ID:VWF_HUMAN DESCRIPTION: RecName: Full=von Willebrand factor; Short=vWF; Contains: RecName: Full=von Willebrand antigen 2; AltName: Full=von Willebrand antigen II; Flags: Precursor; FUNCTION: 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. 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. SUBUNIT: Multimeric. Interacts with F8. INTERACTION: Q76LX8:ADAMTS13; NbExp=5; IntAct=EBI-981819, EBI-981764; P07359:GP1BA; NbExp=2; IntAct=EBI-981819, EBI-297082; Q96CV9:OPTN; NbExp=2; IntAct=EBI-981819, EBI-748974; SUBCELLULAR LOCATION: Secreted. Secreted, extracellular space, extracellular matrix. Note=Localized to storage granules. TISSUE SPECIFICITY: Plasma. DOMAIN: The von Willebrand antigen 2 is required for multimerization of vWF and for its targeting to storage granules. PTM: All cysteine residues are involved in intrachain or interchain disulfide bonds. PTM: N- and O-glycosylated. 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. DISEASE: Defects in VWF are the cause of von Willebrand disease type 2 (VWD2) [MIM:613554]. 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. DISEASE: Defects in VWF are the cause of von Willebrand disease type 3 (VWD3) [MIM:277480]. 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. SIMILARITY: Contains 1 CTCK (C-terminal cystine knot-like) domain. SIMILARITY: Contains 4 TIL (trypsin inhibitory-like) domains. SIMILARITY: Contains 3 VWFA domains. SIMILARITY: Contains 3 VWFC domains. SIMILARITY: Contains 4 VWFD domains. SEQUENCE CAUTION: Sequence=AAB59512.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part; WEB RESOURCE: Name=vWF; Note=von Willebrand factor (vWF) mutation db; URL="http://www.vwf.group.shef.ac.uk/"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/VWF"; WEB RESOURCE: Name=Wikipedia; Note=Von Willebrand factor entry; URL="http://en.wikipedia.org/wiki/Von_Willebrand_factor";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00092 - von Willebrand factor type A domain PF00093 - von Willebrand factor type C domain PF00094 - von Willebrand factor type D domain PF01826 - Trypsin Inhibitor like cysteine rich domain PF08742 - C8 domain PF13519 - von Willebrand factor type A domain PF13768 - von Willebrand factor type A domain PF16164 - VWA N-terminal
ModBase Predicted Comparative 3D Structure on P04275
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
E01056 - cDNA encoding precursor of human Von Willebrand factor(VWF). AK298097 - Homo sapiens cDNA FLJ51654 complete cds, highly similar to von Willebrand factor precursor. X04385 - Human mRNA for pre-pro-von Willebrand factor. GU014837 - Synthetic construct Homo sapiens clone IMAGE:100068741; MGC:198455 von Willebrand factor preproprotein (VWF) gene, encodes complete protein. AB385166 - Synthetic construct DNA, clone: pF1KB6008, Homo sapiens VWF gene for von Willebrand factor precursor, complete cds, without stop codon, in Flexi system. AK301216 - Homo sapiens cDNA FLJ51653 complete cds, highly similar to von Willebrand factor precursor. X04146 - Human mRNA fragment (5'terminus) for von Willebrand factor (vWF). JD114658 - Sequence 95682 from Patent EP1572962. M10321 - Human von Willebrand factor mRNA, 3' end. K03028 - Human von Willebrand factor (vWF) mRNA. JD455710 - Sequence 436734 from Patent EP1572962. JD118836 - Sequence 99860 from Patent EP1572962. AK297600 - Homo sapiens cDNA FLJ59036 complete cds, highly similar to von Willebrand factor precursor. JD272452 - Sequence 253476 from Patent EP1572962. JD218348 - Sequence 199372 from Patent EP1572962. JD498580 - Sequence 479604 from Patent EP1572962. X02672 - Human mRNA for von Willebrand factor (vWF) glycoprotein C-terminus of factor VIII-vWF complex. AK128487 - Homo sapiens cDNA FLJ46634 fis, clone TRACH3000892. U81237 - Human von Willebrand factor mRNA, partial cds. AF086470 - Homo sapiens full length insert cDNA clone ZD87H08. AK292122 - Homo sapiens cDNA FLJ75522 partial cds, highly similar to Homo sapiens von Willebrand factor (VWF), mRNA. BC069030 - Homo sapiens cDNA clone IMAGE:6278278, with apparent retained intron. BC022258 - Homo sapiens von Willebrand factor, mRNA (cDNA clone IMAGE:4688190), complete cds. CU692514 - Synthetic construct Homo sapiens gateway clone IMAGE:100022201 5' read VWF mRNA. M17588 - Human von Willebrand factor (vWF) mRNA, 5' end. JD223149 - Sequence 204173 from Patent EP1572962. JD438394 - Sequence 419418 from Patent EP1572962. JD167873 - Sequence 148897 from Patent EP1572962. JD197567 - Sequence 178591 from Patent EP1572962. JD337444 - Sequence 318468 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P04275 (Reactome details) participates in the following event(s):
