PhaSepDB in 2022: annotating phase separation-related proteins with droplet states, co-phase separation partners and other experimental information

Abstract

Phase separation (PS) proteins form droplets to regulate myriad membraneless organelles (MLOs) and cellular pathways such as transcription, signaling transduction and protein degeneration. PS droplets are usually liquid-like and can convert to hydrogel/solid-like under certain conditions. The PS behavior of proteins is regulated by co-PS partners and mutations, modifications, oligomerizations, repeat regions and alternative splicing of the proteins. With growing interest in PS condensates and associated proteins, we established PhaSepDB 1.0, which provided experimentally verified PS proteins and MLO-related proteins. The past few years witnessed a surge in PS-related research works; thus, we kept updating PhaSepDB. The current PhaSepDB contains 1419 PS entries, 770 low-throughput MLO-related entries and 7303 high-throughput MLO-related entries. We provided more detailed annotations of PS proteins, including PS verification experiments, regions used in experiments, phase diagrams of different experimental conditions, droplet states, co-PS partners and PS regulatory information. We believe that researchers can go further in studying PS proteins with the updated PhaSepDB (http://db.phasep.pro/).

Comparison of Biomolecular Condensate Localization and Protein Phase Separation Predictors

“…Datasets for human phase separating proteins were curated from the DrLLPS [ 18 ], PhaSepDB2.1 [ 20 , 21 ], and PhaSePro [ 19 ] databases, as well as using training data from publications of phase separation predictors. We selected four different condensates for which there are large numbers of components identified.…”

“…Seminal work over the past decade has charted the membership of numerous proteins within a variety of biological condensates utilizing SILAC (stable isotope labeling with amino acids in cell culture) [ 12 ], proximity-labelling-based mass spectrometry approaches [ 13 , 14 ], and other methods [ 15 , 16 , 17 ]. Additionally, there has been a concerted effort in the community to catalog the granulome members [ 18 , 19 , 20 , 21 ]. Significant strides have also been made to best determine which proteins are capable of undergoing phase separation by themselves in vitro [ 9 , 22 , 23 ].…”

The 2023 Nucleic Acids Research Database Issue and the online molecular biology database collection

“…Even MobiDB ( 28 ), focusing on intrinsically disordered proteins, benefits from two AF2-related predictions unforeseen by the original methods developers: predictions of disordered regions and potential interaction motifs contained within them. Other classes of proteins with special structural properties are covered by the new Amylograph ( 29 ) which curates information on amyloid-amyloid interactions and the returning PhaSepDB ( 30 ) for proteins that can participate in phase separation, now doubled in size and with much more detailed annotations. Other notable updating databases include the Biological Magnetic Resonance Data Bank ( 31 ); the eggNOG resource for comparative genomics ( 32 ) which more than doubles the number of species covered; the InterPro protein family compilation ( 33 ) which benefits from an improved interface that includes features inspired by the now-retiring Pfam website ( 34 ); and UniProt ( 35 ) which also has a redesigned website.…”

Study liquid–liquid phase separation with optical microscopy: A methodology review

“…According to PhaSepDB2.1, a database dedicated to phase-separation-related proteins ( http://db.phasep.pro/ ), 868 proteins are associated with LLPS. 56 Proteins that undergo LLPS typically feature either well-folded, repetitive modular domains composed of a series of similar or identical structural units or intrinsically disordered regions (IDRs). These domains play a crucial role in promoting LLPS formation by enabling multivalent intermolecular interactions.…”