Ask about this productRelated genes to: NAT8B Blocking Peptide
- Gene:
- NAT8B NIH gene
- Name:
- N-acetyltransferase 8B (putative, gene/pseudogene)
- Previous symbol:
- -
- Synonyms:
- Hcml2, NAT8BP, CML2
- Chromosome:
- 2p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2006-10-24
- Date modifiied:
- 2019-01-10
Related products to: NAT8B Blocking Peptide
Related articles to: NAT8B Blocking Peptide
- The transcription factor ATF6α has a central role in adapting mammalian cells to ER stress via the unfolded protein response (UPR), prompting efforts to identify ATF6α modulators. Here, an unbiased genome-wide CRISPR-Cas9 screen performed in Chinese Hamster Ovary cells revealed that proteolytic processing of the ATF6α precursor to its active form was impaired in cells lacking the ER-resident solute carrier SLC33A1, a transporter previously implicated in acetyl-CoA import, sialylation, and Nε-lysine protein acetylation. Cells lacking SLC33A1 constitutively trafficked the ATF6α to the Golgi but exhibited impaired Golgi processing and activating proteolysis. IRE1α signalling was derepressed by SLC33A1 deficiency consistent with selective loss of ATF6α-mediated negative feedback in the UPR. -deleted cells accumulated unmodified sialylated N-glycans, precursors to acetylated glycans, likely reflecting impaired glycan processing. Deletion of ER-localised acetyltransferases NAT8 and NAT8B, which catalyse protein Nε-lysine acetylation in the secretory pathway, did not replicate the ATF6α processing defects observed in -deficient cells. Together, our findings highlight a role of SLC33A1-mediated metabolite transport in the post-ER ATF6α maturation, linking small-molecule metabolism to branch-specific signalling in the UPR. - Source: PubMed
Publication date: 2026/04/17
George GintoHarding Heather PKay RichardRon DavidOrdoñez Adriana - Neurons heavily depend on the ability of the secretory pathway to deliver correctly folded polypeptides to the periphery of the cell for the assembly, maintenance, and normal functioning of synapses. The endoplasmic reticulum (ER) acetylation machinery has emerged as a novel branch of the more general ER quality control machinery. It regulates the positive selection of correctly folded nascent glycoproteins, thus ensuring the efficiency of the conventional secretory pathway. ER acetylation requires the activity of two ER-luminal acetylCoA:lysine acetyltransferases, ATase1/NAT8B and ATase2/NAT8. Both acetyltransferases depend on the influx of acetyl-CoA into the ER from the cytosol, which is ensured by the coordinated action of the citrate transporters, SLC25A1 and SLC13A5, and the ER acetyl-CoA transporter, AT-1. Gene duplication events affecting ATase1 and ATase2 are associated with rare disease phenotypes that include autism and intellectual disability with dysmorphism. Here, we generated mice with neuron-specific overexpression of human ATase1 or ATase2. The animals display autistic-like behaviors with altered synaptic plasticity, altered neuronal morphology, and altered synaptic structure and function. Mechanistic assessment demonstrates that widespread proteomic changes and altered dynamics of the secretory pathway underly the synaptic defects. The phenotype of ATase1 and ATase2 overexpressing mice is reminiscent of SLC25A1, SLC13A5 and AT-1 overexpressing models. Therefore, when taken together, our results support the argument that the intracellular citrate/acetyl-CoA pathway, with the ATases acting as the last output, is immediately connected to the pathogenesis of certain rare forms of autism spectrum disorder. - Source: PubMed
Publication date: 2025/09/24
Kalimuthu BalagangadharanLu HaiyanSteenhagen AngeliqueDong QipingGray MitchellRigby Michael JEndresen AndreasChang QiangLi LingjunPuglielli Luigi - Nε-lysine acetylation in the lumen of the ER requires two acetyltransferases, ATase1/NAT8B and ATase2/NAT8. They are type II membrane proteins and belong to the larger GNAT superfamily of acetyltransferases. Their enzymatic activity is tightly coupled to the import of acetyl-CoA in the lumen of the ER by AT-1/SLC33A1. Gene duplication events involving 3q25.31 (harboring ) and 2p13.1 (harboring and ) are associated with autism spectrum disorder with intellectual disability and progeria-like dysmorphism. Here, we report the generation and phenotypic characterization of mice with systemic overexpression of ATase1 (ATase1 sTg) and ATase2 (ATase2 sTg). Overexpression of either ATase at conception was found to be lethal while overexpression at birth was found to cause a progeria-like phenotype that included skin alterations, lordokyphosis, reduced bone density, sarcopenia, splenomegaly, adenomegaly, and systemic inflammation. The phenotype of ATase1 sTg mice displayed incomplete penetrance, while the phenotype of ATase2 sTg displayed full penetrance and was more severe. Mechanistically, the phenotype was linked to altered dynamics of the secretory pathway with defects affecting the quality of the secretome. - Source: PubMed
