Human Transcription Factors Contain a High Fraction of Intrinsically Disordered Regions Essential for Transcriptional Regulation
Abstract
Human transcriptional regulation factors, such as activators, repressors, and enhancer-binding factors are quite different from their prokaryotic counterparts in two respects: the average sequence in human is more than twice as long as that in prokaryotes, while the fraction of sequence aligned to domains of known structure is 31% in human transcription factors (TFs), less than half of that in bacterial TFs (72%). Intrinsically disordered (ID) regions were identified by a disorder-prediction program, and were found to be in good agreement with available experimental data. Analysis of 401 human TFs with experimental evidence from the Swiss-Prot database showed that as high as 49% of the entire sequence of human TFs is occupied by ID regions. More than half of the human TFs consist of a small DNA binding domain (DBD) and long ID regions frequently sandwiching unassigned regions. The remaining TFs have structural domains in addition to DBDs and ID regions. Experimental studies, particularly those with NMR, revealed that the transactivation domains in unbound TFs are usually unstructured, but become structured upon binding to their partners. The sequences of human and mouse TF orthologues are 90.5% identical despite a high incidence of ID regions, probably reflecting important functional roles played by ID regions. In general ID regions occupy a high fraction in TFs of eukaryotes, but not in prokaryotes. Implications of this dichotomy are discussed in connection with their functional roles in transcriptional regulation and evolution.
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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 [323]
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- Authors
- Minezaki, Y., Homma, K., Kinjo, A. R., & Nishikawa, K.
- Affiliations
- National Institute of Genetics (JP)
- Corresponding author
- Nishikawa, Ken
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 359
- Issue
- 4
- Pages
- 1137-1149
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2021632119
- Cited by
- 297
- References
- 87
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 15 · 2023: 15 · 2022: 12 · 2021: 19 · 2020: 10 · 2019: 16 · 2018: 13 · 2017: 16 · 2016: 14 · 2015: 11 · 2014: 12 · 2013: 11 · 2012: 15
- FWCI
- 9.24
- Type
- journal article
- Language
- en
- Update notices
- erratum (2006-10-13)
- Open access
- closed
- Licence
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- 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 › Diffusion and Search Dynamics
- Keywords
- intrinsically disordered regions, transcription factors, transcriptional regulation, DNA-binding domain, transactivation domain, protein structure, protein evolution, orthologs, disorder prediction
- MeSH terms
- Animals, Binding Sites, DNA, Gene Expression Regulation, Humans, Transcription Factors, Transcription, Genetic, Protein Structure, Tertiary, Structural Homology, Protein
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