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30  structures 508  species 0  interactions 17609  sequences 1839  architectures

Family: VWD (PF00094)

Summary: von Willebrand factor type D domain

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von Willebrand factor type D domain Provide feedback

P17554 contains a vwd domain. Its function is unrelated but the similarity is very strong by several methods.

Literature references

  1. Bork P; , FEBS Lett 1993;327:125-130.: The modular architecture of a new family of growth regulators related to connective tissue growth factor. PUBMED:7687569 EPMC:7687569

Internal database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001846

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 [ PUBMED:9759493 , PUBMED:2311582 ].

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 [ PUBMED:10807780 , PUBMED:2311582 ]. 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 [ PUBMED:10807780 , PUBMED:2311582 ].

The VWFD domain can occur in association with a lot of different domains like vitellogenin, VWFC, VWFA, and ZP.

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 (D1-4), 3 VWFA domains, 3 VWFB domains, 2 VWFC domains, an X domain and a C-terminal cystine knot [ PUBMED:22490677 ]. There might be a third VWFC domain within the type B domain region [ PUBMED:2311582 ]. The structure of the VWF D3 domain has been revealed [ PUBMED:30642920 ].
  • 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 alpha-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.

This entry represents the VWFD domain.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

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Curation View help on the curation process

Seed source: Dotter
Previous IDs: vwd;
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Sonnhammer ELL
Number in seed: 41
Number in full: 17609
Average length of the domain: 143.40 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 19.45 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 22.9 22.9
Trusted cut-off 22.9 22.9
Noise cut-off 22.8 22.8
Model length: 157
Family (HMM) version: 27
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the VWD domain has been found. There are 30 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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