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NarP DNA-binding transcriptional dual regulator

Synonyms: NarP-Phosphorylated, NarP
Summary:
NarP, "nitrate/nitrite response regulator NarP," is a transcriptional dual regulator of many anaerobic electron transport and fermentation-related genes in the response to the availability of high concentrations of nitrate or nitrite [20] A microarray analysis suggests that NarP activates 14 operons and represses 37 operons [21, 22] The response regulator NarP belongs to the LuxR/UhpA family []and is part of the two-component system NarQ-NarP. There is intensive cross-regulation with the paralogous two-component system NarX-NarL [4] Each of the sensors, NarQ and NarX, phosphorylates both NarP and NarL, leading to the activation of both proteins. In the absence of nitrate and nitrite, NarX and NarQ stimulate the dephosphorylation of NarL-P and NarP-P [23] This reaction is specific, that is, NarP-P is only dephosphorylated by NarQ.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
NarP Non-Functional   Apo [BPP] [1]
NarP-Phosphorylated Functional Covalent Holo [APPHINH], [BPP], [HIFS], [IMP], [IPI] [1], [2], [3], [4]
Evolutionary Family: LuxR/UhpA
Sensing class: External-Two-component systems
Connectivity class: Local Regulator
Gene name: narP
  Genome position: 2290500-2291147
  Length: 648 bp / 215 aa
Operon name: narP
TU(s) encoding the TF:
Transcription unit        Promoter
narP
narPp


Regulon       
Regulated gene(s) ccmA, ccmB, ccmC, ccmD, ccmE, ccmF, ccmG, ccmH, cysG, fdhF, fdnG, fdnH, fdnI, hcp, hcr, hyaA, hyaB, hyaC, hyaD, hyaE, hyaF, napA, napB, napC, napD, napF, napG, napH, nirB, nirC, nirD, norV, norW, nrfA, nrfB, nrfC, nrfD, nrfE, nrfF, nrfG, poxB, ydeP, ydhT, ydhU, ydhV, ydhW, ydhX, ydhY, yeaR, yoaG, ytfE
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
anaerobic respiration (24)
cytochromes (17)
chaperoning, repair (refolding) (14)
membrane (14)
electron donors (8)
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Regulated operon(s) fdhF, fdnGHI, hcp-hcr-poxB-ltaE-ybjT, hyaABCDEF, napFDAGHBC-ccmABCDEFGH, nirBDC-cysG, norVW, nrfABCDEFG, ydeP, ydhYVWXUT, yeaR-yoaG, ytfE
First gene in the operon(s) fdhF, fdnG, hcp, hcp, hyaA, napF, napF, nirB, norV, nrfA, ydeP, ydhY, yeaR, ytfE
Simple and complex regulons AppY,ArcA,Fis,IscR,NarL,NarP,YdeO
CRP,Cra,FNR,Fis,H-NS,IHF,NarL,NarP
EvgA,H-NS,NagC,NarL,NarP,PhoP,RcsB,UvrY
FNR,FhlA,NarL,NarP
FNR,Fis,FlhDC,IHF,NarL,NarP,NsrR
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[NarP,+](6)
[NarP,-](5)


