cDNA cloning of the two subunits of human CAAX farnesyltransferase and chromosomal mapping of FNTA and FNTB loci and related sequences.
The CAAX farnesyltransferase is a heterodimeric enzyme that attaches a farnesyl group to a single cysteine in several cellular proteins. Substrates include the p21ras proteins, nuclear lamins, and several retinal proteins, all of which end with a "CAAXbox," where C is cysteine, A is an aliphatic amino acid, and X is methionine or serine. Full-length cDNAs for the alpha and beta subunits of the rat farnesyltransferase have been cloned, and both have been shown to be essential for catalytic activity. Here we have used the rat cDNAs to clone cDNAs for the human alpha and beta subunits. Comparison of the human and rat amino acid sequences revealed a remarkable degree of conservation (93% identity for the alpha subunit and 96% identity for the beta subunit). The functional genes for the alpha and beta subunits of human farnesyltransferase (gene symbols, FNTA and FNTB) were localized to human chromosome bands 8p22-q11 and 14q23-q24, respectively, by Southern blot hybridization and PCR analyses of panels of human x Chinese hamster somatic cell hybrid lines and by fluorescence chromosomal in situ hybridization. We also found several related farnesyltransferase genes. FNTAL1 was assigned to 11q13.4-q14.1, FNTAL2 to chromosome 13, and FNTBL1 to chromosome 9.
Andres
D A
DA
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Milatovich
A
A
Ozçelik
T
T
Wenzlau
J M
JM
Brown
M S
MS
Goldstein
J L
JL
Francke
U
U
D019883:Alkyl and Aryl Transferases; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D018076:DNA, Complementary; D051231:Farnesyltranstransferase; D006801:Humans; D006822:Hybrid Cells; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D051381:Rats; D014166:Transferases / Q000235:genetics*
D018076:DNA, Complementary; D014166:Transferases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase