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<p>The THAP (<Emphasis Type="Underline">Th</Emphasis>anatos-<Emphasis Type="Underline">a</Emphasis>ssociated <Emphasis Type="Underline">p</Emphasis>rotein) domain is a DNA-binding domain which binds DNA via a zinc-coordinating C2CH motif. Although THAP domains share a conserved structural fold, they bind different DNA sequences in different THAP proteins which in turn perform distinct cellular functions. In this study, we investigate (using multiple sequence alignment, In Silico motif and secondary structure prediction, protein structure prediction, and protein-DNA docking) THAP domain conservation within the homologs of the human THAP (hTHAP) protein family. We report that there is significant variation in sequence and predicted secondary structure elements across hTHAP homologs. Interestingly, we report that the THAP domain can be either longer or shorter than the conventional 90 residues, and the amino-terminal C2CH motif within the THAP domain serves as a hotspot for insertion or deletion. The amino-terminal hotspot in hTHAP homologs completely change the atomic interactions interface with the DNA binding site. Our results lay the foundation for future studies, which will further our understanding of the evolution of the THAP domain and regulation of its function.</p>

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Evolutionarily distinct binding of amino-terminal hotspots of the human THAP protein family and its homologs

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Hiral M. Sanghavi,
  • Gautam Kumar Sah

摘要

The THAP (Thanatos-associated protein) domain is a DNA-binding domain which binds DNA via a zinc-coordinating C2CH motif. Although THAP domains share a conserved structural fold, they bind different DNA sequences in different THAP proteins which in turn perform distinct cellular functions. In this study, we investigate (using multiple sequence alignment, In Silico motif and secondary structure prediction, protein structure prediction, and protein-DNA docking) THAP domain conservation within the homologs of the human THAP (hTHAP) protein family. We report that there is significant variation in sequence and predicted secondary structure elements across hTHAP homologs. Interestingly, we report that the THAP domain can be either longer or shorter than the conventional 90 residues, and the amino-terminal C2CH motif within the THAP domain serves as a hotspot for insertion or deletion. The amino-terminal hotspot in hTHAP homologs completely change the atomic interactions interface with the DNA binding site. Our results lay the foundation for future studies, which will further our understanding of the evolution of the THAP domain and regulation of its function.