Taxonomic distribution of proteins containing VHP domains

The VHP domain within your query sequence starts at position 629 and ends at position 664, and its E-value is 2.34e-19.

UNC-115, a conserved protein with predicted LIM and actin-binding domains, mediates axon guidance in C. elegans.

Lundquist EA, Herman RK, Shaw JE, Bargmann CI
Neuron. 1998; 21: 385-92

Axon guidance receptors modulate the growth cone cytoskeleton through signaling pathways that are not well understood. Here, we describe the C. elegans unc-115 gene, which encodes a candidate cytoskeletal linker protein that acts in axon guidance. unc-115 mutants have defects in a subset of axons, particularly as the affected axons change environments during outgrowth. The unc-115 gene encodes a putative actin-binding protein that is similar to the human actin-binding protein abLIM/limatin; it has a villin headpiece domain and three LIM domains that could mediate protein interactions. unc-115 is expressed in neurons during their development and is required cell-autonomously in certain neurons for normal axon guidance. We propose that UNC-115 modulates the growth cone actin cytoskeleton in response to signals received by growth cone receptors.

NMR structure of the 35-residue villin headpiece subdomain.

McKnight CJ, Matsudaira PT, Kim PS
Nat Struct Biol. 1997; 4: 180-4

The NMR structure of an autonomously folding subdomain from villin headpiece is reported. It forms a novel three helix structure with the actin-binding residues arrayed on the C-terminal helix.

Cysteine scanning mutagenesis at 40 of 76 positions in villin headpiece maps the F-actin binding site and structural features of the domain.

Doering DS, Matsudaira P
Biochemistry. 1996; 35: 12677-85

Villin headpiece, the 76 amino acid, C-terminal domain of villin, is one of the two F-actin binding sites in villin necessary for F-actin bundling activity. Expression and study of recombinant headpiece revealed the domain to be remarkably thermostable (Tm = 74 degrees C) for a non-disulfide-bonded domain. Forty independent point mutations to cysteine of headpiece have been purified and tested for their actin binding activity, cysteine reactivity, and thermal stability. These assays identify two segments of headpiece, near amino acids 38 and 70 of headpiece, in which mutations to cysteine significantly disrupt cosedimentation of headpiece with F-actin. Assay of the thermal stability of these mutants and assay of the reactivity of the introduced cysteine show that these amino acids are mutations at the protein surface that do not perturb the overall structure of the domain. The actin binding mutants are replacements to cysteine of Lys38, Glu39, Lys65, Lys70, Lys71, Leu75, and Phe76 of headpiece. We propose that these discontinuous segments of charged amino acids define the F-actin binding contacts of the headpiece domain. The assay of mutants for effects on the thermal stability of helical structure as well as the assay of reactivity of the introduced sulfhydryl group identify candidate positions that are involved in the stabilizing core and internal structure of the domain. The cysteine scanning mutagenesis also identifies an amino-terminal subdomain (Val1-Leu35) and a predominantly helical carboxy-terminal subdomain (Pro36-Phe76).

Cloning of human erythroid dematin reveals another member of the villin family.

Rana AP, Ruff P, Maalouf GJ, Speicher DW, Chishti AH
Proc Natl Acad Sci U S A. 1993; 90: 6651-5

Dematin is an actin-bundling protein originally identified in the human erythroid membrane skeleton. Its actin-bundling activity is abolished upon phosphorylation by the cAMP-dependent protein kinase and is restored after dephosphorylation. Here we report the complete primary structure of human erythroid dematin, whose sequence includes a homologue of the "headpiece" sequence found at the C terminus of villin. This headpiece is essential for villin function in inducing microvillar development and actin redistribution. The widespread expression of dematin transcripts in human tissues suggests that dematin and its homologues may substitute for villin in villin-negative tissues to regulate actin reorganization by a phosphorylation-regulated mechanism.