ArticleBMC structural biology2009
Development of an accurate classification system of proteins into structured and unstructured regions that uncovers novel structural domains: its application to human transcription factors.
Article in BMC structural biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- A transcription factor by any other name - function beyond DNA binding and transactivation.EMBO reports · 2026Review
- Distinct domains of ENHANCER OF PINOID hold information for its polarization required for auxin-mediated cotyledon and flower development in Arabidopsis.PLoS genetics · 2025Article
- Dynamic action of an intrinsically disordered protein in DNA compaction that induces mycobacterial dormancy.Nucleic acids research · 2024Article
- Both Intrinsically Disordered Regions and Structural Domains Evolve Rapidly in Immune-Related Mammalian Proteins.International journal of molecular sciences · 2018Article
- Discovery of Cryoprotective Activity in Human Genome-Derived Intrinsically Disordered Proteins.International journal of molecular sciences · 2018Article
- Large-scale aggregation analysis of eukaryotic proteins reveals an involvement of intrinsically disordered regions in protein folding.Scientific reports · 2018Article
- Comprehensive review of methods for prediction of intrinsic disorder and its molecular functions.Cellular and molecular life sciences : CMLS · 2017Review
- The yeast Hsp70 homolog Ssb: a chaperone for general de novo protein folding and a nanny for specific intrinsically disordered protein domains.Current genetics · 2017Review
- On the potential of using peculiarities of the protein intrinsic disorder distribution in mitochondrial cytochromeIntrinsically disordered proteins · 2017Article
- Codon usage is less optimized in eukaryotic gene segments encoding intrinsically disordered regions than in those encoding structural domains.Nucleic acids research · 2016Article
- HP1-Assisted Aurora B Kinase Activity Prevents Chromosome Segregation Errors.Developmental cell · 2016Article
- Amyotrophic Lateral Sclerosis Type 20 - In Silico Analysis and Molecular Dynamics Simulation of hnRNPA1.PloS one · 2016Article
- Multiple cellular proteins interact with LEDGF/p75 through a conserved unstructured consensus motif.Nature communications · 2015Article
- A Method for Systematic Assessment of Intrinsically Disordered Protein Regions by NMR.International journal of molecular sciences · 2015Article
- Intrinsically disordered proteins in cellular signalling and regulation.Nature reviews. Molecular cell biology · 2015Review
- Multiple interactions of the intrinsically disordered region between the helicase and nuclease domains of the archaeal Hef protein.The Journal of biological chemistry · 2014Article
- Comprehensive repertoire of foldable regions within whole genomes.PLoS computational biology · 2013Article
- D²P²: database of disordered protein predictions.Nucleic acids research · 2013Article
- Expanding the proteome: disordered and alternatively folded proteins.Quarterly reviews of biophysics · 2011Article
- Binary classification of protein molecules into intrinsically disordered and ordered segments.BMC structural biology · 2011Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn addition to structural domains, most eukaryotic proteins possess intrinsically disordered (ID) regions. Although ID regions often play important functional roles, their accurate identification is difficult. As human transcription factors (TFs) constitute a typical group of proteins with long ID regions, we regarded them as a model of all proteins and attempted to accurately classify TFs into structural domains and ID regions. Although an extremely high fraction of ID regions besides DNA binding and/or other domains was detected in human TFs in our previous investigation, 20% of the residues were left unassigned. In this report, we exploit the generally higher sequence divergence in ID regions than in structural regions to completely divide proteins into structural domains and ID regions.
resultsThe new dichotomic system first identifies domains of known structures, followed by assignment of structural domains and ID regions with a combination of pre-existing tools and a newly developed program based on sequence divergence, taking un-aligned regions into consideration. The system was found to be highly accurate: its application to a set of proteins with experimentally verified ID regions had an error rate as low as 2%. Application of this system to human TFs (401 proteins) showed that 38% of the residues were in structural domains, while 62% were in ID regions. The preponderance of ID regions makes a sharp contrast to TFs of Escherichia coli (229 proteins), in which only 5% fell in ID regions. The method also revealed that 4.0% and 11.8% of the total length in human and E. coli TFs, respectively, are comprised of structural domains whose structures have not been determined.
conclusionThe present system verifies that sequence divergence including information of unaligned regions is a good indicator of ID regions. The system for the first time estimates the complete fractioning of structured/un-structured regions in human TFs, also revealing structural domains without homology to known structures. These predicted novel structural domains are good targets of structural genomics. When applied to other proteins, the system is expected to uncover more novel structural domains.
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