PMID- 28934129
OWN - NLM
STAT- MEDLINE
DCOM- 20180515
LR  - 20181113
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 10
DP  - 2017 Sep 21
TI  - A Comprehensive Survey of the Roles of Highly Disordered Proteins in Type 2 
      Diabetes.
LID - 10.3390/ijms18102010 [doi]
LID - 2010
AB  - 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-alpha, 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.
FAU - Du, Zhihua
AU  - Du Z
AD  - Department of Molecular Medicine, Morsani College of Medicine, University of 
      South Florida, 12901 Bruce B. Downs Blvd. MDC07, Tampa, FL 33620, USA. 
      duzh@szu.edu.cn.
AD  - Department of Computer Science, College of Computer Science and Software, 
      Shenzhen University, Shenzhen 518060, China. duzh@szu.edu.cn.
FAU - Uversky, Vladimir N
AU  - Uversky VN
AUID- ORCID: 0000-0002-4037-5857
AD  - Department of Molecular Medicine, Morsani College of Medicine, University of 
      South Florida, 12901 Bruce B. Downs Blvd. MDC07, Tampa, FL 33620, USA. 
      vuversky@health.usf.edu.
AD  - 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. vuversky@health.usf.edu.
AD  - Laboratory of New Methods in Biology, Institute for Biological Instrumentation, 
      Russian Academy of Sciences, Institutskaya str., 7, Pushchino, Moscow 142290, 
      Russia. vuversky@health.usf.edu.
LA  - eng
PT  - Journal Article
DEP - 20170921
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Intrinsically Disordered Proteins)
RN  - 0 (Proteome)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Computational Biology/methods
MH  - Diabetes Mellitus, Type 2/genetics/*metabolism/pathology
MH  - Gene Expression
MH  - Gene Ontology
MH  - Humans
MH  - Insulin Receptor Substrate Proteins/chemistry/genetics/*metabolism
MH  - Intrinsically Disordered Proteins/chemistry/genetics/*metabolism
MH  - Molecular Sequence Annotation
MH  - Protein Binding
MH  - Protein Conformation, alpha-Helical
MH  - Protein Conformation, beta-Strand
MH  - Protein Interaction Domains and Motifs
MH  - Protein Interaction Mapping
MH  - *Protein Processing, Post-Translational
MH  - Proteome/chemistry/classification/genetics/*metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
PMC - PMC5666700
OTO - NOTNLM
OT  - KEGG database
OT  - disorder prediction
OT  - intrinsically disordered protein regions
OT  - intrinsically disordered proteins
OT  - posttranslational modifications
OT  - protein-protein interaction
OT  - type 2 diabetes mellitus
COIS- The authors declare no conflict of interest.
EDAT- 2017/09/22 06:00
MHDA- 2018/05/16 06:00
PMCR- 2017/10/01
CRDT- 2017/09/22 06:00
PHST- 2017/07/14 00:00 [received]
PHST- 2017/09/04 00:00 [revised]
PHST- 2017/09/12 00:00 [accepted]
PHST- 2017/09/22 06:00 [entrez]
PHST- 2017/09/22 06:00 [pubmed]
PHST- 2018/05/16 06:00 [medline]
PHST- 2017/10/01 00:00 [pmc-release]
AID - ijms18102010 [pii]
AID - ijms-18-02010 [pii]
AID - 10.3390/ijms18102010 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Sep 21;18(10):2010. doi: 10.3390/ijms18102010.