farnesyl

Farnesyl refers to the farnesyl group, a hydrophobic 15-carbon isoprenoid moiety derived from farnesyl pyrophosphate (FPP). In cells, farnesylation is a post-translational lipid modification in which a farnesyl group is covalently attached to cysteine residues at the C-terminus of proteins that contain a CaaX motif, a reaction catalyzed by the enzyme farnesyltransferase (FTase). The transfer of the farnesyl moiety from FPP to the protein creates a lipid anchor that promotes membrane association and influences subcellular localization and activity.

Farnesylated proteins include many signaling molecules from the Ras superfamily, as well as various enzymes and trafficking factors. The modification enhances membrane targeting and can affect protein–protein interactions, localization, and function within cells.

In medicine, farnesylation has been investigated as a drug target. Farnesyltransferase inhibitors (FTIs) were developed to block oncogenic Ras signaling, but clinical results have shown limited efficacy in cancers driven by KRAS or NRAS, in part because cells can bypass farnesylation by using geranylgeranyltransferase I to attach a geranylgeranyl group. HRAS-driven cancers may be more sensitive to FTIs. Research continues into improved inhibitors and combination strategies, as well as broader roles of farnesylated proteins.

Chemically, the farnesyl group serves as the lipophilic tail appended to target proteins via the CaaX motif, originating from FPP in the mevalonate pathway.