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FLASH GENE
Symbol ADAM8 contributors: mct - updated : 12-02-2016
HGNC name ADAM metallopeptidase domain 8
HGNC id 215
Location 10q26.3      Physical location : 135.075.920 - 135.090.407
Synonym name
  • cell diffenrentiation antigen CD156, identified by monoclonal antibodies
  • a disintegrin and metalloproteinase domain 8
  • CD156a antigen
  • cell surface antigen MS2
    • Synonym symbol(s) CD156, MS2, MGC134985, CD156a
    EC.number 3.4.24.-
    DNA
    TYPE functioning gene
    STRUCTURE 14.45 kb     24 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 - 3316 - 824 - 2007 17979891
    - - 3149 - 742 - 2010 20453887
    - - 3043 - 733 - 2010 20453887
    24 splicing 2238 80 745 - - 20453887
  • also called Delta18a
  • truncated protein, present in several tumor cell lines and not in normal cells
  • alternative splicing variants participate and contribute to the deleterious effects of tumor-derived bone metastasis
  • contained an additional exon 18 of 179&
    • 8201;bp
  • both D18a and D14prime isoforms contribute to increase invasiveness in lung cancer cells
    • 14 splicing 1620 59 5395 - 2010 20453887
  • also called Delta14 prime
  • truncated protein, present in several tumor cell lines and not in normal cells
  • expression levels were markedly increased in lung cancer cells, in conditions mimicking tumor microenvironment
  • both D18a and D14prime isoforms contribute to increase invasiveness in lung cancer cells
  • alternative splicing variants participate and contribute to the deleterious effects of tumor-derived bone metastasis
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   highly
     thymus   highly
    Nervousbrain   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    Nervouscentral  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    Blood/Hematopoieticneutrophil Homo sapiens
    Lymphoid/Immunemacrophage
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • domains similar to hemorrhagic snake venom proteins (HSVP) with a prodomain
  • a Zn-binding site metalloproteinase
  • a disintegrin-like domain
  • a cysteine-rich domain
  • an EGF-like repeat
  • a transmembrane domain
  • a proline-rich SH3 cytoplasmic tail suggesting that it interacts with other cytoplasmic proteins
    • conjugated GlycoP , MetalloP
    HOMOLOGY
    interspecies homolog to murine Adam8
    Homologene
    FAMILY
  • peptidase family M12B
  • ADAM (a disintegrin and metalloprotease domain) family
    • CATEGORY adhesion , antigen
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic,granule
    text present both on the cell surface and in intracellular granules of human neutrophils
    basic FUNCTION
  • playing an important role in osteoclast formation and differentiation
  • involved in cell-cell and cell-matrix interactions
  • may be contributing to ectodomain shedding of CD23
  • involved in ectodomain shedding of membrane proteins and is linked to inflammation and neurodegeneration
  • may play a significant role in tumor invasion that may be detrimental to patients survival
  • stimulates osteoclast differentiation
  • may have a potential relevant role in the function of neutrophils during inflammatory response
  • stimulates osteoclast (OCL) formation
  • modulates the expression and function of SELPLG
  • is the primary protease for the alpha-cleavage of PRNP that appears self-regulated through ADAM8 in muscle
  • mediates cell adhesion and shedding of ligands, receptors and extracellular matrix components
  • mediates an enhanced invasiveness of neutrophils into injured muscle fibers by the removal of their adhesiveness to blood vessels after infiltration into interstitial tissue
  • role in pancreatic cancer signalling
  • could promote the proliferation of normal hepatocytes and render hepatoma carcinoma cells more resistant to apoptosis to play important roles during the progression of hepatocellular carcinoma
    • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • CD23
  • is both associated with SELPLG through the ezrin–radixin–moesin actin-binding proteins and able to cause the proteolytic cleavage of this adhesion receptor
  • is the primary protease responsible for the alpha-cleavage of PRNP in muscle cells
  • ADAM8 can perform alpha-cleavage of PRNP and PRNP can regulate ADAM8 expression
    • cell & other
    REGULATION
    Other N-glycosylation is essential for processing, localization, stability, and activity of ADAM8
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in various tumors including lung and brain tumors
    tumoral     --over  
    of novel truncated forms of ADAM8, associated with increased invasive abilities and osteoclastogenic properties, and correlated with the early development of metastatic lesions
    tumoral     --over  
    in breast tumors and derived metastases compared to normal tissue, especially in triple-negative breast cancers (TNBCs)
    tumoral     --over  
    associated with poor overall survival in patients with hepatocellular carcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • prognostic marker for renal cell carcinomas and the best predictor of distant metastasis
    • Therapy target
    SystemTypeDisorderPubmed
    allergy  
    potential target for therapeutic intervention in allergy and inflammation
    cancerdigestivepancreas
    ADAM8 is a target for PDAC therapy
    cancerreproductivebreast
    represents a promising novel target for treatment of TNBCs, which currently lack targeted therapies and frequently progress with fatal dissemination
    cancerdigestiveliver
    may be a potential target of antiangiogenic therapy for HCC
    ANIMAL & CELL MODELS
  • skeletal muscle of dystrophin-null mice, an animal model for Duchenne Muscular Dystrophy, deteriorates by the lack of Adam8, which is characterized by increased area of muscle degeneration and increased number of necrotic and calcified muscle fibers