International Journal of Molecular Sciences Article Functional Analysis of Human Hub Proteins and Their Interactors Involved in the Intrinsic Disorder-Enriched Interactions Gang Hu 1,†, Zhonghua Wu 1,†, Vladimir N. Uversky 2,3,* ID and Lukasz Kurgan 4,* ID 1 School of Mathematical Sciences and LPMC, Nankai University, 300071 Tianjin, China;
[email protected] (G.H.);
[email protected] (Z.W.) 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 * Correspondence:
[email protected] (V.N.U.);
[email protected] (L.K.) † These authors contributed equally to this work. Received: 1 November 2017; Accepted: 15 December 2017; Published: 19 December 2017 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).