PROSITE documentation PDOC51233VWFD domain profile
Von Willebrand factor (VWF) is a large, multimeric blood glycoprotein synthesized in endothelial cells and megakaryocytes, 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. The type D domain (VWFD) is not only required for blood clotting factor VIII binding but also for normal multimerization of VWF [3,4]. The interaction between blood clotting factor VIII and VWF is necessary for normal survival of blood clotting factor VIII in blood circulation. The VWFD domain is a highly structured region, in which the first conserved Cys has been found to form a disulfide bridge with the second conserved one [3,4].
The VWFD domain can occur in association with a lot of different domains like vitellogenin (see <PDOC51211>), VWFC (see <PDOC00928>), VWFA (see <PDOC50234>), and ZP (see <PDOC00577>).
Proteins with a VWFD domain are listed below:
- Mammalian von Willebrand factor (VWF), a multifunctional protein involved in maintaining homeostasis. It consists of 4 VWFD domains, 3 VWFA domains, 3 VWFB domains, 2 VWFC domains, an X domain and a C-terminal cystine knot. There might be a third VWFC domain within the type B domain region [2].
- Mammalian zonadhesin, which binds in a species-specific manner to the zona pellucida of the egg.
- Mammalian bone morphogenetic protein-binding (BMP-binding) endothelial regulator protein.
- Mammalian α-tectorin, which is one of the major non-collagenous components of the tectorial membrane.
- Mammalian mucins, glycoproteins that are major constituents of the glycocalyx that covers mucosal epithelium.
- Mammalian vitellogenin, a major lipoprotein in many oviparous animals, which is a precursor of a lipid-binding product named as lipovitellin.
We developed a profile that spans the entire VWFD domain.
Last update:April 2021 / Profile revised.
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PROSITE method (with tools and information) covered by this documentation:
| 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 | Jorieux S. Fressinaud E. Goudemand J. Gaucher C. Meyer D. Mazurier C. |
| Title | Conformational changes in the D' domain of von Willebrand factor induced by CYS 25 and CYS 95 mutations lead to factor VIII binding defect and multimeric impairment. | |
| Source | Blood 95:3139-3145(2000). | |
| PubMed ID | 10807780 |
| 4 | 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 |
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