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FLASH GENE
Symbol ADAM9 contributors: mct/pgu - updated : 30-01-2017
HGNC name ADAM metallopeptidase domain 9 (meltrin gamma)
HGNC id 216
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
cell lineage
cell lines myeloma cells
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • domains similar to hemorrhagic snake venom proteins (HSVP)
  • N-terminal prodomain
  • a disrupted Zn-binding site metalloproteinase
  • a disintegrin-like domain
  • a cysteine-rich domain
  • an EGF-like repeat
  • a transmembrane domain
  • a cytoplasmic tail containing two proline-rich sequences, which may bind SH3
    • conjugated GlycoP , MetalloP
    HOMOLOGY
    interspecies homolog to murine Adam9 (86.3pc)
    homolog to rattus Adam9 (85.3pc)
    intraspecies homolog to ADAM12
    Homologene
    FAMILY
  • a disintegrin and metalloprotease domain (ADAM) family
    • CATEGORY adhesion , enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
        intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • playing an important role in cell-cell fusion, intracellular signaling, and other cellular functions
  • involved in cell migration and invasion
  • contributing to heart development
  • functioning as cell adhesion molecule via its disintegrin-cysteine-rich domain
  • playing a role in regulating the motility of cells and modulating MMP synthesis
  • play important roles in pathological retinal neovascularization, and in the development of pathological vessels in the retina and choroid
  • modulates cell-cell and cell-matrix interactions as well as ectodomain shedding of cell surface receptors and ligands
  • ADAM9 expression plays an important role in mediating cell-cell contacts between fibroblasts and melanoma cells and these interactions contribute to proteolytic activities required during invasion of melanoma cells
    • CELLULAR PROCESS protein, post translation
    protein, degradation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
  • MMP14 forms a complex with FGFR2 and ADAM9 in osteoblasts
    • INTERACTION
    DNA
    RNA
    small molecule metal binding, cofactor,
  • one zinc Zn2+ ion per subunit
    • protein
  • binding to SH3 domain containing proteins such as SNX9, SH3GL2
  • binding to MAD2L2
  • binding to integrin alpha (V) beta (5) (to function as an adhesion molecule)
  • interacting with the beta1 integrin subunit on keratinocytes
  • involved in proteolysis of ADAM10 with ADAM15 and the gamma secretase complex
  • ADAM10 activity is regulated by inhibition of ADAM9, and this regulation may be used to control shedding of amyloid precursor protein by enhancing alpha-secretase activity, a key regulatory step in the etiology of Alzheimer disease
  • generally specific inhibition of ADAM9 controls membrane ADAM10 activity, which could be of general relevance
  • requirement for ADAM9 in lipopolysaccharide induced ACE shedding
  • MMP14 inactivates ADAM9, hence protecting FGFR2 from ADAM9-mediated ectodomain shedding on the cell surface
  • interaction between ADAM9 and the intracellular sorting protein, sorting nexin 9 (SNX9), as well as its close homolog SNX18
    • cell & other
  • cell-cell and cell-matrix interactions
    • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CORD12
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast carcinoma, node-positive
    tumoral     --over  
    in non-small cell lung cancer correlates with brain metastasis
    tumoral     --over  
    in gastric carcinoma, and pancreatic cancer
    Susceptibility to sporadic Alzheimer disease (SAD)
    Variant & Polymorphism other
  • promoter polymorphisms which regulate ADAM9 transcription are protective against SAD
    • Candidate gene
  • may be a valid target for gene therapy (Parry 2009)
  • attractive target for the prevention of proliferative retinopathies, choroidal neovascularization, and cancer
    • Marker
    Therapy target
    ANIMAL & CELL MODELS
  • overexpressed in breast carcinoma, node-positive
  • progressive degeneration affecting both rods and cones in Adam9−/− mice