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O-GlcNAc糖基化修饰数据库(O-GlcNAcylation DataBase)
发布时间:2021-07-09

   糖基化修饰是最重要的蛋白质翻译后修饰之一,影响蛋白质的功能并调控细胞信号传导,从而调节各种生物学效应。氧连接N-乙酰葡萄糖胺(O-linked N-acetylglucosamine,O-GlcNAc)糖基化修饰由Hart与Torres于1984年发现,它与传统的蛋白糖基化修饰最大的区别是仅于蛋白质的丝氨酸/苏氨酸残基上加成一个单糖。O-GlcNAc糖基化修饰主要存在于细胞质和细胞核,由于其能快速、可逆的添加及移除,能可逆的竞争某些磷酸化修饰,迅速调节蛋白质的活性,几乎参与了各种细胞代谢途径和信号转导通路,在肿瘤和糖尿病等多种疾病中起着非常重要的调节作用。和蛋白质磷酸化修饰不同,O-GlcNAc糖基化修饰由O-GlcNAc转移酶(O-GlcNAc transferase,OGT)和O-GlcNAc水解酶(O-GlcNAcase,OGA) 唯一一对酶来完成:OGT将N-乙酰葡萄糖胺(GlcNAc)通过β-构型O-连接的糖苷键形式连接到靶蛋白的丝氨酸/苏氨酸的羟基上;而OGA的作用是去除O-GlcNAc修饰。二者如何实现细胞内数千种蛋白质O-GlcNAc修饰的精密调控仍有待阐明。

  基于不同的内部算法和模板肽段,研究人员开发出针对 O-GlcNAc 修饰位点的预测网站(YinOYang 1.2, OGTSite, dbOGAP和O-GlcNAcAtlas等),以提供相关参考。

1. http://csb.cse.yzu.edu.tw/OGTSite/predict.php 


2. http://www.cbs.dtu.dk/services/YinOYang/ 


3. https://oglcnac.org/ 

    O-GlcNAcAtlas is a comprehensive and curated database encapsulating experimentally identified O-GlcNAc sites and proteins in the past 35 years (since its discovery in the early 1980s). We hope it will serve as a great resource to facilitate protein O-GlcNAcylation studies for both basic and translational biomedical research.

   Ma J., et al., OGT Protein Interaction Network (OGT-PIN): A Curated Database of Experimentally Identified Interaction Proteins of OGT. Int. J. Mol. Sci. 2021, 22(17), 9620. DOI: 10.3390/ijms22179620.

    OGT-PIN

    https://oglcnac.org/ogt-pin/search/ 


4. O-GlcNAc-PRED-II : http://121.42.167.206/OGlcPred/

an integrated classification algorithm for identifying O-GlcNAcylation sites based on fuzzy undersampling and a K-means PCA oversampling technique


5.  https://www.oglcnac.mcw.edu/  

 ‘O-GlcNAcome’ databases 

DESIGNED BY THE OLIVIER-VAN STICHELEN LAB @Medical College of Wisconsin

Their website https://www.ovsoglcnaclab.com/ 

The O-GlcNAc modification is a nutrient rheostat that transiently regulates functions, localization, and stability of proteins in response to fluctuations in nutrient intake. Indeed, the nucleotide sugar donor for this modification, UDP-GlcNAc, is the final product of the Hexosamine Biosynthetic Pathway (HBP). This pathway integrates carbohydrate, amino acid, nucleotide, and fatty acid metabolisms to maintain a suitable pool of UDP-GlcNAc. UDP-GlcNAc is then used for glycan synthesis, including O-GlcNAcylation catalyzed by the O-GlcNAc Transferase (OGT). On the other hand, the O-GlcNAcase (OGA) dynamically hydrolyzes O-GlcNAc, releasing the protein's modification.


Wulff-Fuentes E, Berendt RR, Massman L, Danner L, Malard F, Vora J, Kahsay R, and Olivier-Van Stichelen S, The Human O-GlcNAcome Database and Meta-Analysis. Scientific Data 2021 8(1):25


   己糖胺生物合成途径(Hexosamine Biosynthesis Pathway,HBP)利用葡萄糖、乙酰辅酶A、谷氨酰胺和UTP产生UDP-GlcNAc,在N-乙酰氨基葡萄糖转移酶(OGT)的作用下将单个GlcNAc转移至蛋白质的丝氨酸/苏氨酸上。 O-GlcNAc糖基化修饰(O-GlcNAcylation)是动态、可逆的,在N-乙酰葡萄糖苷酶(OGA)的作用下将GlcNAc从蛋白质上移除。

    O-GlcNAc糖基化修饰异常是肿瘤细胞新的重要特征之一,多种类型的肿瘤中HBP流量增加,UDP-GlcNAc浓度升高,高水平的O-GlcNAc糖基化修饰与肿瘤的发生、侵袭和转移密切相关。上皮-间质转化( epithelial-mesenchymal transitions,EMT) 在肿瘤细胞侵袭和转移中起到非常重要的作用。Park等发现,EMT的重要转录因子Snail1蛋白112位的丝氨酸能够被O-GlcNAc糖基化修饰,并竞争性抑制邻近的GSK-3β磷酸化位点,进而降低Snail1的泛素化修饰水平,增加其蛋白稳定性;Snail1的O-GlcNAc修饰增加会抑制上皮钙粘蛋白(E-Cadherin)表达,从而促进EMT进程和乳腺癌细胞的侵袭和迁移能力。O-GlcNAc糖基化修饰作为一种营养感受器,能够对肿瘤细胞代谢进行调控,一些重要的代谢酶(如延胡索酸水合酶FH、丙酮酸激酶PKM2、磷酸甘油酸激酶PGK1等)能够被O-GlcNAc修饰,并影响肿瘤细胞的增殖。越来越多癌症相关的蛋白(如c-Myc、β-Catenin、CHK2、YTHFDF2、SPOP、YAP、TIP60/KAT5等)被证明存在着O-GlcNAc修饰,这种修饰通过多种机制调控蛋白质功能,包括影响蛋白质-蛋白质相互作用、蛋白质稳定性、细胞定位和转录活性等。

   我们课题组关于O-GlcNAc糖基化修饰研究的论文https://www.x-mol.com/groups/cqmu/news/40212