RegulonDB RegulonDB 9.2:Regulon Page

OxyR DNA-binding transcriptional dual regulator

Synonyms: OxyR
OxyR, oxidative stress regulator, is the transcriptional dual regulator for the expression of antioxidant genes in response to oxidative stress, in particular, elevated levels of hydrogen peroxide. The OxyR regulon includes genes involved in peroxide metabolism, redox balance, and peroxide protection by, for example, manganese uptake [13, 17, 29, 30] Moreover, OxyR activates the synthesis of the small, noncoding oxyS RNA. This allows OxyR to regulate as many as 40 additional gene products indirectly by affecting mRNA stability or translation efficiency [31] OxyR acts as a repressor for its own synthesis in both the oxidized and reduced forms [19, 32] In addition, expression of oxyR is positively regulated by cAMP-activated Crp protein during exponential growth and negatively regulated by RpoS when cells enter stationary phase [33] Based on microarray assays, a new function as regulator of S-nitrosylation (a nitrosative stress regulon) under anaerobic conditions has been determined for OxyR [16] and it is distinct from the OxyR regulon activated by oxidative stress [16]
OxyR consists of 305 amino acid residues and is a member of the LysR family of bacterial transcription factors [19, 34] It is a tetramer in solution [35] OxyR consists of two domains, the N-terminal domain, carrying a helix-turn-helix motif, and the C-terminal regulatory domain.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
OxyR     nd nd
Evolutionary Family: LysR
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: oxyR
  Genome position: 4158490-4159407
  Length: 918 bp / 305 aa
Operon name: oxyR
TU(s) encoding the TF:
Transcription unit        Promoter

Regulated gene(s) ahpC, ahpF, dps, dsbG, fhuF, flu, fur, gntP, gor, grxA, hcp, hcr, hemH, isrC, katG, mntH, nfsA, oxyR, oxyS, rimK, sufA, sufB, sufC, sufD, sufE, sufS, trxC, uof, uxuA, uxuB, ybjC, ybjN, ychF, yhjA
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
incorporation of metal ions (6)
sulfur metabolism (6)
detoxification (4)
Transcription related (2)
activator (2)
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Regulated operon(s) ahpCF, dps, dsbG, fhuF, fldA-uof-fur, gntP, gor, grxA, hcp-hcr, hemH, isrC-flu, katG, mntH, oxyR, oxyS, pth-ychF, sufABCDSE, trxC, uxuAB, ybjC-nfsA-rimK-ybjN, yhjA
First gene in the operon(s) ahpC, ahpC, dps, dsbG, fhuF, gntP, gor, grxA, hcp, hemH, isrC, katG, mntH, oxyR, oxyS, sufA, trxC, uof, uxuA, ybjC, ychF, yhjA
Simple and complex regulons CRP,ExuR,OxyR,UxuR
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)

