InterPro domain: IPR026872

Protein farnesyltransferase (FTase) is an enzyme responsible for the posttranslational modification (farnesylation) of proteins carrying a carboxy-terminal CaaX motif, including Ras, Ras homologues, and other small G proteins. FTase catalyses the transfer of a farnesyl moiety from farnesyl pyrophosphate to the cysteine at the CaaX motif, where a is a small aliphatic amino acid and X is the carboxy-terminal residue [ 1 , 2 ]. Prenyltransferase employ a Zn2+ ion to alkylate a thiol group catalyzing the formation of thioether linkages between cysteine residues at or near the C terminus of protein acceptors and the C1 atom of isoprenoid lipids. FTase attaches a 15-carbon farnesyl group to the cysteine within the C-terminal CaaX motif of substrate proteins when X is Ala, Met, Ser, Cys or Gln [ 3 , 4 , 5 ].

FTase is a heterodimeric complex comprised of a regulatory alpha subunit shared with geranylgeranyltransferase I (also a CaaX prenyltransferase) and a unique catalytic beta subunit [ 6 ]. FTase plays important roles in the growth and differentiation of eukaryotic cells. It is essential for embryonic proliferation, but dispensable for adult homeostasis [ 7 ]. In plants, is involved in abscisic acid signal transduction, which modulates a variety of developmental processes and responses to environmental stress [ 8 ]. In yeast, protein farnesylation is important for maintaining normal cell morphology [ 9 ] and for cell cycle progression [ 9 ].

1. Protein farnesylation is critical for maintaining normal cell morphology and canavanine resistance in Schizosaccharomyces pombe. J. Biol. Chem. 275, 429-38
2. Purified yeast protein farnesyltransferase is structurally and functionally similar to its mammalian counterpart. Biochem. J. 289 ( Pt 1), 25-31
3. Structure, mechanism and function of prenyltransferases. Eur. J. Biochem. 269, 3339-54
4. Reaction path of protein farnesyltransferase at atomic resolution. Nature 419, 645-50
5. Cocrystal structure of protein farnesyltransferase complexed with a farnesyl diphosphate substrate. Biochemistry 37, 9612-8
6. Protein prenyltransferases. Genome Biol. 4, 212
7. Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development. Cancer Cell 7, 313-24
8. A protein farnesyl transferase involved in abscisic acid signal transduction in Arabidopsis. Science 273, 1239-41
9. Failure to farnesylate Rheb protein contributes to the enrichment of G0/G1 phase cells in the Schizosaccharomyces pombe farnesyltransferase mutant. Mol. Microbiol. 41, 1339-47