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 Growth Conditions Evidence (Confirmed, Strong, Weak) References
  NarP-Phosphorylated activator fdhFp Sigma54 nd 4299366.0 fdhF nd nd nd [GEA] [5]
  NarP-Phosphorylated repressor fdnGp Sigma70 -109.0 -138.5 fdnG, fdnH, fdnI
agtggtgcgtTTTTCTACCGCTATTGaggtaggtca
1547255 1547270 nd [GEA], [SM] [3], [5]
  NarP-Phosphorylated repressor fdnGp Sigma70 -100.0 -129.5 fdnG, fdnH, fdnI
tttttctaccGCTATTGAGGTAGGTCaatttgcgaa
1547264 1547279 nd [GEA], [SM] [3], [5]
  NarP-Phosphorylated activator hcpp nd -109.0 -139.5 hcp, hcr, poxB
gggatctaccGCCAGAGAGGTATTACgcagagaaaa
913946 913961 [a]
[b]
[GEA], [HIBSCS] [6]
  NarP-Phosphorylated activator hcpp nd -100.0 -130.5 hcp, hcr, poxB
ttggcggcagGGATCTACCGCCAGAGaggtattacg
913937 913952 [a]
[b]
[GEA], [HIBSCS] [6]
  NarP-Phosphorylated repressor hyaAp Sigma70, Sigma38 -10.0 -165.5 hyaA, hyaB, hyaC, hyaD, hyaE, hyaF
gtgcaaaagtTTCACTACGCTTTATTaacaatactt
1031966 1031981 nd [GEA], [HIBSCS] [7]
  NarP-Phosphorylated repressor hyaAp Sigma70, Sigma38 7.0 -149.5 hyaA, hyaB, hyaC, hyaD, hyaE, hyaF
acgctttattAACAATACTTTCTGGCgacgtgcgcc
1031982 1031997 nd [GEA], [HIBSCS] [7]
  NarP-Phosphorylated activator napFp1 Sigma70 -49.0 -125.5 napF, napD, napA, napG, napH, napB, napC, ccmA, ccmB, ccmC, ccmD, ccmE, ccmF, ccmG, ccmH
gatgcataccCCGATCGGGGTAAAACctgtagcagg
2303615 2303630 nd [GEA], [HIBSCS], [SM] [8], [9]
  NarP-Phosphorylated activator napFp1 Sigma70 -40.0 -116.5 napF, napD, napA, napG, napH, napB, napC, ccmA, ccmB, ccmC, ccmD, ccmE, ccmF, ccmG, ccmH
tgtgtcaaagATGCATACCCCGATCGgggtaaaacc
2303606 2303621 nd [GEA], [HIBSCS], [SM] [8], [9]
  NarP-Phosphorylated repressor napFp2 Sigma70 -46.0 -125.5 napF, napD, napA, napG, napH, napB, napC, ccmA, ccmB, ccmC, ccmD, ccmE, ccmF, ccmG, ccmH
gatgcataccCCGATCGGGGTAAAACctgtagcagg
2303615 2303630 [a]
[b]
[GEA], [HIBSCS], [SM] [9]
  NarP-Phosphorylated repressor napFp2 Sigma70 -37.0 -116.5 napF, napD, napA, napG, napH, napB, napC, ccmA, ccmB, ccmC, ccmD, ccmE, ccmF, ccmG, ccmH
tgtgtcaaagATGCATACCCCGATCGgggtaaaacc
2303606 2303621 [a]
[b]
[GEA], [HIBSCS], [SM] [9]
  NarP-Phosphorylated activator nirBp Sigma70 -74.0 -98.5 nirB, nirD, nirC, cysG
tacaaatcagCAATATACCCATTAAGgagtatataa
3493905 3493920 [a] [BCE], [BPP], [GEA], [SM] [3], [10], [11], [12]
  NarP-Phosphorylated activator nirBp Sigma70 -65.0 -89.5 nirB, nirD, nirC, cysG
gcaatataccCATTAAGGAGTATATAaaggtgaatt
3493914 3493929 [a] [BCE], [BPP], [GEA], [SM] [3], [10], [11], [12]
  NarP-Phosphorylated repressor norVp Sigma54 -78.0 -115.5 norV, norW
gatagtcattTTGACTACTCATTAATgggcataatt
2832353 2832368 nd [GEA], [HIBSCS] [13]
  NarP-Phosphorylated repressor norVp Sigma54 -69.0 -106.5 norV, norW
tttgactactCATTAATGGGCATAATtttatttata
2832362 2832377 nd [GEA], [HIBSCS] [13]
  NarP-Phosphorylated activator nrfAp Sigma70 -79.0 -172.5 nrfA, nrfB, nrfC, nrfD, nrfE, nrfF, nrfG
gaggaagataCTGACTAACTCTAAAGtggtatttta
4287584 4287599 [a]
[b]
[BPP], [GEA], [HIBSCS], [SM] [2], [3], [4], [12], [14], [15]
  NarP-Phosphorylated activator nrfAp Sigma70 -70.0 -163.5 nrfA, nrfB, nrfC, nrfD, nrfE, nrfF, nrfG
actgactaacTCTAAAGTGGTATTTTacatgcactt
4287593 4287608 [a]
[b]
[BPP], [GEA], [HIBSCS], [SM] [2], [3], [4], [12], [14], [15]
  NarP-Phosphorylated repressor ydePp Sigma70 nd 1586486.0 ydeP nd nd nd [BPP], [GEA] [16]
  NarP-Phosphorylated repressor ydhYp Sigma38 6.0 -160.5 ydhY, ydhV, ydhW, ydhX, ydhU, ydhT
ctaatcctttATGGTTAggagaaaaaa
1754634 1754641 [a]
[b]
[BPP], [GEA], [HIBSCS], [SM] [17]
  NarP-Phosphorylated repressor ydhYp Sigma38 15.0 -151.5 ydhY, ydhV, ydhW, ydhX, ydhU, ydhT
gccgataaacTAATCCTttatggttag
1754625 1754632 [a]
[b]
[BPP], [GEA], [HIBSCS], [SM] [17]
  NarP-Phosphorylated activator yeaRp Sigma70 -48.0 -93.5 yeaR, yoaG
tttaaataccATTTATTGGTTACTTTttagcaccat
1880034 1880049 nd [AIBSCS], [GEA] [18]
  NarP-Phosphorylated activator yeaRp Sigma70 -39.0 -84.5 yeaR, yoaG
aatttgcattTTAAATACCATTTATTggttactttt
1880025 1880040 nd [AIBSCS], [GEA] [18]
  NarP-Phosphorylated activator ytfEp nd -50.0 -75.5 ytfE
aagctataacCCTTACGTAGCAGAGGcttatttaac
4432051 4432066 nd [AIBSCS] [19]
  NarP-Phosphorylated activator ytfEp nd -41.0 -66.5 ytfE
ttaaggcaaaAGCTATAACCCTTACGtagcagaggc
4432042 4432057 nd [AIBSCS] [19]