Transcription factor binding sites (TFBSs) arrangements       

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Growth Conditions Evidence (Confirmed, Strong, Weak) References
  OxyR activator ahpCp Sigma70 -66.0 -90.0 ahpC, ahpF
638847 638863 [a] [BPP], [GEA], [HIBSCS] [1], [2], [3], [4], [5]
  OxyR activator ahpCp Sigma70 -44.0 -68.0 ahpC, ahpF
638869 638885 [a] [BPP], [GEA], [HIBSCS] [1], [2], [3], [4], [5], [6]
  OxyR activator ahpCp2 Sigma70 -76.0 -328.0 ahpC, ahpF
638609 638625 [a] [BPP], [GEA], [HIBSCS] [5]
  OxyR activator ahpCp2 Sigma70 -53.0 -305.0 ahpC, ahpF
638632 638648 [a] [BPP], [GEA], [HIBSCS] [5]
  OxyR activator dpsp Sigma70 -66.0 -105.0 dps
849008 849024 [a] [HIBSCS] [7]
  OxyR activator dpsp Sigma70 -44.0 -83.0 dps
848986 849002 [a] [HIBSCS] [7]
  OxyR activator dsbGp nd -77.0 -304.0 dsbG
638869 638885 [b] [BPP], [GEA], [HIBSCS] [2], [3], [4], [5], [6]
  OxyR activator dsbGp nd -55.0 -282.0 dsbG
638847 638863 [b] [BPP], [GEA], [HIBSCS] [2], [3], [4], [5]
  OxyR repressor fhuFp Sigma70 -105.0 -136.0 fhuF
4605791 4605807 [a] [BPP], [GEA], [HIBSCS] [5]
  OxyR repressor fhuFp Sigma70 -83.0 -114.0 fhuF
4605769 4605785 [a] [BPP], [GEA], [HIBSCS] [5]
  OxyR repressor fhuFp Sigma70 -21.0 -52.0 fhuF
4605707 4605723 [a] [BPP], [GEA], [HIBSCS] [5]
  OxyR repressor fhuFp Sigma70 2.0 -30.0 fhuF
4605685 4605701 [a] [BPP], [GEA], [HIBSCS] [5]
  OxyR repressor flup Sigma70 2.0 1.0 isrC, flu
2071310 2071326 [a] [BPP], [GEA], [HIBSCS], [SM] [8], [9], [10], [11], [12]
  OxyR repressor flup Sigma70 24.0 23.0 isrC, flu
2071332 2071348 [a] [BPP], [GEA], [HIBSCS], [SM] [8], [9], [10], [11], [12]
  OxyR repressor gntPp Sigma70 -152.0 -190.0 gntP
4551478 4551494 nd [GEA], [HIBSCS] [13]
  OxyR repressor gntPp Sigma70 -130.0 -168.0 gntP
4551456 4551472 nd [GEA], [HIBSCS] [13]
  OxyR activator gorp Sigma70 nd nd gor nd nd [a] [GEA] [14]
  OxyR activator grxAp nd -66.0 -89.0 grxA
890834 890850 [a] [BPP], [GEA], [HIBSCS] [13], [15]
  OxyR activator grxAp nd -44.0 -67.0 grxA
890812 890828 [a] [BPP], [GEA], [HIBSCS] [13], [15]
  OxyR activator hcpp nd nd nd hcp, hcr nd nd nd [BPP], [GEA] [16]
  OxyR activator hemHp Sigma70 -55.0 -79.0 hemH
497968 497984 [b] [BPP], [GEA] [13]
  OxyR activator hemHp Sigma70 -33.0 -57.0 hemH
497990 498006 [b] [BPP], [GEA] [13]
  OxyR activator katGp Sigma70 -66.0 -89.0 katG
4133738 4133754 [a] [BPP], [GEA], [HIBSCS] [2], [3], [4], [5], [6]
  OxyR activator katGp Sigma70 -44.0 -67.0 katG
4133760 4133776 [a] [BPP], [GEA], [HIBSCS] [2], [3], [4], [5], [6]
  OxyR activator mntHp Sigma70 -76.0 -104.0 mntH
2512802 2512818 [a] [GEA], [HIBSCS], [SM] [17], [18]
  OxyR activator mntHp Sigma70 -54.0 -82.0 mntH
2512780 2512796 [a] [AIBSCS], [GEA], [SM] [17], [18]
  OxyR repressor oxyRp Sigma38 -18.0 -51.0 oxyR
4158431 4158447 [b] [BPP], [GEA], [HIBSCS] [2], [4], [19], [20]
  OxyR repressor oxyRp Sigma38 5.0 -29.0 oxyR
4158453 4158469 [b] [BPP], [GEA], [HIBSCS] [2], [4], [19], [20]
  OxyR activator oxySp Sigma70 -67.0 -67.0 oxyS
4158453 4158469 [a] [BPP], [GEA], [HIBSCS] [4], [20]
  OxyR activator oxySp Sigma70 -45.0 -45.0 oxyS
4158431 4158447 [a] [BPP], [GEA], [HIBSCS] [4], [20]
  OxyR activator sufAp Sigma70 -232.0 -264.0 sufA, sufB, sufC, sufD, sufS, sufE
1764642 1764658 [a] [BPP], [GEA] [13], [21], [22], [23], [24]
  OxyR activator sufAp Sigma70 -210.0 -242.0 sufA, sufB, sufC, sufD, sufS, sufE
1764620 1764636 [a] [BPP], [GEA], [SM] [13], [21], [22], [23], [24]
  OxyR activator trxCp Sigma70 -57.0 -117.0 trxC
2718610 2718626 [a] [BPP], [GEA], [HIBSCS] [25]
  OxyR activator trxCp Sigma70 -35.0 -95.0 trxC
2718632 2718648 [a] [BPP], [GEA], [HIBSCS] [25]
  OxyR activator uofp nd -62.0 -166.0 uof, fur
710883 710899 [a] [BPP], [GEA], [HIBSCS] [26]
  OxyR activator uofp nd -40.0 -144.0 uof, fur
710861 710877 [a] [BPP], [GEA], [HIBSCS] [26]
  OxyR repressor uxuAp Sigma70 -54.0 -172.0 uxuA, uxuB
4551456 4551472 nd [GEA], [HIBSCS] [13]
  OxyR repressor uxuAp Sigma70 -32.0 -150.0 uxuA, uxuB
4551478 4551494 nd [GEA], [HIBSCS] [13]
  OxyR repressor ybjCp Sigma70 -72.0 -93.0 ybjC, nfsA, rimK, ybjN
890812 890828 nd [BPP], [GEA], [HIBSCS] [13], [15]
  OxyR repressor ybjCp Sigma70 -50.0 -71.0 ybjC, nfsA, rimK, ybjN
890834 890850 nd [BPP], [GEA], [HIBSCS] [13], [15]
  OxyR repressor ychFp Sigma70 9.5 -61.0 ychF
1257865 1257881 [a] [BPP], [HIBSCS] [27]
  OxyR repressor ychFp Sigma70 31.5 -39.0 ychF
1257843 1257859 [a] [BPP], [HIBSCS] [27]
  OxyR activator yhjAp Sigma70 -86.0 -159.0 yhjA
3669339 3669355 nd [AIBSCS], [BPP] [28]
  OxyR activator yhjAp Sigma70 -64.0 -137.0 yhjA
3669317 3669333 nd [BPP], [HIBSCS] [28]

