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    Met MET proto-oncogene, receptor tyrosine kinase [ Rattus norvegicus (Norway rat) ]

    Gene ID: 24553, updated on 9-Dec-2024

    Summary

    Official Symbol
    Metprovided by RGD
    Official Full Name
    MET proto-oncogene, receptor tyrosine kinaseprovided by RGD
    Primary source
    RGD:3082
    See related
    EnsemblRapid:ENSRNOG00000052745 AllianceGenome:RGD:3082
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Rattus norvegicus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
    Also known as
    Hgfr
    Summary
    Enables several functions, including beta-catenin binding activity; hepatocyte growth factor receptor activity; and phospholipase binding activity. Involved in several processes, including neurogenesis; positive regulation of cellular component organization; and positive regulation of macromolecule metabolic process. Located in several cellular components, including excitatory synapse; postsynaptic membrane; and sperm flagellum. Biomarker of several diseases, including acute kidney failure; hepatobiliary system cancer (multiple); liver benign neoplasm; pancreatitis; and periodontitis. Human ortholog(s) of this gene implicated in autistic disorder; autosomal recessive nonsyndromic deafness 97; carcinoma (multiple); distal arthrogryposis; and multiple myeloma. Orthologous to human MET (MET proto-oncogene, receptor tyrosine kinase). [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Biased expression in Kidney (RPKM 289.7), Liver (RPKM 253.1) and 8 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:
    4q22
    Exon count:
    22
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCr8 (GCF_036323735.1) 4 NC_086022.1 (46756823..46864041)
    RS_2023_06 previous assembly mRatBN7.2 (GCF_015227675.2) 4 NC_051339.1 (45790456..45898139)
    106 previous assembly Rnor_6.0 (GCF_000001895.5) 4 NC_005103.4 (44747467..44854628)

    Chromosome 4 - NC_086022.1Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC103692063 Neighboring gene uncharacterized LOC102550745 Neighboring gene capping actin protein of muscle Z-line subunit alpha 2 Neighboring gene suppression of tumorigenicity 7 Neighboring gene 60S ribosomal protein L23a-like

    Genomic regions, transcripts, and products

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Pathways from PubChem

    General gene information

    Markers

    Gene Ontology Provided by RGD

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables GPI-linked ephrin receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables beta-catenin binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables boss receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables brain-derived neurotrophic factor receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables epidermal growth factor receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables fibroblast growth factor receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables hepatocyte growth factor receptor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables hepatocyte growth factor receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables hepatocyte growth factor receptor activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables hepatocyte growth factor receptor activity ISO
    Inferred from Sequence Orthology
    more info
     
    enables histone H2AXY142 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables histone H3Y41 kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables identical protein binding ISO
    Inferred from Sequence Orthology
    more info
     
    enables insulin receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables insulin-like growth factor receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables macrophage colony-stimulating factor receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables molecular function activator activity ISO
    Inferred from Sequence Orthology
    more info
     
    enables phosphatidylinositol 3-kinase binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables phospholipase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables placental growth factor receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables platelet-derived growth factor alpha-receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables platelet-derived growth factor beta-receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein kinase activity ISO
    Inferred from Sequence Orthology
    more info
     
    enables protein phosphatase binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein phosphatase binding ISO
    Inferred from Sequence Orthology
    more info
     
    enables protein tyrosine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein tyrosine kinase collagen receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein-containing complex binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables semaphorin receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables stem cell factor receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables transmembrane receptor protein tyrosine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables transmembrane-ephrin receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables vascular endothelial growth factor receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    acts_upstream_of D-glucose transmembrane transport ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in Kit signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within adult behavior ISO
    Inferred from Sequence Orthology
    more info
     
    acts_upstream_of_or_within brain development ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in brain-derived neurotrophic factor receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in branching morphogenesis of an epithelial tube IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in branching morphogenesis of an epithelial tube ISO
    Inferred from Sequence Orthology
    more info
     
    acts_upstream_of_or_within cardiac muscle cell development ISO
    Inferred from Sequence Orthology
    more info
     
    acts_upstream_of_or_within cardiac muscle contraction ISO
    Inferred from Sequence Orthology
    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 protein tyrosine kinase signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to arsenic-containing substance IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in cellular response to glucose stimulus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in cellular response to growth factor stimulus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in cellular response to interleukin-6 IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in cellular response to peptide hormone stimulus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in central nervous system neuron differentiation IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in chemical synaptic transmission ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in collagen-activated tyrosine kinase receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in endothelial cell morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in endothelial cell morphogenesis ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in ephrin receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in epidermal growth factor receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of establishment of localization in cell ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in establishment of skin barrier IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in establishment of skin barrier ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in excitatory postsynaptic potential ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in fibroblast growth factor receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in flagellated sperm motility IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    acts_upstream_of_or_within glucose homeostasis ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in hepatocyte growth factor receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within hepatocyte growth factor receptor signaling pathway ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in insulin receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in insulin-like growth factor receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in lactation IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in liver development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in liver development IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    acts_upstream_of_or_within liver development ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in macrophage colony-stimulating factor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in male gonad development IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in modulation of chemical synaptic transmission ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in multicellular organism development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    acts_upstream_of_or_within muscle cell migration ISO
    Inferred from Sequence Orthology
    more info
     
    acts_upstream_of_or_within muscle organ development ISO
    Inferred from Sequence Orthology
    more info
     
    acts_upstream_of_or_within myoblast proliferation ISO
    Inferred from Sequence Orthology
    more info
     
    acts_upstream_of_or_within myotube differentiation ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in negative regulation of Rho protein signal transduction IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of Rho protein signal transduction ISO
    Inferred from Sequence Orthology
    more info
     
