Sequence of human villin: a large duplicated domain homologous with other actin-severing proteins and a unique small carboxy-terminal domain related to villin specificity.
Villin is a calcium-regulated actin-binding protein that caps, severs, and bundles actin filaments in vitro. This 92,500-D protein is a major constituent of the actin bundles within the microvilli of the brush border surface of intestinal and kidney proximal tubule cells. Villin is a very early marker of cells involved in absorption and its expression is highly increased during intestinal cell differentiation. The amino acid sequence deduced from the cDNA sequence revealed that human villin is composed of three domains. The first two domains appear as the result of a duplication: their structural organization is similar. We can then define a basic unit in which a slightly hydrophilic motif is followed by three hydrophobic motifs, similar between themselves and regularly spaced. The duplicated domain is highly homologous to three other actin-severing proteins and this basic structure represents the whole molecule in severin and fragmin, while two basic units compose gelsolin. The third domain which is carboxy terminal is villin specific: it is unique among actin modulating proteins so far known. It could account for its actin-binding properties (dual regulation by calcium of severing and bundling activities). We propose that it may also be related to the subcellular localization of villin in different epithelial cell types.
Arpin
M
M
Institut Pasteur, Département de Biologie Moléculaire, Paris, France.
Pringault
E
E
Finidori
J
J
Garcia
A
A
Jeltsch
J M
JM
Vandekerckhove
J
J
Louvard
D
D
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D003001:Cloning, Molecular; D004247:DNA; D018260:Gelsolin; D005786:Gene Expression Regulation; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology; D008969:Molecular Sequence Data; D015183:Restriction Mapping; D013379:Substrate Specificity
D000199:Actins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018260:Gelsolin; D008840:Microfilament Proteins; C026615:villin; D004247:DNA