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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 [1,2,3,4] 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 α 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.

Bork P.

December 2004 / Pattern and text revised.

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

VWFC_2, PS50184; VWFC domain profile  (MATRIX)

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

• Domain architecture view of Swiss-Prot proteins matching PS50184 • 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 PS50184 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50184 • Scan Swiss-Prot/TrEMBL entries against PS50184 • view ligand binding statistics

Matching PDB structures: 1U5M [ALL]

VWFC_1, PS01208; VWFC domain signature  (PATTERN)

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.

• 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 PS01208 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS01208 • Scan Swiss-Prot/TrEMBL entries against PS01208 • view ligand binding statistics

Matching PDB structures: 1U5M [ALL]

1	Authors	Hunt L.T., Barker W.C.
	Title	von Willebrand factor shares a distinctive cysteine-rich domain with thrombospondin and procollagen.
	Source	Biochem. Biophys. Res. Commun. 144:876-882(1987).
	PubMed ID	3495268

2	Authors	Bork P.
	Title	The modular architecture of a new family of growth regulators related to connective tissue growth factor.
	Source	FEBS Lett. 327:125-130(1993).
	PubMed ID	7687569

3	Authors	Bork P.
	Title	Shuffled domains in extracellular proteins.
	Source	FEBS Lett. 286:47-54(1991).
	PubMed ID	1864378

4	Authors	Voorberg J., Fontijn R., Calafat J., Janssen H., van Mourik J.A., Pannekoek H.
	Title	Assembly and routing of von Willebrand factor variants: the requirements for disulfide-linked dimerization reside within the carboxy-terminal 151 amino acids.
	Source	J. Cell Biol. 113:195-205(1991).
	PubMed ID	2007623

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