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FLASH GENE
Symbol MET contributors: mct/shn - updated : 28-10-2015
HGNC name met proto-oncogene (hepatocyte growth factor receptor)
HGNC id 7029
Corresponding disease
AUTS9 autism spectrum disorder, 9
HPRC hereditary papillary renal carcinoma
OSFD Osteofibrous dysplasia
Location 7q31.2      Physical location : 116.312.458 - 116.438.439
Synonym name
  • HGF/SF receptor
  • Met proto-oncogene tyrosine kinase
  • scatter factor receptor
  • HGF receptor
  • SF receptor
  • oncogene MET
  • hepatocyte growth factor receptor
  • proto-oncogene c-Met
  • tyrosine-protein kinase Met
  • Synonym symbol(s) HGFR, RCCP2, c-Met, AUTS9
    EC.number 2.7.10.1
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head
    STRUCTURE 126.00 kb     21 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • seven repeats of the consensus binding site for the Sp family
  • a LINE regulator sequence in intron 2
  • MAPPING cloned Y linked Y status confirmed
    Map cen - D7S486 - D7S522 - MET - D7S633 - D7S677 - qter
    Physical map
    LRRN3 7q21.12 leucine rich repeat neuronal 3 LOC392092 7 similar to Argininosuccinate synthase (Citrulline--aspartate ligase) DOCK4 7q21.13-q31.1 similar to Argininosuccinate synthase (Citrulline--aspartate ligase) ZNF277 7q31.1 zinc finger protein (C2H2 type) 277 IFRD1 7q31 interferon-related developmental regulator 1 FLJ39575 7q31.1 hypothetical protein FLJ39575 NPM1P14 7q31.1 nucleophosmin 1 (nucleolar phosphoprotein B23, numatrin) pseudogene 14 FLJ13576 7q31.32 hypothetical protein FLJ13576 FLJ31818 7q31.1 hypothetical protein FLJ31818 GPR85 7q31 G protein-coupled receptor 85 LOC389548 7 hypothetical gene supported by BX537645 PPP1R3A 7q11.23 protein phosphatase 1, regulatory (inhibitor) subunit 3A (glycogen and sarcoplasmic reticulum binding subunit, skeletal muscle) FOXP2 7q31 forkhead box P2 HIC 7q31.1 forkhead box P2 TFEC 7q31.2 transcription factor EC TES 7q31.2 testis derived transcript (3 LIM domains) CAV2 7q31.1-q31.2 caveolin 2 CAV1 7q31.2-q31.3 caveolin 1, caveolae protein, 22kDa MET 7q31.2-q31.3 met proto-oncogene (hepatocyte growth factor receptor) CAPZA2 7q31.2-q31.3 capping protein (actin filament) muscle Z-line, alpha 2 ST7 7q31.1-q31.3 suppression of tumorigenicity 7 WNT2 7q31 wingless-type MMTV integration site family member 2 GASZ 7q31.31 GASZ CFTR 7q31.3 cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7) CORTBP2 7q31.3 cortactin binding protein 2 LSM8 7q31.1-q31.3 LSM8 homolog, U6 small nuclear RNA associated (S. cerevisiae) ANKRD7 7q31 ankyrin repeat domain 7 KCND2 7q31-q32 potassium voltage-gated channel, Shal-related subfamily, member 2 TM4SF12 7 transmembrane 4 superfamily member 12 ING3 7q31 inhibitor of growth family, member 3 FLJ21986 7q31.32 hypothetical protein FLJ21986 WNT16 7q31 wingless-type MMTV integration site family, member 16 FAM3C 7q22.1-q31.1 family with sequence similarity 3, member C HCP19 7q31.32 cytochrome c, somatic pseudogene LOC136143 7q31.32 similar to ribosomal protein L18; 60S ribosomal protein L18 PTPRZ1 7q31.3 protein tyrosine phosphatase, receptor-type, Z polypeptide 1 AASS 7q31.3 aminoadipate-semialdehyde synthase LOC389549 7 similar to zinc finger protein 312; forebrain embryonic zinc finger
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 splicing 6641 - 1390 - 2009 19002214
    21 splicing 6695 - 1408 - 2009 19002214
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveesophagus   highly
    Hearing/Equilibriumear   highly
    Reproductivemale systemmale genital tractepididymis   Homo sapiens
    Respiratoryrespiratory tracttrachea  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivespermatozoa Homo sapiens
    cell lineage
    cell lines normal human neuronal progenitor cells, NHNPs
    fluid/secretion
    at STAGE
    Text restricted to midgestation fetal cerebral cortex in portions of the temporal and occipital lobes
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a putative 24-amino acid signal peptide
  • a plexin repeat and a SEMA domain
  • a large glycosylated extracellular ligand-binding domain, derived from the alpha and the N terminal portion of beta chains
  • a single hydrophobic transmembrane domain
  • a Death Defying Domain (DDD), entraping the active site of CASP3 and blocking apoptosis in hepatocytes
  • a cytoplasmic domain with intrinsic tyrosine kinase activity
  • C-terminal domain report nuclear localization
  • secondary structure a 50 kda alpha chain and a 145 kda a beta chain
    mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to Met, Mus musculus
    ortholog to MET, Pan troglodytes
    ortholog to Met , Rattus norvegicus
    intraspecies homolog to MST1R
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • CATEGORY enzyme , protooncogene , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text
  • type 1 membrane protein
  • C-terminal domain report nuclear localization
  • basic FUNCTION
  • role in late myogenesis
