ZDHHC5
Description
The ZDHHC5 (zinc finger DHHC-type palmitoyltransferase 5) is a protein-coding gene located on chromosome 11.
ZDHHC5 is a palmitoyltransferase that catalyzes the addition of palmitate to various protein substrates, including CTNND2, CD36, NOD1, NOD2, STAT3, and S1PR1. This activity plays a role in diverse biological processes, including cell adhesion, fatty acid uptake, bacterial sensing, and cardiac function. It also regulates synapse efficacy by palmitoylating delta-catenin/CTNND2, thereby increasing synaptic delivery and surface stabilization of AMPARs. Under basal conditions, ZDHHC5 remains at the synaptic membrane through FYN-mediated phosphorylation, preventing association with endocytic proteins. Neuronal activity promotes the internalization and trafficking of ZDHHC5 from spines to dendritic shafts, where it palmitoylates delta-catenin/CTNND2. ZDHHC5 regulates cell adhesion at the plasma membrane by palmitoylating GOLGA7B and DSG2. It plays a role in the innate immune response by mediating the palmitoylation of NOD1 and NOD2, enabling their proper recruitment to the bacterial entry site and phagosomes. ZDHHC5 participates in fatty acid uptake by palmitoylating CD36 and targeting it to the plasma membrane. Upon fatty acid binding to CD36, ZDHHC5 is phosphorylated by LYN, leading to inactivation and subsequent CD36 caveolar endocytosis. ZDHHC5 controls oligodendrocyte development by catalyzing STAT3 palmitoylation. It acts as a regulator of the inflammatory response by mediating the palmitoylation of NLRP3 and GSDMD.
ZDHHC5 is also known as DHHC5, ZNF375.
