Summary: von Willebrand factor type A domain
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Von Willebrand factor type A domain Edit Wikipedia article
| von Willebrand factor type A domain | |||||||||||
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 Structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin.[1] | |||||||||||
| Identifiers | |||||||||||
| Symbol | VWA | ||||||||||
| Pfam | PF00092 | ||||||||||
| Pfam clan | CL0128 | ||||||||||
| InterPro | IPR002035 | ||||||||||
| SCOPe | 1lfa / SUPFAM | ||||||||||
| CDD | cd00198 | ||||||||||
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The von Willebrand factor type A (vWA) domain is a protein domain named after its occurrence in von Willebrand factor (vWF), a large multimeric glycoprotein found in blood plasma. Mutant forms of vWF are involved in the aetiology of bleeding disorders.[2] This type A domain is the prototype for a protein superfamily (InterPro: IPR036465; see also Pfam clan).
The vWA 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 vWA 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 vWA 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 vWA 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
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; CMG2;
References
- ^ 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.
- ^ Ruggeri ZM, Ware J (1993). "von Willebrand factor". FASEB J. 7 (2): 308–316. PMID 8440408.
- ^ 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.
- ^ 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.
- ^ Bork P (1991). "Shuffled domains in extracellular proteins". FEBS Lett. 286 (1): 47–54. doi:10.1016/0014-5793(91)80937-X. PMID 1864378.
- ^ 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 by alpha-helices found in human ras-p21". FEBS Lett. 358 (3): 283–286. doi:10.1016/0014-5793(94)01447-9. PMID 7843416.
- ^ 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.
- ^ 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.
- Bork, P; Rohde, K (1991). "More von Willebrand factor type a domains? Sequence similarities with malaria thrombospondin-related anonymous protein, dihydropyridine-sensitive calcium channel and inter-alpha-trypsin inhibitor". The Biochemical Journal. 279 (3): 908–10. doi:10.1042/bj2790908. PMC 1151534. PMID 1659389.
External links
- Eukaryotic Linear Motif resource motif class LIG_IBS_1
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von Willebrand factor type A domain Provide feedback
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Literature references
-
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
| SCOOP: | CobT_C Copine DUF1194 DUF2201 DUF58 Integrin_beta Ku_N Med25_VWA Sec23_trunk Ssl1 Tfb4 TssR vWA-TerF-like VWA_2 VWA_3 VWA_CoxE |
| Similarity to PfamA using HHSearch: | Ku_N Ssl1 VWA_CoxE DUF1194 DUF2201 vWA-TerF-like Med25_VWA CobT_C VWA_2 VWA_3 |
External database links
| HOMSTRAD: | int |
| PRINTS: | PR00453 |
| SCOP: | 1lfa |
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]. The vWF domain fold is 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 alpha-M (CD11b; with bound magnesium) [PUBMED:7867070] and alpha-L (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].
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
Alignments
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| Seed (128) |
Full (40345) |
Representative proteomes | UniProt (102231) |
NCBI (222302) |
Meta (1786) |
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| RP15 (6497) |
RP35 (15211) |
RP55 (31131) |
RP75 (48739) |
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| HTML | |||||||||
| PP/heatmap | 1 | ||||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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| Seed (128) |
Full (40345) |
Representative proteomes | UniProt (102231) |
NCBI (222302) |
Meta (1786) |
||||
|---|---|---|---|---|---|---|---|---|---|
| RP15 (6497) |
RP35 (15211) |
RP55 (31131) |
RP75 (48739) |
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| Raw Stockholm | |||||||||
| Gzipped | |||||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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.
Note: You can also download the data file for the tree.
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
| Seed source: | Prodom |
| Previous IDs: | vwa; |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: |
Sonnhammer ELL  , Bateman A
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| Number in seed: | 128 |
| Number in full: | 40345 |
| Average length of the domain: | 172.00 aa |
| Average identity of full alignment: | 18 % |
| Average coverage of the sequence by the domain: | 29.37 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 175 | ||||||||||||
| Family (HMM) version: | 29 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Interactions
There are 18 interactions for this family. More...
Sushi V-set LRRNT Trypsin VWA Lectin_C Lectin_C Mg_chelatase ICAM_N LRR_8 TED_complement NTR CompInhib_SCIN Anth_Ig ICAM_N Binary_toxB Anth_Ig Integrin_betaStructures
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 340 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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