{PDOC50234}
{PS50234; VWFA}
{BEGIN}
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* VWFA domain profile *
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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
alpha/beta "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 alpha 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 alpha-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-alpha-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: 3.
-Last update: December 2001 / First entry.

[ 1] Sadler J.E.
     "Biochemistry and genetics of von Willebrand factor."
     Annu. Rev. Biochem. 67:395-424(1998).
     PubMed=9759493; DOI=10.1146/annurev.biochem.67.1.395
[ 2] Voorberg J., Fontijn R., van Mourik J.A., Pannekoek H.
     "Domains involved in multimer assembly of von willebrand factor (vWF):
     multimerization is independent of dimerization."
     EMBO J. 9:797-803(1990).
     PubMed=2311582
[ 3] Huizinga E.G., Martijn van der Plas R., Kroon J., Sixma J.J., Gros P.
     "Crystal structure of the A3 domain of human von Willebrand factor:
     implications for collagen binding."
     Structure 5:1147-1156(1997).
     PubMed=9331419
[ 4] Emsley J., Cruz M., Handin R., Liddington R.
     "Crystal structure of the von Willebrand Factor A1 domain and
     implications for the binding of platelet glycoprotein Ib."
     J. Biol. Chem. 273:10396-10401(1998).
     PubMed=9553097

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