ArticlePLoS computational biology2013
Distinct types of disorder in the human proteome: functional implications for alternative splicing.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Modern resources for intrinsic disorder predictions: protein language models, deep learning, meta-servers, and databases.Cellular and molecular life sciences : CMLS · 2026Review
- Integrative Multi-Omics Characterization and Structural Insights into the Poorly Annotated IntegrinGenes · 2025Article
- Cross-species rescue reveals sequence requirements for a rapidly evolving intrinsically disordered region.PLoS biology · 2025Article
- An Analysis of Intrinsic Protein Disorder in Antimicrobial Peptides.The protein journal · 2025Article
- Decoding Missense Variants by Incorporating Phase Separation via Machine Learning.Nature communications · 2024Article
- Challenges in Brugada Syndrome Stratification: InvestigatingInternational journal of molecular sciences · 2023Article
- Orchestrating vesicular and nonvesicular membrane dynamics by intrinsically disordered proteins.EMBO reports · 2023Review
- Systematic identification of conditionally folded intrinsically disordered regions by AlphaFold2.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Shifts in isoform usage underlie transcriptional differences in regulatory T cells in type 1 diabetes.Communications biology · 2023Article
- The Difference in Structural States between Canonical Proteins and Their Isoforms Established by Proteome-Wide Bioinformatics Analysis.Biomolecules · 2022Article
- Discovering molecular features of intrinsically disordered regions by using evolution for contrastive learning.PLoS computational biology · 2022Article
- Protein self-assembly: A new frontier in cell signaling.Current opinion in cell biology · 2021Review
- Disorder in a two-domain neuronal CaCellular and molecular life sciences : CMLS · 2021Article
- IDPology of the living cell: intrinsic disorder in the subcellular compartments of the human cell.Cellular and molecular life sciences : CMLS · 2021Article
- Integrating an Enhanced Sampling Method and Small-Angle X-Ray Scattering to Study Intrinsically Disordered Proteins.Frontiers in molecular biosciences · 2021Article
- tappAS: a comprehensive computational framework for the analysis of the functional impact of differential splicing.Genome biology · 2020Article
- Intrinsically disordered domains: Sequence ➔ disorder ➔ function relationships.Protein science : a publication of the Protein Society · 2019Article
- Entropy and Information within Intrinsically Disordered Protein Regions.Entropy (Basel, Switzerland) · 2019Article
- Proteome-wide signatures of function in highly diverged intrinsically disordered regions.eLife · 2019Article
- Intrinsically Disordered Proteins in Chronic Diseases.Biomolecules · 2019Article
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9 authors.
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Abstract
Intrinsically disordered regions have been associated with various cellular processes and are implicated in several human diseases, but their exact roles remain unclear. We previously defined two classes of conserved disordered regions in budding yeast, referred to as "flexible" and "constrained" conserved disorder. In flexible disorder, the property of disorder has been positionally conserved during evolution, whereas in constrained disorder, both the amino acid sequence and the property of disorder have been conserved. Here, we show that flexible and constrained disorder are widespread in the human proteome, and are particularly common in proteins with regulatory functions. Both classes of disordered sequences are highly enriched in regions of proteins that undergo tissue-specific (TS) alternative splicing (AS), but not in regions of proteins that undergo general (i.e., not tissue-regulated) AS. Flexible disorder is more highly enriched in TS alternative exons, whereas constrained disorder is more highly enriched in exons that flank TS alternative exons. These latter regions are also significantly more enriched in potential phosphosites and other short linear motifs associated with cell signaling. We further show that cancer driver mutations are significantly enriched in regions of proteins associated with TS and general AS. Collectively, our results point to distinct roles for TS alternative exons and flanking exons in the dynamic regulation of protein interaction networks in response to signaling activity, and they further suggest that alternatively spliced regions of proteins are often functionally altered by mutations responsible for cancer.
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