Growth Condition    

 [a] Hydrogen peroxide treatment

 [b] oxidative stress

Alignment and PSSM for OxyR TFBSs    

Aligned TFBS of OxyR   

Position weight matrix (PWM).   
A	9	13	6	12	6	12	11	13	23	12	2	5	27	0	0	17	11	12	7	11
C	4	6	1	6	7	4	1	4	4	13	25	1	3	0	15	0	15	3	5	11
G	1	6	23	14	3	0	5	5	4	4	0	5	4	0	1	9	1	1	10	0
T	20	9	4	2	18	18	17	12	3	5	7	23	0	34	18	8	7	18	12	12

PWM logo   


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
TF-target gene evolutionary conservation
Promoter-target gene evolutionary conservation


 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences

 [SM] Site mutation

 [AIBSCS] Automated inference based on similarity to consensus sequences


 [1] Campos E., Montella C., Garces F., Baldoma L., Aguilar J., Badia J., 2007, Aerobic L-ascorbate metabolism and associated oxidative stress in Escherichia coli., Microbiology. 153(Pt 10):3399-408

 [2] Tartaglia LA., Gimeno CJ., Storz G., Ames BN., 1992, Multidegenerate DNA recognition by the OxyR transcriptional regulator., J Biol Chem. 267(3):2038-45

 [3] Tartaglia LA., Storz G., Ames BN., 1989, Identification and molecular analysis of oxyR-regulated promoters important for the bacterial adaptation to oxidative stress., J Mol Biol. 210(4):709-19

 [4] Toledano MB., Kullik I., Trinh F., Baird PT., Schneider TD., Storz G., 1994, Redox-dependent shift of OxyR-DNA contacts along an extended DNA-binding site: a mechanism for differential promoter selection., Cell. 78(5):897-909

 [5] Zheng M., Wang X., Doan B., Lewis KA., Schneider TD., Storz G., 2001, Computation-directed identification of OxyR DNA binding sites in Escherichia coli., J Bacteriol. 183(15):4571-9

 [6] Storz G., Tartaglia LA., Ames BN., 1990, Transcriptional regulator of oxidative stress-inducible genes: direct activation by oxidation., Science. 248(4952):189-94

 [7] Altuvia S., Almiron M., Huisman G., Kolter R., Storz G., 1994, The dps promoter is activated by OxyR during growth and by IHF and sigma S in stationary phase., Mol Microbiol. 13(2):265-72

 [8] Haagmans W., van der Woude M., 2000, Phase variation of Ag43 in Escherichia coli: Dam-dependent methylation abrogates OxyR binding and OxyR-mediated repression of transcription., Mol Microbiol. 35(4):877-87

