Phase separation is an important mechanism that mediates the spatial distribution of proteins in different cellular compartments. While phase-separated proteins share certain sequence characteristics, including intrinsically disordered regions (IDRs) and prion-like domains, such characteristics are insufficient for making accurate predictions; thus, a proteome-wide understanding of phase separation is currently lacking. Here, we define phase-separated proteomes based on the systematic analysis of immunofluorescence images of 12 073 proteins in the Human Protein Atlas. The analysis of these proteins reveals that phase-separated candidate proteins exhibit higher IDR contents, higher mean net charge and lower hydropathy and prefer to bind to RNA. Kinases and transcription factors are also enriched among these candidate proteins. Strikingly, both phase-separated kinases and phase-separated transcription factors display significantly reduced substrate specificity. Our work provides the first global view of the phase-separated proteome and suggests that the spatial proximity resulting from phase separation reduces the requirement for motif specificity and expands the repertoire of substrates. The source code and data are available at https://github.com/cheneyyu/deepphase.

中文翻译：

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免疫荧光图像中相分离蛋白质的蛋白质组规模分析。

相分离是介导不同细胞区室中蛋白质空间分布的重要机制。虽然相分离的蛋白质具有某些序列特征，包括内在无序区域 (IDR) 和朊病毒样结构域，但这些特征不足以进行准确预测；因此，目前缺乏对相分离的蛋白质组范围的理解。在这里，我们根据人类蛋白质图谱中 12 073 种蛋白质的免疫荧光图像的系统分析来定义相分离的蛋白质组。对这些蛋白质的分析表明，相分离的候选蛋白质表现出更高的 IDR 含量、更高的平均净电荷和更低的亲水性，并且更喜欢与 RNA 结合。在这些候选蛋白中还富含激酶和转录因子。引人注目的是，相分离激酶和相分离转录因子都显示出显着降低的底物特异性。我们的工作提供了相分离蛋白质组的第一个全局视图，并表明相分离产生的空间接近性降低了对基序特异性的要求并扩展了底物的库。源代码和数据可在 https://github.com/cheneyyu/deepphase 获得。