VWF

Von Willebrand Factor (VWF) is a multimeric glycoprotein involved in hemostasis in blood, binds receptors on the surface of platelets and in connective tissue, thereby mediating the adhesion of platelets to sites of vascular injury. From studies it appears that VWF protein uncoils under these circumstances, decelerating passing platelets. VWF protein is deficient or defective in von Willebrand disease (VWD) and is involved in a large number of other diseases, including thrombosis, thrombotic thrombocytopenic purpura, Stroke, Heyde's syndrome, possibly hemolytic-uremic syndrome and so on.

VWF Related Areas

Stem Cell>>Hematopoietic Stem Cell (HSC)>>Hemangioblast>>Endothelial Cell Marker>>VWF

Immunology>>Innate Immunity>>Coagulation>>VWF

Cardiovascular>>Coagulation>>VWF

Cardiovascular>>Platelet>>VWF

VWF Alternative Names

VWF, VWD, F8VWF [Homo sapiens]

Vwf, VWD, 6820430P06Rik, AI551257, B130011O06Rik, C630030D09, F8VWF [Mus musculus]

Summaries for VWF

Entrez Gene summary for VWF:

The glycoprotein encoded by VWF gene functions as both an antihemophilic factor carrier and a platelet-vessel wall mediator in the blood coagulation system. It is crucial to the hemostasis process. Mutations in this gene or deficiencies in this protein result in von Willebrand's disease. An unprocessed pseudogene has been found on chromosome 22. [provided by RefSeq, Jul 2008]

OMIM - description for VWF:

The VWF gene encodes von Willebrand factor (VWF), a large multimeric glycoprotein that plays a central role in the blood coagulation system, serving both as a major mediator of platelet-vessel wall interaction and platelet adhesion, and as a carrier for coagulation factor VIII (F8; ). Diminished or abnormal VWF activity results in von Willebrand disease (VWD; ), a common and complex hereditary bleeding disorder (Ginsburg et al., 1985).

Wikipedia summary for VWF:

Von Willebrand factor (vWF) is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome. Increased plasma levels in a large number of cardiovascular, neoplastic and connective tissue diseases are presumed to arise from adverse changes to the endothelium, and may contribute to an increased risk of thrombosis.

Human VWF Protein General Information

 

• Protein names: von Willebrand factor
  Short name=vWF
• Sequence length: 2813 AA.
• Domain: The von Willebrand antigen 2 is required for multimerization of vWF and for its targeting to storage granules.
• Sequence similarities: Contains 1 CTCK (C-terminal cystine knot-like) domain.
  Contains 4 TIL (trypsin inhibitory-like) domains.
  Contains 3 VWFA domains.
  Contains 3 VWFC domains.
  Contains 4 VWFD domains.
• Post-translational modification: All cysteine residues are involved in intrachain or interchain disulfide bonds.
  N- and O-glycosylated.
• Subunit structure: Multimeric. Interacts with F8.
• Subcellular location: Secreted. Secreted › extracellular space › extracellular matrix. Note: Localized to storage granules.
• Tissue specificity: Plasma.
• Involvement in disease: Defects in VWF are the cause of von Willebrand disease type 1 (VWD1) [MIM:193400]. A common hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 1 is characterized by partial quantitative deficiency of circulating von Willebrand factor, that is otherwise structurally and functionally normal. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma.
  Defects in VWF are the cause of von Willebrand disease type 2 (VWD2) . A hemorrhagic disorder due to defects in von Willebrand factor protein and resulting in impaired platelet aggregation. Von Willebrand disease type 2 is characterized by qualitative deficiency and functional anomalies of von Willebrand factor. It is divided in different subtypes including 2A, 2B, 2M and 2N (Normandy variant). The mutant VWF protein in types 2A, 2B and 2M are defective in their platelet-dependent function, whereas the mutant protein in type 2N is defective in its ability to bind factor VIII. Clinical manifestations are mucocutaneous bleeding, such as epistaxis and menorrhagia, and prolonged bleeding after surgery or trauma.
  Defects in VWF are the cause of von Willebrand disease type 3 (VWD3) . A severe hemorrhagic disorder due to a total or near total absence of von Willebrand factor in the plasma and cellular compartments, also leading to a profound deficiency of plasmatic factor VIII. Bleeding usually starts in infancy and can include epistaxis, recurrent mucocutaneous bleeding, excessive bleeding after minor trauma, and hemarthroses.
• Sequence caution: The sequence AAB59512.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.

General information above from UniProt

Function for VWF Protein

UniProtKB:

VWF is important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. VWF also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma.

Genatlas:

• VWF is antihemophilic factor carrier and a platelet-vessel wall mediator in the blood coagulation system playing a crucial role in the hemostasis process
• VWF 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 (Lacroix-Desmazes 2008)

Phenotype Information for VWF

• Gene/Locus: VWF, F8VWF
• Phenotype: von Willebrand disease, type 1
  von Willebrand disease, type 2A, 2B, 2M, and 2N
  von Willibrand disease, type 3

Phenotype Information for VWF from OMIM (Online Mendelian Inheritance in Man)

Drugs for VWF

Target	Drug Name	Disease	Drug Status
VWF	ALX-0081	Thrombosis, Cardiovascular Disorders	Phase I

Drugs for VWF from TTD (Therapeutic Targets Database)