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FLASH GENE
Symbol MET contributors: mct/shn - updated : 28-10-2016
HGNC name met proto-oncogene (hepatocyte growth factor receptor)
HGNC id 7029
Corresponding disease
AUTS9 autism spectrum disorder, 9
DFNB97 deafness, autosomal recessive 97
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
    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
  • USP8 is involved in deubiquitination of LRIG1, influencing the efficiency of MET degradation
  • 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 , DFNB97
    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