Growth Condition    

 [a] Nitrate treatment

 [b] Nitrite treatment



Alignment and PSSM for NarP TFBSs    

Position weight matrix (PWM).   
A	5	6	1	11	3	0	4	4	0	4	7	4	1	4	5	0	1
C	1	6	1	1	9	7	5	6	2	2	1	3	0	0	0	2	2
G	0	0	0	0	0	1	2	0	1	0	1	0	6	5	7	8	3
T	6	0	10	0	0	4	1	2	9	6	3	5	5	3	0	2	6

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    

 [BPP] Binding of purified proteins

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

 [HIFS] Human inference of function from sequence

 [IMP] Inferred from mutant phenotype

 [IPI] Inferred from physical interaction

 [GEA] Gene expression analysis

 [SM] Site mutation

 [HIBSCS] Human inference based on similarity to consensus sequences

 [BCE] Binding of cellular extracts

 [AIBSCS] Automated inference based on similarity to consensus sequences



Reference(s)    

 [1] Yamamoto K., Hirao K., Oshima T., Aiba H., Utsumi R., Ishihama A., 2005, Functional characterization in vitro of all two-component signal transduction systems from Escherichia coli., J Biol Chem 280(2):1448-56

 [2] Browning DF., Grainger DC., Beatty CM., Wolfe AJ., Cole JA., Busby SJ., 2005, Integration of three signals at the Escherichia coli nrf promoter: a role for Fis protein in catabolite repression., Mol Microbiol 57(2):496-510

 [3] Darwin AJ., Tyson KL., Busby SJ., Stewart V., 1997, Differential regulation by the homologous response regulators NarL and NarP of Escherichia coli K-12 depends on DNA binding site arrangement., Mol Microbiol 25(3):583-95

 [4] Rabin RS., Stewart V., 1993, Dual response regulators (NarL and NarP) interact with dual sensors (NarX and NarQ) to control nitrate- and nitrite-regulated gene expression in Escherichia coli K-12., J Bacteriol 175(11):3259-68

 [5] Wang H., Gunsalus RP., 2003, Coordinate regulation of the Escherichia coli formate dehydrogenase fdnGHI and fdhF genes in response to nitrate, nitrite, and formate: roles for NarL and NarP., J Bacteriol 185(17):5076-85

 [6] Filenko NA., Browning DF., Cole JA., 2005, Transcriptional regulation of a hybrid cluster (prismane) protein., Biochem Soc Trans 33(Pt 1):195-7

 [7] Richard DJ., Sawers G., Sargent F., McWalter L., Boxer DH., 1999, Transcriptional regulation in response to oxygen and nitrate of the operons encoding the [NiFe] hydrogenases 1 and 2 of Escherichia coli., Microbiology 145 ( Pt 10):2903-12

 [8] Darwin AJ., Ziegelhoffer EC., Kiley PJ., Stewart V., 1998, Fnr, NarP, and NarL regulation of Escherichia coli K-12 napF (periplasmic nitrate reductase) operon transcription in vitro., J Bacteriol 180(16):4192-8

 [9] Stewart V., Bledsoe PJ., Williams SB., 2003, Dual overlapping promoters control napF (periplasmic nitrate reductase) operon expression in Escherichia coli K-12., J Bacteriol 185(19):5862-70

 [10] Browning DF., Cole JA., Busby SJ., 2004, Transcription activation by remodelling of a nucleoprotein assembly: the role of NarL at the FNR-dependent Escherichia coli nir promoter., Mol Microbiol 53(1):203-15

 [11] Tyson KL., Bell AI., Cole JA., Busby SJ., 1993, Definition of nitrite and nitrate response elements at the anaerobically inducible Escherichia coli nirB promoter: interactions between FNR and NarL., Mol Microbiol 7(1):151-7

 [12] Wang H., Gunsalus RP., 2000, The nrfA and nirB nitrite reductase operons in Escherichia coli are expressed differently in response to nitrate than to nitrite., J Bacteriol 182(20):5813-22

