Von Willebrand factor - wikipedia Von Willebrand factor VWF Available structures PDB Ortholog search : PDBe RCSB List of PDB id codes 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, 5BV8 Identifiers Aliases VWF, F8VWD, von Willebrand factor External IDs OMIM : 613160 MGI : 98941 HomoloGene : 466 GeneCards : VWF Gene location ( Human ) Chr. Chromosome 12 ( human ) Band 12p13. 31 Start 5,948,874 bp End 6,124,770 bp Gene location ( Mouse ) Chr. Chromosome 6 ( mouse ) Band 6 F3 6 59.32 cM Start 125,546,774 bp End 125,686,679 bp Gene ontology Molecular function chaperone binding protein homodimerization activity collagen binding protein N - terminus binding immunoglobulin binding protease binding integrin binding identical protein binding protein binding Cellular component platelet alpha granule Weibel - Palade body proteinaceous extracellular matrix extracellular region endoplasmic reticulum extracellular exosome platelet alpha granule lumen extracellular matrix Biological process hemostasis blood coagulation, intrinsic pathway platelet degranulation extracellular matrix organization blood coagulation cell - substrate adhesion cell adhesion response to wounding protein homooligomerization platelet activation Sources : Amigo / QuickGO Orthologs Species Human Mouse Entrez 7450 22371 Ensembl ENSG00000110799 ENSMUSG00000001930 UniProt P04275 Q8CIZ8 RefSeq ( mRNA ) NM_000552 NM_011708 RefSeq ( protein ) NP_000543 NP_035838 Location ( UCSC ) Chr 12 : 5.95 -- 6.12 Mb Chr 6 : 125.55 -- 125.69 Mb PubMed search Wikidata View / Edit Human View / Edit Mouse Von Willebrand factor ( vWF ) ( / ˌfʌnˈvɪlɪbrɑːnt / ) 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. Contents 1 Biochemistry 1.1 Synthesis 1.2 Structure 1.3 Function 1.4 Catabolism 2 Role in disease 3 History 4 Interactions 5 See also 6 References 7 External links Biochemistry Synthesis 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. Structure 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 : the D ' / D3 domain, which binds to factor VIII ( Von Willebrand factor type D domain ) the A1 domain, which binds to : platelet GPIb - receptor heparin possibly collagen the A2 domain, which must partially unfold to expose the buried cleavage site for the specific ADAMTS13 protease that inactivates vWF by making much smaller multimers. The partial unfolding is affected by shear flow in the blood, by calcium binding, and by the lump of a sequence - adjacent `` vicinal disulfide '' at the A2 - domain C - terminus. the A3 domain, which binds to collagen ( Von Willebrand factor type A domain ) the C1 domain, in which the RGD motif binds to platelet integrin α β when this is activated ( Von Willebrand factor type C domain ) the `` cystine knot '' domain ( at the C - terminal end of the protein ), which vWF shares with platelet - derived growth factor ( PDGF ), transforming growth factor - β ( TGFβ ) and β - human chorionic gonadotropin ( βHCG, of pregnancy test fame ). ( Von Willebrand factor type C domain ) 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. 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. VWF monomer and multimers Function The interaction of vWF and GP1b alpha. The GP1b receptor on the surface of platelets allows the platelet to bind to vWF, which is exposed upon damage to vasulature. The vWF A1 domain ( yellow ) interacts with the extracellular domain of GP1ba ( blue ). 