The RFX family of transcription factors is characterized by a unique ~75-residue DNA-binding domain. RFX genes have been isolated in yeasts, nematode and vertebrates. The characteristic RFX-type HTH DNA binding domain has been recruited into otherwise very divergent regulatory factors functioning in a diverse spectrum of unrelated systems, including regulation of the mitotic cell cycle in fission yeast, the control of the immune response in mammals, and infection by human hepatitis B virus [1,2].

The RFX-type DNA-binding domain is an unusual member of the winged-helix subfamily of helix-turn-helix domains because it uses a β-hairpin (or wing) to recognize DNA instead of the recognition helix typical of helix-tun-helix domains. It consists of three α-helices (H), three β-strands (S) and three connecting loops (L), arranged in the order H1-S1-H2-L1-H3-L2-S2-W1-S3. The third loop, connecting β-strands S2 and S3, forms wing W1 of the winged-helix motif (see <PDB:1DP7>). In contrast to previously described winged-helix DBDs (typically 110 residues long with two wings, W1 and W2), the shorter RFX-type winged-helix DNA-binding domain has only one wing [3].

Some proteins known to contain a RFX-type winged-helix DNA-binding domain are listed below:

• Human RFX1, a cellular transactivator that is used by the highly pathogenic hepatitis B virus.
• Human RFX2.
• Human RFX3, a transcription factor required for ciliogenesis and islet cell differentiation during endocrine pancreas development.
• Human RFX5, a regulator of MHC class II gene transcription.
• Human ARID2, a component of the SWI/SNF-B (PBAF) chromatin remodeling complex [4].
• Yeast Crt1, an effector of the DNA damage and replication checkpoint.
• Schizosaccharomyces pombe sak1, an essential regulatory protein in the life cycle. It allows cells to exit the mitotic cycle and enter either the stationary phase or the pathway leading to sexual differentiation.

The profile we developed covers the entire RFX-type winged-helix DNA-binding domain.

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