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FLASH GENE
Symbol VWF contributors: mct/pgu - updated : 05-09-2014
HGNC name von Willebrand factor
HGNC id 12726
Corresponding disease
VWF Von Willebrand disease, types I, II A and II B
Location 12p13.31      Physical location : 6.058.039 - 6.233.836
Synonym name coagulation factor VIII VWF (von Willebrand factor)
Synonym symbol(s) F8VWF, VWD
DNA
TYPE functioning gene
STRUCTURE 175.80 kb     52 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked Y status confirmed
Physical map
NTF3 12p13.31 neurotrophin 3 TMEM16B 12p13.3 transmembrane protein 16B VWF 12p13.1 von Willebrand factor CD9 12p13.31 CD9 antigen (p24) FLJ10665 12p13.32 hypothetical protein FLJ10665 TNFRSF1A 12p13.2 tumor necrosis factor receptor superfamily, member 1A SCNN1A 12p13.3 sodium channel, nonvoltage-gated 1 alpha LTBR 12p13.31 lymphotoxin beta receptor (TNFR superfamily, member 3) LOC390283 12 hypothetical gene supported by X15940; NM_000993 LOC390284 12 similar to signal recognition particle 14kDa (homologous Alu RNA binding protein); signal recognition particle 14kD (homologous Alu RNA-binding protein); signal recognition particle 14kD (homologous Alu RNA binding protein) TNFRSF7 12p13 tumor necrosis factor receptor superfamily, member 7 TAPBP-R 12p13.31 TAP binding protein related VAMP1 12p13.31-p13.2 vesicle-associated membrane protein 1 (synaptobrevin 1) PKP2P1 12p13 vesicle-associated membrane protein 1 (synaptobrevin 1) MRPL51 12p13.3-p13.1 mitochondrial ribosomal protein L51 CNAP1 12p13.3 chromosome condensation-related SMC-associated protein 1
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
52 - 8833 - 2813 - 2008 18600088
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Digestivepharynx   highly
 stomach   highly
Lymphoid/Immunespleen    
 thymus    
Nervousnerve   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticmegakaryocyte Homo sapiens
Blood/Hematopoieticplatelet
Cardiovascularendothelial cell Homo sapiens
cell lineage
cell lines
fluid/secretion plasma
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a signal peptide, a large propeptide of 100kDa (the A2 domain required for multimerization of VWF and for its targeting
  • to storage granules)
  • the mature subunit cysteine rich with four distinct types of repeat domains
  • three VWFA domains, A1 domain contains the binding site of chloride ions that control allosterically the proteolysis by ADAMTS13, a novel Ca(+)-binding site at the A2 domain, regulating its cleavage by ADAMTS13
  • four VWFD domains
  • three VWFC domains
  • a c-terminal cystine knot-like (ctck) domain
  • conjugated GlycoP
    mono polymer heptamer
    isoforms Precursor
    HOMOLOGY
    Homologene
    FAMILY
    CATEGORY immunity/defense
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus
    basic FUNCTION
  • antihemophilic factor carrier and a platelet-vessel wall mediator in the blood coagulation system playing a crucial role in the hemostasis process
  • ; may reduce the immunogenicity of FVIII by inhibiting the uptake of F8 by antigen presenting cells, the first step in the development of an immune response against a foreign antigen (PMID :
  • pathogenetic role for VWF-platelet interaction in flow disturbance-induced venous thrombosis
  • having function in endothelial cells
  • required for platelet adhesion to sites of vessel injury, a process vital for both hemostasis and thrombosis
  • large, multimeric plasma glycoprotein that critically mediates hemostasis at sites of vascular injury
  • binds calcium at physiologic calcium concentrations and calcium stabilizes VWF A2 domain by accelerating refolding
  • VWFpropeptide binding to mature VWF occurs in the circulation, which can regulate the hemostatic potential of VWF by reducing VWF binding to platelet GP1BA
  • risk factor for bleeding and thrombosis
  • platelet-vessel wall interaction is mediated by VWF, which thereby plays a major role in physiological hemostasis and thrombotic disease
  • large, multimeric protein that regulates hemostasis by tethering platelets to the subendothelial matrix at sites of vascular damage
  • is one of the most important proteins of the hemostatic systemand its multimeric state is essential for its natural function to guide platelets to sites of injury
  • possible role of complementary mechanisms that are capable of modifying the thrombogenic potential of VWF
  • large multidomain, multimeric glycoprotein that plays an essential role in regulating the balance between blood clotting and bleeding
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS coagulation/hemostasis
    PATHWAY
    metabolism
    signaling
    a component
  • released into the plasma forming disulfide-linked multimeric structure, assembled from dimers
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding to collagen via the VWF-A3 domain
  • binding GP1BA by its A1 and A3 domain
  • domain A2 is cleaved by ADAMTS13(cleavage stimulated by GP1BA)
  • PLD1 is a specific regulator of VWF secretion
  • 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 ADAMTS13 (regulation of VWF multimeric size and platelet-tethering function is carried out by ADAMTS13, a plasma metalloprotease that is constitutively active)
  • interacting with ADAMTS13 (ADAMTS13 regulates the platelet aggregation function of VWF via proteolysis)
  • light chain, particularly the a3 region in the light chain of F8, contains the major binding site for VWF
  • GNA12 plays a prominent role in endothelial cells (ECs) VWF secretion required for hemostasis and thrombosis
  • ADAMTS13 proteolytically regulates the platelet-tethering function of von Willebrand factor (VWF)
  • procoagulant activity of plasma VWF correlates with the length of VWF multimers, which is proteolytically controlled by the metalloprotease ADAMTS13
  • ADAMTS13 is a specific von Willebrand factor (VWF)-cleaving protease, preventing microvascular thrombosis of VWF/platelet thrombi
  • VWF modulates the internalization and presentation of F8-derived peptides on major histocompatibility complex class II
  • cell & other
    REGULATION
    Other neutrophil oxidant hypochlorous acid (HOCl) inhibits VWF proteolysis by ADAMTS13 by oxidizing VWF methionine 1606 (M1606) in the A2 domain
    cleavage of VWF by granzyme M destroys its factor VIII binding capacity
    ASSOCIATED DISORDERS
    corresponding disease(s) VWF
    related resource VonWillebranddisease
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    plasma VWF antigen and VWF RCO were significantly elevated in preeclampsia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • VWF-deficient mice were protected from thrombosis induced by complete (stasis) or partial (stenosis) flow restriction in the inferior vena cava