EWS RNA结合蛋白1（EWSR1）是一种多功能蛋白，其表观遗传标记对多种人类疾病的发病机制起到贡献，如神经退行性疾病、皮肤发育和肿瘤生成过程。然而，EWSR1的具体细胞功能和生理特性仍不清楚。在本研究中，我们使用基于定量质谱的蛋白质组学和串联质谱标记的方法，研究了Ewsr1基因敲除和野生型小鼠脑组织的全基因组蛋白质变化。从鉴定出的9115个蛋白质中，我们选择了118个差异表达蛋白质，这些蛋白质是三个定量数据处理策略的共同部分，包括只进行蛋白质水平的归一化和谱-蛋白质水平的归一化。对这些共同差异表达蛋白质的生物信息学分析显示，在Ewsr1基因敲除小鼠中上调的蛋白质主要与骨重塑的正调节和炎症反应有关。下调的蛋白质与神经递质水平的调节或氨基酸代谢过程有关。总的来说，这些发现为我们在蛋白质水平上理解EWSR1的生理功能和发病机制提供了新的见解。对EWSR1及其蛋白质相互作用的更好理解将推动神经系统疾病的临床研究领域的发展。这些质谱蛋白质组学数据已通过PRIDE合作伙伴库提交到ProteomeXchange联盟，数据集标识符为PXD026994。© 2023年，Springer Nature Limited。

EWS RNA binding protein 1 (EWSR1) is a multifunctional protein whose epigenetic signatures contribute to the pathogenesis of various human diseases, such as neurodegenerative disorders, skin development, and tumorigenic processes. However, the specific cellular functions and physiological characteristics of EWSR1 remain unclear. In this study, we used quantitative mass spectrometry-based proteomics with tandem mass tag labeling to investigate the global proteome changes in brain tissue in Ewsr1 knockout and wild-type mice. From 9115 identified proteins, we selected 118 differentially expressed proteins, which is common to three quantitative data processing strategies including only protein level normalizations and spectrum-protein level normalization. Bioinformatics analysis of these common differentially expressed proteins revealed that proteins up-regulated in Ewsr1 knockout mouse are mostly related to the positive regulation of bone remodeling and inflammatory response. The down-regulated proteins were associated with the regulation of neurotransmitter levels or amino acid metabolic processes. Collectively, these findings provide insight into the physiological function and pathogenesis of EWSR1 on protein level. Better understanding of EWSR1 and its protein interactions will advance the field of clinical research into neuronal disorders. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD026994.© 2023. Springer Nature Limited.