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NtrC DNA-binding transcriptional dual regulator

Synonyms: NtrC-Phosphorylated, NtrC
Summary:
Under nitrogen (N)-limiting conditions, the NtrC transcriptional dual regulator regulates genes involved in the assimilation of nitrogen and in the minimization of the slow growth caused by the N-limited condition [7] Through a cascade of events NtrC appears to regulate as much as 2% of the genome, and many of these genes encode transport systems for nitrogen-containing compounds [7]
NtrC belongs to the two-component system NtrB/NtrC [25] and is a member of the σ54-dependent activator family, whose homologues are widely distributed in bacteria [26] Both genes glnG, encoding the response regulator (NtrC, also called NRI), and glnL, encoding the sensor kinase (NtrB, also called NRII), are organized in the operon glnALG. glnA encodes a glutamine synthetase[27].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
NtrC Non-Functional   Apo [BPP], [GEA], [IDA], [IPI] [1], [2], [3], [4], [5], [6]
NtrC-Phosphorylated Functional Covalent Holo [BPP], [GEA], [IDA], [IPI] [1], [2], [3], [4], [5], [6]
Evolutionary Family: EBP
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: glnG
  Genome position: 4053869-4055278
  Length: 1410 bp / 469 aa
Operon name: glnALG
TU(s) encoding the TF:
Transcription unit        Promoter
glnALG
glnAp1
glnALG
glnAp2
glnLG
glnLp


No gene found!

Regulon       
Regulated gene(s) amtB, argT, astA, astB, astC, astD, astE, cbl, ddpA, ddpB, ddpC, ddpD, ddpF, ddpX, glnA, glnG, glnH, glnK, glnL, glnP, glnQ, hisJ, hisM, hisP, hisQ, nac, patA, potF, potG, potH, potI, relA, rpoE, rseA, rseB, rseC, rutA, rutB, rutC, rutD, rutE, rutF, rutG, yeaG, yeaH, yhdW, yhdX, yhdY, yhdZ
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
membrane (13)
nitrogen metabolism (11)
ABC superfamily, membrane component (9)
Transcription related (7)
ABC superfamily, periplasmic binding component (6)
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Regulated operon(s) argT-hisJQMP, astCADBE, cbl, ddpXABCDF, glnALG, glnHPQ, glnK-amtB, nac, patA, potFGHI, relA-mazEFG, rpoE-rseABC, rutABCDEFG, yeaGH, yhdWXYZ
First gene in the operon(s) argT, astC, cbl, ddpX, glnA, glnA, glnA, glnA, glnH, glnK, glnL, nac, patA, potF, relA, rpoE, rutA, yeaG, yhdW
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[NtrC,+](11)
[NtrC,-](3)


