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    MET MET proto-oncogene, receptor tyrosine kinase [ Homo sapiens (human) ]

    Gene ID: 4233, updated on 23-Jul-2024

    Summary

    Official Symbol
    METprovided by HGNC
    Official Full Name
    MET proto-oncogene, receptor tyrosine kinaseprovided by HGNC
    Primary source
    HGNC:HGNC:7029
    See related
    Ensembl:ENSG00000105976 MIM:164860; AllianceGenome:HGNC:7029
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    DA11; HGFR; AUTS9; RCCP2; c-Met; DFNB97
    Summary
    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]
    Expression
    Broad expression in placenta (RPKM 12.8), liver (RPKM 11.3) and 20 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See MET in Genome Data Viewer
    Location:
    7q31.2
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (116672196..116798377)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (117987305..118113574)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (116312250..116438431)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 4219 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26533 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26534 Neighboring gene Sharpr-MPRA regulatory region 9016 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18557 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18558 Neighboring gene Sharpr-MPRA regulatory region 15503 Neighboring gene caveolin 2 Neighboring gene caveolin 1 Neighboring gene Sharpr-MPRA regulatory region 6449 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18559 Neighboring gene greater CFTR locus negative regulatory element NR2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26535 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26536 Neighboring gene cytosolic oncogenic antisense to MET transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26537 Neighboring gene MPRA-validated peak6696 silencer Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr7:116273493-116274692 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18560 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18561 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18562 Neighboring gene greater CFTR locus negative regulatory element CR3 Neighboring gene greater CFTR locus negative regulatory element CR5 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr7:116363882-116365081 Neighboring gene uncharacterized LOC124901824 Neighboring gene greater CFTR locus negative regulatory element CR6 Neighboring gene greater CFTR locus negative regulatory element CR8 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr7:116412324-116413523 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr7:116416081-116417280 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:116420832-116421760 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:116421761-116422688 Neighboring gene uncharacterized LOC124901731 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr7:116496945-116497602 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:116502260-116503022 Neighboring gene RAB11 binding and LisH domain, coiled-coil and HEAT repeat containing pseudogene Neighboring gene capping actin protein of muscle Z-line subunit alpha 2

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Arthrogryposis, distal, IIa 11
    MedGen: C5774205 OMIM: 620019 GeneReviews: Not available
    Compare labs
    Autosomal recessive nonsyndromic hearing loss 97
    MedGen: C4084709 OMIM: 616705 GeneReviews: Not available
    Compare labs
    Hepatocellular carcinoma
    MedGen: C2239176 OMIM: 114550 GeneReviews: Not available
    Compare labs
    Osteofibrous dysplasia
    MedGen: C4085248 OMIM: 607278 GeneReviews: Not available
    Compare labs
    Papillary renal cell carcinoma type 1
    MedGen: C1336839 OMIM: 605074 GeneReviews: Not available
    Compare labs

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated 2012-09-06)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated 2012-09-06)

    ClinGen Genome Curation Page

    EBI GWAS Catalog

    Description
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog
    Genetic determinants of P wave duration and PR segment.
    EBI GWAS Catalog
    Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables hepatocyte growth factor receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables molecular function activator activity EXP
    Inferred from Experiment
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein phosphatase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein tyrosine kinase activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables protein tyrosine kinase activity TAS
    Traceable Author Statement
    more info
     
    enables semaphorin receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in branching morphogenesis of an epithelial tube IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cell migration IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in cell surface receptor protein tyrosine kinase signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in cell surface receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in endothelial cell morphogenesis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in establishment of skin barrier IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in excitatory postsynaptic potential ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in hepatocyte growth factor receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in liver development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in multicellular organism development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in negative regulation of Rho protein signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of autophagy NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of guanyl-nucleotide exchange factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of hydrogen peroxide-mediated programmed cell death IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of stress fiber assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of thrombin-activated receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in nervous system development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in neuron differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in pancreas development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in phagocytosis IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of endothelial cell chemotaxis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation of microtubule polymerization IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in semaphorin-plexin signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    is_active_in basal plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in basal plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cell surface HDA PubMed 
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
     
