DrLLPS: a data resource of liquid–liquid phase separation in eukaryotes

Abstract

Here, we presented an integrative database named DrLLPS (http://llps.biocuckoo.cn/) for proteins involved in liquid–liquid phase separation (LLPS), which is a ubiquitous and crucial mechanism for spatiotemporal organization of various biochemical reactions, by creating membraneless organelles (MLOs) in eukaryotic cells. From the literature, we manually collected 150 scaffold proteins that are drivers of LLPS, 987 regulators that contribute in modulating LLPS, and 8148 potential client proteins that might be dispensable for the formation of MLOs, which were then categorized into 40 biomolecular condensates. We searched potential orthologs of these known proteins, and in total DrLLPS contained 437 887 known and potential LLPS-associated proteins in 164 eukaryotes. Furthermore, we carefully annotated LLPS-associated proteins in eight model organisms, by using the knowledge integrated from 110 widely used resources that covered 16 aspects, including protein disordered regions, domain annotations, post-translational modifications (PTMs), genetic variations, cancer mutations, molecular interactions, disease-associated information, drug-target relations, physicochemical property, protein functional annotations, protein expressions/proteomics, protein 3D structures, subcellular localizations, mRNA expressions, DNA & RNA elements, and DNA methylations. We anticipate DrLLPS can serve as a helpful resource for further analysis of LLPS.

Relevance of Electrostatic Charges in Compactness, Aggregation, and Phase Separation of Intrinsically Disordered Proteins

“…This is partly due to the fact that this research field is still in its infancy. This area of research will benefit from the growth of dedicated databases, such as AmyPro [166], CPAD [167], DrLLPS [168], or PhasePro [159], and from data analysis through advanced data-mining tools, which will also become increasingly available in the future. According to the IUPAC recommendation, the dimensions of linear flexible macromolecules are usually expressed as the ensemble averages of the end-to-end distance, S, and radius of gyration R g [169].…”

“…This is partly due to the fact that this research field is still in its infancy. This area of research will benefit from the growth of dedicated databases, such as AmyPro [ 166 ], CPAD [ 167 ], DrLLPS [ 168 ], or PhasePro [ 159 ], and from data analysis through advanced data-mining tools, which will also become increasingly available in the future.…”

Protein Databases Related to Liquid–Liquid Phase Separation

“…Six LLPS-related databases, four containing proteins from direct LLPS studies and two constructed based on proteome identification, are described here. The former includes LLPSDB [44], PhaSePro [45], DrLLPS [39], and PhaSepDB [46]. Within all or part of them, deposited proteins are validated by LLPS experiments.…”

“…DrLLPS (http://llps.biocuckoo.cn/) is a gene-centered database and currently holds the largest amount of data [39]. In total, it contains 437,887 proteins in 164 eukaryotes, including 150 scaffold proteins, 987 regulators, and 8148 potential client proteins manually curated from published literature, and their orthologs, which are considered potential LLPS-associated proteins identified via a genome-wide detection by protein sequence blast.…”

“…The intensive investigations in the phase separation of biomolecules provide a data foundation for a more comprehensive and deeper understanding of LLPS in cell biology. Around 40 MLOs have been suggested to be organized via phase separation in eukaryotes, bacteria, and viruses [39], and several studies have reviewed the components and functions of MLOs [40][41][42][43]. Recently, a couple of databases covering the function and formation mechanism of condensates, experimental information, and localization information of LLPS-related proteins such as LLPSDB, PhaSePro, PhaSepDB, DrLLPS, RNAgranuleDB, and HUMAN CELL MAP, have been released.…”