Protein palmitoyltransferase (zDHHC family)

Protein palmitoylation enzymes, most commonly referred to as **protein palmitoyltransferases** or the **zDHHC family**, are a group of enzymes that catalyze the covalent attachment of fatty acids—primarily palmitic acid—to cysteine residues on substrate proteins via a thioester bond. This post-translational modification, known as S-palmitoylation, is reversible and dynamically regulated by two opposing sets of enzymes: the zDHHC-type PATs (which add palmitate) and various thioesterases such as APTs, PPTs, ABHD17A/B/C, which remove it. The zDHHC family is named for its conserved Asp-His-His-Cys motif in the catalytic domain. In mammals there are 23 known zDHHC isoforms (zDHHC1–24; no zDHHC10), with most localized to Golgi or endoplasmic reticulum membranes but some at the plasma membrane. Other specialized acyltransferases include Porcupine (Porcn) for Wnt proteins and Hedgehog acyltransferase (Hhat) for Hedgehog signaling molecules. Palmitoylation increases hydrophobicity, promoting stable association with cellular membranes—especially lipid rafts—and regulates subcellular localization, trafficking between compartments, protein-protein interactions, conformation/stability, and signal transduction. Many key signaling molecules—including G-protein subunits, receptors such as GPCRs/immune receptors/adhesion molecules/pattern recognition receptors—require dynamic cycles of palmitoylation/depalmitoylation for proper function in processes like immune response activation or cell migration. Dysregulation or mutation in these enzymes has been implicated in cancer progression/tumorigenesis through effects on oncogenic signaling pathways; neurodegenerative disorders due to altered synaptic protein targeting; immunologic diseases from improper immune receptor localization/signaling; among other pathologies. Targeting these enzymes is being explored therapeutically. Note on correctness: There is something incorrect about using "Protein palmitoylation enzyme" as a target name—it refers generically to an entire class/family rather than a specific molecular entity. The canonical form should specify "Protein palmitoyltransferase" or "zDHHC-type protein acyltransferase," ideally with an individual isoform if relevant. No approved drugs directly target this enzyme class yet; mechanisms-of-action entries would be speculative at this time. References used above provide detailed mechanistic insight into structure/function/disease relevance but do not list specific drugs/biomarkers/safety concerns currently associated with clinical use against these targets. In summary: "Protein palmitoylation enzyme" refers broadly to several related transferases responsible for S-palmitoylation—a critical regulatory mechanism affecting many cellular processes—with established links to cancer biology/immunity/neurobiology but lacking specificity required for structured drug-target mapping.

Other names

Palmitoylation enzymePalmitoyl acyltransferase (PAT)zDHHC protein familyDHHC-type palmitoyltransferase