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NsrR DNA-binding transcriptional repressor

Synonyms: NsrR-[2Fe-2S]reduced, NsrR-[2Fe-2S]2+ oxidized, NsrR, NsrR-nitric oxide
Summary:
NsrR, the "nitrite-sensitive repressor" [], regulates genes involved in cell protection against nitric oxide (NO) [1, 6]. A microarray analysis showed that this protein regulates directly or indirectly at least 30 genes, some of which are involved in protection against reactive nitrogen species that can be generated by NO [7]. A ChIP-chip analysis (chromatin immunoprecipitation and microarray analysis) revealed that NsrR regulates, in addition, genes involved in motility and/or biofilm development [5]. NsrR also appears to regulate σE-dependent genes in an RseA-independent manner [9]. NsrR belongs to the Rrf2 family [], which includes among others the [2Fe-2S]-containing transcription factor IscR and the iron regulator RirA [11].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
NsrR Functional   Apo [APPHINH], [HIFS], [IEP], [IPI] [1], [2], [3], [4], [5]
NsrR-[2Fe-2S]2+ oxidized Non-Functional Covalent Apo nd nd
NsrR-[2Fe-2S]reduced Functional Covalent Holo nd nd
NsrR-nitric oxide Non-Functional   Holo nd nd
Evolutionary Family: Rrf2
Connectivity class: Local Regulator
Gene name: nsrR
  Genome position: 4406190-4406615
  Length: 426 bp / 141 aa
Operon name: nsrR-rnr-rlmB-yjfIJ
TU(s) encoding the TF:
Transcription unit        Promoter
nsrR-rnr-rlmB-yjfI
nsrRp


Regulon       
Regulated gene(s) aceE, aceF, bamE, bdcA, cdd, dkgB, dsdC, feaB, feaR, fhlA, fliA, fliZ, grxD, hcp, hcr, hmp, hycA, hycB, hycC, hycD, hycE, hycF, hycG, hycH, hycI, hypA, hypB, hypC, hypD, hypE, ihfA, infC, lrp, mepH, mhpT, ndh, norR, nrfA, nrfB, nrfC, nrfD, nrfE, nrfF, nrfG, pgpC, pheM, pheS, pheT, poxB, rfe, rffC, rffG, rffH, rffM, rplT, rpmI, rybB, sodB, sufA, sufB, sufC, sufD, sufE, sufS, tadA,
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Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
membrane (16)
anaerobic respiration (11)
enterobacterial common antigen (surface glycolipid) (11)
surface antigens (ECA, O antigen of LPS) (11)
fermentation (10)
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Regulated operon(s) bamE, bdcA, cdd, dkgB, dsdC, feaB, feaR, fliAZ-tcyJ, grxD, hcp-hcr-poxB-ltaE-ybjT, hmp, hycABCDEFGHI, hypABCDE-fhlA, lrp, mepH, mhpT, ndh, norR, nrfABCDEFG, pdhR-aceEF-lpd, pgpC-tadA, rfe-wzzE-wecBC-rffGHC-wecE-wzxE-wecF-wzyE-rffM, rybB, sodB, sufABCDSE, tehAB, thrS-infC-rpmI-rplT-pheMST-ihfA, tsgA, waaH, ydbD, yeaE, yeaR-yoaG, ygbA, ytfE
First gene in the operon(s) aceE, bamE, bdcA, cdd, dkgB, dsdC, feaB, feaR, fliA, fliA, grxD, hcp, hcp, hmp, hycA, hypA, hypA, lrp, mepH, mhpT, ndh, norR, nrfA, pgpC, rfe, rybB, sodB, sufA, tehA, thrS, thrS, tsgA, ydbD, yeaE, yeaR, ygbA, waaH, ytfE
Simple and complex regulons ArcA,FNR,Fis,Fur,IHF,NsrR,PdhR
ArcA,FNR,NsrR
CRP,CytR,NsrR
CRP,FeaR,NsrR
CRP,IHF,NsrR
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[NsrR,-](35)


