondi541 ↔ 551
Glycosylationi607N-linked (GlcNAc...)Sequence analysis1
Glycosylationi635N-linked (GlcNAc...)Sequence analysis1
Glycosylationi785N-linked (GlcNAc...)Sequence analysis1
Glycosylationi879N-linked (GlcNAc...)Sequence analysis1
Glycosylationi930N-linked (GlcNAc...)Sequence analysis1
Modified residuei966PhosphoserineCombined sources1
Modified residuei977PhosphothreonineCombined sources1
Modified residuei990PhosphoserineCombined sources1
Modified residuei997PhosphoserineCombined sources1
Modified residuei1000PhosphoserineCombined sources1
Modified residuei1003PhosphotyrosineCombined sources1
Modified residuei1230Phosphotyrosine1 Publication1
Modified residuei1234Phosphotyrosine; by autocatalysis1 Publication1
Modified residuei1235Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei1289PhosphothreonineCombined sources1
Modified residuei1349Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei1356Phosphotyrosine; by autocatalysis2 Publications1
Modified residuei1365Phosphotyrosine1 Publication1

Post-translational modificationi

Autophosphorylated in response to ligand binding on Tyr-1234 and Tyr-1235 in the kinase domain leading to further phosphorylation of Tyr-1349 and Tyr-1356 in the C-terminal multifunctional docking site. Dephosphorylated by PTPRJ at Tyr-1349 and Tyr-1365. Dephosphorylated by PTPN1 and PTPN2.5 Publications
Ubiquitinated. Ubiquitination by CBL regulates MET endocytosis, resulting in decreasing plasma membrane receptor abundance, and in endosomal degradation and/or recycling of internalized receptors.1 Publication1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei307 – 308CleavageSequence analysis2

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP08581.
MaxQBiP08581.
PaxDbiP08581.
PeptideAtlasiP08581.
PRIDEiP08581.

2D gel databases

OGPiP08581.

PTM databases

iPTMnetiP08581.
PhosphoSitePlusiP08581.
SwissPalmiP08581.
UniCarbKBiP08581.

Expressioni

Tissue specificityi

Expressed in normal hepatocytes as well as in epithelial cells lining the stomach, the small and the large intestine. Found also in basal keratinocytes of esophagus and skin. High levels are found in liver, gastrointestinal tract, thyroid and kidney. Also present in the brain. Expressed in metaphyseal bone (at protein level) (PubMed:26637977).3 Publications

Gene expression databases

BgeeiENSG00000105976.
CleanExiHS_MET.
ExpressionAtlasiP08581. baseline and differential.
GenevisibleiP08581. HS.

Organism-specific databases

HPAiCAB005282.
CAB018577.
HPA055607.

Interactioni

Subunit structurei

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 (By similarity). Interacts with INPP5D/SHIP1. When phosphorylated at Tyr-1356, 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.By similarity16 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CBLP2268115EBI-1039152,EBI-518228
DNAJA3Q96EY1-22EBI-1039152,EBI-3952284
EGFRP005337EBI-1039152,EBI-297353
FGRP097692EBI-1039152,EBI-1383732
HGFP142104EBI-1039152,EBI-1039104
HGFP14210-62EBI-1039152,EBI-6280319
inlBP251474EBI-1039152,EBI-1379295From a different organism.
INPPL1O153572EBI-1039152,EBI-1384248
KDRP359683EBI-1039152,EBI-1005487
KdrP359183EBI-1039152,EBI-1555005From a different organism.
LCKP062393EBI-1039152,EBI-1348
LYNP079482EBI-1039152,EBI-79452
MUC1P159412EBI-1039152,EBI-2804728
NCK1P163332EBI-1039152,EBI-389883
NCK2O436392EBI-1039152,EBI-713635
PIK3R1P279866EBI-1039152,EBI-79464
PIK3R2O0045911EBI-1039152,EBI-346930
PIK3R3Q9256911EBI-1039152,EBI-79893
PLCG1P1917410EBI-1039152,EBI-79387
PLXNB1O431577EBI-1039152,EBI-1111488
PLXNB2O150312EBI-1039152,EBI-722004
PLXNB3Q9ULL42EBI-1039152,EBI-311073
PTK2Q009445EBI-1039152,EBI-2896409From a different organism.
PTPN1P180313EBI-1039152,EBI-968788
PTPN11Q0612413EBI-1039152,EBI-297779
PTPRBP234672EBI-1039152,EBI-1265766
PTPRJQ129135EBI-1039152,EBI-2264500
RASA1P2093615EBI-1039152,EBI-1026476
SH2B3Q9UQQ22EBI-1039152,EBI-7879749
SH2D1AO608803EBI-1039152,EBI-6983382
SH2D1BO147966EBI-1039152,EBI-3923013
SH2D2AQ9NP317EBI-1039152,EBI-490630
SH2D3CQ8N5H74EBI-1039152,EBI-745980
SHBQ154644EBI-1039152,EBI-4402156
SHC1P293535EBI-1039152,EBI-78835
SHC2P980772EBI-1039152,EBI-7256023
SHC4Q6S5L83EBI-1039152,EBI-9453524
SHDQ96IW22EBI-1039152,EBI-4402781
SLA2Q9H6Q34EBI-1039152,EBI-1222854
SOCS5O751592EBI-1039152,EBI-970130
SOCS6O145444EBI-1039152,EBI-3929549
SRCP129314EBI-1039152,EBI-621482
STAP1Q9ULZ23EBI-1039152,EBI-6083058
SYKP434053EBI-1039152,EBI-78302
TECP426802EBI-1039152,EBI-1383480
TNS1Q9HBL02EBI-1039152,EBI-3389814
TNS2Q63HR22EBI-1039152,EBI-949753
TNS3Q68CZ23EBI-1039152,EBI-1220488
VAV3Q9UKW42EBI-1039152,EBI-297568
YES1P079473EBI-1039152,EBI-515331
ZAP70P434032EBI-1039152,EBI-1211276

