Zhou, JianhongOldfield, Christopher J.Yan, WenyingShen, BairongDunker, A. Keith2021-05-032021-05-032019-07-12Zhou, J., Oldfield, C. J., Yan, W., Shen, B., & Dunker, A. K. (2019). Intrinsically disordered domains: Sequence ➔ disorder ➔ function relationships. Protein Science, 28(9), 1652–1663. https://doi.org/10.1002/pro.36801469-896Xhttps://hdl.handle.net/1805/25856Disordered domains are long regions of intrinsic disorder that ideally have conserved sequences, conserved disorder, and conserved functions. These domains were first noticed in protein–protein interactions that are distinct from the interactions between two structured domains and the interactions between structured domains and linear motifs or molecular recognition features (MoRFs). So far, disordered domains have not been systematically characterized. Here, we present a bioinformatics investigation of the sequence–disorder–function relationships for a set of probable disordered domains (PDDs) identified from the Pfam database. All the Pfam seed proteins from those domains with at least one PDD sequence were collected. Most often, if a set contains one PDD sequence, then all members of the set are PDDs or nearly so. However, many seed sets have sequence collections that exhibit diverse proportions of predicted disorder and structure, thus giving the completely unexpected result that conserved sequences can vary substantially in predicted disorder and structure. In addition to the induction of structure by binding to protein partners, disordered domains are also induced to form structure by disulfide bond formation, by ion binding, and by complex formation with RNA or DNA. The two new findings, (a) that conserved sequences can vary substantially in their predicted disorder content and (b) that homologues from a single domain can evolve from structure to disorder (or vice versa), enrich our understanding of the sequence ➔ disorder ensemble ➔ function paradigm.en-USdisorder–function relationshipsdisorder‐to‐structure transitionsintrinsically disordered domainsArticle