  • important regulator of cell proliferation and differentiation, organ regeneration, embryogenesis and tumorogenesis
  • may play a role in autism susceptibility
  • might be one of the long sought oncogenes controlling progression of primary cancers to metastasis
  • transmembrane receptor tyrosine kinase of the hepatocyte growth factor/scatter factor
  • participates in immune function, peripheral organ development and repair, and the development of the cerebral cortex and cerebellum
  • high-affinity transmembrane receptor tyrosine kinase of the hepatocyte growth factor/scatter factor
  • may play a role in autism susceptibility
  • involvement of MET in the pathogenesis of myopia in general, as well as more rapid progression in refractive error regardless of the initial refractory ability
  • playing a role in human salivary gland development
  • possible role of MET in the pathogenesis of ASD (autism spectrum disorders)
  • may act in consort with EGFR and/or be activated as a compensatory pathway in the presence of EGFR blockade in head and neck carcinoma cells
  • critical effector of TP53, suggesting that inhibition of MET may be an effective antimetastatic approach to treat cancers with TP53 mutations
  • transmembrane tyrosine kinase that can promote cell scattering, migration, and invasion
  • is a tyrosine kinase receptor that may play a role at fertilization
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text embryogenesis and carcinogenesis
    PATHWAY
    metabolism
    signaling
    receptor tyrosine kinase pathway
    a component
  • protein constituent of transmembrane
  • INTERACTION
    DNA
  • FOXP2 binds directly to the 5prime regulatory region of MET, and overexpression of FOXP2 results in transcriptional repression of MET
  • RNA
    small molecule
    protein
  • Grb2
  • c-Src kinase
  • Gab1
  • HGF (Scatter factor 1) and MSP (Scatter Factor 2)
  • E-cadherin/catenin
  • FAP68
  • alpha6beta4
  • Cbl proto-oncogene
  • beta-catenin
  • Plexin B1
  • RanBPM/RanBP9
  • hepatocyte growth factor
  • MUC20P MID:15314156
  • SNAPIN, DCOHM, VAV-1, Sorting nexin 2, Death associated protein kinase 3, SMC-1, Centromeric protein C, and hTID-1
  • SPRY domain-containing SOCS box protein 1, SSB-1
  • SH2-domain-containing inositol 5-phosphatase (SHIP)-2,
  • LRIG1
  • decorinP MID:19433454
  • C-terminus of heat shock protein 70-interacting protein? CHIP
  • role for PPLXNB1 in maintenance of melanocyte survival and proliferation in the skin, suggesting that SEMA4D and PLXNB1 act cooperatively with HGF and MET to regulate MET-dependent effects in human melanocytes
  • MUC1 drives MET-dependent migration and scattering
  • SMYD3 modulates MSTN and MET transcription in primary skeletal muscle cells
  • can directly inhibit CASP3 by way of a novel mechanism and promote hepatocyte survival
  • OVOL1 and OVOL2, are critical inducers of MET in human cancers (pMID: 24124593)
  • is an important regulator of MET receptor tyrosine kinase levels and signaling
  • SEMA3C drives activation of multiple RTKs including EGFR, ERBB2, and MET in a cognate ligand-independent manner via PLXNB1
  • TNS4 recruits signaling molecules, such as DLC1, to focal adhesions, modulates homeostasis of receptor tyrosine kinases, including EGFR and MET, and promotes cell migration
  • cell & other
    REGULATION
    Other FOXP2
    MUC20P MID:15314156
    suppressed by LRIG1
    ASSOCIATED DISORDERS
    corresponding disease(s) HPRC , AUTS9 , OSFD
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation   --over  
    in sporadic PRC
    tumoral   amplification    
    amplified in glioblastomas
    tumoral somatic mutation      
    in childhood hepatocellular carcinomas
    tumoral     --over  
    with LRRK2 in papillary renal cell carcinoma, and in papillary thyroid carcinoma
    tumoral   amplification    
    highly selective and commonly occurs in clear-cell adenocarcinoma
    tumoral somatic mutation     gain of function
    MET activating mutations are genetic markers associated with the cancers of unknown primary origin (CUPs)
    Susceptibility to autism
    Variant & Polymorphism other
  • CC genotype increasing the risk of autism (C allele results in a 2-fold decrease in MET promoter activity and altered binding of specific transcription factor complexes)
  • Candidate gene
    Marker
  • could serve as a biomarker for the prognostication of patients with clear-cell adenocarcinoma and tumor progression
  • Therapy target
    SystemTypeDisorderPubmed
    cancerhead and neck 
    dual blockade of MET and EGFR may be a promising clinical therapeutic strategy for treating HNSCC
    cancerreproductiveovary
    novel therapeutic target for ovarian clear-cell carcinoma
    cancerreproductiveprostate
    c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer
    ANIMAL & CELL MODELS
  • Mutation of Met tyrosine kinase in the mouse genome caused embryonal death, with placenta, liver, and limb muscle defects