GO - Molecular functioni

  • protein phosphatase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110391. 39 interactors.
DIPiDIP-6023N.
IntActiP08581. 86 interactors.
MINTiMINT-4837114.
STRINGi9606.ENSP00000317272.

Chemistry databases

BindingDBiP08581.

Structurei

Secondary structure

11390
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi45 – 47Combined sources3
Beta strandi52 – 58Combined sources7
Beta strandi61 – 66Combined sources6
Beta strandi69 – 74Combined sources6
Turni75 – 77Combined sources3
Beta strandi80 – 84Combined sources5
Beta strandi89 – 91Combined sources3
Beta strandi93 – 95Combined sources3
Beta strandi97 – 99Combined sources3
Helixi103 – 105Combined sources3
Beta strandi111 – 113Combined sources3
Beta strandi119 – 123Combined sources5
Beta strandi125 – 133Combined sources9
Beta strandi135 – 139Combined sources5
Beta strandi141 – 145Combined sources5
Beta strandi155 – 160Combined sources6
Beta strandi182 – 189Combined sources8
Beta strandi192 – 199Combined sources8
Beta strandi213 – 219Combined sources7
Helixi231 – 233Combined sources3
Helixi239 – 241Combined sources3
Turni242 – 244Combined sources3
Beta strandi247 – 255Combined sources9
Beta strandi258 – 268Combined sources11
Beta strandi272 – 274Combined sources3
Beta strandi277 – 281Combined sources5
Beta strandi284 – 286Combined sources3
Beta strandi292 – 300Combined sources9
Beta strandi312 – 314Combined sources3
Beta strandi316 – 323Combined sources8
Helixi327 – 333Combined sources7
Beta strandi341 – 349Combined sources9
Beta strandi356 – 366Combined sources11
Helixi367 – 374Combined sources8
Helixi380 – 382Combined sources3
Beta strandi383 – 385Combined sources3
Helixi387 – 390Combined sources4
Beta strandi392 – 394Combined sources3
Turni395 – 397Combined sources3
Beta strandi418 – 422Combined sources5
Beta strandi424 – 427Combined sources4
Turni429 – 436Combined sources8
Beta strandi439 – 447Combined sources9
Beta strandi450 – 457Combined sources8
Beta strandi462 – 466Combined sources5
Beta strandi469 – 471Combined sources3
Beta strandi476 – 480Combined sources5
Beta strandi490 – 493Combined sources4
Turni496 – 498Combined sources3
Beta strandi501 – 506Combined sources6
Beta strandi509 – 514Combined sources6
Helixi518 – 521Combined sources4
Helixi526 – 531Combined sources6
Helixi534 – 536Combined sources3
Beta strandi538 – 540Combined sources3
Beta strandi545 – 548Combined sources4
Beta strandi552 – 554Combined sources3
Beta strandi557 – 559Combined sources3
Beta strandi564 – 572Combined sources9
Beta strandi580 – 586Combined sources7
Beta strandi590 – 592Combined sources3
Beta strandi595 – 598Combined sources4
Beta strandi602 – 605Combined sources4
Helixi614 – 616Combined sources3
Beta strandi619 – 625Combined sources7
Beta strandi637 – 641Combined sources5
Beta strandi646 – 650Combined sources5
Helixi1048 – 1050Combined sources3
Helixi1055 – 1057Combined sources3
Helixi1060 – 1066Combined sources7
Helixi1067 – 1069Combined sources3
Helixi1073 – 1075Combined sources3
Beta strandi1076 – 1087Combined sources12
Beta strandi1090 – 1098Combined sources9
Beta strandi1100 – 1102Combined sources3
Beta strandi1104 – 1111Combined sources8