Transcription factor regulation    


Transcription factor binding sites (TFBSs) arrangements
      

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  NsrR repressor aceEp Sigma70, Sigma38 -81.0 -129.0 aceE, aceF
aattatccagAAGATGTTGTAAatcaagcgca
 122883 122894 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor bamEp Sigma24 67.0 -53.0 bamE
gtctattatcATCGGCATATTAcagatgagcc
 2753547 2753558 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor bdcAp Sigma70 -18.0 -29.0 bdcA
aaacagttttGTAATGCATGTTacataataaa
 4474077 4474088 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor cddp Sigma70 9.0 -17.0 cdd
gttatcccatTACATGATTATGaggcaacgcc
 2231822 2231833 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor dkgBp Sigma38 -11.0 -80.0 dkgB
cgcaaaaatcCTCTGCATTTTAcgctcttttt
 229082 229093 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor dkgBp Sigma38 64.0 -6.0 dkgB
tagcattaaaAGAGGCATATTAtggctatccc
 229156 229167 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor dsdCp Sigma70 14.0 -104.0 dsdC
atcaatggagTGATTTACATCTaaaaatgaag
 2477728 2477739 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor feaBp1 Sigma70 -184.0 -211.0 feaB
tcgctctgtgAAATGTATTTTTattgttgcat
 1447303 1447314 [APIORCISFBSCS], [CV(GEA)], [GEA] [5], [6]
  NsrR repressor feaRp2 Sigma70 2.0 -25.0 feaR
atgcaacaatAAAAATACATTTcacagagcga
 1447303 1447314 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor fliAp1 Sigma70 -207.0 -237.0 fliA, fliZ, tcyJ
cctacaagttGAATTGCAATTTattgaatttg
 2002021 2002032 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor fliAp1 Sigma70 7.0 -24.0 fliA, fliZ, tcyJ
taatcatgccGATAACTCATATaacgcagggc
 2001808 2001819 [APIORCISFBSCS], [CV(GEA)], [CV(GEA)], [CV(GEA/SM)], [CV(SM)], [GEA], [SM] [5]
  NsrR repressor fliAp2 Sigma28 -218.0 -237.0 fliA, fliZ, tcyJ
cctacaagttGAATTGCAATTTattgaatttg
 2002021 2002032 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor fliAp2 Sigma28 -5.0 -24.0 fliA, fliZ, tcyJ
taatcatgccGATAACTCATATaacgcagggc
 2001808 2001819 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor grxD Sigma70 -13.0 -74.0 grxD
aaagcgtgatGAAAATGTTATTttccgatgcc
 1734170 1734181 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor hcpp nd 6.0 -26.0 hcp, hcr, poxB
taaccttaaaCATGTATATTAAATATAACtttaaaaggt
 913831 913849 [APIORCISFBSCS], [BCE], [CV(GEA)], [CV(GEA)], [CV(GEA/SM)], [CV(SM)], [GEA], [SM] [2], [5], [7]
  NsrR repressor hmpp Sigma38 -38.0 -76.0 hmp
aaaacaccaaAGAACCATTTACattgcagggc
 2685754 2685765 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor hmpp Sigma38 2.0 -37.0 hmp
tttttataagATGCATTTGAGATACATCAattaagatgc
 2685789 2685807 [AIBSCS], [CV(GEA)], [GEA] [1]
  NsrR repressor hmpp Sigma38 20.0 -19.0 hmp
tacatcaattAAGATGCAAAAAaaggaagacc
 2685811 2685822 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor hycAp Sigma54 -70.0 -96.0 hycA, hycB, hycC, hycD, hycE, hycF, hycG, hycH, hycI
acacggcgacGAAATTCATCTTtagcttaaaa
 2850526 2850537 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor hypAp Sigma54 -96.0 -116.0 hypA, hypB, hypC, hypD, hypE, fhlA
ttttaagctaAAGATGAATTTCgtcgccgtgt
 2850526 2850537 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor lrpp Sigma70 52.0 -216.0 lrp
catgcatgtaAATACCATGTTTaccgtgctag
 932374 932385 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor mepHp Sigma70 -61.0 -139.0 mepH
tagctttcacTGCTGCATTTTTttgcgctcgc
 1734291 1734302 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor mhpTp Sigma32 -484.0 -557.0 mhpT
