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This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that are linked via disulfide bonds to form the mature receptor. Further processing of the beta subunit results in the formation of the M10 peptide, which has been shown to reduce lung fibrosis. Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. Mutations in this gene are associated with papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers. Amplification and overexpression of this gene are also associated with multiple human cancers. [provided by RefSeq, May 2016]
Mesenchymal Epithelial Transition MET is a prototypical receptor tyrosine kinase. Its ligand is Hepatocyte Growth Factor (HGF). MET alterations are drivers of human cancer. Amplification and resulting overexpression has been reported in several cancers, and make the receptor's activity independent of HGF. Gene fusions also decouple kinase activity from the cell membrane and render it constitutively active. Finally, exclusion of the juxtamembrane (JM) domain of the kinase by "skipping" of exon 14 activates the kinase.
MET (MET Proto-Oncogene, Receptor Tyrosine Kinase) is a Protein Coding gene. Diseases associated with MET include Renal Cell Carcinoma, Papillary, 1 and Deafness, Autosomal Recessive 97. Among its related pathways are Transcriptional misregulation in cancer and RET signaling. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is MST1R.
The MET receptor, also known as hepatocyte growth factor receptor (HGFR), is a proto-oncogenic receptor tyrosine kinase. The endogenous ligand for MET is hepatocyte growth factor/scatter factor (HGF), a disulfide-linked heterodimeric molecule.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004713 | protein tyrosine kinase activity | TAS | -- |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IBA | 21873635 |
GO:0005008 | hepatocyte growth factor-activated receptor activity | IBA | 21873635 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005576 | extracellular region | IEA | -- |
GO:0005886 | plasma membrane | TAS | -- |
GO:0005887 | integral component of plasma membrane | TAS,IBA | 21873635 |
GO:0009925 | basal plasma membrane | IDA | 15314156 |
GO:0009986 | cell surface | HDA | 19581412 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | RET signaling |
.92
|
.92
|
2 | Apoptotic Pathways in Synovial Fibroblasts |
Cellular Apoptosis Pathway
.85
Mitochondrial Apoptosis
.85
Apoptotic Pathways in Synovial Fibroblasts
.84
p53 Mediated Apoptosis
.84
DHA Signaling
.74
Telomerase Components in Cell Signaling
.72
|
PPAR Pathway
.66
Rac1 Pathway
.65
Actin-Based Motility by Rho Family GTPases
.62
ERK5 Signaling
.61
eIF2 Pathway
.60
Nuclear Receptor Activation by Vitamin-A
.57
|
3 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
4 | GAB1 signalosome |
.89
|
|
5 | MET promotes cell motility |
.45
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000165 | MAPK cascade | TAS | -- |
GO:0001886 | endothelial cell morphogenesis | IDA | 14500721 |
GO:0001889 | liver development | IBA | 21873635 |
GO:0006468 | protein phosphorylation | IEA | -- |
GO:0006909 | phagocytosis | IBA | 21873635 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Crizotinib | Approved | Pharma | Target, inhibitor, Inhibition, Biomarker | C-MET/ALK inhibitor,potent and ATP-competitve, Potent c-MET/ALK inhibitor, cMET Inhibitors, Kinase Inhibitors, Anaplastic lymphoma kinase (ALK) inhibitor | 140 | |
cabozantinib | Approved, Investigational | Pharma | Target, antagonist, inhibitor | Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors | 0 | |
leucovorin | Approved | Pharma | 3692,1548 | |||
Gefitinib | Approved, Investigational | Pharma | EGFR Inhibitors, Kinase Inhibitors, Epidermal growth factor receptor (EGFR) inhibitors | 409 | ||
Tyrosine | Approved, Investigational | Nutra | 1044 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
||
Norleual |
|
334994-34-2 |
|
|
