{PDOC01035} {PS01332; HTH_RRF2_1} {PS51197; HTH_RRF2_2} {BEGIN} ******************************** * 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 ), the gntR-type (see ) and marR-type HTH (see ), wherein the DNA-binding HTH motif is followed by a beta-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 [3-8]. 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. -Consensus pattern: L-x(3)-[GRS]-[LIVY]-x(2)-[STA]-x(2)-G-x(2)-G-G-[FYIV]-x- [LIF] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: March 2009 / Text revised. [ 1] Keon R.G., Fu R., Voordouw G. "Deletion of two downstream genes alters expression of the hmc operon of Desulfovibrio vulgaris subsp. vulgaris Hildenborough." Arch. Microbiol. 167:376-383(1997). PubMed=9148780 [ 2] Bairoch A. Unpublished observations (1999). [ 3] Schwartz C.J., Giel J.L., Patschkowski T., Luther C., Ruzicka F.J., Beinert H., Kiley P.J. "IscR, an Fe-S cluster-containing transcription factor, represses expression of Escherichia coli genes encoding Fe-S cluster assembly proteins." Proc. Natl. Acad. Sci. U.S.A. 98:14895-14900(2001). PubMed=11742080; DOI=10.1073/pnas.251550898 [ 4] Beaumont H.J., Lens S.I., Reijnders W.N., Westerhoff H.V., van Spanning R.J. "Expression of nitrite reductase in Nitrosomonas europaea involves NsrR, a novel nitrite-sensitive transcription repressor." Mol. Microbiol. 54:148-158(2004). PubMed=15458412; DOI=10.1111/j.1365-2958.2004.04248.x [ 5] Rodionov D.A., Dubchak I.L., Arkin A.P., Alm E.J., Gelfand M.S. "Dissimilatory metabolism of nitrogen oxides in bacteria: comparative reconstruction of transcriptional networks." PLoS Comput. Biol. 1:E55-E55(2005). PubMed=16261196; DOI=10.1371/journal.pcbi.0010055 [ 6] Bodenmiller D.M., Spiro S. "The yjeB (nsrR) gene of Escherichia coli encodes a nitric oxide-sensitive transcriptional regulator." J. Bacteriol. 188:874-881(2006). PubMed=16428390; DOI=10.1128/JB.188.3.874-881.2006 [ 7] Tucker N.P., Hicks M.G., Clarke T.A., Crack J.C., Chandra G., Le Brun N.E., Dixon R., Hutchings M.I. "The transcriptional repressor protein NsrR senses nitric oxide directly via a [2Fe-2S] cluster." PLoS ONE 3:E3623-E3623(2008). PubMed=18989365; DOI=10.1371/journal.pone.0003623 [ 8] Isabella V.M., Lapek J.D. Jr., Kennedy E.M., Clark V.L. "Functional analysis of NsrR, a nitric oxide-sensing Rrf2 repressor in Neisseria gonorrhoeae." Mol. Microbiol. 71:227-239(2009). PubMed=19007408; DOI=10.1111/j.1365-2958.2008.06522.x -------------------------------------------------------------------------------- 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 https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}