actgccgagaACGTGCATTTTGtatgcccatc
 374897 374908 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor ndhp Sigma70 6.0 -88.0 ndh
ctcaatagcgAAGAACATTTTCattgctgtaa
 1165992 1166003 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor norRp nd 21.0 3.0 norR
acagtgaggcAAAGATGAGTTTttccgttgat
 2832282 2832293 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor nrfAp Sigma70 -121.0 -214.0 nrfA, nrfB, nrfC, nrfD, nrfE, nrfF, nrfG
ttctttgaggAACATGCAGTTAtgcatgctgt
 4287545 4287556 [APIORCISFBSCS], [CV(GEA)], [GEA] [5], [7]
  NsrR repressor nrfAp Sigma70 -63.0 -156.0 nrfA, nrfB, nrfC, nrfD, nrfE, nrfF, nrfG
taactctaaaGTGGTATTTTACATGCACTtacaattgat
 4287599 4287617 [APIORCISFBSCS], [BCE], [CV(GEA)], [CV(GEA)], [CV(GEA/SM)], [CV(SM)], [GEA], [SM] [5], [8]
  NsrR repressor pgpCp Sigma32 131.0 43.0 pgpC, tadA
gttttttgacTTAGATGGAACAttgcatcagc
 2698503 2698514 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor rfep Sigma70 -1.0 -117.0 rfe, wzzE, wecB, wecC, rffG, rffH, rffC, wecE, wzxE, wecF, wzyE, rffM
catgttatgcAATTTGCATATCaaatggttaa
 3967794 3967805 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor rybBp Sigma24 nd nd rybB
nd
 nd nd [GEA] [9]
  NsrR repressor sodBp Sigma70 -37.0 -92.0 sodB
gcaacagggtAAGTTCATCTTTtgtctcacct
 1735281 1735292 [AIBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor sufAp Sigma70 -68.0 -100.0 sufA, sufB, sufC, sufD, sufS, sufE
aaaagcaggcAAAAAGCATGTTttacggtaaa
 1764481 1764492 [APIORCISFBSCS], [CV(GEA)], [GEA] [5], [10]
  NsrR repressor sufAp Sigma70 -6.0 -38.0 sufA, sufB, sufC, sufD, sufS, sufE
tcattatcacTAACATGCTGTTatacgctgaa
 1764419 1764430 [APIORCISFBSCS], [CV(GEA)], [GEA] [5], [10]
  NsrR repressor tehAp nd -1.0 -38.0 tehA, tehB
aattccataaAATGCATTTCAAATATACTttataaatta
 1500526 1500544 [AIBSCS], [APIORCISFBSCS], [CV(GEA)], [GEA] [1], [5]
  NsrR repressor tehAp nd 28.0 -10.0 tehA, tehB
taaattaaacAAAATGAGTAAGaagatgcaga
 1500558 1500569 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor thrSp nd 80.0 -84.0 thrS, infC, rpmI, rplT, pheM, pheS, pheT, ihfA
catttgttggCTAGATGGTTTCgcaatgaact
 1802649 1802660 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor tsgAp nd -64.0 -113.0 tsgA
atcacctcttAAAATGCAATTTagcaaccgat
 3492450 3492461 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor ydbDp Sigma38 39.0 -40.0 ydbD
acaaaagggaAAGATGCATTTCcctttttttc
 1475099 1475110 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor yeaEp Sigma70 5.0 -84.0 yeaE
acaaattctgATAATGCATCTTtccagggcat
 1865715 1865726 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor yeaRp Sigma70 -32.0 -78.0 yeaR, yoaG
taaccaataaATGGTATTTAAAATGCAAAttatcaggcg
 1880017 1880035 [AIBSCS], [CV(GEA)], [GEA] [4]
  NsrR repressor ygbAp nd -118.0 -140.0 ygbA
tggttccgggAAAGATGCTGTTttgcagcttt
 2856941 2856952 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor ygbAp nd -7.0 -29.0 ygbA
ttaagattaaGATGTAATATAAATACATCttaatgaggt
 2856826 2856844 [AIBSCS], [APIORCISFBSCS], [CV(GEA)], [GEA] [1], [5]
  NsrR repressor ygbAp nd -1.0 -23.0 ygbA
agatgtaataTAAATACATCTTaatgaggtgg
 2856824 2856835 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor yibDp1 Sigma70 -115.0 -183.0 waaH
ataatctgttAAATATGTAAAAtcctgtcagt
 3790259 3790270 [APIORCISFBSCS], [CV(GEA)], [GEA] [5]
  NsrR repressor ytfEp nd -12.0 -38.0 ytfE
ttgccttaaaGATGCATTTAAAATACATCttatcttatt
 4432012 4432030 [AIBSCS], [APIORCISFBSCS], [CV(GEA)], [CV(GEA)], [CV(GEA/SM)], [CV(SM)], [GEA], [SM] [1], [5], [7]


