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MET Gene(Protein Coding)

MET Proto-Oncogene, Receptor Tyrosine Kinase

GCID:
GC07P116672
GIFtS:
79
Genes Participants
UDN Logo

Aliases for MET Gene

Aliases for MET Gene

  • MET Proto-Oncogene, Receptor Tyrosine Kinase 2 3 5
  • Hepatocyte Growth Factor Receptor 2 3
  • Tyrosine-Protein Kinase Met 3 4
  • Scatter Factor Receptor 3 4
  • Proto-Oncogene C-Met 3 4
  • HGF/SF Receptor 3 4
  • HGF Receptor 3 4
  • SF Receptor 3 4
  • EC 2.7.10.1 4 61
  • Met Proto-Oncogene 2
  • EC 2.7.10 61
  • DFNB97 3
  • AUTS9 3
  • RCCP2 3
  • C-Met 3
  • HGFR 3

External Ids for MET Gene

Previous GeneCards Identifiers for MET Gene

  • GC07P114790
  • GC07P115853
  • GC07P115866
  • GC07P115906
  • GC07P116099
  • GC07P116312
  • GC07P110678

Summaries for MET Gene

Entrez Gene Summary for MET Gene

  • 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]

CIViC summary for MET Gene

  • 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.

GeneCards Summary for MET Gene

MET (MET Proto-Oncogene, Receptor Tyrosine Kinase) is a Protein Coding gene. Diseases associated with MET include Renal Cell Carcinoma, Papillary and Autosomal Recessive Nonsyndromic Deafness 97. Among its related pathways are Development IGF-1 receptor signaling and GPCR Pathway. 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.

UniProtKB/Swiss-Prot for MET Gene

  • 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).

  • Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.

Tocris Summary for MET Gene

  • 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.

Gene Wiki entry for MET Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MET Gene

Genomics for MET Gene

Products:

  1. Regulatory Element

Regulatory Elements for MET Gene

Enhancers for MET Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH07G116775 1.5 Ensembl ENCODE dbSUPER 34.3 +104.7 104666 2.6 HDGF ATF1 PKNOX1 ARNT YY1 ZNF766 GATA2 FOS MCM3 NCOA1 MET ENSG00000243243 ENSG00000235427 ENSG00000243220 CAPZA2 GC07P116736
GH07G116715 1.8 FANTOM5 Ensembl ENCODE dbSUPER 25.9 +44.0 44046 2.5 ATF1 PKNOX1 SIN3A GLI4 BRCA1 ZNF2 YY1 GATA2 ZNF302 FOS MET ST7-AS1 GC07M116730
GH07G116780 1.3 Ensembl ENCODE dbSUPER 29.7 +109.3 109333 3.3 NFIB FEZF1 RAD21 TCF12 ZNF121 ELK1 SCRT2 FOS RCOR1 ZHX2 MET CAPZA2 ENSG00000235427 CFTR GC07P116736
GH07G116800 1.6 Ensembl ENCODE dbSUPER 19.3 +131.2 131179 6.9 FOXA2 PKNOX1 ARNT ARID4B SIN3A FEZF1 ZNF2 FOS DEK SP3 MET CAPZA2 GC07P116736
GH07G116797 1.1 ENCODE dbSUPER 21.1 +125.7 125738 1.7 HDAC1 ARNT KLF17 RAD21 CHAMP1 GATA2 ZNF654 NCOA1 CEBPB ZEB2 MET CAPZA2 GC07P116736
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around MET on UCSC Golden Path with GeneCards custom track

Promoters for MET Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000328007 410 2401 MLX ARNT ZFP64 ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 ZNF143
ENSR00000217156 1910 201 PRDM6 JUNB SP7 ZNF101 EZH2

Transcription factor binding sites by QIAGEN in the MET gene promoter:

Genomic Location for MET Gene

Chromosome:
7
Start:
116,672,390 bp from pter
End:
116,798,386 bp from pter
Size:
125,997 bases
Orientation:
Plus strand

Genomic View for MET Gene

Genes around MET on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MET Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MET Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for MET Gene

Proteins for MET Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for MET Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P08581-MET_HUMAN
    Recommended name:
    Hepatocyte growth factor receptor
    Protein Accession:
    P08581
    Secondary Accessions:
    • A1L467
    • B5A932
    • E7EQ94
    • O60366
    • Q12875
    • Q9UDX7
    • Q9UPL8

    Protein attributes for MET Gene

    Size:
    1390 amino acids
    Molecular mass:
    155541 Da
    Quaternary structure:
    • 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. Interacts with LECT2; this interaction may have an antagonistic effect on receptor activation (PubMed:27334921). Interacts with HSP90AA1 and HSP90AB1; the interaction suppresses MET kinase activity (PubMed:26517842).

