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

Gene ID: 4233, updated on 11-Apr-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
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Try the new Transcript table

Genomic context

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 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 phosphorylation IEA
Inferred from Electronic Annotation
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
 
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

    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