DHHCdomain

The DHHC domain is a conserved protein motif found in a family of enzymes known as palmitoyltransferases. These enzymes are responsible for attaching a fatty acid, specifically palmitate, to cysteine residues of various substrate proteins. This process, called S-palmitoylation, is a reversible post-translational modification that plays a critical role in regulating protein localization, trafficking, stability, and function.

DHHC domain-containing proteins are characterized by the presence of a cysteine-rich domain that is essential for their catalytic activity. This domain contains a conserved H-C-H motif, which is crucial for the formation of a thioester intermediate during the palmitoylation reaction. The DHHC domain is typically located within the transmembrane region of these proteins, suggesting their association with cellular membranes.

There are at least 23 known DHHC domain-containing proteins in humans, each with distinct substrate specificities and cellular functions. These enzymes are involved in a wide range of biological processes, including signal transduction, neuronal development, immune responses, and cancer progression. Dysregulation of DHHC enzymes has been implicated in various diseases, making them attractive targets for therapeutic intervention. Research into the precise mechanisms of DHHC-mediated palmitoylation and the functions of individual DHHC proteins continues to expand our understanding of cellular regulation.