Intrinsic disorder can be found in all proteomes of all kingdoms of life and in viruses, being particularly prevalent in the eukaryotes. We conduct a comprehensive analysis of the intrinsic disorder in the human proteins while mapping them into 24 compartments of the human cell. In agreement with previous studies, we show that human proteins are significantly enriched in disorder relative to a generic protein set that represents the protein universe. In fact, the fraction of proteins with long disordered regions and the average protein-level disorder content in the human proteome are about 3 times higher than in the protein universe. Furthermore, levels of intrinsic disorder in the majority of human subcellular compartments significantly exceed the average disorder content in the protein universe. Relative to the overall amount of disorder in the human proteome, proteins localized in the nucleus and cytoskeleton have significantly increased amounts of disorder, measured by both high disorder content and presence of multiple long intrinsically disordered regions. We empirically demonstrate that, on average, human proteins are assigned to 2.3 subcellular compartments, with proteins localized to few subcellular compartments being more disordered than the proteins that are localized to many compartments. Functionally, the disordered proteins localized in the most disorder-enriched subcellular compartments are primarily responsible for interactions with nucleic acids and protein partners. This is the first-time disorder is comprehensively mapped into the human cell. Our observations add a missing piece to the puzzle of functional disorder and its organization inside the cell.

内在失调可以在所有生命王国的所有蛋白质组和病毒中发现，在真核生物中特别普遍。我们将人类蛋白质的内在障碍进行全面分析，同时将它们映射到人类细胞的24个区室中。与以前的研究一致，我们表明相对于代表蛋白质宇宙的通用蛋白质组，人类蛋白质在疾病中显着富集。实际上，人类蛋白质组中具有长无序区域的蛋白质比例和平均蛋白质水平无序含量比蛋白质宇宙中高约3倍。此外，大多数人类亚细胞区室中的内在疾病水平显着超过蛋白质宇宙中的平均疾病含量。相对于人类蛋白质组中疾病的总量，位于核和细胞骨架中的蛋白质的疾病数量显着增加，这通过高疾病含量和多个长的固有内在失调区域的存在来衡量。我们凭经验证明，平均而言，人类蛋白质被分配给2.3个亚细胞区室，与位于多个亚区室的蛋白质相比，位于少数亚细胞区室的蛋白质更加无序。在功能上，位于最富于障碍的亚细胞区室的无序蛋白质主要负责与核酸和蛋白质伴侣的相互作用。这是首次将疾病综合映射到人体细胞中。