Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
55  structures 457  species 1  interaction 2678  sequences 75  architectures

Family: VHP (PF02209)

Summary: Villin headpiece domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Villin". More...

Villin Edit Wikipedia article

villin 1
Identifiers
SymbolVIL1
Alt. symbolsVIL
NCBI gene7429
HGNC12690
OMIM193040
RefSeqNM_007127
UniProtP09327
Other data
LocusChr. 2 q35-q36
villin 2 (ezrin)
Identifiers
SymbolVIL2
NCBI gene7430
HGNC12691
OMIM123900
RefSeqNM_003379
UniProtP15311
Other data
LocusChr. 6 q22-q27
The helix bundle in the headpiece domain of chicken villin.

Villin is a 92.5 kDa tissue-specific actin-binding protein associated with the actin core bundle of the brush border.[1] Villin contains multiple gelsolin-like domains capped by a small (8.5 kDa) "headpiece" at the C-terminus consisting of a fast and independently folding three-helix bundle that is stabilized by hydrophobic interactions.[2] The headpiece domain is a commonly studied protein in molecular dynamics due to its small size and fast folding kinetics and short primary sequence.[3][4]

Structure

Villin is made up of seven domains, six homologous domains make up the N-terminal core and the remaining domain makes up the C-terminal cap.[3] Villin contains three phosphatidylinositol 4,5-biphosphate (PIP2) binding sites, one of which is located at the head piece and the other two in the core.[5] The core domain is approximately 150 amino acid residues grouped in six repeats. On this core is an 87 residue, hydrophobic, C-terminal headpiece[1] The headpiece (HP67) is made up of a compact, 70 amino acid folded protein at the C-terminus. This headpiece contains an F-actin binding domain. Residues K38, E39, K65, 70-73:KKEK, G74, L75 and F76 surround a hydrophobic core and are believed to be involved in the binding of F-actin to villin. Residues E39 and K70 form a salt bridge buried within the headpiece which serves to connect N and C terminals. This salt bridge may also orient and fix the C-terminal residues involved in F-actin binding as in the absence of this salt bridge no binding occurs. A hydrophobic “cap” is formed by residue W64 side chains, which is completely conserved throughout the villin family. Below this cap is a crown of alternative positive and negative charged localities.[5] Villin can undergo post-translational modifications like tyrosine phosphorylation.[6] Villin has the ability to dimerize and the dimerization site is located at the amino end of the protein.[7]

Expression

Villin is an actin binding protein expressed mainly in the brush border of the epithelium in vertebrates but sometimes it is ubiquitously expressed in protists and plants.[4] Villin is found localized in the microvilli of the brush border of the epithelium lining of the gut and renal tubules in vertebrates.[5]

Function

Villin is believed to function in the bundling, nucleation, capping and severing of actin filaments.[1] In vertebrates, the villin proteins help to support the microfilaments of the microvilli of the brush border. However, knockout mice appear to show ultra-structurally normal microvilli reminding us that the function of villin is not definitively known; it may play a role in cell plasticity through F-actin severing.[5] The six-repeat villin core is responsible for Ca2+ actin severing while the headpiece is responsible for actin crosslinking and bundling (Ca independent). Villin is postulated to be the controlling protein for Ca2+ induced actin severing in the brush border. Ca2+ inhibits proteolytic cleavage of the domains of the 6 N-terminal core which inhibits actin severing.[3] In normal mice raising Ca2+ levels induces the severing of actin by villin, whereas in villin knockout mice this activity does not occur in response to heightened Ca2+ levels.[8] In the presence of low concentrations of Ca2+ the villin headpiece functions to bundle actin filaments whereas in the presence of high Ca2+ concentrations the N-terminal caps and severs these filaments.[1] The association of PIP2 with villin inhibits the actin capping and severing action and increases actin binding at the headpiece region, possibly through structural changes in the protein. PIP2 increases actin bundling not only by decreasing the severing action of villin but also through dissociating capping proteins, releasing actin monomers from sequestering proteins and stimulating actin nucleation and cross linking.[3]

Villin subdomain

The C-terminal subdomain of Villin Headpiece VHP67, denoted VHP35, is stabilised in part, by a buried cluster of three phenylalanine residues. Its small size and high helical content are expected to promote rapid folding, and this has been confirmed experimentally.

Structure

It has a simple topology consisting of three α-helices that form a well-packed hydrophobic core.

