The rrf2-type HTH domain is a DNA-binding, winged helix-turn-helix (wHTH)
domain of about 130 residues present in transcription regulators of the rrf2
family. This family of bacterial regulators is named after Desulfovibrio
vulgaris rrf2, a regulator of the hmc operon which encodes
iron-sulfur-containing proteins as well as other proteins involved in electron
transport [1,2]. Other rrf2-type HTH proteins are regulators of genes involved
in nitrite or iron metabolism, or nitric oxide detoxification.
The N-terminal part of the domain shows similarity to the iclR-type (see
<PDOC00807>), the gntR-type (see <PDOC00042>) and marR-type HTH (see
<PDOC00861>), wherein the DNA-binding HTH motif is followed by a β-hairpin
which is called the wing. The C-terminal part of the rrf2-type HTH domain in
most cases contains 3 conserved cysteine residues that may bind an [2Fe-2S]
cluster, like in iscR and nsrR [3,4,5,6,7,8]. The nsrR regulator, which contains an
nitrogen-oxides-sensing Fe-S cluster that is required for DNA binding, is
implicated in denitrification and/or NO detoxification in diverse pathogenic
and environmental bacteria.
Some proteins known to contain a rrf2-type HTH domain:
- Desulfovibrio vulgaris protein rrf2, a repressor of the hmc operon encoding
a cytochrome redox complex for electron transport from hydrogen to sulfate.
- Escherichia coli iscR (for iron-sulfur cluster regulator), a transcription
repressor of the isc operon encoding Fe-S assembly proteins. IscR
reversibly binds a [2Fe-2S] cluster and functions as an autoregulator.
Demetallated iscR (apo-iscR) acts as an activator under oxidative and
- Nitrosomonas europaea nsrR, a nitrite sensitive transcription repressor of
nitrite reductase, involved in detoxification of nitrite.
- Escherichia coli nsrR, a nitric oxide sensitive transcription regulator of
genes that may protect the cell against NO-stress (NO is a damaging agent
of Fe-S clusters).
- Bacillus subtilis protein nsrR, a NO-responsive transcription regulator.
- Streptomyces coelicolor nsrR, a transcription regulator containing an
NO-sensitive [2Fe-2S] cluster that is required for DNA-binding.
- Rhizobium leguminosarum rirA (rhizobial iron regulator), an iron-responsive
regulator involved in Fe uptake.
- Bacillus subtilis protein yrzC.
- Mycobacterium tuberculosis protein Rv1287/MT1325.
- Synechocystis strain PCC 6803 protein slr0846.
The pattern we use to detect these proteins is located in the central part of
these proteins and covers the stronger conserved region , 'the wing', which
starts directly C-terminal to the 'helix-turn-helix' motif of these proteins.
We also developed a profile that covers the entire rrf2-type wHTH, including
the C-terminal region which may bind an iron-sulfur cluster.
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see