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von Willebrand factor; vWF; ristocetin cofactor; factor VIII related antigen; contains: von Willebrand antigen 2 (VWF, F8VWF)
Function:
1) important in the maintenance of hemostasis
2) promotes adhesion of platelets to the sites of vascular injury
3) mediates platelet adhesion to collagen via binding sites for collagen & for glycoprotein Ib & glycoprotein IIb/IIIa on surface of activated platelets
2) acts as a chaperone for coagulation factor VIII
- binds factor VIII preventing association of factor VIII with phospholipid membranes
3) vWF is cleaved by vWF-cleaving protease degrading its platelet adhesion-promoting properties
4) plasmin also cleaves large vWF multimers; however platelet adhesive-promoting properties of vWF are largely retained
Structure:
1) forms large (> 1000 kD) multimers
2) the von Willebrand antigen 2 is required for multimerization of vWF & for its targeting to storage granules
3) multimers consist of 250 kD subunits linked by disulfide bonds
4) all Cys are involved in intrachain or interchain disulfide bonds
5) N- & O-glycosylated
6) contains 1 CTCK (C-terminal cystine knot-like) domain
7) contains 4 TIL (trypsin inhibitory-like) domains
8) contains 3 VWFA domains
9) contains 3 VWFC domains
10) contains 4 VWFD domains
Compartment:
- secreted, extracellular space, extracellular matrix
- localized to storage granules
Expression: plasma
Pathology:
- defects in VWF are the cause of von Willebrand disease
- disruption of HMW vWF multimers may occur with aortic valvular stenosis stenosis & other other forms of turbulent blood flow resulting in secondary von Willebrand disease (Heyde's syndrome)
Interactions
molecular events
Related
von Willebrand factor (VWF) autoantibody
von-Willebrand's disease (vWD)
Specific
recombinant von Willebrand factor (Vonvendi)
General
coagulation factor
glycoprotein
oligomerizing protein
PEST protein
Properties
SIZE: MW = 80 kD
MW = 250 kD
MW = 50-20000 kD
COMPARTMENT: plasma
MOTIF: glycosylation site
PEST region
WKS motif
binding site
EFFECTOR-BOUND: coagulation factor VIII
binding site
FOR-BINDING-OF: glycoprotein IIB/IIIA
binding site
FOR-BINDING-OF: platelet glycoprotein 1b
binding site
FOR-BINDING-OF: collagen
cysteine residue
MODIFICATION: cysteine residue
SECRETED-BY: endothelial cell
Database Correlations
OMIM correlations
UniProt P04275
PFAM correlations
Entrez Gene 7450
Kegg hsa:7450
References
- Cotran et al Robbins Pathologic Basis of Disease,
W.B. Saunders Co, Philadelphia, PA 1989 pg 696
- Kane WH, Davie EW.
Blood coagulation factors V and VIII: structural and
functional similarities and their relationship to hemorrhagic
and thrombotic disorders.
Blood. 1988 Mar;71(3):539-55. Review.
PMID: 3125864
- Andrews BS.
Is the WKS motif the tissue-factor binding site for coagulation
factor VII?
Trends Biochem Sci. 1991 Jan;16(1):31-6. Review.
PMID: 2053135
- Furlan M, Robles R, Lamie B.
Partial purification and characterization of a protease from
human plasma cleaving von Willebrand factor to fragments
produced by in vivo proteolysis.
Blood. 1996 May 15;87(10):4223-34.
PMID: 8639781
- Entrez Gene :accession 7450
- UniProt :accession P04275
- vWF; von Willebrand factor (vWF) mutation db
http://www.vwf.group.shef.ac.uk/
- GeneReviews
http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/VWF
- Wikipedia; Note: Von Willebrand factor entry
http://en.wikipedia.org/wiki/Von_Willebrand_factor
Component-of
antihemophilic factor/von willebrand factor
factor VIII/von Willebrand factor; vWF-rich factor VIII
molecular complex
recombinant factor VIII/von Willebrand factor