Helixi1118 – 1132Combined sources15
Beta strandi1144 – 1146Combined sources3
Beta strandi1149 – 1151Combined sources3
Beta strandi1154 – 1158Combined sources5
Helixi1165 – 1170Combined sources6
Turni1172 – 1174Combined sources3
Helixi1178 – 1197Combined sources20
Helixi1207 – 1209Combined sources3
Beta strandi1210 – 1212Combined sources3
Beta strandi1218 – 1220Combined sources3
Helixi1224 – 1226Combined sources3
Helixi1232 – 1234Combined sources3
Beta strandi1236 – 1238Combined sources3
Turni1239 – 1241Combined sources3
Beta strandi1243 – 1245Combined sources3
Helixi1247 – 1249Combined sources3
Helixi1252 – 1257Combined sources6
Helixi1262 – 1277Combined sources16
Beta strandi1283 – 1287Combined sources5
Helixi1289 – 1291Combined sources3
Helixi1292 – 1297Combined sources6
Helixi1310 – 1319Combined sources10
Helixi1324 – 1326Combined sources3
Helixi1330 – 1342Combined sources13
Turni1354 – 1358Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FYRX-ray2.40I/J/K/L1356-1359[»]
1R0PX-ray1.80A1049-1360[»]
1R1WX-ray1.80A1049-1360[»]
1SHYX-ray3.22B25-567[»]
1SSLNMR-A519-562[»]
1UX3model-A25-656[»]
2G15X-ray2.15A1038-1346[»]
2RFNX-ray2.50A/B1048-1351[»]
2RFSX-ray2.20A1048-1351[»]
2UZXX-ray2.80B/D25-740[»]
2UZYX-ray4.00B/D25-740[»]
2WD1X-ray2.00A1055-1346[»]
2WGJX-ray2.00A1051-1348[»]
2WKMX-ray2.20A1051-1348[»]
3A4PX-ray2.54A1049-1360[»]
3BUXX-ray1.35A/C997-1009[»]
3C1XX-ray2.17A1049-1360[»]
3CCNX-ray1.90A1048-1350[»]
3CD8X-ray2.00A1048-1350[»]
3CE3X-ray2.40A1049-1360[»]
3CTHX-ray2.30A1049-1360[»]
3CTJX-ray2.50A1049-1360[»]
3DKCX-ray1.52A1049-1360[»]
3DKFX-ray1.80A1049-1360[»]
3DKGX-ray1.91A1049-1360[»]
3EFJX-ray2.60A/B1048-1351[»]
3EFKX-ray2.20A/B1048-1351[»]
3F66X-ray1.40A/B1052-1349[»]
3F82X-ray2.50A1049-1360[»]
3I5NX-ray2.00A1048-1350[»]
3L8VX-ray2.40A1049-1360[»]
3LQ8X-ray2.02A1051-1348[»]
3Q6UX-ray1.60A1048-1348[»]
3Q6WX-ray1.75A1048-1348[»]
3QTIX-ray2.00A/B1050-1360[»]
3R7OX-ray2.30A1048-1348[»]
3RHKX-ray1.94A/B1038-1346[»]
3U6HX-ray2.00A1048-1351[»]
3U6IX-ray2.10A1048-1351[»]
3VW8X-ray2.10A1024-1352[»]
3ZBXX-ray2.20A1051-1348[»]
3ZC5X-ray2.20A1051-1348[»]
3ZCLX-ray1.40A1051-1348[»]
3ZXZX-ray1.80A1051-1348[»]
3ZZEX-ray1.87A1051-1348[»]
4AOIX-ray1.90A1051-1348[»]
4AP7X-ray1.80A1051-1348[»]
4DEGX-ray2.00A1048-1351[»]
4DEHX-ray2.00A1048-1351[»]
4DEIX-ray2.05A1048-1351[»]
4EEVX-ray1.80A1038-1346[»]
4GG5X-ray2.42A1038-1346[»]
4GG7X-ray2.27A1038-1346[»]
4IWDX-ray1.99A1048-1348[»]
4K3JX-ray2.80B39-564[»]
4KNBX-ray2.40A/B/C/D1060-1346[»]
4MXCX-ray1.63A1038-1346[»]
4O3TX-ray2.99B25-567[»]
4O3UX-ray3.04B25-567[»]
4R1VX-ray1.20A1055-1345[»]
4R1YX-ray2.00A1055-1346[»]
4XMOX-ray1.75A1048-1350[»]
4XYFX-ray1.85A1048-1351[»]
5DG5X-ray2.60A/B1038-1346[»]
5EOBX-ray1.75A1038-1346[»]
5EYCX-ray1.80A1048-1351[»]
5EYDX-ray1.85A1048-1351[»]
5T3QX-ray2.00A1048-1350[»]
DisProtiDP00317.
ProteinModelPortaliP08581.
SMRiP08581.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08581.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 515SemaPROSITE-ProRule annotationAdd BLAST489
Domaini563 – 655IPT/TIG 1Add BLAST93
Domaini657 – 739IPT/TIG 2Add BLAST83
Domaini742 – 836IPT/TIG 3Add BLAST95
Domaini1078 – 1345Protein kinasePROSITE-ProRule annotationAdd BLAST268

