InterPro domain: IPR001594

This entry refers to the DHHC domain, found in DHHC proteins which are palmitoyltransferases [ 1 ].

Palmitoylation or, more specifically S-acylation, plays important roles in the regulation of protein localization, stability, and activity. It is a post-translational protein modification that involves the attachment of palmitic acid to Cys residues through a thioester linkage. Protein acyltransferases (PATs), also known as palmitoyltransferases, catalyse this reaction by transferring the palmitoyl group from palmitoyl-CoA to the thiol group of Cys residues. They are characterised 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 [ 2 , 3 ].

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

• Drosophila DNZ1 protein [ 4 ]
• Mouse Abl-philin 2 (Aph2) protein. Interacts with c-Abl. May play a role in apoptosis [ 5 ]
• Mammalian ZDHHC9, an integral membrane protein [ 6 ]
• Yeast ankyrin repeat-containing protein AKR1 [ 7 ]
• Yeast Erf2 protein. This protein localizes to the endoplasmic reticulum and seems to be important for Ras function [ 8 ]
• Arabidopsis thaliana tip growth defective 1 [ 9 ]

1. Identification of PSD-95 palmitoylating enzymes. Neuron 44, 987-96
2. Analysis of substrate specificity of human DHHC protein acyltransferases using a yeast expression system. Mol. Biol. Cell 23, 4543-51
3. The canonical DHHC motif is not absolutely required for the activity of the yeast S-acyltransferases Swf1 and Pfa4. J. Biol. Chem. 290, 22448-59
4. The Drosophila STAM gene homolog is in a tight gene cluster, and its expression correlates to that of the adjacent gene ial. Gene 231, 173-86
5. Aph2, a protein with a zf-DHHC motif, interacts with c-Abl and has pro-apoptotic activity. J. Biol. Chem. 277, 28870-6
6. DHHC9 and GCP16 constitute a human protein fatty acyltransferase with specificity for H- and N-Ras. J. Biol. Chem. 280, 31141-8
7. The yeast DHHC cysteine-rich domain protein Akr1p is a palmitoyl transferase. J. Cell Biol. 159, 23-8
8. Erf2, a novel gene product that affects the localization and palmitoylation of Ras2 in Saccharomyces cerevisiae. Mol. Cell. Biol. 19, 6775-87
9. The TIP GROWTH DEFECTIVE1 S-acyl transferase regulates plant cell growth in Arabidopsis. Plant Cell 17, 2554-63