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FLASH GENE
Symbol ADAM15 contributors: mct - updated : 23-06-2017
HGNC name ADAM metallopeptidase domain 15
HGNC id 193
Location 1q21.3      Physical location : 155.023.761 - 155.035.252
Synonym name
  • metargidin
  • a disintegrin and metalloproteinase domain 15 (metargidin)
  • metalloproteinase-like, disintegrin-like, and cysteine-rich protein 15
  • metalloprotease RGD disintegrin protein
  • Synonym symbol(s) MDC15
    EC.number 3.4.24.-
    DNA
    TYPE functioning gene
    STRUCTURE 11.50 kb     23 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • three potential Sp1-binding sites, and mutations in each Sp1 site confirmed each was needed for full activity, while mutation of all three sites abrogated luciferase activity demonstrating that Sp1 was involved in the promoter activity of ADAM15; methylation of this promoter fragment abolished the activity
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 splicing 2823 - 814 - 2009 19718658
    19 splicing 2753 - 772 - 2009 19718658
    22 splicing 2898 - 839 - 2009 19718658
    22 splicing 2895 - 838 - 2009 19718658
  • contain one or both of the two almost identical proline-rich regions encoded by exons 20 and 21, wherein the residues RxLPxxP were found to be indispensable for nephrocystin SH3 binding
  • 23 splicing 2967 - 862 - 2009 19718658
    contain one or both of the two almost identical proline-rich regions encoded by exons 20 and 21, wherein the residues RxLPxxP were found to be indispensable for nephrocystin SH3 binding
    23 splicing 2970 - 863 - 2009 19718658
    contain one or both of the two almost identical proline-rich regions encoded by exons 20 and 21, wherein the residues RxLPxxP were found to be indispensable for nephrocystin SH3 binding
    21 - 2882 - 824 - 2009 19718658
    21 - 2854 - 796 - 2009 19718658
    - - 2242 - 633 - 2009 19718658
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
    Digestivemouthtongue  highly
    Endocrinepancreas   highly
    Reproductivefemale systemuteruscervix highly
    Respiratoryrespiratory tracttrachea  highly
    Skin/Tegumentskin     Homo sapiens
    Urinarykidneynephronrenal capsuleglomerulus 
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningepidermis   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    Skeletonosteoblast Homo sapiens
    Skeletonosteoclast Homo sapiens
    Skin/Tegumentmelanocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one EGF-like domain
  • an Arg-Gly-Asp (RGD) motif in its disintegrin-like domain, interacting with the integrin alphaIIbbeta3 on platelets
  • a metalloproteinase domain
  • conjugated MetalloP
    HOMOLOGY
    interspecies homolog to murine Adam15
    Homologene
    FAMILY
  • peptidase family M12B
  • adamalysin protein family
  • CATEGORY adhesion
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,adherens
        intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    text type 1 membrane protein
    basic FUNCTION
  • may be involved in cell-surface proteolysis, cell adhesion or intracellular protein maturation
  • involved in the restructuring of the mesangial matrix and in the migration of mesangial cells in disease
  • adhesion receptor for platelet GPIIb-IIIa and induces platelet activation
  • overexpressed in adenocarcinoma and highly associated with metastatic progression of prostate and breast cancers
  • involved in cell migration and invasion
  • could drive ITGA5 expression on cell surface via down-regulation of phosphorylated ERK1/2, novel mechanism by which ADAM15 regulates cell-matrix adhesion and migration
  • contribute to the development of vascular inflammation
  • having a novel function in regulating endothelial barrier properties
  • is required for normal skeletal homeostasis and its absence causes increased nuclear translocation of CTNNB1 in osteoblasts leading to increased osteoblast proliferation and function, which results in higher trabecular and cortical bone mass
  • primary role of ADAM15 for exosome-mediated tumor suppression, as well as functional significance of exosomal ADAM protein in antitumor immunity
  • is involved in tumor progression and suppression
  • dispensable for cutaneous wound healing and B16F1 melanoma growth, but significantly contributing to metastasis formation
  • plays an unexpected role in TLR signaling, acting as an anti-inflammatory molecule through impairment of TICAM1-mediated TLR signaling
  • is released into the extracellular space as an exosomal component, and ADAM15-rich exosomes have tumor suppressive functions
  • pro-metastatic role of ADAM15 in lung cancer pogression, suggesting a novel mechanism of ADAM15 in promoting cancer cell invasion through directly targeting MMP9 activation
  • catalytically active disintegrin membrane metalloproteinases that function as molecular signaling switches, shed membrane bound growth factors and/or cleave and inactivate cell adhesion molecules
  • role of ADAM15 in the invasion of human bladder cancer
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor,
  • Zn2+
  • protein
  • ITGAV
  • endophilin 1and sorting nexin 9
  • involved in proteolysis of ADAM10 with ADAM9 and the gamma secretase complex
  • exerts an antiapoptotic effect on osteoarthritic chondrocytes via up-regulation of XIAP
  • PTK2 is a critical intracellular adaptor for ADAM15-dependent enhancement of PTK2/SRC activation
  • is a novel TCAM1-interacting partner
  • participates likely in fertilization through a physical interaction with GRN
  • cell & other
  • platelet-ADAM15 interactions involved in thrombus formation
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in atherosclerotic lesions, in atrial fibrillation
    tumoral     --over  
    in breast cancer and in gastric carcinoma
    constitutional     --over  
    in osteoarthritic (OA) cartilage
    tumoral     --over  
    in pancreatiic cancer
    tumoral     --low  
    in melanoma metastasis compared to primary melanoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularatheroma 
    target for antithrombotic strategies in cardiovascular pathologies
    cancerskin 
    may represent an important protein for the treatment of melanoma
    cancerurinary 
    therapeutic target in patients with advanced bladder cancer
    ANIMAL & CELL MODELS
    Adam15(-/-) mice displayed an increase in bone volume and thickness with an increase in the number and activity of osteoblasts, whereas osteoclasts were apparently unaffected