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1212 – 1390Interaction with RANBP9Add BLAST179
Regioni1320 – 1359Interaction with MUC201 PublicationAdd BLAST40

Domaini

The kinase domain is involved in SPSB1 binding.
The beta-propeller Sema domain mediates binding to HGF.

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family.PROSITE-ProRule annotation
Contains 3 IPT/TIG domains.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 Sema domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1095. Eukaryota.
KOG3610. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00810000125384.
HOGENOMiHOG000220900.
HOVERGENiHBG006348.
InParanoidiP08581.
KOiK05099.
OMAiQRVDLFM.
PhylomeDBiP08581.
TreeFamiTF317402.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
2.60.40.10. 3 hits.
InterProiIPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR011009. Kinase-like_dom.
IPR002165. Plexin_repeat.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016201. PSI.
IPR001627. Semap_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016244. Tyr_kinase_HGF/MSP_rcpt.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
PF01833. TIG. 3 hits.
[Graphical view]
PIRSFiPIRSF000617. TyrPK_HGF-R. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF101912. SSF101912. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF81296. SSF81296. 3 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional soluble isoforms seem to exist.
Isoform 1 (identifier: P08581-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MKAPAVLAPG ILVLLFTLVQ RSNGECKEAL AKSEMNVNMK YQLPNFTAET
60 70 80 90 100
PIQNVILHEH HIFLGATNYI YVLNEEDLQK VAEYKTGPVL EHPDCFPCQD
110 120 130 140 150
CSSKANLSGG VWKDNINMAL VVDTYYDDQL ISCGSVNRGT CQRHVFPHNH
160 170 180 190 200
TADIQSEVHC IFSPQIEEPS QCPDCVVSAL GAKVLSSVKD RFINFFVGNT
210 220 230 240 250
INSSYFPDHP LHSISVRRLK ETKDGFMFLT DQSYIDVLPE FRDSYPIKYV
260 270 280 290 300
HAFESNNFIY FLTVQRETLD AQTFHTRIIR FCSINSGLHS YMEMPLECIL
310 320 330 340 350
TEKRKKRSTK KEVFNILQAA YVSKPGAQLA RQIGASLNDD ILFGVFAQSK
360 370 380 390 400
PDSAEPMDRS AMCAFPIKYV NDFFNKIVNK NNVRCLQHFY GPNHEHCFNR
410 420 430 440 450
TLLRNSSGCE ARRDEYRTEF TTALQRVDLF MGQFSEVLLT SISTFIKGDL
460 470 480 490 500
TIANLGTSEG RFMQVVVSRS GPSTPHVNFL LDSHPVSPEV IVEHTLNQNG
510 520 530 540 550
YTLVITGKKI TKIPLNGLGC RHFQSCSQCL SAPPFVQCGW CHDKCVRSEE
560 570 580 590 600
CLSGTWTQQI CLPAIYKVFP NSAPLEGGTR LTICGWDFGF RRNNKFDLKK
610 620 630 640 650
TRVLLGNESC TLTLSESTMN TLKCTVGPAM NKHFNMSIII SNGHGTTQYS
660 670 680 690 700
TFSYVDPVIT SISPKYGPMA GGTLLTLTGN YLNSGNSRHI SIGGKTCTLK
710 720 730 740 750
SVSNSILECY TPAQTISTEF AVKLKIDLAN RETSIFSYRE DPIVYEIHPT
760 770 780 790 800
KSFISGGSTI TGVGKNLNSV SVPRMVINVH EAGRNFTVAC QHRSNSEIIC
810 820 830 840 850
CTTPSLQQLN LQLPLKTKAF FMLDGILSKY FDLIYVHNPV FKPFEKPVMI
860 870 880 890 900
SMGNENVLEI KGNDIDPEAV KGEVLKVGNK SCENIHLHSE AVLCTVPNDL
910 920 930 940 950
LKLNSELNIE WKQAISSTVL GKVIVQPDQN FTGLIAGVVS ISTALLLLLG
960 970 980 990 1000
FFLWLKKRKQ IKDLGSELVR YDARVHTPHL DRLVSARSVS PTTEMVSNES
1010 1020 1030 1040 1050
VDYRATFPED QFPNSSQNGS CRQVQYPLTD MSPILTSGDS DISSPLLQNT
1060 1070 1080 1090 1100
VHIDLSALNP ELVQAVQHVV IGPSSLIVHF NEVIGRGHFG CVYHGTLLDN
1110 1120 1130 1140 1150
DGKKIHCAVK SLNRITDIGE VSQFLTEGII MKDFSHPNVL SLLGICLRSE
1160 1170 1180 1190 1200
GSPLVVLPYM KHGDLRNFIR NETHNPTVKD LIGFGLQVAK GMKYLASKKF
1210 1220 1230 1240 1250
VHRDLAARNC MLDEKFTVKV ADFGLARDMY DKEYYSVHNK TGAKLPVKWM
1260 1270 1280 1290 1300
ALESLQTQKF TTKSDVWSFG VLLWELMTRG APPYPDVNTF DITVYLLQGR
1310 1320 1330 1340 1350
RLLQPEYCPD PLYEVMLKCW HPKAEMRPSF SELVSRISAI FSTFIGEHYV
1360 1370 1380 1390
HVNATYVNVK CVAPYPSLLS SEDNADDEVD TRPASFWETS
Length:1,390
Mass (Da):155,541
Last modified:July 7, 2009 - v4
Checksum:i9CF896D1273905C3
GO
Isoform 2 (identifier: P08581-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     755-755: S → STWWKEPLNIVSFLFCFAS

