IsoProDB: an integrated map of human protein isoforms for accelerated research

Abstract Emerging studies highlight the importance of protein isoforms, which often exhibit distinct functional roles and contribute to physiological diversity, disease mechanisms, and phenotypic variation, despite originating from the same gene. However, comprehensive isoform-level resources that characterize protein isoforms remain limited. IsoProDB is an integrative and unified one-stop database that aligns protein isoforms from RefSeq and UniProtKB, enabling cross-sequence visualization for protein isoform analysis in humans. It integrates features such as domain architecture, intrinsically disordered regions, sequence variants, transmembrane topology, and 52 distinct post-translational modifications (PTMs) mapped to protein isoforms from multiple resources. Currently, IsoProDB enables users to perform gene wise comparative analyses across 110 149 protein isoforms derived from 20 536 protein-coding genes for all integrated features, supported by effective visualizations. This provides insights into conserved and nonconserved PTM sites, domains, isoform-specific membrane localization, the impact of variants on protein function, and disease relevance across protein isoforms. With specific isoforms emerging as markers and theragnostic targets for various disorders, IsoProDB is integrated with multiple global resources for easy navigation and exploration of multiomics information on isoforms.