palmitoylproteiinin

Palmitoylproteiinin, also referred to as palmitoylated protein in English, is a post‑translationally modified protein that undergoes covalent attachment of palmitic acid, a 16‑carbon saturated fatty acid. This fatty acid linkage is typically formed through a thioester bond between the carboxyl group of palmitate and the thiol side chain of a cysteine residue on the target protein. Palmitoylation is an enzyme‑mediated process carried out by a family of palmitoyl‑transferases known as zDHHC proteins, named for their Asp-His-His-Cys catalytic motif. In mammals, more than 20 zDHHC enzymes have been identified, each exhibiting distinct substrate preferences and subcellular localizations.

The addition of a palmitate group influences the protein in several ways. It increases lipid solubility, thereby promoting membrane association or anchoring of otherwise soluble proteins. Palmitoylation can also modulate protein trafficking, stability, and interaction with other proteins or lipid microdomains. Because the thioester bond is reversible, palmitoylation serves as a dynamic regulatory switch that allows rapid changes in protein localization and activity in response to cellular signals. Depalmitoylation is catalyzed by palmitoyl‑protein thioesterases, such as APT1 and APT2, which remove the fatty acid and return the protein to a cytosolic or unmodified state.

The biological roles of palmitoylproteins span diverse processes, including signal transduction (e.g., the palmitoylation of Ras family GTPases), neuronal function (e.g., PSD‑95 and other postsynaptic density proteins), and immune responses. Dysregulation of palmitoylation machinery has been implicated in disorders such as cancer, neurodegeneration, and viral pathogenesis. Consequently, components of the palmitoylation system are being explored as therapeutic targets, with inhibitors of specific zDHHC enzymes under investigation for their potential to modulate aberrant protein palmitoylation in disease contexts.