    Three dimensional structures from OCA and Proteopedia for MET Gene

    Alternative splice isoforms for MET Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MET Gene

Protein Expression for MET Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for MET Gene

P08581:
  • IGRGHFGCVYHGTLLDND
  • KANLSGG
  • KSEMNVNM
  • SPILTSGDSD
  • VDTYYDDQLISCGSV
  • FLWLKKRKQ
  • DNINMAL
  • SVRRLKET
  • LHEHHIFLGATNYIYVLNEEDLQKVAE
  • SGGVWKDN
  • RDLAARN
  • SCTLTLSEST
  • APLEGGT
  • GNENVLEIKGNDIDPEAVKGEVLKVGNKSCE
  • LVQAVQHVVIGP
  • EYKTGPV
  • IDPEAVKGEVLKVGNKSCENIH
  • LDSHPVS
  • MNVNMKYQLPNFTA
  • VLLGNESC
  • KGDLTIANLGTSEGRF
  • STVLGKVIVQPDQN
  • AVLCTVP
  • KPGAQLA
  • LIGFGLQVA
  • LPVKWMA
  • GFMFLTDQSY
  • SILECYTP
  • NSSYFPDH
  • KDRFINFFVGNTI
  • GVFAQSKPDSAEPM
  • ELVSRISAIFS
  • CPDCVVSALG
  • FVQCGWC
  • HVVIGPSSLIVHFNEVIGRGHFGCVYHGTLLD
  • LGKVIVQPDQNFTGLI
  • GECKEAL
  • DEYRTEFTTA
  • TVACQHRS
  • PDQNFTGLIAGV
  • EGSPLVVLPYMKHGDLRNFIRNE
  • RGTCQRH
  • HFQSCSQCL
  • ELNIEWKQA
  • CVAPYPSLLSS
  • FIYFLTVQ
  • DLLKLNS
  • PVITSISP
  • YREDPIV
  • RPSFSELVS
  • YQLPNFTAET
  • IPLNGLGC
  • FHTRIIRFCS
  • CAFPIKY
  • GGTLLTL
  • SKYFDLIYVH
  • QPEYCPD
  • LKCTVGPA
  • DDILFGVFAQSKPDSAEP
  • FTVKVADFGLAR
  • HGTTQYSTFSYVDP
  • KQIKDLGSELVRYD
  • SGTWTQQICLPAIYKVFP
  • KLKIDLA
  • NTLKCTVG
  • KSDVWSFG
  • HTPHLDRLVSARS
  • EVMLKCWHP
  • CGWDFGF
  • FSYREDP
  • DCSSKAN
  • FLTDQSYIDVLP
  • MKDFSHPNV
  • KCVRSEEC
  • NNKFDLKKT
  • YVHNPVF
  • CRQVQYPLTD
  • FFNKIVNKNNV
  • EMPLECILTEKR
  • LECYTPAQ
  • FRDSYPIKY
  • EDPIVYEIHPTKSFISGGSTITG
  • TGPVLEHP
  • DLFMGQF
  • DKEYYSV
  • WMALESL
  • GKNLNSVS
  • EVFNILQAAYV
  • FVHRDLA
  • TCTLKSVS
  • LHSISVRR
  • VLLTSISTF
  • FEKPVMIS

Post-translational modifications for MET Gene

  • 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.
  • Ubiquitinated. Ubiquitination by CBL regulates MET endocytosis, resulting in decreasing plasma membrane receptor abundance, and in endosomal degradation and/or recycling of internalized receptors.
  • Ubiquitination at posLast=962962
  • Glycosylation at posLast=4545, posLast=106106, Asn149, posLast=202202, Asn399, posLast=405405, Asn607, Asn635, Asn785, posLast=879879, and posLast=930930
  • Modification sites at PhosphoSitePlus

