DHHC protein acyltransferase (DHHC-PAT)

DHHC protein acyltransferases are a family of enzymes responsible for the post-translational modification known as S-acylation (commonly palmitoylation), in which a long-chain fatty acid such as palmitate is covalently attached to cysteine residues of substrate proteins via a thioester bond. The family is defined by a conserved Asp-His-His-Cys (DHHC) cysteine-rich domain motif, which is essential for its enzymatic activity. These multipass transmembrane proteins localize mainly to intracellular membranes and play crucial roles in regulating protein localization, stability, and function by modulating the membrane association of numerous signaling proteins. In humans, there are 23 known DHHC genes, each with specificity for different substrates. Dysregulation or mutation of DHHC acyltransferases has been implicated in diverse diseases including cancers and neurodegenerative disorders. Their essential biological functions and links to disease make them an emerging class of therapeutic targets, but specific, clinically useful modulators remain in early development.

Other names

DHHC S-acyltransferasePalmitoyltransferaseProtein acyltransferase (PAT)ZDHHC (gene/protein nomenclature, e.g., ZDHHC20)

Inhibition of acyltransferase (palmitoyltransferase) activity, usually by competitive or covalent inhibition of the active site cysteine