Rathod Jagat, Yen Han-Chen, Liang Biqing, Tseng Yan-Yuan, Chen Chien-Sheng, Wu Wei-Sheng
Department of Earth Sciences, College of Sciences, National Cheng Kung University, Tainan 701, Taiwan.
Department of Electrical Engineering, College of Electrical Engineering and Computer Science, National Cheng Kung University, Tainan 701, Taiwan.
Comput Struct Biotechnol J. 2021 Jun 24;19:3692-3707. doi: 10.1016/j.csbj.2021.06.035. eCollection 2021.
Phosphoinositides (PIs) are a family of eight lipids consisting of phosphatidylinositol (PtdIns) and its seven phosphorylated forms. PIs have important regulatory functions in the cell including lipid signaling, protein transport, and membrane trafficking. Yeast has been recognized as a eukaryotic model system to study lipid-protein interactions. Hundreds of yeast PI-binding proteins have been identified, but this research knowledge remains scattered. Besides, the complete PI-binding spectrum and potential PI-binding domains have not been interlinked. No comprehensive databases are available to support the lipid-protein interaction research on phosphoinositides. Here we constructed the first knowledgebase of Yeast Phosphoinositide-Binding Proteins (YPIBP), a repository consisting of 679 PI-binding proteins collected from high-throughput proteome-array and lipid-array studies, QuickGO, and a rigorous literature mining. The YPIBP also contains protein domain information in categories of lipid-binding domains, lipid-related domains and other domains. The YPIBP provides search and browse modes along with two enrichment analyses (PI-binding enrichment analysis and domain enrichment analysis). An interactive visualization is given to summarize the PI-domain-protein interactome. Finally, three case studies were given to demonstrate the utility of YPIBP. The YPIBP knowledgebase consolidates the present knowledge and provides new insights of the PI-binding proteins by bringing comprehensive and in-depth interaction network of the PI-binding proteins. YPIBP is available at http://cosbi7.ee.ncku.edu.tw/YPIBP/.
磷酸肌醇（PIs）是一类由磷脂酰肌醇（PtdIns）及其七种磷酸化形式组成的八种脂质。PIs在细胞中具有重要的调节功能，包括脂质信号传导、蛋白质运输和膜 trafficking。酵母已被公认为研究脂质-蛋白质相互作用的真核模型系统。已经鉴定出数百种酵母PI结合蛋白，但这些研究知识仍然分散。此外，完整的PI结合谱和潜在的PI结合结构域尚未相互关联。没有综合数据库可支持对磷酸肌醇的脂质-蛋白质相互作用研究。在这里，我们构建了第一个酵母磷酸肌醇结合蛋白（YPIBP）知识库，该知识库包含从高通量蛋白质组阵列和脂质阵列研究、QuickGO以及严格的文献挖掘中收集的679种PI结合蛋白。YPIBP还包含脂质结合结构域、脂质相关结构域和其他结构域类别的蛋白质结构域信息。YPIBP提供搜索和浏览模式以及两种富集分析（PI结合富集分析和结构域富集分析）。给出了交互式可视化以总结PI-结构域-蛋白质相互作用组。最后，给出了三个案例研究以证明YPIBP的实用性。YPIBP知识库整合了现有知识，并通过提供PI结合蛋白的全面而深入的相互作用网络，为PI结合蛋白提供了新的见解。YPIBP可在http://cosbi7.ee.ncku.edu.tw/YPIBP/上获取。