Alignment and PSSM for NsrR TFBSs    

Aligned TFBS of NsrR   
  Sequence
  TAAGATGCATTTGAG
  AAAGATGCATTTAAA
  AAAGATGCATTTCCC
  TAAAATGCATTTCAA
  TAAAATGCAATTTAG
  AAAGATGCATTATCA
  TAACATGCATTACAA
  AAAGATGCTGTTTTG
  AAACATGCTTTTTGC
  TAAGATGTATTTATA
  TAAAATGCAAATTAT
  AAACATGTATATTAA
  GAACATGCAGTTATG
  TAAGATGCAAAAAAA
  TAACATGCTGTTATA
  AAAGATGAATTTCGT
  AAACATGGTATTTAC
  AAAGATGAGTTTTTC
  AAAGATGAACTTACC
  TTAGATGTAAATCAC
  TAAATTGCAATTCAA
  AAAGAGGCATATTAT
  TTACATGCACTTACA
  AAAAATACATTTCAC
  GAAAATGTTATTTTC
  AAAAATGCAGCAGTG
  TTACATGATTATGAG
  GAAGATGTTGTAAAT
  TAAAATGCAGAGGAT
  GAACGTGCATTTTGT
  AAATATGTAAAATCC
  GAAAATGTTCTTCGC
  CAATTTGCATATCAA
  TAATATGCCGATGAT
  TTAGATGGAACATTG
  CAAAATGAGTAAGAA
  GTAAATGGTTCTTTG
  TTATATGAGTTATCG
  CTAGATGGTTTCGCA

Position weight matrix (PWM). NsrR matrix-quality result    
A	14	32	39	11	36	0	1	6	25	9	11	9	8	19	13
C	3	0	0	9	0	0	0	22	1	3	3	1	9	7	10
G	6	0	0	15	1	1	38	4	3	7	0	1	7	4	9
T	16	7	0	4	2	38	0	7	10	20	25	28	15	9	7

Consensus    
;	consensus.strict             	tAAgATGcattttac
;	consensus.strict.rc          	GTAAAATGCATCTTA
;	consensus.IUPAC              	wAAsATGcatttyav
;	consensus.IUPAC.rc           	BTRAAATGCATSTTW
;	consensus.regexp             	[at]AA[cg]ATGcattt[ct]a[acg]
;	consensus.regexp.rc          	[CGT]T[AG]AAATGCAT[CG]TT[AT]

