英国欧洲分子生物学实验室（EMBL）Pedro Beltrao和David Ochoa研究组发现人类磷酸化蛋白质组的功能全观。相关论文在线发表在2019年12月9日的《自然—生物技术》上。

研究组手动整理了112种富含磷的蛋白质数据集，这些数据是由104种不同的人类细胞类型或组织产生的。他们重新分析了通过质量控制标准的6,801个蛋白质组学实验，创建了一个包含119,809个人类磷酸化位点的参考磷酸化蛋白质组。为了对功能部位进行优先排序，他们使用机器来学习鉴别59个特征蛋白质组学、结构、调控或进化相关性表征，并将它们整合为一个功能性评分。他们的方法确定了跨越不同分子机制、过程和疾病的调节性磷酸化 位点，并揭示了基因组规模的遗传倾向性。实验验证了几种调节性磷酸位点，包括确定SMAR / SNF染色质重塑复合体SMARCC2中磷酸化位点在神经元分化中的作用。

研究人员表示，蛋白质磷酸化是几乎所有细胞过程中调节蛋白质功能的关键翻译后修饰。尽管已经在人细胞中鉴定出数以万计的磷酸化位点，但是仍缺乏确定每个磷酸位点功能重要性的方法。

附：英文原文

Title: The functional landscape of the human phosphoproteome

Author: David Ochoa, Andrew F. Jarnuczak, Cristina Viitez, Maja Gehre, Margaret Soucheray, Andr Mateus, Askar A. Kleefeldt, Anthony Hill, Luz Garcia-Alonso, Frank Stein, Nevan J. Krogan, Mikhail M. Savitski, Danielle L. Swaney, Juan A. Vizcano, Kyung-Min Noh, Pedro Beltrao

Issue&Volume: 2019-12-09

Abstract: Protein phosphorylation is a key post-translational modification regulating protein function in almost all cellular processes. Although tens of thousands of phosphorylation sites have been identified in human cells, approaches to determine the functional importance of each phosphosite are lacking. Here, we manually curated 112 datasets of phospho-enriched proteins, generated from 104 different human cell types or tissues. We re-analyzed the 6,801 proteomics experiments that passed our quality control criteria, creating a reference phosphoproteome containing 119,809 human phosphosites. To prioritize functional sites, we used machine learning to identify 59 features indicative of proteomic, structural, regulatory or evolutionary relevance and integrate them into a single functional score. Our approach identifies regulatory phosphosites across different molecular mechanisms, processes and diseases, and reveals genetic susceptibilities at a genomic scale. Several regulatory phosphosites were experimentally validated, including identifying a role in neuronal differentiation for phosphosites in SMARCC2, a member of the SWI/SNF chromatin-remodeling complex.

DOI: 10.1038/s41587-019-0344-3

Source: https://www.nature.com/articles/s41587-019-0344-3