InterPro domain: IPR006449

This family of sequences describe farnesyl-diphosphate farnesyltransferase, also known as squalene synthase, as found in eukaryotes. This family is related to phytoene synthases. Tentatively identified archaeal homologues lack the C-terminal predicted transmembrane region universally conserved among members of this family and therefore are not included in this group.

These enzymes catalyse the formation of squalene by the reductive dimerisation of two farnesyl diphosphate molecules in a two-step reaction. This reaction occurs at the final branch point of the isoprenoid biosynthesis pathway, and is the first committed step in cholesterol biosynthesis.

2 farnesyl diphosphate ---> presqualene diphosphate ---> squalene

The human enzyme ( P37268 ) is a membrane-bound monomer which folds as a single domain [ 1 ].

This family also includes squalene synthase-like (SSL) proteins from green alga. SSL-3 (botryococcene synthase) produces botryococcene when coexpressed with SSL-1 (presqualene diphosphate synthase). SSL-3 has no activity with farnesyl diphosphate as substrate [ 2 ]. SSL-2 (Botryococcus squalene synthase) produces squalene when coexpressed with SSL-1 and bisfarnesyl ether [ 3 ].

1. Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis. J. Biol. Chem. 275, 30610-7
2. Identification of unique mechanisms for triterpene biosynthesis in Botryococcus braunii. Proc. Natl. Acad. Sci. U.S.A. 108, 12260-5