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Int. J. Mol. Sci. 2017, 18(10), 2010; doi:10.3390/ijms18102010

A Comprehensive Survey of the Roles of Highly Disordered Proteins in Type 2 Diabetes

1,2,* and 1,3,4,*
1
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd. MDC07, Tampa, FL 33620, USA
2
Department of Computer Science, College of Computer Science and Software, Shenzhen University, Shenzhen 518060, China
3
USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd. MDC07, Tampa, FL 33620, USA
4
Laboratory of New Methods in Biology, Institute for Biological Instrumentation, Russian Academy of Sciences, Institutskaya str., 7, Pushchino, Moscow 142290, Russia
*
Authors to whom correspondence should be addressed.
Received: 14 July 2017 / Revised: 4 September 2017 / Accepted: 12 September 2017 / Published: 21 September 2017
(This article belongs to the Section Molecular Biophysics)
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Abstract

Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with hyperglycemia (high blood sugar) related to either insulin resistance or insufficient insulin production. Among the various molecular events and players implicated in the manifestation and development of diabetes mellitus, proteins play several important roles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database has information on 34 human proteins experimentally shown to be related to the T2DM pathogenesis. It is known that many proteins associated with different human maladies are intrinsically disordered as a whole, or contain intrinsically disordered regions. The presented study shows that T2DM is not an exception to this rule, and many proteins known to be associated with pathogenesis of this malady are intrinsically disordered. The multiparametric bioinformatics analysis utilizing several computational tools for the intrinsic disorder characterization revealed that IRS1, IRS2, IRS4, MAFA, PDX1, ADIPO, PIK3R2, PIK3R5, SoCS1, and SoCS3 are expected to be highly disordered, whereas VDCC, SoCS2, SoCS4, JNK9, PRKCZ, PRKCE, insulin, GCK, JNK8, JNK10, PYK, INSR, TNF-α, MAPK3, and Kir6.2 are classified as moderately disordered proteins, and GLUT2, GLUT4, mTOR, SUR1, MAPK1, IKKA, PRKCD, PIK3CB, and PIK3CA are predicted as mostly ordered. More focused computational analyses and intensive literature mining were conducted for a set of highly disordered proteins related to T2DM. The resulting work represents a comprehensive survey describing the major biological functions of these proteins and functional roles of their intrinsically disordered regions, which are frequently engaged in protein–protein interactions, and contain sites of various posttranslational modifications (PTMs). It is also shown that intrinsic disorder-associated PTMs may play important roles in controlling the functions of these proteins. Consideration of the T2DM proteins from the perspective of intrinsic disorder provides useful information that can potentially lead to future experimental studies that may uncover latent and novel pathways associated with the disease. View Full-Text
Keywords: type 2 diabetes mellitus; KEGG database; intrinsically disordered proteins; intrinsically disordered protein regions; protein–protein interaction; posttranslational modifications; disorder prediction type 2 diabetes mellitus; KEGG database; intrinsically disordered proteins; intrinsically disordered protein regions; protein–protein interaction; posttranslational modifications; disorder prediction
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Du, Z.; Uversky, V.N. A Comprehensive Survey of the Roles of Highly Disordered Proteins in Type 2 Diabetes. Int. J. Mol. Sci. 2017, 18, 2010.

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