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191  structures 2209  species 7  interactions 10632  sequences 753  architectures

Family: VWA (PF00092)

Summary: von Willebrand factor type A domain

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This is the Wikipedia entry entitled "Von Willebrand factor type A domain". More...

Von Willebrand factor type A domain Edit Wikipedia article

von Willebrand factor type A domain
PDB 1lfa EBI.jpg
Structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin.[1]
Identifiers
Symbol VWA
Pfam PF00092
InterPro IPR002035
SCOP 1lfa
SUPERFAMILY 1lfa
CDD cd00198

The von Willebrand factor is a large multimeric glycoprotein found in blood plasma. Mutant forms are involved in the aetiology of bleeding disorders.[2] In von Willebrand factor, the type A domain (vWF) is the prototype for a protein superfamily. The vWF domain is found in various plasma proteins: complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen types VI, VII, XII and XIV; and other extracellular proteins.[3][4][5] Although the majority of VWA-containing proteins are extracellular, the most ancient ones present in all eukaryotes are all intracellular proteins involved in functions such as transcription, DNA repair, ribosomal and membrane transport and the proteasome. A common feature appears to be involvement in multiprotein complexes. Proteins that incorporate vWF domains participate in numerous biological events (e.g. cell adhesion, migration, homing, pattern formation, and signal transduction), involving interaction with a large array of ligands.[3] A number of human diseases arise from mutations in VWA domains. Secondary structure prediction from 75 aligned vWF sequences has revealed a largely alternating sequence of alpha-helices and beta-strands.[4] Fold recognition algorithms were used to score sequence compatibility with a library of known structures: the vWF domain fold was predicted to be a doubly wound, open, twisted beta-sheet flanked by alpha-helices.[6] 3D structures have been determined for the I-domains of integrins CD11b (with bound magnesium)[7] and CD11a (with bound manganese).[8] The domain adopts a classic alpha/beta Rossmann fold and contains an unusual metal ion coordination site at its surface. It has been suggested that this site represents a general metal ion-dependent adhesion site (MIDAS) for binding protein ligands.[7] The residues constituting the MIDAS motif in the CD11b and CD11a I-domains are completely conserved, but the manner in which the metal ion is coordinated differs slightly.[8]

Human proteins containing this domain[edit]

ANTXR1; ANTXR2; BF; C2; CACHD1; CACNA2D1; CACNA2D2; CACNA2D3; CACNA2D4; CFB; CLCA1; CLCA2; CLCA4; COCH; COL12A1; COL14A1; COL20A1; COL21A1; COL22A1; COL28; COL6A1; COL6A2; COL6A3; COL7A1; COLA1L; CaCC1; ITGA1; ITGA10; ITGA11; ITGA2; ITGAD; ITGAE; ITGAL; ITGAM; ITGAX; ITIH1; ITIH2; ITIH3; ITIH4; ITIH5; ITIH5L; LOC285929; LOC340267; LOC389462; LOH11CR2A; MATN1; MATN2; MATN3; MATN4; PARP4; SEL-OB; SVEP1; VIT; VWA1; VWA2; VWF; hCLCA1; hCLCA2;

References[edit]

  1. ^ Qu A, Leahy DJ (October 1995). "Crystal structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin". Proc. Natl. Acad. Sci. U.S.A. 92 (22): 10277–81. doi:10.1073/pnas.92.22.10277. PMC 40779. PMID 7479767. 
  2. ^ Ruggeri ZM, Ware J (1993). "von Willebrand factor". FASEB J. 7 (2): 308–316. PMID 8440408. 
  3. ^ a b Colombatti A, Bonaldo P, Doliana R (1993). "Type A modules: interacting domains found in several non-fibrillar collagens and in other extracellular matrix proteins". Matrix 13 (4): 297–306. doi:10.1016/S0934-8832(11)80025-9. PMID 8412987. 
  4. ^ a b Smith KF, Haris PI, Chapman D, Perkins SJ, Williams SC, Sim RB (1994). "The secondary structure of the von Willebrand factor type A domain in factor B of human complement by Fourier transform infrared spectroscopy. Its occurrence in collagen types VI, VII, XII and XIV, the integrins and other proteins by averaged structure predictions". J. Mol. Biol. 238 (1): 104–119. doi:10.1006/jmbi.1994.1271. PMID 8145250. 
  5. ^ Bork P (1991). "Shuffled domains in extracellular proteins". FEBS Lett. 286 (1): 47–54. doi:10.1016/0014-5793(91)80937-X. PMID 1864378. 
  6. ^ Perkins SJ, Edwards YJ (1995). "The protein fold of the von Willebrand factor type A domain is predicted to be similar to the open twisted beta-sheet flanked b y alpha-helices found in human ras-p21". FEBS Lett. 358 (3): 283–286. doi:10.1016/0014-5793(94)01447-9. PMID 7843416. 
  7. ^ a b Lee JO, Rieu P, Arnaout MA, Liddington R (1995). "Crystal structure of the A domain from the alpha subunit of integrin CR3 (CD11b/CD18)". Cell 80 (4): 631–638. doi:10.1016/0092-8674(95)90517-0. PMID 7867070. 
  8. ^ a b Leahy DJ, Qu A (1995). "Crystal structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin". Proc. Natl. Acad. Sci. U.S.A. 92 (22): 10277–10281. doi:10.1073/pnas.92.22.10277. PMC 40779. PMID 7479767. 