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 : Factor VIII is bound to vWF while inactive in circulation ; factor VIII degrades rapidly when not bound to vWF. Factor VIII is released from vWF by the action of thrombin. In the absence of vWF, factor VIII has a half - life of 1 - 2 hours ; when carried by intact vWF, factor VIII has a half - life of 8 - 12 hours. vWF binds to collagen, e.g., when it is exposed in endothelial cells due to damage occurring to the blood vessel. Endothelium also releases vWF which forms additional links between the platelets ' glycoprotein Ib / IX / V and the collagen fibrils vWF binds to platelet gpIb when it forms a complex with gpIX and gpV ; this binding occurs under all circumstances, but is most efficient under high shear stress ( i.e., rapid blood flow in narrow blood vessels, see below ). vWF binds to other platelet receptors when they are activated, e.g., by thrombin ( i.e., when coagulation has been stimulated ). 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. Catabolism 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. Role in disease Main article : Von Willebrand disease Hereditary or acquired defects of vWF lead to von Willebrand disease ( vWD ), a bleeding diathesis of the skin and mucous membranes, causing nosebleeds, menorrhagia, and gastrointestinal bleeding. The point at which the mutation occurs determines the severity of the bleeding diathesis. There are three types ( I, II and III ), and type II is further divided in several subtypes. Treatment depends on the nature of the abnormality and the severity of the symptoms. Most cases of vWD are hereditary, but abnormalities of vWF may be acquired ; aortic valve stenosis, for instance, has been linked to vWD type IIA, causing gastrointestinal bleeding - an association known as Heyde 's syndrome. In thrombotic thrombocytopenic purpura ( TTP ) and hemolytic uremic syndrome ( HUS ), ADAMTS13 either is deficient or has been inhibited by antibodies directed at the enzyme. This leads to decreased breakdown of the ultra-large multimers of vWF and microangiopathic hemolytic anemia with deposition of fibrin and platelets in small vessels, and capillary necrosis. In TTP, the organ most obviously affected is the brain ; in HUS, the kidney. Higher levels of vWF are more common among people that have had ischemic stroke ( from blood - clotting ) for the first time. Occurrence is not affected by ADAMTS13, and the only significant genetic factor is the person 's blood group. High plasma vWF levels were found to be an independent predictor of major bleeding in anticoagulated atrial fibrillation patients. History vWF is named after Dr. Erik von Willebrand ( 1870 -- 1949 ), a Finnish doctor who in 1924 first described a hereditary bleeding disorder in families from the Åland islands, who had a tendency for cutaneous and mucosal bleeding, including menorrhagia. Although von Willebrand could not identify the definite cause, he distinguished von Willebrand disease ( vWD ) from hemophilia and other forms of bleeding diathesis. In the 1950s, vWD was shown to be caused by a plasma factor deficiency ( instead of being caused by platelet disorders ), and, in the 1970s, the vWF protein was purified. Interactions Von Willebrand factor has been shown to interact with Collagen, type I, alpha 1. Recently, It has been reported that the cooperation and interactions within the Von Willebrand factors enhances the adsorption probability in the primary haemostasis. Such cooperation is proven by calculating the adsorption probability of flowing vWF once it