||
PF 04217903 mesylate |
|
956906-93-7 |
|
|
||
SGX 523 |
|
1022150-57-7 |
|
|
Compound | Action | Cas Number |
---|---|---|
Norleual | Highly potent HGF/c-MET inhibitor; also AT4 antagonist | 334994-34-2 |
PF 04217903 mesylate | Highly selective MET inhibitor | 956906-93-7 |
PHA 665752 | Potent and selective MET inhibitor | 477575-56-7 |
SGX 523 | Selective and potent c-MET kinase inhibitor | 1022150-57-7 |
SU 11274 | Selective inhibitor of MET kinase activity | 658084-23-2 |
Compound | Action | Cas Number |
---|---|---|
(R)-Crizotinib | C-MET/ALK inhibitor,potent and ATP-competitve | 877399-52-5 |
Altiratinib | c-MET/TIE-2/VEGFR inhibitor | 1345847-93-9 |
AMG-208 | C-Met inhibitor,potent and highly selective | 1002304-34-8 |
AMG-458 | Potent c-Met inhibitor | 913376-83-7 |
BMS-777607 | C-Met inhibitor, potent and selective | 1025720-94-8 |
BMS-794833 | Met/VEGFR-2 inhibitor,potent and ATP-competitive | 1174046-72-0 |
Cabozantinib (XL184, BMS-907351) | VEGFR2/Met/Ret/Kit/FLT//AXL inhibitor | 849217-68-1 |
Cabozantinib malate (XL184) | MET andVEGF receptor2 inhibitor | 1140909-48-3 |
EMD-1214063 | C-Met inhibitor,potent and selective | 1100598-32-0 |
Foretinib (GSK1363089) | VEGF and HGF receptor inhibitor | 849217-64-7 |
Golvatinib (E7050) | C-Met/VEGFR-2 inhibitor | 928037-13-2 |
INCB28060 | C-Met inhibitor,ATP-competitive and novel | 1029712-80-8 |
JNJ-38877605 | C-Met inhibitor,ATP-competitive | 943540-75-8 |
LY2801653 | MET inhibitor | 1206799-15-6 |
MGCD-265 | Met/Flt/Flk/Ron/Tie-2 inhibitor | 875337-44-3 |
MK-2461 | C-Met (WT/mutants) inhibitor | 917879-39-1 |
MK-8033 | C-MET inhibitor | 1001917-37-8 |
NPS-1034 | MET inhibitor | 1221713-92-3 |
NVP-BVU972 | C-Met inhibitor,potent and selective | 1185763-69-2 |
PF-04217903 | C-Met inhibitor,selective and ATP-competitive | 956905-27-4 |
PF-04217903 methanesulfonate | C-Met inhibitor,selective and ATP-competitive | 956906-93-7 |
PHA-665752 | C-Met inhibitor,potent and ATP-competitive | 477575-56-7 |
SGX-523 | MET inibitor, highly selective, ATP-competitive | 1022150-57-7 |
SU11274 | C-Met inhibitor,potent and selective | 658084-23-2 |
SU5416 | VEGF receptor inhibitor and AHR agonist | 204005-46-9 |
TAE226 (NVP-TAE226) | FAK inhibitor,potent and ATP-competitive | 761437-28-9 |
Tivantinib (ARQ 197) | C-Met inhibitor,non-ATP-competitive | 905854-02-6 |
ZM 323881 HCl | 193000-39-4 |
ExUns: | 1a | · | 1b | ^ | 2 | ^ | 3 | ^ | 4 | ^ | 5 | ^ | 6 | ^ | 7 | ^ | 8 | ^ | 9 | ^ | 10 | ^ | 11a | · | 11b | ^ | 12 | ^ | 13 | ^ | 14 | ^ | 15 | ^ | 16 | ^ | 17 | ^ | 18 | ^ | 19 | ^ | 20 | ^ | 21 | ^ | 22a | · | 22b |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SP1: | - | ||||||||||||||||||||||||||||||||||||||||||||||||
SP2: | - | - | |||||||||||||||||||||||||||||||||||||||||||||||
SP3: |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | MET 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | MET 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | MET 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | Met 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Met 30 |
|
||
Oppossum (Monodelphis domestica) |
Mammalia | MET 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | MET 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | C-MET 31 |
|
OneToOne | |
MET 30 |
|
||||
Lizard (Anolis carolinensis) |
Reptilia | MET 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | met 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | met-A 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | met 30 31 |
|
OneToOne | |
Dr.18290 30 |
|
||||
Worm (Caenorhabditis elegans) |
Secernentea | F11E6.8 32 |
|
|
|
T14E8.1a 32 |
|
|
|||
T14E8.1b 32 |
|
|
|||
kin-16 32 |
|
|
|||
kin-23 32 |
|
|
|||
R09D1.12 32 |
|
|
|||
F09A5.2 32 |
|
|
|||
F09G2.1 32 |
|
|
|||
R09D1.13 32 |
|
|
|||
svh-2 31 |
|
OneToMany | |||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
OneToMany | |
Sea Vase (Ciona intestinalis) |
Ascidiacea | Cin.8531 30 |
|