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


Evidence    

 [APPHINH] Assay of protein purified to homogeneity from its native host

 [HIFS] Human inference of function from sequence

 [IEP] Inferred from expression pattern

 [IPI] Inferred from physical interaction

 [APIORCISFBSCS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [CV(GEA)] cross validation(GEA)

 [GEA] Gene expression analysis

 [CV(GEA/SM)] cross validation(GEA/SM)

 [CV(SM)] cross validation(SM)

 [SM] Site mutation

 [BCE] Binding of cellular extracts

 [AIBSCS] Automated inference based on similarity to consensus sequences


Reference(s)    

 [1] Bodenmiller DM., Spiro S., 2006, The yjeB (nsrR) gene of Escherichia coli encodes a nitric oxide-sensitive transcriptional regulator., J Bacteriol 188(3):874-81

 [2] Chismon DL., Browning DF., Farrant GK., Busby SJ., 2010, Unusual organization, complexity and redundancy at the Escherichia coli hcp-hcr operon promoter., Biochem J 430(1):61-8

 [3] Efromovich S., Grainger D., Bodenmiller D., Spiro S., 2008, Genome-wide identification of binding sites for the nitric oxide-sensitive transcriptional regulator NsrR., Methods Enzymol 437:211-33

 [4] Lin HY., Bledsoe PJ., Stewart V., 2007, Activation of yeaR-yoaG operon transcription by the nitrate-responsive regulator NarL is independent of oxygen- responsive regulator Fnr in Escherichia coli K-12., J Bacteriol 189(21):7539-48

 [5] Partridge JD., Bodenmiller DM., Humphrys MS., Spiro S., 2009, NsrR targets in the Escherichia coli genome: new insights into DNA sequence requirements for binding and a role for NsrR in the regulation of motility., Mol Microbiol 73(4):680-94

 [6] Rankin LD., Bodenmiller DM., Partridge JD., Nishino SF., Spain JC., Spiro S., 2008, Escherichia coli NsrR regulates a pathway for the oxidation of 3-nitrotyramine to 4-hydroxy-3-nitrophenylacetate., J Bacteriol 190(18):6170-7

 [7] Filenko N., Spiro S., Browning DF., Squire D., Overton TW., Cole J., Constantinidou C., 2007, The NsrR regulon of Escherichia coli K-12 includes genes encoding the hybrid cluster protein and the periplasmic, respiratory nitrite reductase., J Bacteriol 189(12):4410-7

 [8] Browning DF., Lee DJ., Spiro S., Busby SJ., 2010, Down-regulation of the Escherichia coli K-12 nrf promoter by binding of the NsrR nitric oxide-sensing transcription repressor to an upstream site., J Bacteriol 192(14):3824-8

 [9] Thompson KM., Rhodius VA., Gottesman S., 2007, {sigma}E Regulates and Is Regulated by a Small RNA in Escherichia coli., J Bacteriol 189(11):4243-56

 [10] Chhabra S., Spiro S., 2015, Inefficient translation of nsrR constrains behaviour of the NsrR regulon in Escherichia coli., Microbiology 161(10):2029-38

 [11] Schwartz CJ., Giel JL., Patschkowski T., Luther C., Ruzicka FJ., Beinert H., Kiley PJ., 2001, 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(26):14895-900

 [12] Rodionov DA., Dubchak IL., Arkin AP., Alm EJ., Gelfand MS., 2005, Dissimilatory metabolism of nitrogen oxides in bacteria: comparative reconstruction of transcriptional networks., PLoS Comput Biol 1(5):e55

 [13] Cairrao F., Cruz A., Mori H., Arraiano CM., 2003, Cold shock induction of RNase R and its role in the maturation of the quality control mediator SsrA/tmRNA., Mol Microbiol 50(4):1349-60


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