Cited by 298Protein Structure and DynamicsGenomics and Chromatin DynamicsDiffusion and Search Dynamics

Human Transcription Factors Contain a High Fraction of Intrinsically Disordered Regions Essential for Transcriptional Regulation

Minezaki, Yoshiaki, Homma, Keiichi, Kinjo, Akira R., Nishikawa, Ken·2006·Journal of Molecular Biology

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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Crossref · 10.1016/j.jmb.2006.04.016

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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].”

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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
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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