Abstract

Arginine phosphorylation (pArg) is recently discovered as a ubiquitous protein N-phosphorylation in bacteria. However, its prevalence and roles in mammalian cells remain largely unknown due to the lack of established workflow and the inherent lability of phosphoramidate (P–N) bond. Emerging evidences suggest that N-phosphorylation may extensively exist in eu-karyotes and play crucial roles. We report a phosphoproteomic workflow, which allows for the first time revealing the widespread occurrence of pArg in human cells by mass spectrometry. By virtue of this approach, we identified 152 high-confidence pArg sites derived from 118 proteins. Remarkably, the discovered pArg phosphorylation motif and gene ontology hint a possible cellular function of arginine phosphorylation which may regulate the favorability of propeptide convertase substrate. The obtained pArg dataset paves a way for a better understanding of the biological functions of eukaryotic pArg in the future.

中文翻译：

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人体细胞中精氨酸的广泛磷酸化-质谱揭示的新型蛋白质PTM

摘要

最近发现精氨酸磷酸化（pArg）是细菌中普遍存在的蛋白质N-磷酸化。但是，由于缺乏既定的工作流程以及氨基磷酸酯（PN）键固有的不稳定性，其在哺乳动物细胞中的流行和作用仍然未知。新兴证据表明，N-磷酸化可能广泛存在于真核生物中，并起关键作用。我们报告了一个磷酸化蛋白质组学的工作流程，它首次通过质谱揭示了人类细胞中pArg的广泛存在。通过这种方法，我们鉴定出了源自118种蛋白质的152个高可信度pArg位点。显着地，发现的pArg磷酸化基序和基因本体暗示精氨酸磷酸化的可能的细胞功能，其可能调节前肽转化酶底物的有利性。获得的pArg数据集为将来更好地了解真核pArg的生物学功能铺平了道路。