PROSITE documentation PDOC50216
DHHC domain profile


Palmitoylation or, more specificaly S-acylation, plays important roles in the regulation of protein localization, stability, and activity. It is a posttranslational protein modification that involves the attachment of palmitic acid to Cys residues through a thioester linkage. Protein acyltransferases (PATs), also known as palmitoyltransferases, catalyze this reaction by transferring the palmitoyl group from palmitoyl-CoA to the thiol group of Cys residues. They are characterized by the presence of 50-residue-long domain called the DHHC domain, which in most but not all cases is also cysteine-rich and gets its name from a highly conserved DHHC signature tetrapeptide (Asp-His-His-Cys). The Cys residue within the DHHC domain forms a stable acyl intermediate and transfers the acyl chain to the Cys residues of a target protein [1,2].

Some of the proteins containing a DHHC domain are listed below:

  • Drosophila DNZ1 protein.
  • Mouse Abl-philin 2 (Aph2) protein. Interacts with c-Abl. May play a role in apoptosis.
  • Mammalian ZDHHC9, an integral membrane protein.
  • Yeast ankyrin repeat-containing protein AKR1.
  • Yeast Erf2 protein. This protein localizes to the endoplasmic reticulum and seems to be important for Ras function [3].
  • Arabidopsis thaliana tip growth defective 1 [4].

The profile we developed covers the entire DHHC domain.

Last update:

May 2016 / Text revised.


Technical section

PROSITE method (with tools and information) covered by this documentation:

DHHC, PS50216; DHHC domain profile  (MATRIX)


1AuthorsOhno Y. Kashio A. Ogata R. Ishitomi A. Yamazaki Y. Kihara A.
TitleAnalysis of substrate specificity of human DHHC protein acyltransferases using a yeast expression system.
SourceMol. Biol. Cell 23:4543-4551(2012).
PubMed ID23034182

2AuthorsGonzalez Montoro A. Chumpen Ramirez S. Valdez Taubas J.
TitleThe canonical DHHC motif is not absolutely required for the activity of the yeast S-acyltransferases Swf1 and Pfa4.
SourceJ. Biol. Chem. 290:22448-22459(2015).
PubMed ID26224664

3AuthorsBartels D.J. Mitchell D.A. Dong X. Deschenes R.J.
TitleErf2, a novel gene product that affects the localization and palmitoylation of Ras2 in Saccharomyces cerevisiae.
SourceMol. Cell. Biol. 19:6775-6787(1999).
PubMed ID10490616

4AuthorsHemsley P.A. Kemp A.C. Grierson C.S.
TitleThe TIP GROWTH DEFECTIVE1 S-Acyl Transferase Regulates Plant Cell Growth in Arabidopsis.
SourcePlant Cell 17:2554-2563(2005).
PubMed ID16100337

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