Palmitoyltransferase ZDHHC3 (ZDHHC3)

Palmitoyltransferase ZDHHC3 (ZDHHC3) is a zinc finger DHHC domain-containing enzyme that catalyzes the addition of palmitate, a fatty acid, to cysteine residues on substrate proteins—a process known as S-palmitoylation[1][4]. This modification regulates protein membrane targeting, stability, and function. ZDHHC3 is an integral membrane protein mainly localized in the Golgi apparatus, where it modifies a wide range of substrates, including those important in neuronal function and G protein-coupled receptor signaling[1][4]. It has been specifically demonstrated to mediate palmitoylation of Cadm4, which is crucial for myelination in the central nervous system; loss of ZDHHC3 activity results in demyelination, neuroinflammation, and cognitive deficits in animal models[3]. ZDHHC3 is being explored as a therapeutic target in neurodegenerative diseases, cancer, and autoimmune diseases, but development is challenged by the lack of selective inhibitors and potential for broad biological disruption due to its fundamental role in protein palmitoylation[2][3].

Other names

Palmitoyltransferase ZDHHC3ZDHHC3DHHC3DHHC-3Protein DHHC1GODZZinc finger DHHC domain-containing protein 3Zinc finger protein 373HSD49ZNF373Golgi-specific DHHC Zinc Finger ProteinAcyltransferase ZDHHC3DHHC1 proteinGolgi apparatus-specific protein with DHHC zinc finger domainZinc finger DHHC-type containing 3Zinc finger DHHC-type palmitoyltransferase 3

Irreversible or reversible inhibition of the palmitoyltransferase (DHHC) active site, blocking S-palmitoylation of substrate proteins