Note: No experimental confirmation available.
Show »
Length:1,408
Mass (Da):157,712
Checksum:iC5F64DCBBC13CC88
GO
Isoform 3 (identifier: P08581-3) [UniParc]FASTAAdd to basket
Also known as: Soluble MET variant 4

The sequence of this isoform differs from the canonical sequence as follows:
     755-764: SGGSTITGVG → RHVNIALIQR
     765-1390: Missing.

Show »
Length:764
Mass (Da):85,745
Checksum:iBBCBC4197C9C18DE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti237V → A in ACF47606 (PubMed:18593464).Curated1
Sequence conflicti508K → R in ACF47606 (PubMed:18593464).Curated1
Sequence conflicti720F → S in ACF47606 (PubMed:18593464).Curated1
Sequence conflicti1191G → A in AAA59591 (PubMed:2819873).Curated1
Sequence conflicti1272L → V in AAA59591 (PubMed:2819873).Curated1
Sequence conflicti1272L → V in CAB56793 (Ref. 2) Curated1
Sequence conflicti1272L → V in AAA59590 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_041738143R → Q.1 PublicationCorresponds to variant rs35469582dbSNPEnsembl.1
Natural variantiVAR_064855150H → Y Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. 1 Publication1
Natural variantiVAR_041739156S → L.1 PublicationCorresponds to variant rs56311081dbSNPEnsembl.1
Natural variantiVAR_041740168E → D Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. 2 PublicationsCorresponds to variant rs55985569dbSNPEnsembl.1
Natural variantiVAR_032478238L → S.Corresponds to variant rs34349517dbSNPEnsembl.1
Natural variantiVAR_032479316I → M.Corresponds to variant rs35225896dbSNPEnsembl.1
Natural variantiVAR_006285320A → V.1 PublicationCorresponds to variant rs35776110dbSNPEnsembl.1
Natural variantiVAR_032480375N → S.1 PublicationCorresponds to variant rs33917957dbSNPEnsembl.1
Natural variantiVAR_064856385C → Y Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. 1 PublicationCorresponds to variant rs752055485dbSNPEnsembl.1
Natural variantiVAR_032481773P → L in gastric cancer. 1 PublicationCorresponds to variant rs771333219dbSNPEnsembl.1
Natural variantiVAR_075757841F → V in DFNB97. 1 PublicationCorresponds to variant rs794728016dbSNPEnsembl.1
Natural variantiVAR_076584964 – 1010Missing in OSFD; loss of CBL-mediated destabilization. 1 PublicationAdd BLAST47
Natural variantiVAR_032482970R → C.2 PublicationsCorresponds to variant rs34589476dbSNPEnsembl.1
Natural variantiVAR_032483991P → S in gastric cancer; prolonged tyrosine phosphorylation in response to HGF/SF; transforming activity in athymic nude mice. 1 PublicationCorresponds to variant rs768678989dbSNPEnsembl.1
Natural variantiVAR_032484992T → I Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. 4 PublicationsCorresponds to variant rs56391007dbSNPEnsembl.1
Natural variantiVAR_0765851003Y → S Probable disease-associated mutation found in lesional sample from a patient with sporadically occurring, unilateral osteofibrous dysplasia; somatic mutation; complete loss of ligand-induced CBL-mediated ubiquitination, resulting in protein stabilization. 1 Publication1
Natural variantiVAR_0324851092V → I in RCCP; constitutive autophosphorylation. 3 PublicationsCorresponds to variant rs786202724dbSNPEnsembl.1
Natural variantiVAR_0324861094H → L in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. 1 Publication1
