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Von Willebrand factor (VWF) is a large, multimeric blood glycoprotein that is required for normal hemostasis. Mutant forms are involved in the most common inherited bleeding disorder (von Willebrand disease: VWD). VWF mediates the adhesion of platelets to sites of vascular damage by binding to specific platelet membrane glycoproteins and to constituents of exposed connective tissue. It is also essential for the transport of the blood clotting factor VIII [1,2].

VWF is a large multidomain protein. Among those domains the type A domain is known to be distributed in at least 22 human proteins, all of them being extracellular. In VWF there is 3 repeats of the type A domain (A1,A2,A3) that have been shown to bind other proteins like collagen and heparin. The 3D structure of A1 and A3 has been published [3,4]. The domain adopts a classic α/β "Rossmann" fold.

The following proteins have been found to contain a VWFA domain:

• Complement factors B, C2, CR3 and CR4.
• Collagen type VI.
• Collagen type VII.
• Collagen type XII.
• Collagen type XIV.
• Integrin α chains. In these proteins, the VWFA domain is known as a 'I- domain'.
• Human cartilage matrix protein. Major component of the extracellular matrix of nonarticular cartilage. Binds to collagen.
• Mammalian calcium channel α-2/delta subunits.
• Cochlin. In human, defects in COCH are the cause of mucopolysaccharide depositions in the channels of cochlear and vesicular nerves. These depositions cause degeneration of dendritic fibers.
• Epithelial chloride channel protein. Voltage-gate chloride channel.
• Inter-α-trypsin inhibitor heavy chains H1, H2 and H4. They are involved in a variety of immune phenomena.
• Mouse matrilin-2.
• Plasmodium berghei sporozoite surface protein 2.
• Caenorhabditis elegans unc-36 protein.

We developed a profile that spans the whole domain.

December 2001 / First entry.

PROSITE method (with tools and information) covered by this documentation:

VWFA, PS50234; VWFA domain profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: 3

• Domain architecture view of Swiss-Prot proteins matching PS50234 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50234 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50234 • Scan Swiss-Prot/TrEMBL entries against PS50234 • view ligand binding statistics

Matching PDB structures: 1AO3 1AOX 1ATZ 1AUQ ... [ALL]

1	Authors	Sadler J.E.
	Title	Biochemistry and genetics of von Willebrand factor.
	Source	Annu. Rev. Biochem. 67:395-424(1998).
	PubMed ID	9759493
	DOI	10.1146/annurev.biochem.67.1.395

2	Authors	Voorberg J., Fontijn R., van Mourik J.A., Pannekoek H.
	Title	Domains involved in multimer assembly of von willebrand factor (vWF): multimerization is independent of dimerization.
	Source	EMBO J. 9:797-803(1990).
	PubMed ID	2311582

3	Authors	Huizinga E.G., Martijn van der Plas R., Kroon J., Sixma J.J., Gros P.
	Title	Crystal structure of the A3 domain of human von Willebrand factor: implications for collagen binding.
	Source	Structure 5:1147-1156(1997).
	PubMed ID	9331419

4	Authors	Emsley J., Cruz M., Handin R., Liddington R.
	Title	Crystal structure of the von Willebrand Factor A1 domain and implications for the binding of platelet glycoprotein Ib.
	Source	J. Biol. Chem. 273:10396-10401(1998).
	PubMed ID	9553097

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