See also

References

  1. ^ a b c d Friederich E, Vancompernolle K, Louvard D, Vandekerckhove J (September 1999). "Villin function in the organization of the actin cytoskeleton. Correlation of in vivo effects to its biochemical activities in vitro". The Journal of Biological Chemistry. 274 (38): 26751–60. doi:10.1074/jbc.274.38.26751. PMID 10480879.
  2. ^ Ghoshdastider U, Popp D, Burtnick LD, Robinson RC (November 2013). "The expanding superfamily of gelsolin homology domain proteins". Cytoskeleton. 70 (11): 775–95. doi:10.1002/cm.21149. PMID 24155256.
  3. ^ a b c d Bazari WL, Matsudaira P, Wallek M, Smeal T, Jakes R, Ahmed Y (July 1988). "Villin sequence and peptide map identify six homologous domains". Proceedings of the National Academy of Sciences of the United States of America. 85 (14): 4986–90. Bibcode:1988PNAS...85.4986B. doi:10.1073/pnas.85.14.4986. PMC 281672. PMID 2839826.
  4. ^ a b Klahre U, Friederich E, Kost B, Louvard D, Chua NH (January 2000). "Villin-like actin-binding proteins are expressed ubiquitously in Arabidopsis". Plant Physiology. 122 (1): 35–48. doi:10.1104/pp.122.1.35. PMC 58842. PMID 10631247.
  5. ^ a b c d Meng J, Vardar D, Wang Y, Guo HC, Head JF, McKnight CJ (September 2005). "High-resolution crystal structures of villin headpiece and mutants with reduced F-actin binding activity". Biochemistry. 44 (36): 11963–73. doi:10.1021/bi050850x. PMID 16142894.
  6. ^ Panebra A, Ma SX, Zhai LW, Wang XT, Rhee SG, Khurana S (September 2001). "Regulation of phospholipase C-gamma(1) by the actin-regulatory protein villin". American Journal of Physiology. Cell Physiology. 281 (3): C1046–58. doi:10.1152/ajpcell.2001.281.3.C1046. PMID 11502583.
  7. ^ George SP, Wang Y, Mathew S, Srinivasan K, Khurana S (September 2007). "Dimerization and actin-bundling properties of villin and its role in the assembly of epithelial cell brush borders". The Journal of Biological Chemistry. 282 (36): 26528–41. doi:10.1074/jbc.M703617200. PMID 17606613.
  8. ^ Revenu C, Courtois M, Michelot A, Sykes C, Louvard D, Robine S (2007). "Villin severing activity enhances actin-based motility in vivo". Molecular Biology of the Cell. 18 (3): 827–38. doi:10.1091/mbc.E06-05-0423. PMC 1805090. PMID 17182858.

Further reading

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Villin headpiece domain Provide feedback

No Pfam abstract.

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003128

Villin is an F-actin bundling protein involved in the maintenance of the microvilli of the absorptive epithelia. The villin-type "headpiece" domain is a modular motif found at the extreme C terminus of larger "core" domains in over 25 cytoskeletal proteins in plants and animals, often in assocation with the Gelsolin repeat. Although the headpiece is classified as an F-actin-binding domain, it has been shown that not all headpiece domains are intrinsically F-actin-binding motifs, surface charge distribution may be an important element for F-actin recognition [PUBMED:11977079]. An autonomously folding, 35 residue, thermostable subdomain (HP36) of the full-length 76 amino acid residue villin headpiece, is the smallest known example of a cooperatively folded domain of a naturally occurring protein. The structure of HP36, as determined by NMR spectroscopy, consists of three short helices surrounding a tightly packed hydrophobic core [PUBMED:12095260].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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

Loading domain graphics...

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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...

View options

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
(226)
Full
(2678)
Representative proteomes UniProt
(4153)
NCBI
(12422)
Meta
(24)
RP15
(498)
RP35
(1067)
RP55
(1641)
RP75
(1931)
Jalview View  View  View  View  View  View  View  View  View 
HTML View  View               
PP/heatmap 1 View               

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(226)
Full
(2678)
Representative proteomes UniProt
(4153)
NCBI
(12422)
Meta
(24)
RP15
(498)
RP35
(1067)
RP55
(1641)
RP75
(1931)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

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
(226)
Full
(2678)
Representative proteomes UniProt
(4153)
NCBI
(12422)
Meta
(24)
RP15
(498)
RP35
(1067)
RP55
(1641)
RP75
(1931)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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.

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 View help on the curation process

Seed source: Alignment kindly provided by SMART
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: SMART
Number in seed: 226
Number in full: 2678
Average length of the domain: 36.00 aa
Average identity of full alignment: 46 %
Average coverage of the sequence by the domain: 3.82 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.7 21.7
Trusted cut-off 21.7 22.4
Noise cut-off 21.5 21.5
Model length: 36
Family (HMM) version: 19
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Hide

Weight segments by...


Change the size of the sunburst

Small
Large

Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

Align selected sequences to HMM

Generate a FASTA-format file

Clear selection

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There is 1 interaction for this family. More...

VHP

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 VHP domain has been found. There are 55 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.

Loading structure mapping...