Protein prenyltransferases catalyze the transfer of an isoprenyl moiety to a cysteine at or near the C-terminus of several eukaryotic proteins. They are heterodimeric enzymes consisting of α and β subunits. The α subunit is thought to participate in a stable complex with the isoprenyl substrate; the β subunit binds the peptide substrate. There are three types of protein prenyltransferases. The α subunits of two types, i.e. farnesyltransferase and geranylgeranyltransferase I are encoded by the same gene, FNTA. These proteins bind the same motif (the CaaX box) around the cysteine in their substrates. The third type, geranylgeranyl transferase type II (Rab GG transferase) recognizes a different, non-CaaX motif [1].

Both the α and β subunit show repetitive sequence motifs [2]. These repeats have distinct structural and functional implications and are unrelated to each other. The conserved domain of the α subunit consists of about 35 amino acids and is repeated five times. The domain folds into a pair of antiparallel α helices, which are packed in a parallel arrangement with adjacent domains in a superhelical pattern (see <PDB:1TN6>). A conserved tryptophan in the fourth position of the second helix interacts with both the first helix and the neighboring helix of the next repeat [3].

Two types of protein prenyltransferase α subunits are known:

• Farnesyltransferase/geranylgeranyltransferase type-1 subunit α (EC 2.5.1.58) (EC 2.5.1.59).
• Geranylgeranyl transferase type-2 subunit α (EC 2.5.1.60).

The profile we developed covers the entire protein prenyltransferases α subunit repeat.