Phosphorylation is an essential post-translational modification for almost all cellular processes. Several global phosphoproteomics analyses have revealed phosphorylation profiles under different conditions. Beyond identification of phospho-sites, protein structures add another layer of information about their functionality. In this study, we systematically characterize phospho-sites based on their 3D locations in the protein and establish a location map for phospho-sites. More than 250,000 phospho-sites have been analyzed, of which 8,686 sites match at least one structure and are stratified based on their respective 3D positions. Core phospho-sites possess two distinct groups based on their dynamicity. Dynamic core phosphorylations are significantly more functional compared with static ones. The dynamic core and the interface phospho-sites are the most functional among all 3D phosphorylation groups. Our analysis provides global characterization and stratification of phospho-sites from a structural perspective that can be utilized for predicting functional relevance and filtering out false positives in phosphoproteomic studies.

磷酸化是几乎所有细胞过程的重要翻译后修饰。几项全球磷酸蛋白质组学分析揭示了不同条件下的磷酸化谱。除了识别磷酸化位点之外，蛋白质结构还增加了有关其功能的另一层信息。在这项研究中，我们根据它们在蛋白质中的 3D 位置系统地表征磷酸化位点，并建立磷酸化位点的位置图。已经分析了超过 250,000 个磷酸化位点，其中 8,686 个位点与至少一种结构相匹配，并根据它们各自的 3D 位置进行分层。基于其动态性，核心磷酸化位点具有两个不同的组。与静态磷酸化相比，动态核心磷酸化功能明显更强。动态核心和界面磷酸化位点是所有 3D 磷酸化基团中功能最多的。我们的分析从结构角度提供了磷酸化位点的全局表征和分层，可用于预测功能相关性和过滤掉磷酸化蛋白质组学研究中的假阳性。