CysDBase: A comprehensive database of Cysteine Post-Translational Modifications (PTMs) across protein sequence, structure, microenvironment, enzyme class, cellular localization, biological pathway, and taxonomy

The reactive thiol group of cysteine (Cys) acts as a nucleophile and undergoes many cysteine post-translational modifications (Cys-PTMs). Cys-PTMs, called protein redox switch, contribute to various cellular and physiological processes, including reactive oxygen species (ROS)-induced signalling, ROS mitigation, and scavenging. Consolidation of Cys-PTMs into a database would facilitate the mechanistic elucidation of biological processes and therapeutic applications. The existing databases store information on cysteine motifs, oxidation states, a few of the Cys-PTMs, etc., specific to species or kingdoms, and lack general applicability. There was no mention of the impact of the protein microenvironments and cellular localizations on the Cys-PTMs. The current study reports a database containing seven Cys-PTMs (disulphide, S-nitrosylation, S-palmitoylation, S-glutathionylation, S-sulphenylation, metal-binding, and thioether), 11 features, 33 06 395 UniProt IDs, and 1 14 56 639 cysteine residues, across the taxonomy, encompassing cellular organelles, enzyme classes, sequence motifs, protein structures, and microenvironments. The maximum number of cysteine residues is reported here compared to 16 contemporary cysteine databases. Twenty-one types of metal-binding cysteines and thioether modifications are reported for the first time. Enzyme classes, cellular localization, taxonomic preferences, and microenvironment around Cys-PTMs were systematically analysed and curated, indicating the pathogenic involvement of those Cys-PTMs. The database has a web access (https://cysdbase.bits-hyderabad.ac.in/) and a programmatic access via GitHub link (https://github.com/devhimd19/CysDBase). The query inputs to the repositories are UniProt ID, biological pathway, location, or genus name. Query outputs are 11 biological features, namely, protein name, Cys-PTMs, cysteine residue number, cysteine sequence motif, cell organelle, biological pathway, protein microenvironment (buried fraction and relative hydrophobicity [rHpy]), EC number and enzyme class, secondary structure, organism, and PubMed ID.