InterPro: IPR002088 Protein prenyltransferase, alpha subunit

Protein prenylation is the posttranslational attachment of either a farnesyl group or a geranylgeranyl group via a thioether linkage (-C-S-C-) to a cysteine at or near the carboxyl terminus of the protein. Farnesyl and geranylgeranyl groups are polyisoprenes, unsaturated hydrocarbons with a multiple of five carbons; the chain is 15 carbons long in the farnesyl moiety and 20 carbons long in the geranylgeranyl moiety. There are three different protein prenyltransferases in humans: farnesyltransferase (FT) and geranylgeranyltransferase 1 (GGT1) share the same motif (the CaaX box) around the cysteine in their substrates, and are thus called CaaX prenyltransferases, whereas geranylgeranyltransferase 2 (GGT2, also called Rab geranylgeranyltransferase) recognises a different motif and is thus called a non-CaaX prenyltransferase. Protein prenyltransferases are currently known only in eukaryotes, but they are widespread, being found in vertebrates, insects, nematodes, plants, fungi and protozoa, including several parasites.

Each protein consists of two subunits, alpha and beta; the alpha subunit of FT and GGT1 is encoded by the same gene, FNTA. The alpha subunit is thought to participate in a stable complex with the isoprenyl substrate; the beta subunit binds the peptide substrate. In the alpha subunits of both types of protein prenyltransferases, seven tetratricopeptide repeats are formed by pairs of helices that are stabilised by conserved intercalating residues. The alpha subunits of GGT2 in mammals and plants also have an immunoglobulin-like domain between the fifth and sixth tetratricopeptide repeat, as well as leucine-rich repeats at the carboxyl terminus. The functions of these additional domains in GGT2 are as yet undefined, but they are apparently not directly involved in the interaction with substrates and Rab escort proteins. The tetratricopeptide repeats of the alpha subunit form a right-handed superhelix, which embraces the (alpha-alpha)6 barrel of the beta subunit [1].