Natural variantiVAR_0324871094H → R in RCCP; causes malignant transformation in cell lines. 2 PublicationsCorresponds to variant rs121913243dbSNPEnsembl.1
Natural variantiVAR_0324881094H → Y in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. 1 PublicationCorresponds to variant rs121913244dbSNPEnsembl.1
Natural variantiVAR_0324891106H → D in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. 2 Publications1
Natural variantiVAR_0062861131M → T in RCCP; germline mutation. 2 PublicationsCorresponds to variant rs121913668dbSNPEnsembl.1
Natural variantiVAR_0324901173T → I in HCC. 1 PublicationCorresponds to variant rs121913675dbSNPEnsembl.1
Natural variantiVAR_0062871188V → L in RCCP; germline mutation. 2 PublicationsCorresponds to variant rs121913669dbSNPEnsembl.1
Natural variantiVAR_0062881195L → V in RCCP; somatic mutation. 1 PublicationCorresponds to variant rs121913673dbSNPEnsembl.1
Natural variantiVAR_0062891220V → I in RCCP; germline mutation. 1 PublicationCorresponds to variant rs121913670dbSNPEnsembl.1
Natural variantiVAR_0062911228D → H in RCCP; somatic mutation. 1 Publication1
Natural variantiVAR_0062901228D → N in RCCP; germline mutation. 1 PublicationCorresponds to variant rs121913671dbSNPEnsembl.1
Natural variantiVAR_0062921230Y → C in RCCP; germline mutation. 2 PublicationsCorresponds to variant rs121913246dbSNPEnsembl.1
Natural variantiVAR_0324911230Y → D in RCCP; constitutive autophosphorylation; causes malignant transformation in cell lines. 2 Publications1
Natural variantiVAR_0062931230Y → H in RCCP; somatic mutation. 1 PublicationCorresponds to variant rs121913247dbSNPEnsembl.1
Natural variantiVAR_0324921244K → R in HCC. 1 PublicationCorresponds to variant rs121913677dbSNPEnsembl.1
Natural variantiVAR_0324931250M → I in HCC. 1 PublicationCorresponds to variant rs121913676dbSNPEnsembl.1
Natural variantiVAR_0062941250M → T in RCCP; somatic mutation. 2 PublicationsCorresponds to variant rs121913245dbSNPEnsembl.1
Natural variantiVAR_0648571294V → I Found in a case of cancer of unknown primary origin; the mutated receptor is still functional and can sustain the transformed phenotype; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_042447755 – 764SGGSTITGVG → RHVNIALIQR in isoform 3. 1 Publication10
Alternative sequenceiVSP_005005755S → STWWKEPLNIVSFLFCFAS in isoform 2. 1 Publication1
Alternative sequenceiVSP_042448765 – 1390Missing in isoform 3. 1 PublicationAdd BLAST626

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02958 mRNA. Translation: AAA59591.1.
X54559 mRNA. Translation: CAB56793.1.
EU826570 mRNA. Translation: ACF47606.1.
AC002080 Genomic DNA. Translation: AAB54047.1.
AC002543 Genomic DNA. Translation: AAC60383.1.
AC004416 Genomic DNA. Translation: AAF66137.2.
CH236947 Genomic DNA. Translation: EAL24359.1.
CH471070 Genomic DNA. Translation: EAW83509.1.
BC130420 mRNA. Translation: AAI30421.1.
U08818 mRNA. Translation: AAB60323.1. Sequence problems.
M35074 mRNA. Translation: AAA59590.1.
CCDSiCCDS43636.1. [P08581-1]
CCDS47689.1. [P08581-2]
PIRiA40175. TVHUME.
RefSeqiNP_000236.2. NM_000245.3. [P08581-1]
NP_001120972.1. NM_001127500.2. [P08581-2]
UniGeneiHs.132966.

