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FLASH GENE
Symbol ADAMTS9 contributors: mct - updated : 24-01-2019
HGNC name ADAM metallopeptidase with thrombospondin type 1 motif, 9
HGNC id 13202
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
40 - 7335 - 1935 - 2003 12514189
preprotein
  • a 1648 aa mature protein of 184.2 kda
  • - - 5644 - 1629 - 2003 12514189
    preprotein, shorter than isoform 1 with a distinct C-terminus
    - - 3694 - 1072 - 2003 12514189
    preprotein, shorter than isoform 1 with a distinct C-terminus
    38 - 7251 - 1907 - 2003 12514189
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Endocrinepancreas    
    Hearing/Equilibriumear   predominantly
    Nervousbrain    
     nerve   highly
     spinal cord    
    Reproductivefemale systemovary   
    Respiratorylung    
     respiratory tractlarynx  moderately
    Urinarykidney    
    Visualeyeretina   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Nervouscentral   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text ubiquitous
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a 18 aa signal sequence of 2.1 kda
  • a peptidase M12B
  • a disintegrin-like domain
  • fifteen thrombospondin type 1 (TSP1) domains
  • a spacer domain without cysteine residue
  • a unique C-terminal domain called the "GON domain"
  • conjugated GlycoP , MetalloP
    isoforms Precursor a 1917 aa proprotein of 214.4 kda given a 1648 aa mature protein of 184.2 kda
    HOMOLOGY
    interspecies homolog to C.elegans Gon1
    homolog to rattus Adamts9 (88.2 pc)
    homolog to murine Adamts9
    Homologene
    FAMILY
  • ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family
  • CATEGORY chaperone/stress , enzyme , regulatory
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,cytoplasm,cytoskeleton,intermed filament
    text
  • proteinaceous extracellular matrix
  • localizes near basal bodies of primary cilia, and endocytosis is required for the localization of ADAMTS9 near the basal bodies
  • basic FUNCTION
  • cleaving the large aggregating proteoglycans, aggrecan and versican
  • acting as an intramolecular chaperone whose glycosylation is critical for secretion of the mature enzyme (propeptide activity)
  • is a putative tumor suppressor gene in nasopharyngeal carcinoma (NPC) that is significantly associated with lymph node metastases
  • participates in melanoblast development and is a tumor suppressor in esophageal and nasopharyngeal cancer
  • ADAMTS9 is a novel, constitutive, endogenous angiogenesis inhibitor that operates cell-autonomously in ECs via molecular mechanisms that are distinct from those used by ADAMTS1
  • novel function of ADAMTS9 in the ER that promotes protein transport from the ER to the Golgi (this function is GON-domain dependent but protease activity independent)
  • is a critical tumor suppressor of gastric cancer progression at least in part through suppression of oncogenic AKT/MTOR signaling
  • potential role of ADAMTS9 in the remodeling of the ECM in these structures by degradation of versican
  • CELLULAR PROCESS cell life, cell death/apoptosis
    protein, degradation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism protein
    signaling
    glycoprotein catabolic process
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+ (1 ion per subunit)
  • protein
  • PADI2 regulates the expression of the TNFRSF1B, ADAMTS9, and RAB6B transcripts in mast cells
  • is a cytokine-inducible gene that contains binding sites for NFKB1 within its promoter region
  • NFKB1 may be involved in IL1B-induced activation of ADAMTS9 in human chondrocytes
  • cell & other
    REGULATION
    induced by the pathways MAPK and NFKB, thought to be responsible pathways for the induction of ADAMTS9 gene
    Other precursor cleaved by a furin endopeptidase
    ASSOCIATED DISORDERS
    corresponding disease(s) NPHP21
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in hereditary renal tumors
    tumoral        
    in gastric cancer cell lines
    tumoral        
    by epigenetic disruption in colorectal cancer
    Susceptibility to type 2 diabetes
    Variant & Polymorphism other
  • ADAMTS9 genetic risk variants were associated with type 2 diabetes
  • ADAMTS9 rs4607103 C allele is one of the few gene variants proposed to increase the risk of type 2 diabetes through an impairment of insulin sensitivity
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    ADAMTS9 is a potential novel mode of treating insulin resistance.
    ANIMAL & CELL MODELS
  • mice lacking Adamts9 selectively in skeletal muscle have improved insulin sensitivity