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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 |CITS:[9230919][7855431]|. A microarray analysis suggests that NarP activates 14 operons and represses 37 operons |CITS:[16377617][16417494]|.
The response regulator NarP belongs to the LuxR/UhpA family |CITS:[2559300][2314271]| and is part of the two-component system NarQ-NarP. There is intensive cross-regulation with the paralogous two-component system NarX-NarL |CITS:[12546643][8501030]|. 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 |CITS:[8051011][8473280]|. This reaction is specific, that is, NarP-P is only dephosphorylated by NarQ. The system discriminates between nitrate and nitrite. In the presence of nitrate both sensors phosphorylate NarL and NarP to the same extent. In the presence of nitrite, autophosphorylation of NarX is low and NarX acts primarily as a phosphatase for NarL-P |CITS:[9426129][9006026][10464202]|. In contrast, NarQ phosphorylates NarL and NarP in response to both nitrate and nitrite. Therefore, with nitrite, NarP-P is the major regulator, and with nitrate both NarL and NarP are functional |CITS:[10464202][10542156]|.
NarP consists of the N-terminal receiver domain and a C-terminal DNA-binding 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
NarP Non-Functional   Apo [BPP], [IPI] [1]
NarP-Phosphorylated Functional Covalent Holo [BPP], [IPI] [1]
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, 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 (13)
electron donors (7)
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Regulated operon(s) fdhF, fdnGHI, hcp-hcr, hyaABCDEF, napFDAGHBC-ccmABCDEFGH, nirBDC-cysG, norVW, nrfABCDEFG, ydeP, ydhYVWXUT, yeaR-yoaG, ytfE
First gene in the operon(s) fdhF, fdnG, 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,-](5)
[NarP,+](6)


