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We are deeply saddened by the passing of Amos Bairoch (1957–2025), the creator of PROSITE. We wish to dedicate our latest paper, published shortly before his death, to him. He will always be a source of inspiration to us.
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Amos Bairoch

PROSITE documentation PDOC50216
DHHC domain profile


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PURL: https://purl.expasy.org/prosite/documentation/PDOC50216

Description

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.

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Technical section

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

DHHC, PS50216; DHHC domain profile  (MATRIX)


References

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
DOI10.1091/mbc.E12-05-0336

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
DOI10.1074/jbc.M115.651356

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
DOI10.1105/tpc.105.031237



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