    located_in membrane NAS
    Non-traceable Author Statement
    more info
    PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     
    located_in postsynapse IEA
    Inferred from Electronic Annotation
    more info
     
    part_of receptor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     

    General protein information

    Preferred Names
    hepatocyte growth factor receptor
    Names
    HGF receptor
    HGF/SF receptor
    SF receptor
    proto-oncogene c-Met
    scatter factor receptor
    tyrosine-protein kinase Met
    NP_000236.2
    NP_001120972.1
    NP_001311330.1
    NP_001311331.1
    XP_011514525.1
    XP_047276356.1
    XP_054214230.1
    XP_054214231.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008996.1 RefSeqGene

      Range
      5001..130982
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_662

    mRNA and Protein(s)

    1. NM_000245.4NP_000236.2  hepatocyte growth factor receptor isoform b preproprotein

      See identical proteins and their annotated locations for NP_000236.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice junction at the end of an exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.
      Source sequence(s)
      AA278232, AC002080, BX648782, DB223186, X54559
      Consensus CDS
      CCDS43636.1
      UniProtKB/Swiss-Prot
      A1L467, B5A932, E7EQ94, O60366, P08581, Q12875, Q9UDX7, Q9UPL8
      Related
      ENSP00000380860.3, ENST00000397752.8
      Conserved Domains (7) summary
      cd11278
      Location:25516
      Sema_MET; The Sema domain, a protein interacting module, of MET (also called hepatocyte growth factor receptor, HGFR)
      smart00423
      Location:519561
      PSI; domain found in Plexins, Semaphorins and Integrins
      smart00429
      Location:838934
      IPT; ig-like, plexins, transcription factors
      cd01179
      Location:657740
      IPT_plexin_repeat2; Second repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present ...
      cd01180
      Location:563656
      IPT_plexin_repeat1; First repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present ...
      cd01181
      Location:742837
      IPT_plexin_repeat3; Third repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present ...
      cd05058
      Location:10821343
      PTKc_Met_Ron; Catalytic domain of the Protein Tyrosine Kinases, Met and Ron
    2. NM_001127500.3NP_001120972.1  hepatocyte growth factor receptor isoform a preproprotein

      See identical proteins and their annotated locations for NP_001120972.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
      Source sequence(s)
      AC002080, AC002543, BC130420, BX648782, DB223186, J02958
      Consensus CDS
      CCDS47689.1
      Related
      ENSP00000317272.6, ENST00000318493.11
      Conserved Domains (8) summary
      cd11278
      Location:25516
      Sema_MET; The Sema domain, a protein interacting module, of MET (also called hepatocyte growth factor receptor, HGFR)
      smart00423
      Location:519561
      PSI; domain found in Plexins, Semaphorins and Integrins
      smart00429
      Location:856952
      IPT; ig-like, plexins, transcription factors
      cd01179
      Location:657740
      IPT_plexin_repeat2; Second repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present ...
      cd01180
      Location:563656
      IPT_plexin_repeat1; First repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present ...
      cd05058
      Location:11001361
      PTKc_Met_Ron; Catalytic domain of the Protein Tyrosine Kinases, Met and Ron
      pfam07714
      Location:10961355
      Pkinase_Tyr; Protein tyrosine kinase
      cl15674
      Location:742855
      IPT; Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as Transcription factor ImmunoGlobin (TIG) domains. They are present in intracellular transcription factors, cell surface receptors (such as plexins and scatter factor ...
    3. NM_001324401.3NP_001311330.1  hepatocyte growth factor receptor isoform c precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) encodes isoform c, which lacks a portion of the beta subunit.
      Source sequence(s)
      AC002080, DB223186, EU176015
      UniProtKB/TrEMBL
      B5A929, E6Y365, H7C174
      Related
      ENSP00000398776.2, ENST00000422097.2
      Conserved Domains (6) summary
      cd11278
      Location:25516
      Sema_MET; The Sema domain, a protein interacting module, of MET (also called hepatocyte growth factor receptor, HGFR)
      smart00423
      Location:519561
      PSI; domain found in Plexins, Semaphorins and Integrins
      smart00429
      Location:838918
      IPT; ig-like, plexins, transcription factors
      cd01179
      Location:657740
      IPT_plexin_repeat2; Second repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present ...
      cd01180
      Location:563656
      IPT_plexin_repeat1; First repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present ...
      cl15674
      Location:742837
      IPT; Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as Transcription factor ImmunoGlobin (TIG) domains. They are present in intracellular transcription factors, cell surface receptors (such as plexins and scatter factor ...
    4. NM_001324402.2NP_001311331.1  hepatocyte growth factor receptor isoform d

