Cloning, characterization, and chromosomal localization of human superillin (SVIL).
Supervillin is a 205-kDa F-actin binding protein originally isolated from bovine neutrophils. This protein is tightly associated with both actin filaments and plasma membranes, suggesting that it forms a high-affinity link between the actin cytoskeleton and the membrane. Human supervillin cDNAs cloned from normal human kidney and from the cervical carcinoma HeLa S3 predict a bipartite structure with three potential nuclear localization signals in the NH2-terminus and three potential actin-binding sequences in the COOH-terminus. In fact, throughout its length, the COOH-terminal half of supervillin is similar to segments 2-6 plus the COOH-terminal "headpiece" of villin, an actin-binding protein in intestinal microvilli. A comparison of the bovine and human sequences indicates that supervillin is highly conserved at the amino acid level, with 79.2% identity of the NH2-terminus and conservation of three of the four nuclear localization signals found in bovine supervillin. The COOH-terminus is even more conserved, with 95.1% amino acid identity overall and 100% conservation of the villin-like headpiece. Supervillin mRNAs are expressed in all human tissue tested, bu are most abundant in muscle, bone marrow, thyroid gland, and salivary gland; comparatively little message is found in brain. Human supervillin mRNA is approximately 7.5 kb; this message is especially abundant in HeLa S3 cervical carcinoma, SW480 adenocarcinoma, and A549 lung carcinoma cell lines. The human supervillin gene (SVIL) is localized to a single chromosomal locus at 10p11.2, a region that is deleted in some prostate tumors.
Pope
R K
RK
Department of Cell Biology, University of Massachusetts Medical Center, Worcester Foundation Campus, Shrewsbury, Massachusetts 01545, USA. POPE@SCI.WFBR.EDU
Pestonjamasp
K N
KN
Smith
K P
KP
Wulfkuhle
J D
JD
Strassel
C P
CP
Lawrence
J B
JB
Luna
E J
EJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008565:Membrane Proteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D008840:Microfilament Proteins; D019913:Nuclear Localization Signals; D012333:RNA, Messenger; C109413:SVIL protein, human