Identification of a novel sequence motif recognised by the ankyrin-repeat domain of zDHHC17/13 S-acyl-transferases

Kimon Lemonidis, Maria C. Sanchez-Perez, Luke H. Chamberlain

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42 Citations (Scopus)
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S-acylation is a major post-translational modification affecting several cellular processes and being particularly important for neuronal functions. This modification is catalysed by a family of transmembrane S-acyl-transferases that contain a conserved zinc-finger DHHC (zDHHC) domain. Typically, eukaryote genomes encode for 7-24 distinct zDHHC enzymes, with 2 members also harbouring an ankyrin-repeat (AR) domain at their cytosolic N-terminus. The AR domain of zDHHC enzymes is predicted to engage in numerous interactions, and facilitates both substrate recruitment and S-acylation-independent functions; however, the sequence/structural features recognised by this module remain unknown. The two mammalian AR-containing S-acyltransferases are the Golgi-localised zDHHC17 and zDHHC13, also known as Huntingtin-interacting proteins 14 and 14-like, respectively; these are highly expressed in brain, and their loss in mice leads to neuropathological deficits that are reminiscent of Huntington disease. Here, we report that zDHHC17 and zDHHC13 recognise via their AR domain, evolutionary conserved and closely related sequences of a [VIAP][VIT]xxQP consensus in SNAP25, SNAP23, Cysteine-String Protein, Huntingtin, Cytoplasmic Linker Protein 3 and Microtubule Associated Protein 6. This novel AR-binding sequence motif is found in regions predicted to be unstructured, and is present in a number of zDHHC17 substrates and zDHHC17/13-interacting S-acylated proteins. This is the first study to identify a motif recognised by AR-containing zDHHCs.
Original languageEnglish
Number of pages24
JournalJournal of Biological Chemistry
Early online date21 Jul 2015
Publication statusPublished - 4 Sep 2015


  • Golgi
  • Huntington disease
  • membrane enzyme
  • protein palmitoylation
  • substrate specificity
  • S-acylation
  • ankyrin-repeat domain
  • zDHHC13
  • zDHHC17


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