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) encodes isoform d, which lacks a predicted signal peptide compared to isoforms a-c.
      Source sequence(s)
      AC002080, AC002543, AC004416, AI630755
      UniProtKB/TrEMBL
      B4DLF5
      Conserved Domains (8) summary
      smart00423
      Location:89131
      PSI; domain found in Plexins, Semaphorins and Integrins
      smart00429
      Location:408504
      IPT; ig-like, plexins, transcription factors
      cd01179
      Location:227310
      IPT_plexin_repeat2; Second repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present ...
      cd01180
      Location:133226
      IPT_plexin_repeat1; First repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present ...
      cd05058
      Location:652913
      PTKc_Met_Ron; Catalytic domain of the Protein Tyrosine Kinases, Met and Ron
      pfam07714
      Location:648907
      Pkinase_Tyr; Protein tyrosine kinase
      cl15674
      Location:312407
      IPT; Immunoglobulin-like fold, Plexins, Transcription factors (IPT). IPTs are also known as Transcription factor ImmunoGlobin (TIG) domains. They are present in intracellular transcription factors, cell surface receptors (such as plexins and scatter factor ...
      cl15693
      Location:186
      Sema; The Sema domain, a protein interacting module, of semaphorins and plexins

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      116672196..116798377
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011516223.2XP_011514525.1  hepatocyte growth factor receptor isoform X1

      Conserved Domains (8) summary
      cd11278
      Location:44535
      Sema_MET; The Sema domain, a protein interacting module, of MET (also called hepatocyte growth factor receptor, HGFR)
      smart00423
      Location:538580
      PSI; domain found in Plexins, Semaphorins and Integrins
      smart00429
      Location:857953
      IPT; ig-like, plexins, transcription factors
      cd01179
      Location:676759
      IPT_plexin_repeat2; Second repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present ...
      cd01180
      Location:582675
      IPT_plexin_repeat1; First repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present ...
      cd01181
      Location:761856
      IPT_plexin_repeat3; Third repeat of the IPT domain of Plexins and Cell Surface Receptors (PCSR) . Plexins are involved in the regulation of cell proliferation and of cellular adhesion and repulsion receptors. In general, there are three copies of the IPT domain present ...
      cd05058
      Location:11011362
      PTKc_Met_Ron; Catalytic domain of the Protein Tyrosine Kinases, Met and Ron
      pfam07714
      Location:10971356
      Pkinase_Tyr; Protein tyrosine kinase
    2. XM_047420400.1XP_047276356.1  hepatocyte growth factor receptor isoform X2

      UniProtKB/TrEMBL
      B5A931
      Related
      ENSP00000410980.2, ENST00000436117.3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      117987305..118113574
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054358255.1XP_054214230.1  hepatocyte growth factor receptor isoform X1

    2. XM_054358256.1XP_054214231.1  hepatocyte growth factor receptor isoform X2

      UniProtKB/TrEMBL
      B5A931