 [9] Henderson IR., Owen P., 1999, The major phase-variable outer membrane protein of Escherichia coli structurally resembles the immunoglobulin A1 protease class of exported protein and is regulated by a novel mechanism involving Dam and oxyR., J Bacteriol. 181(7):2132-41

 [10] Waldron DE., Owen P., Dorman CJ., 2002, Competitive interaction of the OxyR DNA-binding protein and the Dam methylase at the antigen 43 gene regulatory region in Escherichia coli., Mol Microbiol. 44(2):509-20

 [11] Wallecha A., Correnti J., Munster V., van der Woude M., 2003, Phase variation of Ag43 is independent of the oxidation state of OxyR., J Bacteriol. 185(7):2203-9

 [12] Wallecha A., Munster V., Correnti J., Chan T., van der Woude M., 2002, Dam- and OxyR-dependent phase variation of agn43: essential elements and evidence for a new role of DNA methylation., J Bacteriol. 184(12):3338-47

 [13] Zheng M., Wang X., Templeton LJ., Smulski DR., LaRossa RA., Storz G., 2001, DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide., J Bacteriol. 183(15):4562-70

 [14] Becker-Hapak M., Eisenstark A., 1995, Role of rpoS in the regulation of glutathione oxidoreductase (gor) in Escherichia coli., FEMS Microbiol Lett. 134(1):39-44

 [15] Tao K., 1997, oxyR-dependent induction of Escherichia coli grx gene expression by peroxide stress., J Bacteriol. 179(18):5967-70

 [16] Seth D., Hausladen A., Wang YJ., Stamler JS., 2012, Endogenous protein S-Nitrosylation in E. coli: regulation by OxyR., Science. 336(6080):470-3

 [17] Anjem A., Varghese S., Imlay JA., 2009, Manganese import is a key element of the OxyR response to hydrogen peroxide in Escherichia coli., Mol Microbiol. 72(4):844-58

 [18] Kehres DG., Janakiraman A., Slauch JM., Maguire ME., 2002, Regulation of Salmonella enterica serovar Typhimurium mntH transcription by H(2)O(2), Fe(2+), and Mn(2+)., J Bacteriol. 184(12):3151-8

 [19] Christman MF., Storz G., Ames BN., 1989, OxyR, a positive regulator of hydrogen peroxide-inducible genes in Escherichia coli and Salmonella typhimurium, is homologous to a family of bacterial regulatory proteins., Proc Natl Acad Sci U S A. 86(10):3484-8

 [20] Kullik I., Toledano MB., Tartaglia LA., Storz G., 1995, Mutational analysis of the redox-sensitive transcriptional regulator OxyR: regions important for oxidation and transcriptional activation., J Bacteriol. 177(5):1275-84

 [21] Jang S., Imlay JA., 2010, Hydrogen peroxide inactivates the Escherichia coli Isc iron-sulphur assembly system, and OxyR induces the Suf system to compensate., Mol Microbiol. 78(6):1448-67

 [22] Lee JH., Yeo WS., Roe JH., 2004, Induction of the sufA operon encoding Fe-S assembly proteins by superoxide generators and hydrogen peroxide: involvement of OxyR, IHF and an unidentified oxidant-responsive factor., Mol Microbiol. 51(6):1745-55

 [23] Outten FW., Djaman O., Storz G., 2004, A suf operon requirement for Fe-S cluster assembly during iron starvation in Escherichia coli., Mol Microbiol. 52(3):861-72

 [24] Yeo WS., Lee JH., Lee KC., Roe JH., 2006, IscR acts as an activator in response to oxidative stress for the suf operon encoding Fe-S assembly proteins., Mol Microbiol. 61(1):206-18

 [25] Ritz D., Patel H., Doan B., Zheng M., Aslund F., Storz G., Beckwith J., 2000, Thioredoxin 2 is involved in the oxidative stress response in Escherichia coli., J Biol Chem. 275(4):2505-12

 [26] Zheng M., Doan B., Schneider TD., Storz G., 1999, OxyR and SoxRS regulation of fur., J Bacteriol. 181(15):4639-43

 [27] Wenk M., Ba Q., Erichsen V., Macinnes K., Wiese H., Warscheid B., Koch HG., 2012, A Universally Conserved ATPase Regulates the Oxidative Stress Response in Escherichia coli., J Biol Chem. 287(52):43585-98

