Intrinsic Disorder in Transcription Factors
Open accessAbstract
Intrinsic disorder (ID) is highly abundant in eukaryotes, which reflect the greater need for disorder-associated signaling and transcriptional regulation in nucleated cells. Although several well-characterized examples of intrinsically disordered proteins in transcriptional regulation have been reported, no systematic analysis has been reported so far. To test for the general prevalence of intrinsic disorder in transcriptional regulation, we used the predictor of natural disorder regions (PONDR) to analyze the abundance of intrinsic disorder in three transcription factor datasets and two control sets. This analysis revealed that from 94.13 to 82.63% of transcription factors possess extended regions of intrinsic disorder, relative to 54.51 and 18.64% of the proteins in two control datasets, which indicates the significant prevalence of intrinsic disorder in transcription factors. This propensity of transcription factors to intrinsic disorder was confirmed by cumulative distribution function analysis and charge-hydropathy plots. The amino acid composition analysis showed that all three transcription factor datasets were substantially depleted in order-promoting residues and significantly enriched in disorder-promoting residues. Our analysis of the distribution of disorder within the transcription factor datasets revealed that (a) the AT-hooks and basic regions of transcription factor DNA-binding domains are highly disordered; (b) the degree of disorder in transcription factor activation regions is much higher than that in DNA-binding domains; (c) the degree of disorder is significantly higher in eukaryotic transcription factors than in prokaryotic transcription factors; and (d) the level of alpha-MoRF (molecular recognition feature) prediction is much higher in transcription factors. Overall, our data reflected the fact that eukaryotes with well-developed gene transcription machinery require transcription factor flexibility to be more efficient.
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Greater than 90% of transcription factors either contain IDRs or are entirely intrinsically disordered.
“Greater than 90% of transcription factors either contain IDRs or are entirely intrinsically disordered, thus it is not surprising that transcription factors regulated by cell signaling are also likely to include intrinsically disorder [275, 323].”
From Intrinsically disordered proteins play diverse roles in cell signaling (2022) · cites this paper as [275]
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- Authors
- Liu, J., Perumal, N. B., Oldfield, C. J., Su, E. W., Uversky, V. N., & Dunker, A. K.
- Affiliations
- Eli Lilly (United States) (US)
- Corresponding author
- Uversky, Vladimir N.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-05-13
- Volume
- 45
- Issue
- 22
- Pages
- 6873-6888
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- PMC
- PMC2538555
- OpenAlex
- W2011983814
- Cited by
- 792
- References
- 102
- Citations by year
- 2026: 33 · 2025: 49 · 2024: 44 · 2023: 49 · 2022: 60 · 2021: 68 · 2020: 54 · 2019: 37 · 2018: 33 · 2017: 36 · 2016: 29 · 2015: 31 · 2014: 35 · 2013: 30 · 2012: 32
- FWCI
- 14.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Digital Commons - University of South Florida (University of South Florida) (submittedVersion)
- IU Indianapolis University Library
- Funders
- Eli Lilly and Company
- Temple University
- National Institutes of Health
- Russian Academy of Sciences (R01 LM007688-01A1)
- U.S. National Library of Medicine (R01LM007688)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- intrinsic disorder, intrinsically disordered proteins, transcription factors, transcriptional regulation, amino acid composition, AT-hook, DNA-binding domain, transactivation domain, molecular recognition features, protein flexibility
- MeSH terms
- Amino Acid Sequence, Humans, Molecular Sequence Data, Protein Conformation, Transcription Factors, Protein Structure, Tertiary, Databases, Protein
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