Von Willebrand factor

1AO3, 1ATZ, 1AUQ, 1FE8, 1FNS, 1IJB, 1IJK, 1M10, 1OAK, 1U0N, 2ADF, 3GXB, 3HXO, 3HXQ, 3PPV, 3PPW, 3PPX, 3PPY, 3ZQK, 4DMU, 1UEX, 2MHP, 2MHQ, 4C29, 4C2A, 4C2B, 4NT5, 5BV8745022371ENSG00000110799ENSMUSG00000001930P04275Q8CIZ8NM_000552NM_011708NP_000543NP_035838von Willebrand factor (VWF) (/ˌfʌnˈvɪlɪbrɑːnt/) is a blood glycoprotein involved in hemostasis. It is deficient and 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 predict an increased risk of thrombosis.1ao3: A3 DOMAIN OF VON WILLEBRAND FACTOR1atz: HUMAN VON WILLEBRAND FACTOR A3 DOMAIN1auq: A1 DOMAIN OF VON WILLEBRAND FACTOR1fe8: CRYSTAL STRUCTURE OF THE VON WILLEBRAND FACTOR A3 DOMAIN IN COMPLEX WITH A FAB FRAGMENT OF IGG RU5 THAT INHIBITS COLLAGEN BINDING1fns: CRYSTAL STRUCTURE OF THE VON WILLEBRAND FACTOR (VWF) A1 DOMAIN I546V MUTANT IN COMPLEX WITH THE FUNCTION BLOCKING FAB NMC41ijb: The von Willebrand Factor mutant (I546V) A1 domain1ijk: The von Willebrand Factor mutant (I546V) A1 domain-botrocetin Complex1m10: Crystal structure of the complex of Glycoprotein Ib alpha and the von Willebrand Factor A1 Domain1oak: CRYSTAL STRUCTURE OF THE VON WILLEBRAND FACTOR (VWF) A1 DOMAIN IN COMPLEX WITH THE FUNCTION BLOCKING NMC-4 FAB1sq0: Crystal Structure of the Complex of the Wild-type Von Willebrand Factor A1 domain and Glycoprotein Ib alpha at 2.6 Angstrom Resolution1u0n: The ternary von Willebrand Factor A1-glycoprotein Ibalpha-botrocetin complex1uex: Crystal structure of von Willebrand Factor A1 domain complexed with snake venom bitiscetin2adf: Crystal Structure and Paratope Determination of 82D6A3, an Antithrombotic Antibody Directed Against the von Willebrand factor A3-Domain von Willebrand factor (VWF) (/ˌfʌnˈvɪlɪbrɑːnt/) is a blood glycoprotein involved in hemostasis. It is deficient and 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 predict an increased risk of thrombosis. VWF is a large multimeric glycoprotein present in blood plasma and produced constitutively as ultra-large VWF in endothelium (in the Weibel-Palade bodies), megakaryocytes (α-granules of platelets), and subendothelial connective tissue. The basic VWF monomer is a 2050-amino acid protein. Every monomer contains a number of specific domains with a specific function; elements of note are: Monomers are subsequently N-glycosylated, arranged into dimers in the endoplasmic reticulum and into multimers in the Golgi apparatus by crosslinking of cysteine residues via disulfide bonds. With respect to the glycosylation, VWF is one of only a few proteins that carry ABO blood group system antigens. vWFs coming out of the Golgi are packaged into storage organelles, Weibel-Palade bodies (WPBs) in endothelial cells and α-granules in platelets. Multimers of VWF can be extremely large, >20,000 kDa, and consist of over 80 subunits of 250 kDa each. Only the large multimers are functional. Some cleavage products that result from VWF production are also secreted but probably serve no function. Von Willebrand Factor's primary function is binding to other proteins, in particular factor VIII, and it is important in platelet adhesion to wound sites. It is not an enzyme and, thus, has no catalytic activity. VWF binds to a number of cells and molecules. The most important ones are: VWF plays a major role in blood coagulation. Therefore, VWF deficiency or dysfunction (von Willebrand disease) leads to a bleeding tendency, which is most apparent in tissues having high blood flow shear in narrow vessels. From studies it appears that VWF uncoils under these circumstances, decelerating passing platelets. Recent research also suggests that von Willebrand Factor is involved in the formation of blood vessels themselves, which would explain why some people with von Willebrand disease develop vascular malformations (predominantly in the digestive tract) that can bleed excessively. The biological breakdown (catabolism) of VWF is largely mediated by the enzyme ADAMTS13 (acronym of 'a disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13'). It is a metalloproteinase that cleaves VWF between tyrosine at position 842 and methionine at position 843 (or 1605–1606 of the gene) in the A2 domain. This breaks down the multimers into smaller units, which are degraded by other peptidases.