Autoinhibited Protein Database: a curated database of autoinhibitory domains and their autoinhibition mechanisms

Autoinhibition, a crucial allosteric self-regulation mechanism in cell signaling, ensures signal propagation exclusively in the presence of specific molecular inputs. The heightened focus on autoinhibited proteins stems from their implication in human diseases, positioning them as potential causal factors or therapeutic targets. However, the absence of a comprehensive knowledgebase impedes a thorough understanding of their roles and applications in drug discovery. Addressing this gap, we introduce Autoinhibited Protein Database (AiPD), a curated database standardizing information on autoinhibited proteins. AiPD encompasses details on autoinhibitory domains (AIDs), their targets, regulatory mechanisms, experimental validation methods, and implications in diseases, including associated mutations and post-translational modifications. AiPD comprises 698 AIDs from 532 experimentally characterized autoinhibited proteins and 2695 AIDs from their 2096 homologs, which were retrieved from 864 published articles. AiPD also includes 42 520 AIDs of computationally predicted autoinhibited proteins. In addition, AiPD facilitates users in investigating potential AIDs within a query sequence through comparisons with documented autoinhibited proteins. As the inaugural autoinhibited protein repository, AiPD significantly aids researchers studying autoinhibition mechanisms and their alterations in human diseases. It is equally valuable for developing computational models, analyzing allosteric protein regulation, predicting new drug targets, and understanding intervention mechanisms AiPD serves as a valuable resource for diverse researchers, contributing to the understanding and manipulation of autoinhibition in cellular processes.Database URL: http://ssbio.cau.ac.kr/databases/AiPD.