Document Type
Article
Publication Date
2017
Keywords
intrinsic disorder, protein-protein interactions, hub proteins, intrinsically disordered proteins, human proteome
Digital Object Identifier (DOI)
https://doi.org/10.3390/ijms18122761
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.
Rights Information
This work is licensed under a Creative Commons Attribution 4.0 License.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
International Journal of Molecular Sciences, v. 18, issue 12, art. 2761
Scholar Commons Citation
Hu, Gang; Wu, Zhonghua; Uversky, Vladimir N.; and Kurgan, Lukasz, "Functional Analysis of Human Hub Proteins and Their Interactors Involved in the Intrinsic Disorder-Enriched Interactions" (2017). Molecular Medicine Faculty Publications. 265.
https://digitalcommons.usf.edu/mme_facpub/265
Supplementary Materials
