HGNC Approved Gene Symbol: PGGT1B
Cytogenetic location: 5q22.3 Genomic coordinates (GRCh38): 5:115,204,012-115,262,877 (from NCBI)
Protein geranylgeranyltransferase type I (GGTase-I) transfers a geranylgeranyl group to the cysteine residue of candidate proteins containing a C-terminal CAAX motif in which 'A' is an aliphatic amino acid and 'X' is leucine. The enzyme is composed of a 48-kD alpha subunit (FNTA; 134635) and a 43-kD beta subunit, encoded by the PGGT1B gene. The FNTA gene encodes the alpha subunit for both GGTase-I and the related enzyme farnesyltransferase (summary by Zhang et al., 1994).
Zhang et al. (1994) obtained overlapping cDNA clones containing the complete coding sequences of the genes encoding the rat and human beta subunits (PGGT1B). The sequences from both species encode a 377-amino acid polypeptide with a predicted molecular mass of 42.4 kD (human) and 42.5 kD (rat). Amino acid sequence comparisons suggested that the mammalian beta-subunit protein is the counterpart of the Saccharomyces cerevisiae gene CDC43. Zhang et al. (1994) coexpressed the beta-subunit cDNA and an FNTA cDNA in E. coli and produced recombinant GGTase-I with electrophoretic and enzymatic properties indistinguishable from those of native GGTase-I.
Lee et al. (2010) used conditional knockout alleles for Fntb (134636), which encodes the beta subunit of farnesyltransferase (FTase), Pggt1b, 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.
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]
Zhang, F. L., Diehl, R. E., Kohl, N. E., Gibbs, J. B., Giros, B., Casey, P. J., Omer, C. A. cDNA cloning and expression of rat and human protein geranylgeranyltransferase type-I. J. Biol. Chem. 269: 3175-3180, 1994. [PubMed: 8106351]