Zinc finger DHHC-type palmitoyltransferase 6 (ZDHHC6)

Zinc finger DHHC-type palmitoyltransferase 6 (ZDHHC6) is a multi-spanning transmembrane enzyme localized in the endoplasmic reticulum. It mediates reversible S-palmitoylation— the transfer of fatty acids such as palmitate or stearate to cysteine residues of substrate proteins—influencing their hydrophobicity, assembly, stability, trafficking, and activity[1][2][3][5]. ZDHHC6 uniquely undergoes regulatory cycles of multi-site palmitoylation mediated by the upstream palmitoyltransferase ZDHHC16 and depalmitoylation by acyl protein thioesterases; these modifications tightly control its stability and function[1]. It has broad substrate specificity and modifies diverse ER-associated transmembrane proteins, such as calnexin, E3 ligase gp78, inositol triphosphate receptor (IP3 receptor), transferrin receptor, TMPRSS2, and bone marrow stromal antigen 2, among others[1][2][3]. ZDHHC6 contributes to cellular homeostasis and signaling, with dysfunction implicated in neurodegenerative disease (neuronal ceroid lipofuscinosis)[5]. Direct pharmacological targeting of ZDHHC6 is not established and specific interacting drugs are not reported; its role in reversible lipid modification makes it a putative target for diseases involving protein trafficking and ER function[1][2][3][4][5].

Other names

Zinc finger DHHC-type palmitoyltransferase 6ZDHHC6Palmitoyltransferase ZDHHC6ZNF376DHHC-6FLJ21952Stearoyltransferase ZDHHC6Transmembrane protein H4Zinc finger protein 376

Drugs that affect ZDHHC6 would likely inhibit or modulate S-palmitoylation of its substrate proteins, potentially altering protein localization, stability, and function