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FLASH GENE
Symbol ADAMTS13 contributors: mct/pgu - updated : 23-02-2017
HGNC name ADAM metallopeptidase with thrombospondin type 1 motif, 13
HGNC id 1366
Corresponding disease
TTPF thrombotic thrombocytopenic purpura, familial
Location 9q34.2      Physical location : 136.279.458 - 136.324.507
Synonym name
  • von Willebrand factor-cleaving protease
  • a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 13
    • Synonym symbol(s) VWFCP, C9orf8, FLJ42993, MGC118899, MGC118900, TTP, DKFZp434C2322, vWF-CP; ADAM-TS13, ADAMTS-13
    EC.number 3.4.24.87
    DNA
    TYPE functioning gene
    STRUCTURE 45.05 kb     29 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D9S1776 - D9S1682 - D9S1863 - D9S179 - D9S1847 - D9S1830 - D9S164 - D9S1818 - D9S1826 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    29 - 4941 153.6 1427 - 1998 9828245
    - - 3346 - 344 placenta 1998 9828245
    frameshift resulting from skipping exon 17
    29 - 4680 144.2 1340 - 1998 9828245
    lacking two internal fragments
    29 - 4773 147.5 1371 - 1998 9828245
    lacking a fragment in the 3'coding region
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon  
     liver   highly
    Nervousbrain   moderately
    Reproductivefemale systemovary   
     male systemtestis   
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a N terminal signal sequence
  • a propeptide domain
  • a reprolysin-type catalytic domain and disintegrin loop
  • a thrombospondin type I (TSP1) module
  • a cysteine-rich/spacer domains essential for VWF-CP activity, required for ADAMTS13 binding to von Willebrand factor
  • seven TSP-like modules
  • a WXXW motif in its thrombospondin type 1 repeat domain (TSR1), important for the secretion of ADAMTS13 and that modulates the proteolytic cleavage of VWF by ADAMTS13 under denaturing conditions
  • a disintegrin-like domain having an essential role
    • in ADAMTS13 function
  • at the C terminus two segments with homology to the CUB domain, thrombospondin type 1 and CUB domains modulating interaction with von Willebrand factor (VWF C-terminal binding site may participate as the initial step of a multistep interaction ultimately leading to proteolysis of VWF by ADAMTS13)
    • conjugated MetalloP
    mono polymer heptamer
    isoforms Precursor
    HOMOLOGY
    interspecies homolog to murine Adamts13
    Homologene
    FAMILY
  • ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) protein family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text plasma (low level)
    basic FUNCTION
  • specifically cleaves the Tyr-1605-Met-1606 bond in the A2 domain of von Willebrand factor (VWF) to regulate the polymer distribution of VWF in circulation, which is critical for primary hemostasis
  • may playing a functional role in the local regulation of platelet function at the site of vascular injury or thrombus formation
  • could participate in the pathophysiology of preeclampsia
  • regulates the platelet aggregation function of VWF via proteolysis)
  • ADAMTS13 activity is an important determinant in platelet-vessel wall interaction
  • ADAMTS13 function is dependent upon multiple exosites that specifically bind the unraveled VWF A2 domain and enable proteolysis
  • regulates blood coagulation by cleaving von Willebrand factor (VWF), reducing its procoagulant activity
  • might have a potential regulation role for VWF inside cells
  • regulates a key physiological process of coagulation in the circulation by cleaving VWF multimers into small, inactive fragments
    • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    text normal vascular homeostasis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • cooperative activity between the middle carboxyl-terminal THBS1 repeats and the distal carboxyl-terminal CUB domains of ADAMTS13 may be crucial for recognition and cleavage of VWF under flow
  • interacting with THBS1 (THBS1 played competitively inhibitory role in ADAMTS13 binding and cleaving of VWF, and the potential competition might happen within A2 and A3 domains)
  • F8 accelerates proteolytic cleavage of VWF by ADAMTS13 under fluid shear stress
  • interacting with VWF (regulation of VWF multimeric size and platelet-tethering function is carried out by ADAMTS13, a plasma metalloprotease that is constitutively active)
  • binding of ADAMTS13 to Lys-PLG may play an important role to localize these two proteases at sites of thrombus formation or vascular injury where the fibrinolytic system is activated
  • PPIB is an important factor in the proper maturation and secretion of ADAMTS13
  • ADAMTS13-induced endothelial cell angiogenesis occurs via the upregulation of VEGFA and phosphorylation of KDR and this angiogenic activity depends on the C-terminal TSP1 repeats of ADAMTS13
  • ADAMTS13 proteolytically regulates the platelet-tethering function of von Willebrand factor (VWF)
  • ADAMTS13 is a specific von Willebrand factor (VWF)-cleaving protease, preventing microvascular thrombosis of VWF/platelet thrombi
  • is the key protease that regulates the multimeric state of VWF
    • cell & other
  • binding to endothelial cell plasma membrane through its COOH-terminal thrombospondin type 1 repeats
  • prebound ADAMTS13 to endothelial cells exhibits increased proteolysis of VWF
    • REGULATION
    activated by GP1BA for the cleavage of VWF
    Other is regulated by substrate-induced allosteric activation, which may optimize VWF cleavage under fluid shear stress
    becomes conformationally activated on demand through interaction of its C-terminal CUB domains with VWF, making it susceptible to immune recognition
    ASSOCIATED DISORDERS
    corresponding disease(s) TTPF
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    in preeclampsia
    constitutional     --low  
    in the maternal and cord blood were lower in the preeclampsia group than in the control group
    Susceptibility to thrombotic disorders
    Variant & Polymorphism SNP , other ADAMTS13-binding IgG are present in patients with thrombotic thrombocytopenic purpura
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Adamts13 deficiency in mice does not affect adipose tissue development
  • Adamts13 levels are significantly reduced in the plasma of CypB-deficient mice