crosses another adsorbed one. Such cooperation is held within a wide range of shear rates. See also Von Willebrand disease Bernard - Soulier syndrome References ^ Jump up to : GRCh38 : Ensembl release 89 : ENSG00000110799 - Ensembl, May 2017 ^ Jump up to : GRCm38 : Ensembl release 89 : ENSMUSG00000001930 - Ensembl, May 2017 Jump up ^ `` Human PubMed Reference : ''. Jump up ^ `` Mouse PubMed Reference : ''. ^ Jump up to : Sadler JE ( 1998 ). `` Biochemistry and genetics of von Willebrand factor ''. Annual Review of Biochemistry. 67 : 395 -- 424. doi : 10.1146 / annurev. biochem. 67.1. 395. PMID 9759493. Jump up ^ Jakobi AJ, Mashaghi A, Tans SJ, Huizinga EG. Calcium modulates force sensing by the von Willebrand factor A2 domain. Blood. 2011 April 28, 117 : 17. Nature Commun. 2011 Jul 12 ; 2 : 385. ( 1 ) Jump up ^ Luken BM, Winn LY, Emsley J, Lane DA, Crawley JT ( June 2010 ). `` The importance of vicinal cysteines, C1669 and C1670, for von Willebrand factor A2 domain function ''. Blood. 115 ( 23 ) : 4910 -- 3. doi : 10.1182 / blood - 2009 - 12 - 257949. PMC 2890177. PMID 20354169. Jump up ^ Randi AM, Laffan MA ( January 2017 ). `` Von Willebrand factor and angiogenesis : basic and applied issues ''. Journal of Thrombosis and Haemostasis. 15 ( 1 ) : 13 -- 20. doi : 10.1111 / jth. 13551. PMID 27778439. Jump up ^ Levy GG, Motto DG, Ginsburg D ( July 2005 ). `` ADAMTS13 turns 3 ''. Blood. 106 ( 1 ) : 11 -- 7. doi : 10.1182 / blood - 2004 - 10 - 4097. PMID 15774620. Jump up ^ Sadler JE, Budde U, Eikenboom JC, Favaloro EJ, Hill FG, Holmberg L, Ingerslev J, Lee CA, Lillicrap D, Mannucci PM, Mazurier C, Meyer D, Nichols WL, Nishino M, Peake IR, Rodeghiero F, Schneppenheim R, Ruggeri ZM, Srivastava A, Montgomery RR, Federici AB ( October 2006 ). `` Update on the pathophysiology and classification of von Willebrand disease : a report of the Subcommittee on von Willebrand Factor ''. Journal of Thrombosis and Haemostasis. 4 ( 10 ) : 2103 -- 14. doi : 10.1111 / j. 1538 - 7836.2006. 02146. x. PMID 16889557. Jump up ^ Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F, Bauters A, Decoene C, Goudemand J, Prat A, Jude B ( July 2003 ). `` Acquired von Willebrand syndrome in aortic stenosis ''. The New England Journal of Medicine. 349 ( 4 ) : 343 -- 9. doi : 10.1056 / NEJMoa022831. PMID 12878741. Jump up ^ Moake JL ( January 2004 ). `` von Willebrand factor, ADAMTS - 13, and thrombotic thrombocytopenic purpura ''. Seminars in Hematology. 41 ( 1 ) : 4 -- 14. doi : 10.1053 / j. seminhematol. 2003.10. 003. PMID 14727254. Jump up ^ Denorme, F ( 2016 ). `` The VWF - GPIb axis in ischaemic stroke : lessons from animal models ''. Thrombosis and Haemostasis. 116 ( 4 ) : 597 -- 604. doi : 10.1160 / TH16 - 01 - 0036. PMID 27029413. Jump up ^ Roldán V, Marín F, Muiña B, Torregrosa JM, Hernández - Romero D, Valdés M, Vicente V, Lip GY ( June 2011 ). `` Plasma von Willebrand factor levels are an independent risk factor for adverse events including mortality and major bleeding in anticoagulated atrial fibrillation patients ''. Journal of the American College of Cardiology. 57 ( 25 ) : 2496 -- 504. doi : 10.1016 / j. jacc. 2010.12. 033. PMID 21497043. Jump up ^ von Willebrand EA ( 1926 ). `` Hereditär pseudohemofili '' ( Hereditary pseudo haemophilia ). Fin Läkaresällsk Handl ( in Swedish ). 68 : 87 -- 112. Reproduced in Von Willebrand EA ( May 1999 ). `` Hereditary pseudohaemophilia ''. Haemophilia. 5 ( 3 ) : 223 -- 31 ; discussion 222. doi : 10.1046 / j. 1365 - 2516.1999. 