ArticleInternational journal of molecular sciences2017
Functional Analysis of Human Hub Proteins and Their Interactors Involved in the Intrinsic Disorder-Enriched Interactions.
Article in International journal of molecular sciences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed.
- Amyloid-β, Tau Protein, α-Synuclein, TDP-43, and FUS in Mixed Pathology: And Intrinsic Disorder to Rule Them All.International journal of molecular sciences · 2026Review
- Prediction of Intrinsically Disordered Regions That Bind RNA with DisoRDPbind.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Comparative assessment of binding residue predictions in intrinsically disordered regions.Protein science : a publication of the Protein Society · 2025Article
- Intrinsic Disorder and Phase Separation Coordinate Exocytosis, Motility, and Chromatin Remodeling in the Human Acrosomal Proteome.Proteomes · 2025Article
- Evaluation of predictions of disordered binding regions in the CAID2 experiment.Computational and structural biotechnology journal · 2025Review
- Prediction of Disordered Linkers Using APOD.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Accurate and Fast Prediction of Intrinsic Disorder Using flDPnn.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Comprehensive assessment of AlphaFold's predictions of secondary structure and solvent accessibility at the amino acid-level in eukaryotic, bacterial and archaeal proteins.Computational and structural biotechnology journal · 2025Article
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- Unveiling hidden connections in omics data via pyPARAGON: an integrative hybrid approach for disease network construction.Briefings in bioinformatics · 2024Article
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- Tutorial: a guide for the selection of fast and accurate computational tools for the prediction of intrinsic disorder in proteins.Nature protocols · 2023Review
- The Sherpa hypothesis: Phenotype-Preserving Disordered Proteins stabilize the phenotypes of neurons and oligodendrocytes.NPJ systems biology and applications · 2023Article
- Clinical Network Systems Biology: Traversing the Cancer Multiverse.Journal of clinical medicine · 2023Review
- A Systematic Approach to the Discovery of Protein-Protein Interaction Stabilizers.ACS central science · 2023Article
- Illuminating Intrinsically Disordered Proteins with Integrative Structural Biology.Biomolecules · 2023Review
- Computational prediction of disordered binding regions.Computational and structural biotechnology journal · 2023Review
- Enrichment patterns of intrinsic disorder in proteins.Biophysical reviews · 2022Review
- Thermostable Proteins from HaCaT Keratinocytes Identify a Wide Breadth of Intrinsically Disordered Proteins and Candidates for Liquid-Liquid Phase Separation.International journal of molecular sciences · 2022Article
- Intrinsically Disordered Proteins: An Overview.International journal of molecular sciences · 2022Review
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Authors and funding
4 authors.
Funding
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Abstract
Some of the intrinsically disordered proteins and protein regions are promiscuous interactors that are involved in one-to-many and many-to-one binding. Several studies have analyzed enrichment of intrinsic disorder among the promiscuous hub proteins. We extended these works by providing a detailed functional characterization of the disorder-enriched hub protein-protein interactions (PPIs), including both hubs and their interactors, and by analyzing their enrichment among disease-associated proteins. We focused on the human interactome, given its high degree of completeness and relevance to the analysis of the disease-linked proteins. We quantified and investigated numerous functional and structural characteristics of the disorder-enriched hub PPIs, including protein binding, structural stability, evolutionary conservation, several categories of functional sites, and presence of over twenty types of posttranslational modifications (PTMs). We showed that the disorder-enriched hub PPIs have a significantly enlarged number of disordered protein binding regions and long intrinsically disordered regions. They also include high numbers of targeting, catalytic, and many types of PTM sites. We empirically demonstrated that these hub PPIs are significantly enriched among 11 out of 18 considered classes of human diseases that are associated with at least 100 human proteins. Finally, we also illustrated how over a dozen specific human hubs utilize intrinsic disorder for their promiscuous PPIs.
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