Genome annotation databases

EnsembliENST00000318493; ENSP00000317272; ENSG00000105976. [P08581-2]
ENST00000397752; ENSP00000380860; ENSG00000105976. [P08581-1]
ENST00000436117; ENSP00000410980; ENSG00000105976. [P08581-3]
GeneIDi4233.
KEGGihsa:4233.
UCSCiuc003vij.4. human. [P08581-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Wikipedia

C-MET entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J02958 mRNA. Translation: AAA59591.1.
X54559 mRNA. Translation: CAB56793.1.
EU826570 mRNA. Translation: ACF47606.1.
AC002080 Genomic DNA. Translation: AAB54047.1.
AC002543 Genomic DNA. Translation: AAC60383.1.
AC004416 Genomic DNA. Translation: AAF66137.2.
CH236947 Genomic DNA. Translation: EAL24359.1.
CH471070 Genomic DNA. Translation: EAW83509.1.
BC130420 mRNA. Translation: AAI30421.1.
U08818 mRNA. Translation: AAB60323.1. Sequence problems.
M35074 mRNA. Translation: AAA59590.1.
CCDSiCCDS43636.1. [P08581-1]
CCDS47689.1. [P08581-2]
PIRiA40175. TVHUME.
RefSeqiNP_000236.2. NM_000245.3. [P08581-1]
NP_001120972.1. NM_001127500.2. [P08581-2]
UniGeneiHs.132966.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FYRX-ray2.40I/J/K/L1356-1359[»]
1R0PX-ray1.80A1049-1360[»]
1R1WX-ray1.80A1049-1360[»]
1SHYX-ray3.22B25-567[»]
1SSLNMR-A519-562[»]
1UX3model-A25-656[»]
2G15X-ray2.15A1038-1346[»]
2RFNX-ray2.50A/B1048-1351[»]
2RFSX-ray2.20A1048-1351[»]
2UZXX-ray2.80B/D25-740[»]
2UZYX-ray4.00B/D25-740[»]
2WD1X-ray2.00A1055-1346[»]
2WGJX-ray2.00A1051-1348[»]
2WKMX-ray2.20A1051-1348[»]
3A4PX-ray2.54A1049-1360[»]
3BUXX-ray1.35A/C997-1009[»]
3C1XX-ray2.17A1049-1360[»]
3CCNX-ray1.90A1048-1350[»]
3CD8X-ray2.00A1048-1350[»]
3CE3X-ray2.40A1049-1360[»]
3CTHX-ray2.30A1049-1360[»]
3CTJX-ray2.50A1049-1360[»]
3DKCX-ray1.52A1049-1360[»]
3DKFX-ray1.80A1049-1360[»]
3DKGX-ray1.91A1049-1360[»]
3EFJX-ray2.60A/B1048-1351[»]
3EFKX-ray2.20A/B1048-1351[»]
3F66X-ray1.40A/B1052-1349[»]
3F82X-ray2.50A1049-1360[»]
3I5NX-ray2.00A1048-1350[»]
3L8VX-ray2.40A1049-1360[»]
3LQ8X-ray2.02A1051-1348[»]
3Q6UX-ray1.60A1048-1348[»]
3Q6WX-ray1.75A1048-1348[»]
3QTIX-ray2.00A/B1050-1360[»]
3R7OX-ray2.30A1048-1348[»]
3RHKX-ray1.94A/B1038-1346[»]
3U6HX-ray2.00A1048-1351[»]
3U6IX-ray2.10A1048-1351[»]
3VW8X-ray2.10A1024-1352[»]
3ZBXX-ray2.20A1051-1348[»]
3ZC5X-ray2.20A1051-1348[»]
3ZCLX-ray1.40A1051-1348[»]
3ZXZX-ray1.80A1051-1348[»]
3ZZEX-ray1.87A1051-1348[»]
4AOIX-ray1.90A1051-1348[»]
4AP7X-ray1.80A1051-1348[»]
4DEGX-ray2.00A1048-1351[»]
4DEHX-ray2.00A1048-1351[»]
4DEIX-ray2.05A1048-1351[»]
4EEVX-ray1.80A1038-1346[»]
4GG5X-ray2.42A1038-1346[»]
4GG7X-ray2.27A1038-1346[»]
4IWDX-ray1.99A1048-1348[»]
4K3JX-ray2.80B39-564[»]
4KNBX-ray2.40A/B/C/D1060-1346[»]
4MXCX-ray1.63A1038-1346[»]
4O3TX-ray2.99B25-567[»]
4O3UX-ray3.04B25-567[»]
4R1VX-ray1.20A1055-1345[»]
4R1YX-ray2.00A1055-1346[»]
4XMOX-ray1.75A1048-1350[»]
4XYFX-ray1.85A1048-1351[»]
5DG5X-ray2.60A/B1038-1346[»]
5EOBX-ray1.75A1038-1346[»]
5EYCX-ray1.80A1048-1351[»]
5EYDX-ray1.85A1048-1351[»]
5T3QX-ray2.00A1048-1350[»]
DisProtiDP00317.
ProteinModelPortaliP08581.
SMRiP08581.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110391. 39 interactors.
DIPiDIP-6023N.
IntActiP08581. 86 interactors.
MINTiMINT-4837114.
STRINGi9606.ENSP00000317272.