 [13] da Costa PN., Teixeira M., Saraiva LM., 2003, Regulation of the flavorubredoxin nitric oxide reductase gene in Escherichia coli: nitrate repression, nitrite induction, and possible post-transcription control., FEMS Microbiol Lett 218(2):385-93

 [14] Browning DF., Beatty CM., Wolfe AJ., Cole JA., Busby SJ., 2002, Independent regulation of the divergent Escherichia coli nrfA and acsP1 promoters by a nucleoprotein assembly at a shared regulatory region., Mol Microbiol 43(3):687-701

 [15] Tyson KL., Cole JA., Busby SJ., 1994, Nitrite and nitrate regulation at the promoters of two Escherichia coli operons encoding nitrite reductase: identification of common target heptamers for both NarP- and NarL-dependent regulation., Mol Microbiol 13(6):1045-55

 [16] Yoshida M., Ishihama A., Yamamoto K., 2015, Cross talk in promoter recognition between six NarL-family response regulators of Escherichia coli two-component system., Genes Cells 20(7):601-12

 [17] Partridge JD., Browning DF., Xu M., Newnham LJ., Scott C., Roberts RE., Poole RK., Green J., 2008, Characterization of the Escherichia coli K-12 ydhYVWXUT operon: regulation by FNR, NarL and NarP., Microbiology 154(Pt 2):608-18

 [18] 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

 [19] 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

 [20] Unden G., Bongaerts J., 1997, Alternative respiratory pathways of Escherichia coli: energetics and transcriptional regulation in response to electron acceptors., Biochim Biophys Acta 1320(3):217-34

 [21] Constantinidou C., Hobman JL., Griffiths L., Patel MD., Penn CW., Cole JA., Overton TW., 2006, A reassessment of the FNR regulon and transcriptomic analysis of the effects of nitrate, nitrite, NarXL, and NarQP as Escherichia coli K12 adapts from aerobic to anaerobic growth., J Biol Chem 281(8):4802-15

 [22] Overton TW., Griffiths L., Patel MD., Hobman JL., Penn CW., Cole JA., Constantinidou C., 2006, Microarray analysis of gene regulation by oxygen, nitrate, nitrite, FNR, NarL and NarP during anaerobic growth of Escherichia coli: new insights into microbial physiology., Biochem Soc Trans 34(Pt 1):104-7

 [23] Walker MS., DeMoss JA., 1993, Phosphorylation and dephosphorylation catalyzed in vitro by purified components of the nitrate sensing system, NarX and NarL., J Biol Chem 268(12):8391-3

 [24] Williams SB., Stewart V., 1997, Discrimination between structurally related ligands nitrate and nitrite controls autokinase activity of the NarX transmembrane signal transducer of Escherichia coli K-12., Mol Microbiol 26(5):911-25

 [25] Lin AV., Stewart V., 2010, Functional roles for the GerE-family carboxyl-terminal domains of nitrate response regulators NarL and NarP of Escherichia coli K-12., Microbiology 156(Pt 10):2933-43

 [26] Darwin AJ., Li J., Stewart V., 1996, Analysis of nitrate regulatory protein NarL-binding sites in the fdnG and narG operon control regions of Escherichia coli K-12., Mol Microbiol 20(3):621-32

 [27] Browning DF., Lee DJ., Wolfe AJ., Cole JA., Busby SJ., 2006, The Escherichia coli K-12 NarL and NarP proteins insulate the nrf promoter from the effects of integration host factor., J Bacteriol 188(21):7449-56

 [28] Wu H., Tyson KL., Cole JA., Busby SJ., 1998, Regulation of transcription initiation at the Escherichia coli nir operon promoter: a new mechanism to account for co-dependence on two transcription factors., Mol Microbiol 27(2):493-505

 [29] Squire DJ., Xu M., Cole JA., Busby SJ., Browning DF., 2009, Competition between NarL-dependent activation and Fis-dependent repression controls expression from the Escherichia coli yeaR and ogt promoters., Biochem J 420(2):249-57

 [30] Stewart V., Bledsoe PJ., 2005, Fnr-, NarP- and NarL-dependent regulation of transcription initiation from the Haemophilus influenzae Rd napF (periplasmic nitrate reductase) promoter in Escherichia coli K-12., J Bacteriol 187(20):6928-35

 [31] Browning DF., Cole JA., Busby SJ., 2000, Suppression of FNR-dependent transcription activation at the Escherichia coli nir promoter by Fis, IHF and H-NS: modulation of transcription initiation by a complex nucleo-protein assembly., Mol Microbiol 37(5):1258-69

 [32] Darwin AJ., Stewart V., 1995, Nitrate and nitrite regulation of the Fnr-dependent aeg-46.5 promoter of Escherichia coli K-12 is mediated by competition between homologous response regulators (NarL and NarP) for a common DNA-binding site., J Mol Biol 251(1):15-29



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