{PDOC00928}
{PS01208; VWFC_1}
{PS50184; VWFC_2}
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* VWFC domain signature and profile *
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The VWFC  domain  is named after the von Willebrand factor (VWF) type C repeat
which is  found  twice  in  this multidomain protein [1,2]. It has a length of
about 70  amino acids covering 10 well conserved cysteines. Proteins with such
a domain [1-4] are listed below.

 - Human  von Willebrand factor  (VWF),  a multifunctional protein involved in
   maintaining homeostasis.  It consists of 4 VWFD domains,  3 VWFA domains, 3
   VWFB domains, 3 VWFC domains, an X domain and a C-terminal cystine knot [2].
 - Silk  moth hemocytin, an humoral lectin which is involved in a self-defence
   mechanism. It  is  composed  of 2 FA58C domains (see <PDOC00988>), a C-type
   lectin domain   (see   <PDOC00537>),  2  VWFC  domains,  and  a  CTCK  (see
   <PDOC00912>).
 - Several  vertebrate heavily glycosylated  mucins. Human mucin 2 is secreted
   by the  epithelia  of  different  mucus membrane-containing organs. It is a
   highly polymorphic  multidomain molecule. Rat intestinal mucin-like peptide
   coats the  epithelia  of  the  intestines.  Both  proteins  share a modular
   architecture similar  to  VWF. Xenopus mucin B.1 contains a Sushi domain, a
   VWFC domain,  a  X  domain and a C-terminal cystine knot. Other mucins that
   contain the  VWFC  domain  are  human tracheobronchial mucin (MUC5), bovine
   submaxillary mucin-like protein, human and pig apomucin.
 - Cef-10/cyr61/CTGF/fisp-12/nov  protein  family.  The members of this family
   are structurally  related  to   insulin-like growth factor binding proteins
   (see <PDOC00194>) and could  function  as  growth  factor-binding proteins.
   They contain an insulin-like growth factor-binding domain, a VWFC repeat, a
   thrombospondin type 1 repeat (Tsp1) and a C-terminal cystine knot.
 - Vertebrate  thrombospondins  1  and 2. These adhesive glycoproteins mediate
   cell-to-cell and cell-to-matrix interactions. They are composed of a common
   thrombospondin N-terminal  domain  (TspN),  a VWFC domain, three Tsp type 1
   repeats (Tsp1), 3 to 4 EGF-like domains and 7 calcium-binding Tsp3 repeats.
 - Vertebrate propeptides of fibrillar collagens alpha 1(I, II & III) and 2(V)
   chains that  contain  an  N-terminal  VWFC  domain, a collagenous region of
   about 1000  amino  acids  and  a  C-terminus  common to fibrillar collagens
   (COLFI domain).
 - Vertebrate  integral  membrane  protein  DGCR2/IDD,  a  potential  adhesion
   receptor with  1  LDL-receptor  class  A domain (see <PDOC00929>), a C-type
   lectin and a VWFC domain.
 - Chordin, a Xenopus developmental protein that contains four VWFC domains.

Of these proteins, the best characterized one is the von Willebrand factor for
which the duplicated VWFC domain is thought to participate in oligomerization,
but not in  the initial dimerization step [4].  The presence of this region in
other  complex-forming  proteins leads to the assumption  that the VWFC domain
might be involved in forming larger protein complexes [1,2].

The profile we developed covers the entire VWFC domain.

-Consensus pattern: C-x(2,3)-C-{CG}-C-x(6,14)-C-x(3,4)-C-x(2,10)-C-x(9,16)-
                    C-C-x(2,4)-C
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: 7.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Expert(s) to contact by email:
           Bork P.; bork@embl-heidelberg.de

-Last update: December 2004 / Pattern and text revised.

[ 1] Hunt L.T., Barker W.C.
     "von Willebrand factor shares a distinctive cysteine-rich domain with
     thrombospondin and procollagen."
     Biochem. Biophys. Res. Commun. 144:876-882(1987).
     PubMed=3495268
[ 2] Bork P.
     "The modular architecture of a new family of growth regulators related
     to connective tissue growth factor."
     FEBS Lett. 327:125-130(1993).
     PubMed=7687569
[ 3] Bork P.
     "Shuffled domains in extracellular proteins."
     FEBS Lett. 286:47-54(1991).
     PubMed=1864378
[ 4] Voorberg J., Fontijn R., Calafat J., Janssen H., van Mourik J.A.,
     Pannekoek H.
     "Assembly and routing of von Willebrand factor variants: the
     requirements for disulfide-linked dimerization reside within the
     carboxy-terminal 151 amino acids."
     J. Cell Biol. 113:195-205(1991).
     PubMed=2007623

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