External links[edit]

This article incorporates text from the public domain Pfam and InterPro IPR002035

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von Willebrand factor type A domain Provide feedback

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Literature references

  1. Bork P, Rohde K; , Biochem J 1991;279:908-911.: More von Willebrand factor type A domains? Sequence similarities with malaria thrombospondin-related anonymous protein, dihydropyridine-sensitive calcium channel and inter-alpha-trypsin inhibitor. PUBMED:1659389 EPMC:1659389


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002035

The von Willebrand factor is a large multimeric glycoprotein found in blood plasma. Mutant forms are involved in the aetiology of bleeding disorders [PUBMED:8440408]. In von Willebrand factor, the type A domain (vWF) is the prototype for a protein superfamily. The vWF domain is found in various plasma proteins: complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen types VI, VII, XII and XIV; and other extracellular proteins [PUBMED:8412987, PUBMED:8145250, PUBMED:1864378]. Although the majority of VWA-containing proteins are extracellular, the most ancient ones present in all eukaryotes are all intracellular proteins involved in functions such as transcription, DNA repair, ribosomal and membrane transport and the proteasome. A common feature appears to be involvement in multiprotein complexes. Proteins that incorporate vWF domains participate in numerous biological events (e.g. cell adhesion, migration, homing, pattern formation, and signal transduction), involving interaction with a large array of ligands [PUBMED:8412987]. A number of human diseases arise from mutations in VWA domains. Secondary structure prediction from 75 aligned vWF sequences has revealed a largely alternating sequence of alpha-helices and beta-strands [PUBMED:8145250]. Fold recognition algorithms were used to score sequence compatibility with a library of known structures: the vWF domain fold was predicted to be a doubly-wound, open, twisted beta-sheet flanked by alpha-helices [PUBMED:7843416]. 3D structures have been determined for the I-domains of integrins CD11b (with bound magnesium) [PUBMED:7867070] and CD11a (with bound manganese) [PUBMED:7479767]. The domain adopts a classic alpha/beta Rossmann fold and contains an unusual metal ion coordination site at its surface. It has been suggested that this site represents a general metal ion-dependent adhesion site (MIDAS) for binding protein ligands [PUBMED:7867070]. The residues constituting the MIDAS motif in the CD11b and CD11a I-domains are completely conserved, but the manner in which the metal ion is coordinated differs slightly [PUBMED:7479767].

Gene Ontology

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Domain organisation

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

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Pfam Clan

This family is a member of clan vWA-like (CL0128), which has the following description:

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The clan contains the following 16 members:

CobT_C Copine DUF1194 DUF2201 DUF444 DUF58 Ku_N Med25_VWA Sec23_trunk Ssl1 Tfb4 VWA vWA-TerF-like VWA_2 VWA_3 VWA_CoxE

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(189)
Full
(10632)
Representative proteomes NCBI
(16265)
Meta
(2130)
RP15
(1087)
RP35
(1482)
RP55
(2603)
RP75
(4154)
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Format an alignment

  Seed
(189)
Full
(10632)
Representative proteomes NCBI
(16265)
Meta
(2130)
RP15
(1087)
RP35
(1482)
RP55
(2603)
RP75
(4154)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(189)
Full
(10632)
Representative proteomes NCBI
(16265)
Meta
(2130)
RP15
(1087)
RP35
(1482)
RP55
(2603)
RP75
(4154)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

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

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

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

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prodom
Previous IDs: vwa;
Type: Domain
Author: Sonnhammer ELL, Bateman A
Number in seed: 189
Number in full: 10632
Average length of the domain: 166.70 aa
Average identity of full alignment: 19 %
Average coverage of the sequence by the domain: 31.03 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 23.0 23.0
Trusted cut-off 23.0 23.0
Noise cut-off 22.9 22.9
Model length: 178
Family (HMM) version: 23
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 7 interactions for this family. More...

LRR_1 LRRNT Lectin_C VWA Trypsin Sushi C1-set

Structures

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 VWA domain has been found. There are 191 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 seqence.

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