R-HSA-114671 vWF binds to collagen R-HSA-114670 GPIb-IX-V binds to vWF:Collagen complex R-HSA-354149 Interaction of integrin alphaIIb beta3 with Fibrinogen R-HSA-481007 Exocytosis of platelet alpha granule contents R-HSA-158118 factor VIII + von Willebrand factor multimer -> factor VIII:von Willibrand factor multimer R-HSA-158137 factor VIII:von Willibrand factor multimer -> factor VIIIa + factor VIIIa B A3 acidic polypeptide + von Willibrand factor multimer R-HSA-429529 Thrombin binding to GP1b:IX:V R-HSA-430076 GP1b-IX-V binds 14-3-3-zeta R-HSA-430096 GP1b-IX-V binds filamin R-HSA-430073 GPIb-IX-V binding to 14-3-3 zeta is reduced by shear stress R-HSA-377641 Clustering of Integrin alphaIIb beta3 complexes R-HSA-377643 Dephosphorylation of inactive SRC by PTPB1 R-HSA-377644 Release of CSK from SRC R-HSA-377640 Autophosphorylation of SRC R-HSA-354066 Translocation of FADK1 to Focal complexes R-HSA-429415 SYK binds to integrin alphaIIb beta3 R-HSA-443402 GP1b-IX-V:13-3-3-zeta complexes with p85 PI3K R-HSA-354087 Recruitment of GRB2 to p-FADK1 R-HSA-372705 Recruitment of p130Cas to FADK1 R-HSA-354124 Phosphorylation of pFADK1 by SRC R-HSA-354073 Autophosphorylation of FADK1 at Y397 R-HSA-429441 SYK activation by SRC R-HSA-354165 Interaction of SOS with GRB2 bound to FADK1 R-HSA-372697 Crk binding to p130cas R-HSA-372693 Phosphorylation of p130Cas by SRC-FADK1 complex R-HSA-5672972 MAP2Ks and MAPKs bind to the activated RAF complex R-HSA-6802912 High kinase activity BRAF mutants bind MAP2Ks and MAPKs R-HSA-6802914 RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs R-HSA-6802925 Mutant RAS:p-RAF complexes bind MAP2Ks and MAPKs R-HSA-6802934 p-BRAF and RAF fusion dimers bind MAP2Ks and MAPKs R-HSA-6802942 RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs R-HSA-5672980 Dissociation of RAS:RAF complex R-HSA-6802932 Dissociation of BRAF/RAF fusion complex R-HSA-6803227 Dissociation of high activity BRAF complexes R-HSA-6803230 Dissociation of moderate activity BRAF complexes R-HSA-6803233 Dissociation of oncogenic RAS:RAF complex R-HSA-6803234 Dissociation of paradoxically activated RAS:BRAF complexes R-HSA-5672978 RAF phosphorylates MAP2K dimer R-HSA-5672973 MAP2Ks phosphorylate MAPKs R-HSA-6802918 Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants R-HSA-6802943 RAS:GTP:inactive p-RAF complexes phosphorylate MAP2Ks R-HSA-6802919 RAS:GTP:moderate kinase activity p-RAF complexes phosphorylate MAP2Ks R-HSA-6802921 Activated MAP2Ks phosphorylate MAPKs downstream of moderate kinase activity BRAF mutants R-HSA-6802911 High kinase activity BRAF complexes phosphorylate MAP2Ks R-HSA-6802910 Activated MAP2Ks phosphorylate MAPKs downstream of high kinase activity BRAF mutants R-HSA-6802926 Mutant RAS:p-RAF complexes phosphorylate MAP2Ks R-HSA-6802922 Activated MAP2Ks phosphorylate MAPKs downstream of oncogenic RAS R-HSA-6802933 p-BRAF and RAF fusion dimers phosphorylate MAP2Ks R-HSA-6802935 MAPKs are phosphorylated downstream of BRAF and RAF fusion dimers R-HSA-75892 Platelet Adhesion to exposed collagen R-HSA-354192 Integrin alphaIIb beta3 signaling R-HSA-114608 Platelet degranulation R-HSA-109582 Hemostasis R-HSA-140837 Intrinsic Pathway of Fibrin Clot Formation R-HSA-76009 Platelet Aggregation (Plug Formation) R-HSA-430116 GP1b-IX-V activation signalling R-HSA-9006921 Integrin signaling R-HSA-76005 Response to elevated platelet cytosolic Ca2+ R-HSA-140877 Formation of Fibrin Clot (Clotting Cascade) R-HSA-76002 Platelet activation, signaling and aggregation R-HSA-354194 GRB2:SOS provides linkage to MAPK signaling for Integrins R-HSA-372708 p130Cas linkage to MAPK signaling for integrins R-HSA-162582 Signal Transduction R-HSA-5674135 MAP2K and MAPK activation R-HSA-6802948 Signaling by high-kinase activity BRAF mutants R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants R-HSA-6802949 Signaling by RAS mutants R-HSA-6802952 Signaling by BRAF and RAF fusions R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF R-HSA-5673001 RAF/MAP kinase cascade R-HSA-6802957 Oncogenic MAPK signaling R-HSA-5684996 MAPK1/MAPK3 signaling R-HSA-5663202 Diseases of signal transduction R-HSA-5683057 MAPK family signaling cascades R-HSA-1643685 Disease
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
