CLONING, CHARACTERIZATION, AND CHROMOSOMAL LOCALIZATION OF HUMAN SUPERVILLIN (SVIL)

Supervillin is a 205-kDa F-actin binding protein originally isolated f rom bovine neutrophils. This protein is tightly associated with both a ctin filaments and plasma membranes, suggesting that it forms a high-a ffinity link between the actin cytoskeleton and the membrane. Human su pervillin cDNAs cloned from normal human kidney and from the cervical carcinoma HeLa S3 predict a bipartite structure with three potential n uclear localization signals in the NH2-terminus and three potential ac tin-binding sequences in the COOH-terminus. In fact, throughout its le ngth, the COOH-terminal half of supervillin is similar to segments 2-6 plus the COOH-terminal ''headpiece'' of villin, an actin-binding prot ein in intestinal microvilli. A comparison of the bovine and human seq uences indicates that supervillin is highly conserved at the amino aci d level, with 79.2% identity of the NH2-terminus and conservation of t hree of the four nuclear localization signals found in bovine supervil lin. The COOH-terminus is even more highly conserved, with 95.1% amino acid identity overall and 100% conservation of the villin-like headpi ece. Supervillin mRNAs are expressed in all human tissues tested, but are most abundant in muscle, bone marrow, thyroid gland, and salivary gland; comparatively little message is found in brain. Human supervill in mRNA is similar to 7.5 kb; this message is especially abundant in H eLa S3 cervical carcinoma, SW480 adenocarcinoma, and A549 lung carcino ma cell lines. The human supervillin gene (SVIL) is localized to a sin gle chromosomal locus at 10p11.2, a region that is deleted in some pro state tumors. (C) 1998 Academic Press.