Other Protein References for MET Gene

ENSEMBL proteins:
REFSEQ proteins:

Assay Products

  • Cloud-Clone Corp Assay Kits for MET

Domains & Families for MET Gene

Gene Families for MET Gene

HGNC:
IUPHAR :

Protein Domains for MET Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for MET Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P08581

UniProtKB/Swiss-Prot:

MET_HUMAN :
  • The kinase domain is involved in SPSB1 binding.
  • Belongs to the protein kinase superfamily. Tyr protein kinase family.
Domain:
  • The kinase domain is involved in SPSB1 binding.
  • The beta-propeller Sema domain mediates binding to HGF.
Family:
  • Belongs to the protein kinase superfamily. Tyr protein kinase family.
genes like me logo Genes that share domains with MET: view

Function for MET Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for MET Gene

GENATLAS Biochemistry:
met proto-oncogene,transmembrane receptor (tyrosine kinase) for hepatocyte growth factor,with two alternatively spliced isoforms,important regulator of cell proliferation and differentiation,organ regeneration,embryogenesis and tumorogenesis,amplified in the glioblastomas,mutated in childhood hepatocellular carcinomas and hereditary papillary renal carcinomas (role in the acceleration of carcinogenesis),paralog to MST1R
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
UniProtKB/Swiss-Prot EnzymeRegulation:
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.
UniProtKB/Swiss-Prot 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. May regulate cortical bone osteogenesis (By similarity).
UniProtKB/Swiss-Prot Function:
Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.

Enzyme Numbers (IUBMB) for MET Gene

Gene Ontology (GO) - Molecular Function for MET Gene

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 IEA --
GO:0005008 hepatocyte growth factor-activated receptor activity TAS 10871856
genes like me logo Genes that share ontologies with MET: view
genes like me logo Genes that share phenotypes with MET: view

Human Phenotype Ontology for MET Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for MET Gene

MGI Knock Outs for MET:

Animal Model Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for MET

No data available for Transcription Factor Targets and HOMER Transcription for MET Gene

Localization for MET Gene

Subcellular locations from UniProtKB/Swiss-Prot for MET Gene

Membrane; Single-pass type I membrane protein.
Isoform 3: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MET gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytosol 3
cytoskeleton 2
nucleus 2
endoplasmic reticulum 2
mitochondrion 1
peroxisome 1
lysosome 1
endosome 1

Gene Ontology (GO) - Cellular Components for MET Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005622 intracellular IEA --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 1846706
GO:0009925 basal plasma membrane IDA 15314156
genes like me logo Genes that share ontologies with MET: view

Pathways & Interactions for MET Gene

SuperPathways for MET Gene

PathCards logo More details on SuperPathways for MET
SuperPathway Contained pathways
1 RET signaling
Frs2-mediated activation
.95
GRB2 events in EGFR signaling
.95
MAPK1/MAPK3 signaling
.95
Prolonged ERK activation events
.95
RAF/MAP kinase cascade
.95
SHC1 events in EGFR signaling
.95
Signaling by Leptin
.95
SOS-mediated signalling
.95
VEGFR2 mediated cell proliferation
.95
ARMS-mediated activation
.95
Signalling to ERKs
.95
Signalling to p38 via RIT and RIN
.95
Signalling to RAS
.95
Interleukin receptor SHC signaling
.95
Interleukin-3, 5 and GM-CSF signaling
.94
Interleukin-2 signaling
.94
Downstream signal transduction
.94
Signaling by PDGF
.94
DAP12 signaling
.92
RET signaling
.92
Insulin receptor signalling cascade
.92
Signaling by Insulin receptor
.92
IRS-mediated signalling
.91
Signaling by EGFR
.90
FCERI mediated MAPK activation
.90
IGF1R signaling cascade
.90
IRS-related events triggered by IGF1R
.90
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
.90
NCAM signaling for neurite out-growth
.89
DAP12 interactions
.89
NGF signalling via TRKA from the plasma membrane
.87
MAPK family signaling cascades
.87
Signaling by SCF-KIT
.85
Signalling by NGF
.81
Fc epsilon receptor (FCERI) signaling
.79
VEGFA-VEGFR2 Pathway
.78
Signaling by VEGF
.76
Gastrin-CREB signalling pathway via PKC and MAPK
.56
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
Negative regulation of the PI3K/AKT network
.93
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
.93
PIP3 activates AKT signaling
.91
Role of LAT2/NTAL/LAB on calcium mobilization
.91
GAB1 signalosome
.89
PI3K/AKT activation
.89
Constitutive Signaling by Aberrant PI3K in Cancer
.75
PI3K/AKT Signaling in Cancer
.72
5 MET promotes cell motility
MET promotes cell motility
.45
Signaling by MET
.45
MET activates PTK2 signaling
.01
MET activates RAP1 and RAC1
.01
MET activates RAS signaling
.01
MET interacts with TNS proteins
.01
MET Receptor Activation
.01
MET receptor recycling
.01
genes like me logo Genes that share pathways with MET: view

