PROSITE documentation PDOC01035
Rrf2-type HTH domain profile


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 Fe-limited conditions.
  • 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 [2], '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.

Last update:

March 2009 / Text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

HTH_RRF2_2, PS51197; Rrf2-type HTH domain profile  (MATRIX)

HTH_RRF2_1, PS01332; Rrf2-type HTH domain signature  (PATTERN)


1AuthorsKeon R.G. Fu R. Voordouw G.
TitleDeletion of two downstream genes alters expression of the hmc operon of Desulfovibrio vulgaris subsp. vulgaris Hildenborough.
SourceArch. Microbiol. 167:376-383(1997).
PubMed ID9148780

2AuthorsBairoch A.
SourceUnpublished observations (1999).

3AuthorsSchwartz C.J. Giel J.L. Patschkowski T. Luther C. Ruzicka F.J. Beinert H. Kiley P.J.
TitleIscR, an Fe-S cluster-containing transcription factor, represses expression of Escherichia coli genes encoding Fe-S cluster assembly proteins.
SourceProc. Natl. Acad. Sci. U.S.A. 98:14895-14900(2001).
PubMed ID11742080

4AuthorsBeaumont H.J. Lens S.I. Reijnders W.N. Westerhoff H.V. van Spanning R.J.
TitleExpression of nitrite reductase in Nitrosomonas europaea involves NsrR, a novel nitrite-sensitive transcription repressor.
SourceMol. Microbiol. 54:148-158(2004).
PubMed ID15458412

5AuthorsRodionov D.A. Dubchak I.L. Arkin A.P. Alm E.J. Gelfand M.S.
TitleDissimilatory metabolism of nitrogen oxides in bacteria: comparative reconstruction of transcriptional networks.
SourcePLoS Comput. Biol. 1:E55-E55(2005).
PubMed ID16261196

6AuthorsBodenmiller D.M. Spiro S.
TitleThe yjeB (nsrR) gene of Escherichia coli encodes a nitric oxide-sensitive transcriptional regulator.
SourceJ. Bacteriol. 188:874-881(2006).
PubMed ID16428390

7AuthorsTucker N.P. Hicks M.G. Clarke T.A. Crack J.C. Chandra G. Le Brun N.E. Dixon R. Hutchings M.I.
TitleThe transcriptional repressor protein NsrR senses nitric oxide directly via a [2Fe-2S] cluster.
SourcePLoS ONE 3:E3623-E3623(2008).
PubMed ID18989365

8AuthorsIsabella V.M. Lapek J.D. Jr. Kennedy E.M. Clark V.L.
TitleFunctional analysis of NsrR, a nitric oxide-sensing Rrf2 repressor in Neisseria gonorrhoeae.
SourceMol. Microbiol. 71:227-239(2009).
PubMed ID19007408

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