Chemistry databases

BindingDBiP08581.
ChEMBLiCHEMBL3717.
DrugBankiDB08875. Cabozantinib.
DB08865. Crizotinib.
GuidetoPHARMACOLOGYi1815.

PTM databases

iPTMnetiP08581.
PhosphoSitePlusiP08581.
SwissPalmiP08581.
UniCarbKBiP08581.

Polymorphism and mutation databases

BioMutaiMET.
DMDMi251757497.

2D gel databases

OGPiP08581.

Proteomic databases

EPDiP08581.
MaxQBiP08581.
PaxDbiP08581.
PeptideAtlasiP08581.
PRIDEiP08581.

Protocols and materials databases

DNASUi4233.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000318493; ENSP00000317272; ENSG00000105976. [P08581-2]
ENST00000397752; ENSP00000380860; ENSG00000105976. [P08581-1]
ENST00000436117; ENSP00000410980; ENSG00000105976. [P08581-3]
GeneIDi4233.
KEGGihsa:4233.
UCSCiuc003vij.4. human. [P08581-1]

Organism-specific databases

CTDi4233.
DisGeNETi4233.
GeneCardsiMET.
HGNCiHGNC:7029. MET.
HPAiCAB005282.
CAB018577.
HPA055607.
MalaCardsiMET.
MIMi114550. phenotype.
164860. gene.
605074. phenotype.
607278. phenotype.
616705. phenotype.
neXtProtiNX_P08581.
OpenTargetsiENSG00000105976.
Orphaneti106. Autism.
47044. Familial papillary renal cell carcinoma.
PharmGKBiPA30763.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1095. Eukaryota.
KOG3610. Eukaryota.
COG0515. LUCA.
GeneTreeiENSGT00810000125384.
HOGENOMiHOG000220900.
HOVERGENiHBG006348.
InParanoidiP08581.
KOiK05099.
OMAiQRVDLFM.
PhylomeDBiP08581.
TreeFamiTF317402.

Enzyme and pathway databases

BioCyciZFISH:HS02838-MONOMER.
BRENDAi2.7.10.1. 2681.
ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-2219530. Constitutive Signaling by Aberrant PI3K in Cancer.
R-HSA-416550. Sema4D mediated inhibition of cell attachment and migration.
R-HSA-5673001. RAF/MAP kinase cascade.
R-HSA-6806942. MET Receptor Activation.
R-HSA-6807004. Negative regulation of MET activity.
R-HSA-6811558. PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
R-HSA-8851805. MET activates RAS signaling.
R-HSA-8851907. MET activates PI3K/AKT signaling.
R-HSA-8865999. MET activates PTPN11.
R-HSA-8874081. MET activates PTK2 signaling.
R-HSA-8875513. MET interacts with TNS proteins.
R-HSA-8875555. MET activates RAP1 and RAC1.
R-HSA-8875656. MET receptor recycling.
R-HSA-8875791. MET activates STAT3.
SignaLinkiP08581.
SIGNORiP08581.

Miscellaneous databases

ChiTaRSiMET. human.
EvolutionaryTraceiP08581.
GeneWikiiC-Met.
GenomeRNAii4233.
PROiP08581.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105976.
CleanExiHS_MET.
ExpressionAtlasiP08581. baseline and differential.
GenevisibleiP08581. HS.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
2.60.40.10. 3 hits.
InterProiIPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR011009. Kinase-like_dom.
IPR002165. Plexin_repeat.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR016201. PSI.
IPR001627. Semap_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
IPR016244. Tyr_kinase_HGF/MSP_rcpt.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]
PfamiPF07714. Pkinase_Tyr. 1 hit.
PF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
PF01833. TIG. 3 hits.
[Graphical view]
PIRSFiPIRSF000617. TyrPK_HGF-R. 1 hit.
PRINTSiPR00109. TYRKINASE.
SMARTiSM00429. IPT. 4 hits.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMiSSF101912. SSF101912. 1 hit.
SSF56112. SSF56112. 1 hit.
SSF81296. SSF81296. 3 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMET_HUMAN
AccessioniPrimary (citable) accession number: P08581
Secondary accession number(s): A1L467
, B5A932, E7EQ94, O60366, Q12875, Q9UDX7, Q9UPL8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: July 7, 2009
Last modified: November 30, 2016
This is version 222 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.