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

Gene ID: 4233, updated on 24-Nov-2020

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
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
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

Genomic context

See MET in Genome Data Viewer
Location:
7q31.2
Exon count:
24
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 7 NC_000007.14 (116672196..116798386)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (116312406..116438440)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene caveolin 1 Neighboring gene greater CFTR locus negative regulatory element NR2 Neighboring gene cytosolic oncogenic antisense to MET transcript Neighboring gene greater CFTR locus negative regulatory element CR3 Neighboring gene greater CFTR locus negative regulatory element CR5 Neighboring gene greater CFTR locus negative regulatory element CR6 Neighboring gene greater CFTR locus negative regulatory element CR8 Neighboring gene HNF1 motif-containing MPRA enhancer 7 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 Neighboring gene greater CFTR locus negative regulatory element CR9

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
Deafness, autosomal recessive 97
MedGen: C4084709 OMIM: 616705 GeneReviews: Not available
Compare labs
Discovery and refinement of loci associated with lipid levels.
GeneReviews: Not available
Genetic determinants of P wave duration and PR segment.
GeneReviews: Not available
Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis.
GeneReviews: Not available
Hepatocellular carcinoma
MedGen: C2239176 OMIM: 114550 GeneReviews: Not available
Compare labs
Osteofibrous dysplasia
MedGen: C4085248 OMIM: 607278 GeneReviews: Not available
Compare labs
Renal cell carcinoma, papillary, 1
MedGen: C0007134 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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
hepatocyte growth factor-activated receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein phosphatase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein tyrosine kinase activity NAS
Non-traceable Author Statement
more info
PubMed 
protein tyrosine kinase activity TAS
Traceable Author Statement
more info
 
semaphorin receptor activity IEA
Inferred from Electronic Annotation
more info
 
transmembrane receptor protein tyrosine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Process Evidence Code Pubs
MAPK cascade TAS
Traceable Author Statement
more info
 
branching morphogenesis of an epithelial tube IMP
Inferred from Mutant Phenotype
more info
PubMed 
cell migration IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cell surface receptor signaling pathway NAS
Non-traceable Author Statement
more info
PubMed 
endothelial cell morphogenesis IDA
Inferred from Direct Assay
more info
PubMed 
entry of bacterium into host cell TAS
Traceable Author Statement
more info
 
establishment of skin barrier IMP
Inferred from Mutant Phenotype
more info
PubMed 
hepatocyte growth factor receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
liver development IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
multicellular organism development IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of Rho protein signal transduction IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of autophagy NAS
Non-traceable Author Statement
more info
PubMed 
negative regulation of guanyl-nucleotide exchange factor activity IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of hydrogen peroxide-mediated programmed cell death IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of stress fiber assembly IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of thrombin-activated receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
nervous system development IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
neuron differentiation IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
pancreas development IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
peptidyl-tyrosine phosphorylation IEA
Inferred from Electronic Annotation
more info
 
phagocytosis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of endothelial cell chemotaxis IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of microtubule polymerization IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of protein kinase B signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of protein kinase B signaling TAS
Traceable Author Statement
more info
 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
semaphorin-plexin signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
transmembrane receptor protein tyrosine kinase signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Component Evidence Code Pubs
basal plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
basal plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
cell surface HDA PubMed 
extracellular region IEA
Inferred from Electronic Annotation
more info
 
integral component of membrane NAS
Non-traceable Author Statement
more info
PubMed 
integral component of plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
receptor complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 

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_006716053.1
XP_011514525.1

NCBI Reference Sequences (RefSeq)

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
    P08581
    UniProtKB/TrEMBL
    A0A024R759
    Related
    ENSP00000380860.3, ENST00000397752.7
    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: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
    pfam07714
    Location:10781337
    Pkinase_Tyr; Protein tyrosine kinase
  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
    UniProtKB/Swiss-Prot
    P08581
    UniProtKB/TrEMBL
    A0A024R728
    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
    E6Y365
    Related
    ENSP00000410980.2, ENST00000436117.2
    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: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p13 Primary Assembly

    Range
    116672196..116798386
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011516223.1XP_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_006715990.2XP_006716053.1  hepatocyte growth factor receptor isoform X2

    See identical proteins and their annotated locations for XP_006716053.1

    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

RNA

  1. XR_001744772.1 RNA Sequence

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