Accessory proteins of the zDHHC family of S-acylation enzymes

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Almost two decades have passed since seminal work in Saccharomyces cerevisiae identified zinc finger DHHC domain containing (zDHHC) enzymes as S-acyltransferases. These enzymes are ubiquitous in the eukarya domain, with twenty-three distinct ZDHHC genes in the human genome. zDHHC enzymes mediate the bulk of S-acylation (also known as palmitoylation) reactions in cells, transferring acyl chains to cysteine thiolates, and in so-doing affecting the stability, localisation and function of several thousand proteins. Studies using purified components have shown that the minimal requirements for S-acylation are an appropriate zDHHC enzyme-substrate pair and fatty acyl-CoA. However, additional proteins including GCP16, Golga7b, huntingtin and selenoprotein K, have been suggested to regulate the activity, stability and trafficking of certain zDHHC enzymes. In this Review, we discuss the role of these accessory proteins as essential components of the cellular S-acylation system.
Original languageEnglish
Number of pages25
JournalJournal of Cell Science
Publication statusAccepted/In press - 10 Sep 2020


  • s-acylation
  • palmitoylation
  • zDHHC enzyme
  • huntingtin
  • selenoprotein K


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