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Pritišanac, I. ; Alderson, T.R. ; Kolarić, Đ. ; Zarin, T.* ; Xie, S.* ; Lu, A.* ; Alam, A.* ; Maqsood, A.* ; Youn, J.Y.* ; Forman-Kay, J.D.* ; Moses, A.M.*

A functional map of the human intrinsically disordered proteome.

Proc. Natl. Acad. Sci. U.S.A. 123:e2604562123 (2026)
Publ. Version/Full Text Research data DOI
Open Access Hybrid
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Intrinsically disordered regions (IDRs) represent at least one-third of the human proteome and defy the established structure–function paradigm. Because IDRs often have limited positional sequence conservation, the functional classification of IDRs using standard bioinformatics is generally not possible. Here, we show that evolutionarily conserved molecular features of IDRs enable clustering of the human disordered proteome (IDRome) into a map with strong functional enrichments. We quantify how conserved IDR features correlate with functional terms and, for a subset of terms, provide proteome-wide predictions of annotations for IDRs. Further, we show that conserved features of IDRs can predict protein localization to different biomolecular condensates and underlie elevated intracluster connectivity in condensate-associated IDRs, as well as enrich for short-linear motif-binding domains among interaction partners. We highlight patterns of conservation in disordered proteins with unknown function and in clusters enriched for proteins encoded by disease-risk genes. Our map of the human IDR-ome should be a valuable resource that aids in the discovery of new IDR biology.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Biomolecular Condensates ; Interaction Networks ; Intrinsically Disordered Proteins ; Molecular Features ; Protein Functional Prediction; Phase-separation; Molecular Recognition; Nuclear-import; Stress Granule; Proteins; Sequence; Domains; Regions; Determinants; Prediction
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 123, Issue: 21, Pages: , Article Number: e2604562123 Supplement: ,
Publisher National Academy of Sciences
Publishing Place 2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Institute of Structural Biology (STB)
Grants Hospital for Sick Children (HSC)
Canada Foundation for Innovation (CFI)
Canada Research Chairs (CRC)
Canadian Institutes of Health Research (CIHR)
Helmholtz Association ((sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic)(sic))
Government of Canada (travelGoC)