DisProt in 2024: improving function annotation of intrinsically disordered proteins
Maria Cristina Aspromonte, María Victoria Nugnes, Federica Quaglia, Adel Bouharoua, Vasileios Sagris, Vasilis J. Promponas, Anastasia Chasapi, Erzsébet Fichó, Galo Ezequiel Balatti, Gustavo Parisi, Martín González Buitrón, Gábor Erdős, Mátyás Pajkos, Zsuzsanna Dosztányi, László Dobson, Alessio Del Conte, Damiano Clementel, Edoardo Salladini, Emanuela Leonardi, Fatemeh Kordevani, Hamidreza Ghafouri, Luiggi G Tenorio Ku, Alexander Miguel Monzón, Carlo Ferrari, Zsófia E. Kálmán, Juliet F. Nilsson, Jaime Santos, Carlos Pintado‐Grima, Salvador Ventura, Veronika Ács, Rita Pancsa, Mariane Gonçalves-Kulik, Miguel A. Andrade‐Navarro, Pedro José Barbosa Pereira, Sonia Longhi, Philippe Le Mercier, Julian A. Bergier, Péter Tompa, Tamás Lázár, Silvio C. E. Tosatto, Damiano Piovesan
Abstract
DisProt (URL: https://disprot.org) is the gold standard database for intrinsically disordered proteins and regions, providing valuable information about their functions. The latest version of DisProt brings significant advancements, including a broader representation of functions and an enhanced curation process. These improvements aim to increase both the quality of annotations and their coverage at the sequence level. Higher coverage has been achieved by adopting additional evidence codes. Quality of annotations has been improved by systematically applying Minimum Information About Disorder Experiments (MIADE) principles and reporting all the details of the experimental setup that could potentially influence the structural state of a protein. The DisProt database now includes new thematic datasets and has expanded the adoption of Gene Ontology terms, resulting in an extensive functional repertoire which is automatically propagated to UniProtKB. Finally, we show that DisProt's curated annotations strongly correlate with disorder predictions inferred from AlphaFold2 pLDDT (predicted Local Distance Difference Test) confidence scores. This comparison highlights the utility of DisProt in explaining apparent uncertainty of certain well-defined predicted structures, which often correspond to folding-upon-binding fragments. Overall, DisProt serves as a comprehensive resource, combining experimental evidence of disorder information to enhance our understanding of intrinsically disordered proteins and their functional implications.