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Background  The highly conserved bHLH (basic Helix-Loop-Helix) domain, found in many transcription factors, has been well characterized separately in Plants, Animals, and Fungi. While conserved, even functionally constrained sites have varied since the Eukarya split. Our research identifies those slightly variable sites that were highly characteristic of Plants, Animals, or Fungi.    Results  Through discriminant analysis, we identified five highly discerning DNA-binding amino acid sites. Additionally, by incorporating Kingdom specific HMMs, we were able to construct a tool to quickly and accurately identify and classify bHLH sequences using these sites.    Conclusions  We conclude that highly discerning sites identified through our analysis were likely under functional constraints specific to each Kingdom. We also demonstrated the utility of our tool by identifying and classifying previously unknown bHLH domains in both characterized genomes and from sequences in a large environmental sample.

Accurate discrimination of bHLH domains in plants, animals, and fungi using biologically meaningful sites