Ask about this productRelated genes to: ZDHHC5 antibody
- Gene:
- ZDHHC5 NIH gene
- Name:
- zinc finger DHHC-type containing 5
- Previous symbol:
- -
- Synonyms:
- KIAA1748, ZNF375, DHHC5
- Chromosome:
- 11q12.1
- Locus Type:
- gene with protein product
- Date approved:
- 2002-04-04
- Date modifiied:
- 2017-02-20
Related products to: ZDHHC5 antibody
Related articles to: ZDHHC5 antibody
- ZDHHC5, a key member of the DHHC family of palmitoyltransferases, catalyzes S-acylation-a reversible post-translational modification involving the covalent attachment of fatty acids, typically palmitate, to specific cysteine residues on target proteins. This lipid modification plays a critical regulatory role in protein trafficking, membrane association, stability, and the assembly of signaling complexes, thereby modulating diverse cellular processes such as cell proliferation, inflammatory signaling, and metabolic homeostasis. Accumulating evidence underscores the significant involvement of ZDHHC5 in various pathological states, particularly in oncogenesis and cancer progression. Nevertheless, the comprehensive landscape of ZDHHC5-regulated molecular networks across disease contexts remains incompletely understood. In this review, we summarize the structural architecture and catalytic mechanism of ZDHHC5, and elaborate on its biological functions with an emphasis on its role in major signaling pathways and disease pathogenesis. Furthermore, we assess the therapeutic potential of targeting ZDHHC5 through selective inhibitors, discuss current challenges and emerging opportunities in drug development, and highlight how artificial intelligence may accelerate the discovery of novel therapeutic strategies by enabling deeper mechanistic insights into ZDHHC5 function and regulation. - Source: PubMed
Publication date: 2026/05/07
Wang Yan-WenLiu Yan-JunCao Ke-FanWang RanYu JingLi XiangJiang Yi-FangYang Guan-JunChen Jiong - While osteoporosis (OP) affects over 200 million people globally, the causal roles of protein palmitoylation and its upstream epigenetic regulation in the pathogenesis of the disease remain undefined. We aimed to investigate whether DNA methylation causally influences OP risk by modulating the expression of palmitoylation-related genes. We employed an integrated multi-omics causal inference framework, combining 2-sample Mendelian randomization (MR), summary-data-based MR, Bayesian colocalization, and 2-step mediation MR analyses. Data were sourced from large-scale consortia: the FinnGen study (genome-wide association study: 10,461 cases, 473,264 controls), eQTLGen, GTEx (expression quantitative trait loci), and the GoDMC database (methylation quantitative trait loci). Two-sample MR identified ZDHHC5 as a protective factor (odds ratio = 0.81, 95% confidence interval: 0.76-0.87; P = 6.8 × 10-9) and the depalmitoylase PPT1 as a risk factor (odds ratio = 1.06, 95% confidence interval: 1.03-1.08; P = 7.9 × 10-5) for OP. These findings were corroborated by summary-data-based analysis, and colocalization confirmed a shared causal variant at the ZDHHC5 locus (posterior probability of H4 = 0.947). Mediation analysis revealed that DNA methylation is a central mechanistic link: methylation at site cg13473383 mediated 92.7% of ZDHHC5's protective effect, while sites cg04560534 and cg07033722 mediated 74.8% and 43.4%, respectively, of PPT1's risk effect. This study is the first to establish a causal epigenetic-palmitoylation axis in OP. The genes ZDHHC5 and PPT1, regulated by specific DNA methylation sites, represent novel potential therapeutic targets and biomarkers, offering fresh insights for precision medicine strategies against bone loss. - Source: PubMed
Wang ChaoZhu YongRuan Zhe - Innate immune responses must be coordinated with the cellular metabolic state. The intracellular pattern recognition receptor NOD1 detects bacterial peptidoglycans and initiates signaling from cellular membranes, a process regulated by ZDHHC5-mediated palmitoylation. Using biochemical analyses and immune-competent cell models, we show that AMP-activated protein kinase (AMPK) integrates metabolic cues into NOD1 signaling by regulating ZDHHC5. AMPK phosphorylates ZDHHC5 at Ser296 and Ser380, weakens its association with Golga7B, and promotes its displacement from the plasma membrane, thereby reducing NOD1 palmitoylation, membrane localization, and downstream signaling. Conversely, stimulation with the NOD1 agonist C12-iE-DAP suppresses AMPK activity, stabilizing ZDHHC5 at the membrane and sustaining NOD1 activation. These findings define a reciprocal regulatory circuit linking metabolic stress sensing and innate immune signaling, and illustrate how metabolic pathways govern the spatial control of pattern recognition receptors in innate immunity. - Source: PubMed
Publication date: 2026/03/05
Mi ShaojieZhu YueLi QianZhang WanjunPei HuadongYao FengGuo XuewuChen Yali - Intracranial aneurysms (IAs) can cause life-threatening subarachnoid hemorrhage upon rupture, yet their molecular mechanisms remain poorly understood. Proteins encoded by the ZDHHC genes mediate protein palmitoylation and are involved in brain injury processes, but their relationship with IA rupture is unclear. - Source: PubMed
Publication date: 2026/02/19
Zhang WanjingLiu LuHou YajunWang Weiqi - Autoimmunity leading to rheumatoid arthritis (RA) involves CD4 T cell recruitment into synovial tissue. However, metabolic conditions supporting the survival and pro-inflammatory effector functions of these tissue-invading T cells remain poorly understood. Lipidomic analysis identified the inflamed synovium as a lipid-rich environment. In functional studies, administration of the free fatty acid oleic acid exacerbated synovitis. Tissue-invading CD4 T cells responded to fatty acid with rapid cell lysis, releasing cytoplasmic and nuclear content into the extracellular space. This T cell lytic death required sequestration of the pore-forming molecule gasdermin D and the acyltransferase zDHHC5 to lipid droplets, which translocated to the plasma membrane to trigger membrane rupture and pyroptotic cell death. Targeting lipid droplet formation in CD4 T cells through perilipin-2 knockdown or inhibiting gasdermin activation by blocking protein acylation proved highly effective in suppressing synovitis. Thus, autoimmune CD4 T cells lack metabolic resilience, are primed to undergo pyroptosis in lipid-rich environments, and deliver pro-inflammatory cargo to surrounding tissue. - Source: PubMed
Publication date: 2026/02/18
Kumar JitendraTakashima YoshinoriMorales JoseWong BrandonWerner LinaGoronzy Isabel NRubino SeleneTrousdale Robert TBerry Gerald JGoronzy Jörg JWeyand Cornelia M