Zinc finger DHHC-type palmitoyltransferase 2 (ZDHHC2)

Zinc finger DHHC-type palmitoyltransferase 2 (ZDHHC2) is an enzyme of the protein S-acyltransferase family, characterized by a DHHC (Asp-His-His-Cys) domain and a zinc finger motif, responsible for catalyzing the post-translational palmitoylation (and related acylation) of numerous protein substrates[1][3]. ZDHHC2 localizes primarily to the Golgi apparatus, endoplasmic reticulum, and plasma membrane, where it regulates critical processes such as synapse assembly, protein trafficking, and membrane localization. In immune cells, ZDHHC2 palmitoylates and stabilizes B-RAF and C-RAF kinases, modulating their autophagic turnover and activating the ERK signaling pathway, which is vital for cytokine production and host defense against pathogens such as *Mycobacterium tuberculosis*[2]. Reduced ZDHHC2 expression is associated with increased metastasis and poor prognosis in several cancers, suggesting a potential role as a tumor suppressor[3]. Deficiency of ZDHHC2 impairs immune responses and neural plasticity, underscoring its physiological importance and potential as a therapeutic target.

Other names

ZDHHC2DHHC2ZNF372Reduced expression associated with metastasis proteinReduced expression in cancer proteinZinc finger DHHC domain-containing protein 2Zinc finger DHHC-type palmitoyltransferase 2Zinc finger DHHC-type containing 2Palmitoyltransferase ZDHHC2Zinc finger protein 372REAMRECReamRecAcyltransferase ZDHHC2Testis tissue sperm-binding protein Li 56e

Palmitoylation inhibition: Drugs inhibiting S-palmitoyltransferase activity would block post-translational protein lipidation, affecting stability and signaling of client proteins (e.g., B-RAF, C-RAF).