farnesylated

Farnesylated describes a molecule, usually a protein, that has a farnesyl group covalently attached to it. The farnesyl group is a 15-carbon isoprenoid, and in proteins this lipid is typically linked through a thioether bond to a cysteine residue near the protein’s C-terminus in a CaaX motif (Cys–two aliphatic residues–any amino acid X).

The attachment is carried out by farnesyltransferase, which recognizes the CaaX motif and transfers the farnesyl moiety from farnesyl pyrophosphate to the cysteine. After prenylation, most substrates undergo further processing: the AAX residues are cleaved by a protease such as Rce1, and the exposed carboxyl group of the farnesylated cysteine is often methylated by isoprenylcysteine carboxyl methyltransferase (ICMT). Some proteins may be farnesylated but not fully processed, depending on their sequence and cellular context.

Farnesylation enhances hydrophobicity and promotes association with cellular membranes, especially the inner leaflet of the plasma membrane. This membrane targeting is important for the function and localization of many signaling proteins, including members of the Ras and Rheb families, as well as lamin precursors such as prelamin A.

Clinically, farnesylation is a target for drug development. Farnesyltransferase inhibitors have been explored as anticancer agents to disrupt oncogenic signaling; however, therapeutic results have been variable, and compensatory pathways can limit efficacy. Detection and study of farnesylated proteins use methods such as mass spectrometry and metabolic labeling. In synthetic contexts, a molecule can be described as farnesylated if it bears a covalently attached farnesyl group.