Publication date: 2025/09/10
Cheng Tzu-LinWu FeixuanHaque Md EzazulThiel Abigail RWang DanqingHelgager Jeffrey JLi LingjunPuglielli Luigi - Autophagy has an important association with tumorigenesis, progression, and prognosis. However, the mechanism of autophagy-regulated genes on the risk prognosis of bladder cancer (BC) patients has not been fully elucidated yet. In this study, we created a prognostic model of BC risk based on autophagy-related genes, which further illustrates the value of genes associated with autophagy in the treatment of BC. We first downloaded human autophagy-associated genes and BC datasets from Human Autophagy Database and The Cancer Genome Atlas (TCGA) database, and finally obtained differential prognosis-associated genes for autophagy by univariate regression analysis and differential analysis of cancer versus normal tissues. Subsequently, we downloaded two datasets from Gene Expression Omnibus (GEO), GSE31684 and GSE15307, to expand the total number of samples. Based on these genes, we distinguished the molecular subtypes (C1, C2) and gene classes (A, B) of BC by consistent clustering analysis. Using the genes merged from TCGA and the two GEO datasets, we conducted least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis to obtain risk genes and construct autophagy-related risk prediction models. The accuracy of this risk prediction model was assessed by receiver operating characteristic (ROC) and calibration curves, and then nomograms were constructed to predict the survival of bladder cancer patients at 1, 3, and 5 years, respectively. According to the median value of the risk score, we divided BC samples into the high- and low-risk groups. Kaplan-Meier (K-M) survival analysis was performed to compare survival differences between subgroups. Then, we used single sample gene set enrichment analysis (ssGSEA) for immune cell infiltration abundance, immune checkpoint genes, immunotherapy response, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, and tumor mutation burden (TMB) analysis for different subgroups. We also applied quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) techniques to verify the expression of these six genes in the model. Finally, we chose the IMvigor210 dataset for external validation. Six risk genes associated with autophagy (SPOCD1, FKBP10, NAT8B, LDLR, STMN3, and ANXA2) were finally screened by LASSO regression algorithm and multivariate Cox regression analysis. ROC and calibration curves showed that the model established was accurate and reliable. Univariate and multivariate regression analyses were used to verify that the risk model was an independent predictor. K-M survival analysis indicated that patients in the high-risk group had significantly worse overall survival than those in the low-risk group. Analysis by algorithms such as correlation analysis, gene set variation analysis (GSVA), and ssGSEA showed that differences in immune microenvironment, enrichment of multiple biologically active pathways, TMB, immune checkpoint genes, and human leukocyte antigens (HLAs) were observed in the different risk groups. Then, we constructed nomograms that predicted the 1-, 3-, and 5-year survival rates of different BC patients. In addition, we screened nine sensitive chemotherapeutic drugs using the correlation between the obtained expression status of risk genes and drug sensitivity results. Finally, the external dataset IMvigor210 verified that the model is reliable and efficient. We established an autophagy-related risk prognostic model that is accurate and reliable, which lays the foundation for future personalized treatment of bladder cancer. - Source: PubMed
Publication date: 2023/01/23
Shen ChongYan YanYang ShaoboWang ZejinWu ZhouliangLi ZhiZhang ZheLin YudaLi PengHu Hailong - N-lysine acetylation in the ER lumen is a recently discovered quality control mechanism that ensures proteostasis within the secretory pathway. The acetyltransferase reaction is carried out by two type-II membrane proteins, ATase1/NAT8B and ATase2/NAT8. Prior studies have shown that reducing ER acetylation can induce reticulophagy, increase ER turnover, and alleviate proteotoxic states. Here, we report the generation of Atase1 and Atase2 mice and show that these two ER-based acetyltransferases play different roles in the regulation of reticulophagy and macroautophagy. Importantly, knockout of Atase1 alone results in activation of reticulophagy and rescue of the proteotoxic state associated with Alzheimer's disease. Furthermore, loss of Atase1 or Atase2 results in widespread adaptive changes in the cell acetylome and acetyl-CoA metabolism. Overall, our study supports a divergent role of Atase1 and Atase2 in cellular biology, emphasizing ATase1 as a valid translational target for diseases characterized by toxic protein aggregation in the secretory pathway. - Source: PubMed
Publication date: 2021/04/12
Rigby Michael JLawton Alexis JKaur GulpreetBanduseela Varuna CKamm William ELakkaraju AparnaDenu John MPuglielli Luigi