 [28] Partridge JD., Poole RK., Green J., 2007, The Escherichia coli yhjA gene, encoding a predicted cytochrome c peroxidase, is regulated by FNR and OxyR., Microbiology. 153(Pt 5):1499-509

 [29] Storz G., Tartaglia LA., Ames BN., 1990, The OxyR regulon., Antonie Van Leeuwenhoek. 58(3):157-61

 [30] Mongkolsuk S., Helmann JD., 2002, Regulation of inducible peroxide stress responses., Mol Microbiol. 45(1):9-15

 [31] Altuvia S., Weinstein-Fischer D., Zhang A., Postow L., Storz G., 1997, A small, stable RNA induced by oxidative stress: role as a pleiotropic regulator and antimutator., Cell. 90(1):43-53

 [32] Tao K., Makino K., Yonei S., Nakata A., Shinagawa H., 1991, Purification and characterization of the Escherichia coli OxyR protein, the positive regulator for a hydrogen peroxide-inducible regulon., J Biochem (Tokyo). 109(2):262-6

 [33] Gonzalez-Flecha B., Demple B., 1997, Transcriptional regulation of the Escherichia coli oxyR gene as a function of cell growth., J Bacteriol. 179(19):6181-6

 [34] Tao K., Makino K., Yonei S., Nakata A., Shinagawa H., 1989, Molecular cloning and nucleotide sequencing of oxyR, the positive regulatory gene of a regulon for an adaptive response to oxidative stress in Escherichia coli: homologies between OxyR protein and a family of bacterial activator proteins., Mol Gen Genet. 218(3):371-6

 [35] Kullik I., Stevens J., Toledano MB., Storz G., 1995, Mutational analysis of the redox-sensitive transcriptional regulator OxyR: regions important for DNA binding and multimerization., J Bacteriol. 177(5):1285-91

 [36] Lee C., Lee SM., Mukhopadhyay P., Kim SJ., Lee SC., Ahn WS., Yu MH., Storz G., Ryu SE., 2004, Redox regulation of OxyR requires specific disulfide bond formation involving a rapid kinetic reaction path., Nat Struct Mol Biol. 11(12):1179-85

 [37] Zaim J., Kierzek AM., 2003, The structure of full-length LysR-type transcriptional regulators. Modeling of the full-length OxyR transcription factor dimer., Nucleic Acids Res. 31(5):1444-54

 [38] Zheng M., Aslund F., Storz G., 1998, Activation of the OxyR transcription factor by reversible disulfide bond formation., Science. 279(5357):1718-21

 [39] Aslund F., Zheng M., Beckwith J., Storz G., 1999, Regulation of the OxyR transcription factor by hydrogen peroxide and the cellular thiol-disulfide status., Proc Natl Acad Sci U S A. 96(11):6161-5

 [40] Hausladen A., Privalle CT., Keng T., DeAngelo J., Stamler JS., 1996, Nitrosative stress: activation of the transcription factor OxyR., Cell. 86(5):719-29

 [41] Choi H., Kim S., Mukhopadhyay P., Cho S., Woo J., Storz G., Ryu S., 2001, Structural basis of the redox switch in the OxyR transcription factor., Cell. 105(1):103-13

 [42] Knapp GS., Hu JC., 2010, Specificity of the E. coli LysR-type transcriptional regulators., PLoS One. 5(12):e15189

 [43] Muraoka S., Okumura R., Ogawa N., Nonaka T., Miyashita K., Senda T., 2003, Crystal structure of a full-length LysR-type transcriptional regulator, CbnR: unusual combination of two subunit forms and molecular bases for causing and changing DNA bend., J Mol Biol. 328(3):555-66

 [44] Gusarov I., Nudler E., 2012, S-nitrosylation signaling in Escherichia coli., Sci Signal. 5(228):pe26

 [45] Tao K., Zou C., Fujita N., Ishihama A., 1995, Mapping of the OxyR protein contact site in the C-terminal region of RNA polymerase alpha subunit., J Bacteriol. 177(23):6740-4

 [46] Chiang SM., Schellhorn HE., 2012, Regulators of oxidative stress response genes in Escherichia coli and their functional conservation in bacteria., Arch Biochem Biophys. 525(2):161-9