SIGNOR curated interactions for MET Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MET Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0001886 endothelial cell morphogenesis IDA 14500721
GO:0006468 protein phosphorylation IEA --
GO:0007165 signal transduction TAS 1846706
GO:0007166 cell surface receptor signaling pathway NAS 2819873
genes like me logo Genes that share ontologies with MET: view

Drugs & Compounds for MET Gene

Products:

  1. Drug

(134) Drugs for MET Gene - From: DrugBank, PharmGKB, ClinicalTrials, ApexBio, DGIdb, FDA Approved Drugs, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Crizotinib Approved Pharma Inhibition, Biomarker, inhibitor, Target C-MET/ALK inhibitor,potent and ATP-competitve, cMET Inhibitors, Kinase Inhibitors, Anaplastic lymphoma kinase (ALK) inhibitor, Potent c-MET/ALK inhibitor 104
cabozantinib Approved Pharma inhibitor, Target, antagonist Kinase Inhibitors, Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) inhibitors 0
Cometriq Approved November 2012 Pharma Inhibition, inhibitor, Biomarker RTK, HGFR, VEGFR2, KIT, Flt3, and Tie-2 inhibitor, cMET Inhibitors 0
Cetuximab Approved Pharma EGFR Inhibitors, Therapeutic Antibodies, Epidermal growth factor receptor (EGFR) inhibitors 752
Docetaxel Approved May 1996, Investigational Pharma Microtubulin disassembly inhibitor, Tubulin and VEGF inhibitor, Taxanes, Microtubule stabilizer 1967

(31) Additional Compounds for MET Gene - From: Novoseek, Tocris, and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
 Full agonist, Agonist 58-64-0
PF 04217903 mesylate
956906-93-7

(5) Tocris Compounds for MET Gene

Compound Action Cas Number
Crizotinib Potent c-MET/ALK inhibitor 877399-52-5
PF 04217903 mesylate Highly selective MET inhibitor 956906-93-7
PHA 665752 Potent and selective MET inhibitor 477575-56-7
SU 11274 Selective inhibitor of MET kinase activity 658084-23-2
SU 5416 VEGFR inhibitor. Also inhibits KIT, RET, MET and FLT3 204005-46-9

(33) ApexBio Compounds for MET Gene

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
BMS-817378 Potent ATP competitive inhibitor of Met/VEGFR2 1174161-69-3
Cabozantinib (XL184, BMS-907351) VEGFR2/Met/Ret/Kit/FLT//AXL inhibitor 849217-68-1
Cabozantinib malate (XL184) MET andVEGF receptor2 inhibitor 1140909-48-3
c-Met inhibitor 1 Inhibitor of the c-Met receptor 1357072-61-7
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
LY2801653 dihydrochloride MET inhibitor 1206801-37-7
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
MK-8033 hydrochloride C-Met/Ron inhibitor 1283000-43-0
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
Tyrosine kinase inhibitor Tyrosine-kinase inhibitor 1021950-26-4
ZM 323881 HCl 193000-39-4
genes like me logo Genes that share compounds with MET: view

Drug Products

Transcripts for MET Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for MET Gene

(6) REFSEQ mRNAs :
(31) Additional mRNA sequences :
(254) Selected AceView cDNA sequences:
(7) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for MET Gene

Met proto-oncogene (hepatocyte growth factor receptor):
Representative Sequences:

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for MET

Alternative Splicing Database (ASD) splice patterns (SP) for MET Gene

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:

Relevant External Links for MET Gene

GeneLoc Exon Structure for
MET
ECgene alternative splicing isoforms for
MET

Expression for MET Gene

Products:

