Large-scale analysis of redox-sensitive conditionally disordered protein regions reveal their widespread nature and key roles in high-level eukaryotic processes

Gábor Erdos; Bálint Mészáros; Dana Reichmann; Zsuzsanna Dosztányi

Gene Ontology (GO) annotations for human proteins were taken from the 24/05/2018 version of the EBI GOA database [26] . Only those biological process terms were considered that are attached to at least one protein with at least one predicted redox-sensitive structural switch. In order to enable the analysis of fairly generic and high level processes, only those terms were kept which are reachable from the root term (biological_process) with at most four steps following only 'is a' or 'part of' relations. These terms were further filtered for ancestry, and if two terms were in ancestor/child relationship, only the child term was kept. The resulting set of GO terms were manually split into four groups based on the level of biological process they describe. This yielded the GO molecular slim, containing 61 terms describing basic molecular processes; the GO network slim, containing 77 terms describing pathway/network level processes; GO cell slim, with 103 terms describing cellular processes; and GO organism slim, with 183 terms describing organism level biological processes. The enrichment of each term among redox-sensitive conditionally disordered proteins was assessed comparing the occurrence of the term in the RSCDP set and the human proteome. 1,000 sets of 5,488 proteins were taken from the human proteome randomly, and were evaluated for term occurrences, yielding an average and standard error for expected occurrence. The enrichment of each term in RSCDP is expressed as the difference between the observed and expected occurrences in standard error deviations. The supplementary material shows the enrichment values for all terms in all four slims.