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38  structures 134  species 0  interactions 900  sequences 43  architectures

Family: VHP (PF02209)

Summary: Villin headpiece domain

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

Villin Edit Wikipedia article

villin 1
Symbol VIL1
Alt. symbols VIL
Entrez 7429
HUGO 12690
OMIM 193040
RefSeq NM_007127
UniProt P09327
Other data
Locus Chr. 2 q35-q36
villin 2 (ezrin)
Symbol VIL2
Entrez 7430
HUGO 12691
OMIM 123900
RefSeq NM_003379
UniProt P15311
Other data
Locus Chr. 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. The headpiece domain is a commonly studied protein in molecular dynamics due to its small size and fast folding kinetics and short primary sequence.[2][3]


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.[2] 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.[4] 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.[4] Villin can undergo post-translational modifications like tyrosine phosphorylation.[5] Villin has the ability to dimerize and the dimerization site is located at the amino end of the protein.[6]


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.[3] Villin is found localized in the microvilli of the brush border of the epithelium lining of the gut and renal tubes in vertebrates.[4]


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.[4] 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.[2] 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.[7] 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.[2]

Villin subdomain[edit]

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.


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

See also[edit]


  1. ^ a b c d Friederich, E, Vancompernolle, K, Louvard, D, Vandekerckhove, J (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. ^ a b c d Bazari, WL, Matsudaira, P, Wallek, M, Smeal, T, Jakes, R, Ahmed, Y (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. doi:10.1073/pnas.85.14.4986. PMC 281672. PMID 2839826. 
  3. ^ a b Klahre, U, Friederich, E, Kost, B, Louvard, D, Chua, NH. (2000). "Villin-Like Actin-Binding Proteins Are Expressed Ubiquitously in Arabidopsis". Plant Physiol 122 (1): 35–48. doi:10.1104/pp.122.1.35. PMC 58842. PMID 10631247. 
  4. ^ a b c d Meng, J, Vardar, D, Wang, Y, Guo, HC, Head, JF, McKnight, CJ (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. 
  5. ^ Panebra A, Ma SX, Zhai LW, Wang XT, Rhee SG, Khurana S (2001). "Regulation of phospholipase C-gamma(1) by the actin-regulatory protein villin". Am. J. Physiol., Cell Physiol. 281 (3): C1046–58. PMID 11502583. 
  6. ^ George SP, Wang Y, Mathew S, Srinivasan K, Khurana S (2007). "Dimerization and actin-bundling properties of villin and its role in the assembly of epithelial cell brush borders". J. Biol. Chem. 282 (36): 26528–41. doi:10.1074/jbc.M703617200. PMID 17606613. 
  7. ^ “Subcellular structure and cellular dynamics - UMR 144 CNRS/Institut Curie”. Institut Curie. 2004.

Further reading[edit]

“The Villin Family”. The University of Endinburgh. 2000.

External links[edit]

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Villin headpiece domain Provide feedback

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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].

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Domain organisation

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Seed source: Alignment kindly provided by SMART
Previous IDs: none
Type: Domain
Author: SMART
Number in seed: 15
Number in full: 900
Average length of the domain: 35.90 aa
Average identity of full alignment: 47 %
Average coverage of the sequence by the domain: 4.18 %

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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 21.7 21.7
Trusted cut-off 23.6 21.8
Noise cut-off 21.4 21.4
Model length: 36
Family (HMM) version: 14
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Species distribution

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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 VHP domain has been found. There are 38 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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