00302. x. PMID 10444294. Jump up ^ Pareti FI, Fujimura Y, Dent JA, Holland LZ, Zimmerman TS, Ruggeri ZM ( November 1986 ). `` Isolation and characterization of a collagen binding domain in human von Willebrand factor ''. The Journal of Biological Chemistry. 261 ( 32 ) : 15310 -- 5. PMID 3490481. Jump up ^ Heidari M, Mehrbod M, Ejtehadi MR, Mofrad MR ( August 2015 ). `` Cooperation within von Willebrand factors enhances adsorption mechanism ''. Journal of the Royal Society, Interface. 12 ( 109 ) : 20150334. doi : 10.1098 / rsif. 2015.0334. PMC 4535404. PMID 26179989. External links GeneReviews / NCBI / NIH / UW entry on von Willebrand Factor Deficiency. Includes : Type 1 von Willebrand Disease, Type 2A von Willebrand Disease, Type 2B von Willebrand Disease, Type 2M von Willebrand Disease, Type 2N von Willebrand Disease, Type 3 von Willebrand Disease Proteins involved in coagulation Coagulation factors Primary hemostasis vWF platelet membrane glycoproteins : Ib ( A IX ) IIb / IIIa ( IIb IIIa ) VI Intrinsic pathway HMWK / Bradykinin Prekallikrein / Kallikrein XII `` Hageman '' XI IX VIII Extrinsic pathway III `` Tissue factor '' VII Common pathway X V II `` ( Pro ) thrombin '' I `` Fibrin '' Fibrinogen ( FGA, FGG ) XIII Coagulation inhibitors Antithrombin ( inhibits II, IX, X, XI, XII ) Protein C ( inhibits V, VIII ) / Protein S ( cofactor for protein C ) Protein Z ( inhibits X ) ZPI ( inhibits X, XI ) TFPI ( inhibits III ) Thrombolysis / fibrinolysis Plasmin tPA / urokinase PAI - 1 / 2 α2 - AP α2 - macroglobulin TAFI PDB gallery 1ao3 : A3 DOMAIN OF VON WILLEBRAND FACTOR 1atz : HUMAN VON WILLEBRAND FACTOR A3 DOMAIN 1auq : A1 DOMAIN OF VON WILLEBRAND FACTOR 1fe8 : CRYSTAL STRUCTURE OF THE VON WILLEBRAND FACTOR A3 DOMAIN IN COMPLEX WITH A FAB FRAGMENT OF IGG RU5 THAT INHIBITS COLLAGEN BINDING 1fns : CRYSTAL STRUCTURE OF THE VON WILLEBRAND FACTOR ( VWF ) A1 DOMAIN I546V MUTANT IN COMPLEX WITH THE FUNCTION BLOCKING FAB NMC4 1ijb : The von Willebrand Factor mutant ( I546V ) A1 domain 1ijk : The von Willebrand Factor mutant ( I546V ) A1 domain - botrocetin Complex 1m10 : Crystal structure of the complex of Glycoprotein Ib alpha and the von Willebrand Factor A1 Domain 1oak : CRYSTAL STRUCTURE OF THE VON WILLEBRAND FACTOR ( VWF ) A1 DOMAIN IN COMPLEX WITH THE FUNCTION BLOCKING NMC - 4 FAB 1sq0 : Crystal Structure of the Complex of the Wild - type Von Willebrand Factor A1 domain and Glycoprotein Ib alpha at 2.6 Angstrom Resolution 1u0n : The ternary von Willebrand Factor A1 - glycoprotein Ibalpha - botrocetin complex 1uex : Crystal structure of von Willebrand Factor A1 domain complexed with snake venom bitiscetin 2adf : Crystal Structure and Paratope Determination of 82D6A3, an Antithrombotic Antibody Directed Against the von Willebrand factor A3 - Domain Retrieved from `` https://en.wikipedia.org/w/index.php?title=Von_Willebrand_factor&oldid=835736835 '' Categories : Genes on human chromosome 12 Blood proteins Coagulation system Glycoproteins Hidden categories : CS1 Swedish - language sources ( sv ) All articles with unsourced statements Articles with unsourced statements from August 2011 Talk Contents About Wikipedia Català Čeština Deutsch Español فارسی Français Italiano Nederlands 日本 語 Norsk Polski Português Română Русский Svenska Українська 8 more Edit links This page was last edited on 10 April 2018, at 13 : 30. 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Question: what is the function of von willebrand factor
Answer: binding to other proteins