ZDHHC2

ZDHHC2 (Zinc finger DHHC-type containing 2), also known as Huntingtin Interacting Protein 14 (HIP14), is a human gene that encodes a palmitoyltransferase enzyme. This enzyme belongs to the DHHC family of protein S-acyltransferases (PATs), a group of enzymes responsible for catalyzing the S-palmitoylation of proteins.

Function

ZDHHC2/HIP14 is involved in the post-translational modification of proteins through palmitoylation, which is the addition of a palmitoyl group (a saturated fatty acid) to cysteine residues. Palmitoylation affects protein localization, stability, trafficking, and interaction with other proteins. HIP14 is known to palmitoylate Huntingtin (HTT), the protein that, when mutated, causes Huntington's disease.

Role in Huntington's Disease

HIP14's interaction with Huntingtin is of particular interest due to its potential role in Huntington's disease pathogenesis. It is believed that HIP14 regulates the trafficking and aggregation of Huntingtin, and disruptions in its function may contribute to the development or progression of the disease. Studies suggest that altered palmitoylation of Huntingtin can influence its toxicity and aggregation properties.

Other Substrates and Functions

Besides Huntingtin, ZDHHC2 likely palmitoylates other proteins, contributing to a variety of cellular processes. Research continues to uncover the full range of its substrates and functional roles.

Tissue Distribution

ZDHHC2 is expressed in various tissues, with notable expression in the brain. Its widespread expression suggests a broad role in cellular function and signaling.

Related Genes and Proteins

ZDHHC2 belongs to a larger family of ZDHHC palmitoyltransferases, each with potentially distinct substrate specificities and cellular functions. Other members of the ZDHHC family include ZDHHC3, ZDHHC5, and ZDHHC7, among others. These proteins share the characteristic DHHC domain, which is essential for their catalytic activity.

Clinical Significance

While mutations in ZDHHC2 have not been definitively linked to specific human diseases outside of its indirect association with Huntington's Disease, its role in protein palmitoylation and its interaction with Huntingtin make it a potential therapeutic target for Huntington's disease and possibly other neurological disorders. Further research is needed to fully understand its clinical significance.