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The Ets family of transcription factors shares a 85 amino acid domain, named the ETS domain, which appears responsible for their DNA binding activity. This domain did not show any clear similarity with already known DNA binding motifs. Hydrophobic Cluster Analysis (HCA), a sensitive method able to detect protein structural relationships even at low sequence identity, was chosen in order to compare the ETS domain with other conventional DNA binding motifs. HCA analysis combined with known three-dimensional NMR data, suggests that the ETS domain may be structurally related to the Myb DNA binding domain and possibly to the HMG one. Indeed, the ETS domain is likely to contain two helix-loop-helix motifs.

Predicted common structural features of DNA-binding domains from Ets, Myb and HMG transcription factors