  1. Primer

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MET Gene

mRNA expression in normal human tissues for MET Gene
mRNA expression by BioGPS for MET GenemRNA expression by GTEx for MET Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for MET Gene

This gene is overexpressed in Serum (29.7), Amniocyte (16.0), Breast (8.5), and Pancreas (6.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for MET Gene



NURSA nuclear receptor signaling pathways regulating expression of MET Gene:

MET

SOURCE GeneReport for Unigene cluster for MET Gene:

Hs.132966

mRNA Expression by UniProt/SwissProt for MET Gene:

P08581-MET_HUMAN
Tissue specificity: 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).

Evidence on tissue expression from TISSUES for MET Gene

  • Liver(4.6)
  • Nervous system(4.6)
  • Lung(3.4)
  • Intestine(3.1)
  • Kidney(2.9)
  • Heart(2.4)
  • Muscle(2.4)
  • Stomach(2.4)
  • Lymph node(2.3)
  • Skin(2.3)
  • Thyroid gland(2.3)
  • Blood(2.2)
  • Pancreas(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for MET Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • nervous
  • reproductive
  • skeletal muscle
  • skeleton
  • urinary
Organs:
Head and neck:
  • brain
  • cerebellum
  • cranial nerve
  • ear
  • eye
  • head
  • inner ear
  • middle ear
  • mouth
  • outer ear
  • salivary gland
  • skull
Thorax:
  • breast
  • esophagus
Abdomen:
  • kidney
  • liver
  • spleen
Pelvis:
  • testicle
Limb:
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • nail
  • toe
  • upper limb
General:
  • blood vessel
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • skin
genes like me logo Genes that share expression patterns with MET: view

Primer Products

No data available for mRNA differential expression in normal tissues and Protein tissue co-expression partners for MET Gene

Orthologs for MET Gene

This gene was present in the common ancestor of animals.

Orthologs for MET Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia MET 34 35
  • 99.52 (n)
dog
(Canis familiaris)
 Mammalia MET 34 35
  • 90.92 (n)
cow
(Bos Taurus)
 Mammalia MET 34 35
  • 90.46 (n)
mouse
(Mus musculus)
 Mammalia Met 34 16 35
  • 86.44 (n)
rat
(Rattus norvegicus)
 Mammalia Met 34
  • 85.17 (n)
oppossum
(Monodelphis domestica)
 Mammalia MET 35
  • 85 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia MET 35
  • 81 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves C-MET 35
  • 74 (a)
 OneToOne
MET 34
  • 72.08 (n)
lizard
(Anolis carolinensis)
 Reptilia MET 35
  • 70 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia met 34
  • 66.01 (n)
African clawed frog
(Xenopus laevis)
 Amphibia met-A 34
zebrafish
(Danio rerio)
 Actinopterygii met 34 35
  • 56.06 (n)
Dr.18290 34
worm
(Caenorhabditis elegans)
 Secernentea F11E6.8 36
  • 46 (a)
T14E8.1a 36
  • 39 (a)
T14E8.1b 36
  • 39 (a)
kin-16 36
  • 36 (a)
kin-23 36
  • 33 (a)
R09D1.12 36
  • 33 (a)
F09A5.2 36
  • 31 (a)
F09G2.1 36
  • 31 (a)
R09D1.13 36
  • 31 (a)
svh-2 35
  • 19 (a)
 OneToMany
sea squirt
(Ciona savignyi)
 Ascidiacea -- 35
  • 46 (a)
 OneToMany
sea squirt
(Ciona intestinalis)
 Ascidiacea Cin.8531 34
Species where no ortholog for MET was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MET Gene

ENSEMBL:
Gene Tree for MET (if available)
TreeFam:
Gene Tree for MET (if available)

