Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115.
Drosophila RNAi Screening Center, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115.
G3 (Bethesda). 2019 Jan 9;9(1):1-11. doi: 10.1534/g3.118.200637.
Post-translational modification (PTM) serves as a regulatory mechanism for protein function, influencing their stability, interactions, activity and localization, and is critical in many signaling pathways. The best characterized PTM is phosphorylation, whereby a phosphate is added to an acceptor residue, most commonly serine, threonine and tyrosine in metazoans. As proteins are often phosphorylated at multiple sites, identifying those sites that are important for function is a challenging problem. Considering that any given phosphorylation site might be non-functional, prioritizing evolutionarily conserved phosphosites provides a general strategy to identify the putative functional sites. To facilitate the identification of conserved phosphosites, we generated a large-scale phosphoproteomics dataset from embryos collected from six closely-related species. We built iProteinDB (https://www.flyrnai.org/tools/iproteindb/), a resource integrating these data with other high-throughput PTM datasets, including vertebrates, and manually curated information for At iProteinDB, scientists can view the PTM landscape for any protein and identify predicted functional phosphosites based on a comparative analysis of data from closely-related species. Further, iProteinDB enables comparison of PTM data from to that of orthologous proteins from other model organisms, including human, mouse, rat, , , and .
蛋白质翻译后修饰（PTM）是蛋白质功能的调控机制，影响其稳定性、相互作用、活性和定位，在许多信号通路中至关重要。最具特征的 PTM 是磷酸化，其中一个磷酸基团被添加到受体残基上，在后生动物中最常见的是丝氨酸、苏氨酸和酪氨酸。由于蛋白质通常在多个位点被磷酸化，因此确定对功能重要的位点是一个具有挑战性的问题。考虑到任何给定的磷酸化位点可能是非功能性的，优先考虑进化保守的磷酸化位点提供了一种识别潜在功能位点的通用策略。为了促进保守磷酸化位点的识别，我们从六个密切相关的物种中收集的胚胎中生成了一个大规模的磷酸蛋白质组学数据集。我们构建了 iProteinDB（https://www.flyrnai.org/tools/iproteindb/），这是一个资源，将这些数据与其他高通量 PTM 数据集（包括脊椎动物）以及用于 At 的手动编目信息整合在一起。在 iProteinDB 中，科学家可以查看任何 蛋白质的 PTM 图谱，并根据来自密切相关 物种的数据进行比较分析，识别预测的功能性磷酸化位点。此外，iProteinDB 使能够比较 来自 的 PTM 数据与来自其他模式生物（包括人类、小鼠、大鼠、斑马鱼、秀丽隐杆线虫和黑腹果蝇）的同源蛋白的 PTM 数据。
