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Int. J. Mol. Sci. 2017, 18(12), 2761; doi:10.3390/ijms18122761

Functional Analysis of Human Hub Proteins and Their Interactors Involved in the Intrinsic Disorder-Enriched Interactions

1
School of Mathematical Sciences and LPMC, Nankai University, 300071 Tianjin, China
2
Department of Molecular Medicine and Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
3
Laboratory of New Methods in Biology, Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino, Moscow region 142290, Russia
4
Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USA
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 1 November 2017 / Revised: 13 December 2017 / Accepted: 15 December 2017 / Published: 19 December 2017
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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. View Full-Text
Keywords: intrinsic disorder; protein-protein interactions; hub proteins; intrinsically disordered proteins; human proteome intrinsic disorder; protein-protein interactions; hub proteins; intrinsically disordered proteins; human proteome
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MDPI and ACS Style

Hu, G.; Wu, Z.; Uversky, V.N.; Kurgan, L. Functional Analysis of Human Hub Proteins and Their Interactors Involved in the Intrinsic Disorder-Enriched Interactions. Int. J. Mol. Sci. 2017, 18, 2761.

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