HGNC Approved Gene Symbol: FNTB
Cytogenetic location: 14q23.3 Genomic coordinates (GRCh38): 14:64,986,895-65,062,650 (from NCBI)
The CAAX farnesyltransferase (FTase) is an alpha/beta heterodimeric enzyme that attaches a farnesyl group to a single cysteine in several cellular proteins, all of which end with a 'CAAX box,' where C is cysteine, A is an aliphatic amino acid, and X is methionine or serine. This posttranslational modification provides a mechanism for membrane localization of proteins that lack a transmembrane domain (summary by Andres et al., 1993).
Using rat FNTA (134635) and FNTB cDNA, Andres et al. (1993) cloned the corresponding human cDNAs. FNTB encodes a predicted 487-amino acid protein that shares 96% sequence identity with the rat homolog.
Andres et al. (1993) localized the FNTB gene to 14q23-q24 by Southern blot hybridization and PCR analyses of panels of human/Chinese hamster somatic cell hybrid lines and by fluorescence chromosomal in situ hybridization. They found a related farnesyltransferase gene, FNTBL1, on chromosome 9.
Long et al. (2002) presented a complete series of structures representing the major steps along the reaction coordinate of the enzyme protein farnesyltransferase. From these observations, Long et al. (2002) deduced the determinants of substrate specificity and an unusual mechanism in which product release requires binding of substrate, analogous to classically processive enzymes. A structural model for the transition state consistent with previous mechanistic studies was also constructed.
Lee et al. (2010) used conditional knockout alleles for Fntb, Pggt1b (602031), which encodes the beta subunit of GGTase-I, and a keratin-14 (KRT14; 148066)-Cre transgene to create mice lacking FTase or GGTase-I in skin keratinocytes. Keratinocyte-specific Fntb knockout mice were viable but developed severe alopecia. The interfollicular epidermis of Fntb-deficient mice appeared normal; however, keratinocytes from these mice could not proliferate in culture. As expected, nonfarnesylated prelamin A (LMNA; 150330) and nonfarnesylated DNAJA1 (602837) accumulated in Fntb-deficient keratinocytes. Keratinocyte-specific Pggt1b knockout mice survived development but died shortly after birth. Like Fntb-deficient keratinocytes, Pggt1b-deficient keratinocytes did not proliferate in culture. Lee et al. (2010) concluded that both FTase and GGTase-I are required for the homeostasis of skin keratinocytes.
Andres, D. A., Milatovich, A., Ozcelik, T., Wenzlau, J. M., Brown, M. S., Goldstein, J. L., Francke, U. cDNA cloning of the two subunits of human CAAX farnesyltransferase and chromosomal mapping of FNTA and FNTB loci and related sequences. Genomics 18: 105-112, 1993. [PubMed: 8276393] [Full Text: https://doi.org/10.1006/geno.1993.1432]
Lee, R., Chang, S. Y., Trinh, H., Tu, Y., White, A. C., Davies, B. S. J., Bergo, M. O., Fong, L. G., Lowry, W. E., Young, S. G. Genetic studies on the functional relevance of the protein prenyltransferases in skin keratinocytes. Hum. Molec. Genet. 19: 1603-1617, 2010. [PubMed: 20106865] [Full Text: https://doi.org/10.1093/hmg/ddq036]
Long, S. B., Casey, P. J., Beese, L. S. Reaction path of protein farnesyltransferase at atomic resolution. Nature 419: 645-650, 2002. [PubMed: 12374986] [Full Text: https://doi.org/10.1038/nature00986]