    acts_upstream_of_or_within negative regulation of gene expression ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in negative regulation of guanyl-nucleotide exchange factor activity ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in negative regulation of hydrogen peroxide-mediated programmed cell death IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of hydrogen peroxide-mediated programmed cell death ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in negative regulation of peptidyl-threonine phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of stress fiber assembly IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of stress fiber assembly ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in negative regulation of thrombin-activated receptor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of thrombin-activated receptor signaling pathway ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in negative regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    acts_upstream_of_or_within negative regulation of transforming growth factor beta production ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in neuron differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in neuron migration IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in neuron migration IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in oligodendrocyte development IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in pancreas development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in pancreas development IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    acts_upstream_of_or_within placenta development ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in platelet-derived growth factor receptor-alpha signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in platelet-derived growth factor receptor-beta signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive chemotaxis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive chemotaxis ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in positive chemotaxis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    acts_upstream_of_or_within positive regulation of D-glucose transmembrane transport ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in positive regulation of DNA replication IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    acts_upstream_of_or_within positive regulation of MAPK cascade ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in positive regulation of dendrite morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of endothelial cell chemotaxis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of endothelial cell chemotaxis ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in positive regulation of endothelial cell chemotaxis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of microtubule polymerization IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of microtubule polymerization ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in positive regulation of mitotic nuclear division IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of neuron projection development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    acts_upstream_of_or_within positive regulation of p38MAPK cascade ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in positive regulation of peptidyl-serine phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of peptidyl-threonine phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of transcription by RNA polymerase II ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    acts_upstream_of_or_within protein autophosphorylation ISO
    Inferred from Sequence Orthology
    more info
     
    acts_upstream_of_or_within reactive oxygen species metabolic process ISO
    Inferred from Sequence Orthology
    more info
     
    acts_upstream_of_or_within regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling ISO
    Inferred from Sequence Orthology
    more info
     
    acts_upstream_of_or_within regulation of cellular response to oxidative stress ISO
    Inferred from Sequence Orthology
    more info
     
    acts_upstream_of_or_within regulation of interleukin-6 production ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in regulation of plasma membrane bounded cell projection organization IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to acidic pH IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in response to organic cyclic compound IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in response to peptide hormone IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in response to xenobiotic stimulus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in semaphorin-plexin signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in semaphorin-plexin signaling pathway ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in semaphorin-plexin signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    acts_upstream_of_or_within skeletal muscle tissue development ISO
    Inferred from Sequence Orthology
    more info
     
    involved_in vascular endothelial growth factor receptor-1 signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in vascular endothelial growth factor signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    is_active_in basal plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in basal plasma membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in basal plasma membrane ISO
    Inferred from Sequence Orthology
    more info
     
    located_in dendrite IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in excitatory synapse IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in extracellular space IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in membrane IEA
    Inferred from Electronic Annotation
    more info
     
    located_in membrane ISO
    Inferred from Sequence Orthology
    more info
     
    located_in neuronal cell body IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in postsynaptic membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of receptor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in sperm flagellum IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    hepatocyte growth factor receptor
    Names
    HGF receptor
    HGF/SF receptor
    SF receptor
    c-Met
    met proto-oncogene tyrosine kinase
    proto-oncogene c-Met
    scatter factor receptor
    tyrosine-protein kinase Met
    XP_006236191.1
    XP_038962952.1

    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.

    mRNA and Protein(s)

    1. NM_001433463.1NP_001420392.1  hepatocyte growth factor receptor isoform 2 precursor

      Status: VALIDATED

      Source sequence(s)
      JAXUCZ010000004
      UniProtKB/Swiss-Prot
      P97523, P97579, Q63119, Q63964
      UniProtKB/TrEMBL
      A0A8I6GEH2
    2. NM_031517.3NP_113705.2  hepatocyte growth factor receptor isoform 1 precursor

      Status: VALIDATED

      Source sequence(s)
      JAXUCZ010000004
      UniProtKB/Swiss-Prot
      P97523, P97579, Q63119, Q63964
      UniProtKB/TrEMBL
      A0A0G2JY19, A0A9K3Y8B9, Q2IBC7
      Related
      ENSRNOP00000104256.1, ENSRNOT00000157473.1

    RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

    Reference GRCr8

    Genomic

    1. NC_086022.1 Reference GRCr8

      Range
      46756823..46864041
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006236129.5XP_006236191.1  hepatocyte growth factor receptor isoform X1

      Related
      ENSRNOP00000070486.2, ENSRNOT00000086902.3
      Conserved Domains (8) summary
      smart00423
      Location:520562
      PSI; domain found in Plexins, Semaphorins and Integrins
      smart00429
      Location:839903
      IPT; ig-like, plexins, transcription factors
      cd01179
      Location:658741
      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:564657
      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:10831344
      PTKc_Met_Ron; Catalytic domain of the Protein Tyrosine Kinases, Met and Ron
      pfam07714
      Location:10791338
      Pkinase_Tyr; Protein tyrosine kinase
      cl15674
      Location:743838
      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:25517
      Sema; The Sema domain, a protein interacting module, of semaphorins and plexins
    2. XM_039107024.2XP_038962952.1  hepatocyte growth factor receptor isoform X2

      Related
      ENSRNOP00000085968.1, ENSRNOT00000115453.2
      Conserved Domains (7) summary
      smart00423
      Location:520562
      PSI; domain found in Plexins, Semaphorins and Integrins
      smart00429
      Location:839903
      IPT; ig-like, plexins, transcription factors
      cd01179
      Location:658741
      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:564657
      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:10361297
      PTKc_Met_Ron; Catalytic domain of the Protein Tyrosine Kinases, Met and Ron
      cl15674
      Location:743838
      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:25517
      Sema; The Sema domain, a protein interacting module, of semaphorins and plexins