zinc finger DHHC-type palmitoyltransferase 17 (zDHHC17)

zDHHC17 (HIP14) is a member of the human zDHHC family of protein S-palmitoyltransferases, characterized by a highly conserved DHHC cysteine-rich domain. The enzyme possesses an N-terminal ankyrin-repeat domain, which confers highly specific substrate recognition, notably for neuronal proteins such as huntingtin, SNAP25, CSP, ankyrin-B, and others. zDHHC17 catalyzes the post-translational modification of substrate proteins through the covalent linkage of palmitate (a fatty acid) to cysteine residues, regulating their membrane association, trafficking, stability, and signaling function. Its activity is pivotal for normal neurological development and synaptic function, and dysregulation or loss of zDHHC17 activity is linked to the pathogenesis of several neurological diseases, most notably Huntington's disease. Therapeutic targeting is challenging due to the broad physiological importance and the significant overlap among DHHC family members.

Other names

HIP14 (huntingtin-interacting protein 14)zDHHC17

Irreversible inhibition of palmitoyltransferase active site cysteines (2-bromopalmitate). Interference with palmitoylation-dependent protein trafficking and localization.