Palmitoyltransferase ZDHHC19 (ZDHHC19)

Palmitoyltransferase ZDHHC19 (ZDHHC19) is a zinc finger protein and enzyme belonging to the DHHC (Asp-His-His-Cys) family of protein acyltransferases, specifically catalyzing *protein S-palmitoylation*, a reversible post-translational modification where a palmitate group (a long-chain fatty acid) is attached to substrate proteins on cysteine residues. ZDHHC19 is testis-enriched and localized to the plasma membrane in spermatids, forming a complex with the transmembrane protein TEX38, which is required for sperm head shaping during spermiogenesis; disruption of ZDHHC19 results in male infertility due to abnormal sperm morphology and faulty membrane trafficking, possibly through mis-palmitoylation of critical substrate proteins like ARRDC5. In addition to its role in reproduction, ZDHHC19 has been implicated in promoting Chikungunya virus replication by palmitoylating viral proteins and plays a part in autophagy regulation by modifying proteins such as SQSTM1. Its activity is governed by autoacylation of a critical cysteine residue within its DHHC motif, and it is a potential target for nonhormonal male contraceptive approaches that seek to modulate its palmitoyltransferase function.

Other names

DHHC-19MGC33345Zinc finger DHHC domain-containing protein 19DHHC19zinc finger DHHC-type containing 19

Drugs or inhibitors (hypothetical) would block S-palmitoylation activity, thereby disrupting membrane protein trafficking or sperm morphogenesis. Experimental disruption has been proposed as a nonhormonal male contraceptive strategy.