Paralogs for MET Gene

Paralogs for MET Gene

(94) SIMAP similar genes for MET Gene using alignment to 22 proteins:

genes like me logo Genes that share paralogs with MET: view

Variants for MET Gene

Sequence variations from dbSNP and Humsavar for MET Gene

SNP ID Clin Chr 07 pos Sequence Context AA Info Type
rs121913243 Pathogenic, Renal cell carcinoma papillary (RCCP) [MIM:605074] 116,777,410(+) ATATC(A/C/G)TGGGA nc-transcript-variant, reference, missense
rs121913244 Renal cell carcinoma papillary (RCCP) [MIM:605074] 116,777,409(+) TATAT(C/T)ATGGG nc-transcript-variant, reference, missense
rs121913245 Renal cell carcinoma papillary (RCCP) [MIM:605074] 116,783,420(+) GTGGA(C/T)GGCTT nc-transcript-variant, reference, missense
rs121913246 Pathogenic, Renal cell carcinoma papillary (RCCP) [MIM:605074] 116,783,360(+) CATGT(A/G)TGATA nc-transcript-variant, reference, missense
rs121913247 Uncertain significance, Renal cell carcinoma papillary (RCCP) [MIM:605074] 116,783,359(+) ACATG(C/T)ATGAT nc-transcript-variant, reference, missense

Structural Variations from Database of Genomic Variants (DGV) for MET Gene

Variant ID Type Subtype PubMed ID
esv1092803 CNV insertion 17803354
esv274927 CNV gain+loss 21479260
nsv1018515 CNV loss 25217958
nsv1024485 CNV gain 25217958
nsv1110498 CNV duplication 24896259
nsv1146334 CNV duplication 26484159
nsv366908 CNV insertion 16902084
nsv7405 OTHER inversion 18451855
nsv831107 CNV gain 17160897

Variation tolerance for MET Gene

Residual Variation Intolerance Score: 22.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.48; 64.37% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for MET Gene

Human Gene Mutation Database (HGMD)
MET
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MET

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MET Gene

Disorders for MET Gene

MalaCards: The human disease database

(57) MalaCards diseases for MET Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
renal cell carcinoma, papillary
  • renal cell carcinoma
autosomal recessive nonsyndromic deafness 97
  • autosomal recessive deafness 97
hepatocellular carcinoma
  • hepatocellular carcinoma, somatic
autism 9
autosomal recessive non-syndromic sensorineural deafness type dfnb
  • autosomal recessive isolated neurosensory deafness type dfnb
- elite association - COSMIC cancer census association via MalaCards
Search MET in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

MET_HUMAN
  • Deafness, autosomal recessive, 97 (DFNB97) [MIM:616705]: A 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. {ECO:0000269 PubMed:25941349}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Hepatocellular carcinoma (HCC) [MIM:114550]: A 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. {ECO:0000269 PubMed:9927037}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Note=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.
  • Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein.
  • Note=Defects in MET may be associated with gastric cancer.
  • Note=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.
  • Osteofibrous dysplasia (OSFD) [MIM:607278]: A 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. {ECO:0000269 PubMed:26637977}. Note=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. {ECO:0000269 PubMed:26637977}.
  • Renal cell carcinoma papillary (RCCP) [MIM:605074]: A 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. {ECO:0000269 PubMed:10327054, ECO:0000269 PubMed:10417759, ECO:0000269 PubMed:10433944, ECO:0000269 PubMed:9140397, ECO:0000269 PubMed:9563489}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for MET

Genetic Association Database (GAD)
MET
Human Genome Epidemiology (HuGE) Navigator
MET
Tumor Gene Database (TGDB):
MET
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
MET
genes like me logo Genes that share disorders with MET: view

No data available for Genatlas for MET Gene

Publications for MET Gene

  1. A mutation of MET, encoding hepatocyte growth factor receptor, is associated with human DFNB97 hearing loss. (PMID: 25941349) Mujtaba G. … Naz S. (J. Med. Genet. 2015) 2 3 4 64
  2. Ethnic differences and functional analysis of MET mutations in lung cancer. (PMID: 19723643) Krishnaswamy S. … Salgia R. (Clin. Cancer Res. 2009) 3 22 46 64
  3. Met gene copy number predicts the prognosis for completely resected non-small cell lung cancer. (PMID: 19037978) Okuda K. … Fujii Y. (Cancer Sci. 2008) 3 22 46 64
  4. Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. (PMID: 18593464) Jin P. … Paleolog E.M. (Arthritis Res. Ther. 2008) 3 4 22 64
  5. A genetic variant that disrupts MET transcription is associated with autism. (PMID: 17053076) Campbell D.B. … Levitt P. (Proc. Natl. Acad. Sci. U.S.A. 2006) 3 4 46 64

Products for MET Gene