Fine‐mapping of <i>ZDHHC2</i> identifies risk variants for schizophrenia in the Han Chinese population

Zhang, Han; Li, Xiuli; Ma, Chuanchuan; Wang, Ke; Zhou, Juan; Chen, Jianhua; Wang, Yonggang; Shi, Yongyong

doi:10.1002/mgg3.1190

Cited by 7 publications

(5 citation statements)

References 42 publications

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“…In addition to zDHHC8, analysis of a genome-wide association study and expression quantitative trait loci data from more than 9000 SCZ patients revealed that zDHHC18 was one of the highest-scoring genes associated with SCZ ( Zhao et al, 2018 ). Moreover, researchers refined the variants of zDHHC2 based on its identification as a candidate gene for SCZ and validated that these variants were risk factors for SCZ in a Chinese Han population ( Zhang et al, 2020 ). Recently, the structure of zDHHC5 was found to be altered in SCZ patients ( Shimell et al, 2021 ).…”

Section: The Role Of Zdhhc In Neurological Diseasesmentioning

confidence: 99%

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

Liao,

Huang,

Liu

et al. 2024

Front. Pharmacol.

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S-palmitoylation is a reversible posttranslational modification, and the palmitoylation reaction in human-derived cells is mediated by the zDHHC family, which is composed of S-acyltransferase enzymes that possess the DHHC (Asp-His-His-Cys) structural domain. zDHHC proteins form an autoacylation intermediate, which then attaches the fatty acid to cysteine a residue in the target protein. zDHHC proteins sublocalize in different neuronal structures and exert dif-ferential effects on neurons. In humans, many zDHHC proteins are closely related to human neu-rological disor-ders. This review focuses on a variety of neurological disorders, such as AD (Alz-heimer’s disease), HD (Huntington’s disease), SCZ (schizophrenia), XLID (X-linked intellectual disability), attention deficit hyperactivity disorder and glioma. In this paper, we will discuss and summarize the research progress regarding the role of zDHHC proteins in these neu-rological disorders.

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Section: The Role Of Zdhhc In Neurological Diseasesmentioning

confidence: 99%

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

Liao,

Huang,

Liu

et al. 2024

Front. Pharmacol.

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“…Localization Biological functions ZDHHC1 ER Ablation of ZDHHC1-mediated p53 palmitoylation help cancer cells escape from the suppression of p53. 605 ZDHHC2 ER, Golgi, dendritic vesicle in neuron ZDHHC2 plays a critical role in inflammatory response of psoriasis 606 ; ZDHHC2 is critical for the proliferation and the survival of B cells 607 ; ZDHHC2 shows association with neurological diseases [608][609][610] ; The C-terminal domain of ZDHHC2 can regulate intracellular localization in neurons 611 ; palmitoylation of SARS-CoV-2 spike protein is critical for virus entry. 612 ZDHHC3 Golgi Palmitoylation of PD-L1 by ZDHHC3 inhibits antitumor immunity in vitro 613 ; palmitoylation of ACE2 by ZDHHC3 is critical for the membrane-targeting of extracellular vesicles secretion 614 ; elevated expression of ZDHHC3 is correlated with poor survival in breast cancer 615 ; high ZDHHC3 levels inhibits synaptic plasticity and memory in high-fat diet (HFD) mice 616 ; ZDHHC3 regulates the infection of primary and latent herpes simplex Virus 1.…”

Section: Genementioning

confidence: 99%

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

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“…Of note, ZDHHC2 is a member of the important DHHC family in neuroendocrine cells [143], which can mediate palmitoylation of PSD-95 and AKAP79/150, impacting synaptic targeting of AMPARs [144,145]. Studies have shown that ZDHHC2 can catalyze the Spalmitoylation of two conserved cysteine residues (Cys36 and Cys129) within the A and C basic regions of AKAP79/150 [146].…”

Section: Post-translational Modification Of Akap79/150mentioning

confidence: 99%

Targeting AKAP79/150 in Human Disorders: An Emerging Opportunity for Future Therapies?

Chen,

Chu,

et al. 2023

PNEURO

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A-kinase anchoring protein 79/150 (AKAP79/150) is an important scaffolding protein, which anchors various important proteins to locate in appropriate synaptic domains to regulate excitatory synaptic intensity. With sweeping advances in the biology of AKAP79/150 and its critical role in the pathophysiology of various human disorders, more and more evidence is breeding new opportunities for potential therapeutic intervention in an attempt to improve the clinical outcomes of those patients. Herein, we review the basic structure and main functions of AKAP79/150, focusing on the pathophysiological mechanisms of AKAP79/150 in different human disorders, with a particular emphasis on the inflammatory pain, epilepsy, and depression, to discuss their potential therapeutic intervention value in patients with those diseases.

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Fine‐mapping of ZDHHC2 identifies risk variants for schizophrenia in the Han Chinese population

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 7 publications

References 42 publications

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Targeting AKAP79/150 in Human Disorders: An Emerging Opportunity for Future Therapies?

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