PhaSepDB: a database of liquid–liquid phase separation related proteins

Abstract It's widely appreciated that liquid–liquid phase separation (LLPS) underlies the formation of membraneless organelles, which function to concentrate proteins and nucleic acids. In the past few decades, major efforts have been devoted to identify the phase separation associated proteins and elucidate their functions. To better utilize the knowledge dispersed in published literature, we developed PhaSepDB (http://db.phasep.pro/), a manually curated database of phase separation associated proteins. Currently, PhaSepDB includes 2914 non-redundant proteins localized in different organelles curated from published literature and database. PhaSepDB provides protein summary, publication reference and sequence features of phase separation associated proteins. The sequence features which reflect the LLPS behavior are also available for other human protein candidates. The online database provides a convenient interface for the research community to easily browse, search and download phase separation associated proteins. As a centralized resource, we believe PhaSepDB will facilitate the future study of phase separation.

[1]  T. Mittag,et al.  Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates , 2019, Cell.

[2]  Catarina Nunes,et al.  MSGP: the first database of the protein components of the mammalian stress granules , 2019, Database J. Biol. Databases Curation.

[3]  Lucas Pelkmans,et al.  A Systems-Level Study Reveals Regulators of Membrane-less Organelles in Human Cells. , 2018, Molecular cell.

[4]  Daniel S. Day,et al.  Coactivator condensation at super-enhancers links phase separation and gene control , 2018, Science.

[5]  E. Fraenkel,et al.  Unexpected similarities between C9ORF72 and sporadic forms of ALS/FTD suggest a common disease mechanism , 2018, eLife.

[6]  Nicolas L. Fawzi,et al.  Protein Phase Separation: A New Phase in Cell Biology. , 2018, Trends in cell biology.

[7]  J. Taylor,et al.  Ubiquitin Modulates Liquid-Liquid Phase Separation of UBQLN2 via Disruption of Multivalent Interactions. , 2018, Molecular cell.

[8]  Christopher J Oldfield,et al.  Intrinsically Disordered Proteome of Human Membrane‐Less Organelles , 2018, Proteomics.

[9]  Hong Lin,et al.  Pi-Pi contacts are an overlooked protein feature relevant to phase separation , 2018, eLife.

[10]  Nicolas L. Fawzi,et al.  Mechanistic View of hnRNPA2 Low-Complexity Domain Structure, Interactions, and Phase Separation Altered by Mutation and Arginine Methylation. , 2018, Molecular cell.

[11]  Gene W. Yeo,et al.  Context-Dependent and Disease-Specific Diversity in Protein Interactions within Stress Granules , 2018, Cell.

[12]  Ka Wan Li,et al.  Comparative Analyses of Data Independent Acquisition Mass Spectrometric Approaches: DIA, WiSIM‐DIA, and Untargeted DIA , 2018, Proteomics.

[13]  Silvio C. E. Tosatto,et al.  MobiDB 3.0: more annotations for intrinsic disorder, conformational diversity and interactions in proteins , 2017, Nucleic Acids Res..

[14]  Jean-Baptiste Morlot,et al.  P-Body Purification Reveals the Condensation of Repressed mRNA Regulons. , 2017, Molecular cell.

[15]  Mustafa Mir,et al.  Phase separation drives heterochromatin domain formation , 2017, Nature.

[16]  Alma L. Burlingame,et al.  Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin , 2017, Nature.

[17]  Devin P. Sullivan,et al.  A subcellular map of the human proteome , 2017, Science.

[18]  Anthony A. Hyman,et al.  Biomolecular condensates: organizers of cellular biochemistry , 2017, Nature Reviews Molecular Cell Biology.

[19]  Rohit V Pappu,et al.  CIDER: Resources to Analyze Sequence-Ensemble Relationships of Intrinsically Disordered Proteins , 2017, Biophysical journal.

[20]  Cathy H. Wu,et al.  UniProt: the universal protein knowledgebase , 2016, Nucleic Acids Research.

[21]  R. Parker,et al.  Distinct stages in stress granule assembly and disassembly , 2016, eLife.

[22]  Monika Fuxreiter,et al.  The Structure and Dynamics of Higher-Order Assemblies: Amyloids, Signalosomes, and Granules , 2016, Cell.

[23]  Ronald D. Vale,et al.  Phase separation of signaling molecules promotes T cell receptor signal transduction , 2016, Science.

[24]  B. Lowell,et al.  Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit , 2016, eLife.

[25]  Anthony Barsic,et al.  ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure , 2016, Cell.

[26]  Roy Parker,et al.  Formation and Maturation of Phase-Separated Liquid Droplets by RNA-Binding Proteins. , 2015, Molecular cell.

[27]  Marco Y. Hein,et al.  A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation , 2015, Cell.

[28]  D. Weil,et al.  P-body assembly requires DDX6 repression complexes rather than decay or Ataxin2/2L complexes , 2015, Molecular biology of the cell.

[29]  Bin Zhang,et al.  PhosphoSitePlus, 2014: mutations, PTMs and recalibrations , 2014, Nucleic Acids Res..

[30]  Alex Lancaster,et al.  PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition , 2014, Bioinform..

[31]  Jimin Pei,et al.  Cell-free Formation of RNA Granules: Low Complexity Sequence Domains Form Dynamic Fibers within Hydrogels , 2012, Cell.

[32]  Silvio C. E. Tosatto,et al.  ESpritz: accurate and fast prediction of protein disorder , 2012, Bioinform..

[33]  A. Hyman,et al.  Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytes , 2011, Proceedings of the National Academy of Sciences.

[34]  Roland L. Dunbrack,et al.  PONDR-FIT: a meta-predictor of intrinsically disordered amino acids. , 2010, Biochimica et biophysica acta.

[35]  A. Hyman,et al.  Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation , 2009, Science.

[36]  Ralf P. Richter,et al.  FG-Rich Repeats of Nuclear Pore Proteins Form a Three-Dimensional Meshwork with Hydrogel-Like Properties , 2006, Science.

[37]  Lei Li,et al.  Dynamic nature of cleavage bodies and their spatial relationship to DDX1 bodies, Cajal bodies, and gems. , 2005, Molecular biology of the cell.

[38]  Zoran Obradovic,et al.  Length-dependent prediction of protein intrinsic disorder , 2006, BMC Bioinformatics.

[39]  Zoran Obradovic,et al.  Optimizing Long Intrinsic Disorder Predictors with Protein Evolutionary Information , 2005, J. Bioinform. Comput. Biol..

[40]  Marc S. Cortese,et al.  Comparing and combining predictors of mostly disordered proteins. , 2005, Biochemistry.

[41]  J. Gall,et al.  Dynamics of coilin in Cajal bodies of the Xenopus germinal vesicle. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Cathy H. Wu,et al.  UniProt: the Universal Protein knowledgebase , 2004, Nucleic Acids Res..

[43]  P. Romero,et al.  Sequence complexity of disordered protein , 2001, Proteins.

[44]  V. Uversky,et al.  Why are “natively unfolded” proteins unstructured under physiologic conditions? , 2000, Proteins.