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
  NarP-Phosphorylated activator fdhFp Sigma54 nd nd fdhF nd nd [GEA] [2]
  NarP-Phosphorylated repressor fdnGp Sigma70 -109.0 -138.5 fdnG, fdnH, fdnI
agtggtgcgtTTTTCTACCGCTATTGaggtaggtca
1547255 1547270 [GEA], [SM] [2], [3]
  NarP-Phosphorylated repressor fdnGp Sigma70 -100.0 -129.5 fdnG, fdnH, fdnI
tttttctaccGCTATTGAGGTAGGTCaatttgcgaa
1547264 1547279 [GEA], [SM] [2], [3]
  NarP-Phosphorylated activator hcpp nd -109.0 -139.5 hcp, hcr
ttttctctgcGTAATACCTCTCTGGCggtagatccc
913946 913961 [GEA], [HIBSCS] [4]
  NarP-Phosphorylated activator hcpp nd -100.0 -130.5 hcp, hcr
cgtaatacctCTCTGGCGGTAGATCCctgccgccaa
913937 913952 [GEA], [HIBSCS] [4]
  NarP-Phosphorylated repressor hyaAp Sigma70 -10.0 -165.5 hyaA, hyaB, hyaC, hyaD, hyaE, hyaF
gtgcaaaagtTTCACTACGCTTTATTaacaatactt
1031966 1031981 [GEA], [HIBSCS] [5]
  NarP-Phosphorylated repressor hyaAp Sigma70 7.0 -149.5 hyaA, hyaB, hyaC, hyaD, hyaE, hyaF
acgctttattAACAATACTTTCTGGCgacgtgcgcc
1031982 1031997 [GEA], [HIBSCS] [5]
  NarP-Phosphorylated activator napFp1 Sigma70 -49.0 -125.5 napF, napD, napA, napG, napH, napB, napC, ccmA, ccmB, ccmC, ccmD, ccmE, ccmF, ccmG, ccmH
cctgctacagGTTTTACCCCGATCGGggtatgcatc
2303615 2303630 [GEA], [HIBSCS], [SM] [6], [7]
  NarP-Phosphorylated activator napFp1 Sigma70 -40.0 -116.5 napF, napD, napA, napG, napH, napB, napC, ccmA, ccmB, ccmC, ccmD, ccmE, ccmF, ccmG, ccmH
ggttttacccCGATCGGGGTATGCATctttgacaca
2303606 2303621 [GEA], [HIBSCS], [SM] [6], [7]
  NarP-Phosphorylated repressor napFp2 Sigma70 -46.0 -125.5 napF, napD, napA, napG, napH, napB, napC, ccmA, ccmB, ccmC, ccmD, ccmE, ccmF, ccmG, ccmH
cctgctacagGTTTTACCCCGATCGGggtatgcatc
2303615 2303630 [GEA], [HIBSCS], [SM] [7]
  NarP-Phosphorylated repressor napFp2 Sigma70 -37.0 -116.5 napF, napD, napA, napG, napH, napB, napC, ccmA, ccmB, ccmC, ccmD, ccmE, ccmF, ccmG, ccmH
ggttttacccCGATCGGGGTATGCATctttgacaca
2303606 2303621 [GEA], [HIBSCS], [SM] [7]
  NarP-Phosphorylated activator nirBp Sigma70 -74.0 -98.5 nirB, nirD, nirC, cysG
tacaaatcagCAATATACCCATTAAGgagtatataa
3493905 3493920 [BCE], [BPP], [GEA], [SM] [3], [8], [9], [10]
  NarP-Phosphorylated activator nirBp Sigma70 -65.0 -89.5 nirB, nirD, nirC, cysG
gcaatataccCATTAAGGAGTATATAaaggtgaatt
3493914 3493929 [BCE], [BPP], [GEA], [SM] [3], [8], [9], [10]
  NarP-Phosphorylated repressor norVp Sigma54 -78.0 -115.5 norV, norW
gatagtcattTTGACTACTCATTAATgggcataatt
2832353 2832368 [GEA], [HIBSCS] [11]
  NarP-Phosphorylated repressor norVp Sigma54 -69.0 -106.5 norV, norW
tttgactactCATTAATGGGCATAATtttatttata
2832362 2832377 [GEA], [HIBSCS] [11]
  NarP-Phosphorylated activator nrfAp Sigma70 -79.0 -172.5 nrfA, nrfB, nrfC, nrfD, nrfE, nrfF, nrfG
gaggaagataCTGACTAACTCTAAAGtggtatttta
4287584 4287599 [BPP], [GEA], [HIBSCS], [SM] [3], [10], [12], [13], [14], [15]
  NarP-Phosphorylated activator nrfAp Sigma70 -70.0 -163.5 nrfA, nrfB, nrfC, nrfD, nrfE, nrfF, nrfG
actgactaacTCTAAAGTGGTATTTTacatgcactt
4287593 4287608 [BPP], [GEA], [HIBSCS], [SM] [3], [10], [12], [13], [14], [15]
  NarP-Phosphorylated repressor ydePp Sigma70 nd nd ydeP nd nd [BPP], [GEA] [16]
  NarP-Phosphorylated repressor ydhYp Sigma38 6.0 -160.0 ydhY, ydhV, ydhW, ydhX, ydhU, ydhT
ttttttctccTAACCATaaaggattag
1754634 1754640 [BPP], [GEA], [HIBSCS], [SM] [17]
  NarP-Phosphorylated repressor ydhYp Sigma38 15.0 -151.0 ydhY, ydhV, ydhW, ydhX, ydhU, ydhT
ctaaccataaAGGATTAgtttatcggc
1754625 1754631 [BPP], [GEA], [HIBSCS], [SM] [17]
  NarP-Phosphorylated activator yeaRp Sigma70 -48.0 -93.5 yeaR, yoaG
atggtgctaaAAAGTAACCAATAAATggtatttaaa
1880034 1880049 [AIBSCS], [GEA] [18]
  NarP-Phosphorylated activator yeaRp Sigma70 -39.0 -84.5 yeaR, yoaG
aaaagtaaccAATAAATGGTATTTAAaatgcaaatt
1880025 1880040 [AIBSCS], [GEA] [18]
  NarP-Phosphorylated activator ytfEp nd -50.0 -75.5 ytfE
gttaaataagCCTCTGCTACGTAAGGgttatagctt
4432051 4432066 [AIBSCS] [19]
  NarP-Phosphorylated activator ytfEp nd -41.0 -66.5 ytfE
gcctctgctaCGTAAGGGTTATAGCTtttgccttaa
4432042 4432057 [AIBSCS] [19]


Alignment and PSSM for NarP TFBSs    

Aligned TFBS of NarP   
  Sequence
 

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

 [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] 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

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

 [5] 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

 [6] 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

 [7] 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

 [8] 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

 [9] 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

 [10] 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

 [11] 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

 [12] 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

 [13] 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

 [14] 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

 [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 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



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