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
  NtrC-Phosphorylated activator argTp Sigma54 -190.0 -248.0 argT, hisJ, hisQ, hisM, hisP
actccgctgtTGCCCTGTTTCAGGGCAattttgcaac
2428031 2428047 [AIBSCS], [GEA] [7]
  NtrC-Phosphorylated activator argTp Sigma54 -83.0 -141.0 argT, hisJ, hisQ, hisM, hisP
tatcttcaacTTCAGGACAATAATGCAacgtcttatt
2427924 2427940 [AIBSCS], [GEA] [7]
  NtrC-Phosphorylated activator astCp2 Sigma54 -275.0 -337.0 astC, astA, astD, astB, astE
gttgttaatgATGTCAACGATGGCGCAaaaaatgccc
1832311 1832327 [AIBSCS], [BPP], [GEA] [8]
  NtrC-Phosphorylated activator astCp2 Sigma54 -253.0 -315.0 astC, astA, astD, astB, astE
gcgcaaaaaaTGCCCGCTTTTGGTGCGcgctgcgtca
1832289 1832305 [AIBSCS], [BPP], [GEA] [8]
  NtrC-Phosphorylated activator astCp2 Sigma54 -233.0 -295.0 astC, astA, astD, astB, astE
tggtgcgcgcTGCGTCAGAATGGCGCAgtaatttcca
1832269 1832285 [AIBSCS], [BPP], [GEA] [8]
  NtrC-Phosphorylated activator cblp Sigma70 nd nd cbl nd nd [GEA] [7]
  NtrC-Phosphorylated activator ddpXp Sigma54 -109.0 -140.0 ddpX, ddpA, ddpB, ddpC, ddpD, ddpF
cttcccctctTGCACCAAAACTGCACTacgctgcaca
1563208 1563224 [AIBSCS], [GEA] [7]
  NtrC-Phosphorylated activator ddpXp Sigma54 -88.0 -119.0 ddpX, ddpA, ddpB, ddpC, ddpD, ddpF
tgcactacgcTGCACAAATGTTGATCAaaagttaaaa
1563187 1563203 [AIBSCS], [GEA] [7]
  NtrC-Phosphorylated repressor glnAp1 Sigma70 -25.0 -213.0 glnA, glnL, glnG
caaaggtcatTGCACCAACATGGTGCTtaatgtttcc
4058239 4058255 [BPP], [GEA], [HIBSCS], [SM] [9], [10], [11], [12]
  NtrC-Phosphorylated repressor glnAp1 Sigma70 8.0 -181.0 glnA, glnL, glnG
tttccattgaAGCACTATATTGGTGCAacattcacat
4058207 4058223 [BPP], [GEA], [HIBSCS], [SM] [9], [10], [11], [12]
  NtrC-Phosphorylated repressor glnAp1 Sigma70 27.0 -162.0 glnA, glnL, glnG
ttggtgcaacATTCACATCGTGGTGCAgcccttttgc
4058188 4058204 [BPP], [GEA], [HIBSCS], [SM] [9], [10], [12], [13]
  NtrC-Phosphorylated repressor glnAp1 Sigma70 48.0 -141.0 glnA, glnL, glnG
ggtgcagcccTTTTGCACGATGGTGCGcatgataacg
4058167 4058183 [GEA], [HIBSCS], [SM] [10], [13]
  NtrC-Phosphorylated repressor glnAp1 Sigma70 71.0 -118.0 glnA, glnL, glnG
tgcgcatgatAACGCCTTTTAGGGGCAatttaaaagt
4058144 4058160 [GEA], [HIBSCS] [10], [13]
  NtrC-Phosphorylated activator glnAp2 Sigma54 -140.0 -213.0 glnA, glnL, glnG
caaaggtcatTGCACCAACATGGTGCTtaatgtttcc
4058239 4058255 [BPP], [GEA], [HIBSCS], [SM] [9], [10], [11], [12], [14]
  NtrC-Phosphorylated activator glnAp2 Sigma54 -108.0 -181.0 glnA, glnL, glnG
tttccattgaAGCACTATATTGGTGCAacattcacat
4058207 4058223 [BPP], [GEA], [HIBSCS], [SM] [9], [10], [11], [12]
  NtrC-Phosphorylated activator glnAp2 Sigma54 -89.0 -162.0 glnA, glnL, glnG
ttggtgcaacATTCACATCGTGGTGCAgcccttttgc
4058188 4058204 [BPP], [GEA], [HIBSCS], [SM] [9], [10], [12], [13], [14]
  NtrC-Phosphorylated activator glnAp2 Sigma54 -68.0 -141.0 glnA, glnL, glnG
ggtgcagcccTTTTGCACGATGGTGCGcatgataacg
4058167 4058183 [GEA], [HIBSCS], [SM] [10], [13]
  NtrC-Phosphorylated activator glnAp2 Sigma54 -45.0 -118.0 glnA, glnL, glnG
tgcgcatgatAACGCCTTTTAGGGGCAatttaaaagt
4058144 4058160 [GEA], [HIBSCS] [10], [13]
  NtrC-Phosphorylated repressor glnHp2 Sigma54 -135.0 -178.0 glnH, glnP, glnQ
ctgtgttgagTGCACAATTTTAGCGCAccagattggt
848174 848190 [BPP], [HIBSCS] [15]
  NtrC-Phosphorylated activator glnHp2 Sigma54 -122.0 -165.0 glnH, glnP, glnQ
acaattttagCGCACCAGATTGGTGCCccagaatggt
848161 848177 [BPP], [HIBSCS] [15]
  NtrC-Phosphorylated activator glnHp2 Sigma54 -109.0 -152.0 glnH, glnP, glnQ
accagattggTGCCCCAGAATGGTGCAtcttcagggt
848148 848164 [BPP], [HIBSCS] [15]
  NtrC-Phosphorylated repressor glnHp2 Sigma54 -79.0 -122.0 glnH, glnP, glnQ
tcagggtattGCCCTATAAATCGTGCAtcacgttttt
848118 848134 [BPP], [HIBSCS] [15]
  NtrC-Phosphorylated activator glnKp Sigma54 -87.0 -129.0 glnK, amtB
taacgcactgTGCACTGTCATAGTGCGttttcatttt
472461 472477 [HIBSCS] [16]
  NtrC-Phosphorylated repressor glnLp Sigma70 3.0 -30.0 glnL, glnG
aaagctataaTGCACTAAAATGGTGCAacctgttcag
4056361 4056377 [BPP], [HIBSCS], [SM] [17], [18]
  NtrC-Phosphorylated activator nacp Sigma54 -152.0 -197.0 nac
tattgggtaaTGAACCATCGTGGTGCAtaccctcctt
2062122 2062138 [HIBSCS] [19]
  NtrC-Phosphorylated activator patAp Sigma38 -543.0 -579.0 patA
atccgggtgaCGCACCATGTTGTGCGGctgcccttgt
3218907 3218923 [AIBSCS], [IEP] [20]
  NtrC-Phosphorylated activator patAp Sigma38 -193.0 -229.0 patA
ttaattatctTGCCCAAAAATCAGGCAattattgccc
3219257 3219273 [AIBSCS], [GEA] [21], [22]
  NtrC-Phosphorylated activator patAp Sigma38 -171.0 -207.0 patA
aggcaattatTGCCCTGAAAACGTGCAtttgcgcagc
3219279 3219295 [AIBSCS], [GEA] [21], [22]
  NtrC-Phosphorylated activator potFp1 Sigma54 nd nd potF, potG, potH, potI nd nd [GEA] [7]
  NtrC-Phosphorylated activator relAp4 Sigma54 nd nd relA nd nd [BPP], [GEA] [23]
  NtrC-Phosphorylated activator rpoEp2b Sigma70 -33.5 -360.5 rpoE, rseA, rseB, rseC
ttggtcagcaTAGCATCATGTTGTGCGGataaacacct
2710364 2710381 [BPP], [HIBSCS] [24]
  NtrC-Phosphorylated activator rutAp Sigma54 -145.0 -160.0 rutA, rutB, rutC, rutD, rutE, rutF, rutG
ctcgaccttcTGCACTCTCATCGCGCAcagatgcatg
1074163 1074179 [AIBSCS], [GEA] [7]
  NtrC-Phosphorylated activator rutAp Sigma54 -124.0 -139.0 rutA, rutB, rutC, rutD, rutE, rutF, rutG
cgcgcacagaTGCATGTTTTATGTGCAactgttttga
1074142 1074158 [AIBSCS], [GEA] [7]
  NtrC-Phosphorylated activator yeaGp1 Sigma54 nd nd yeaG, yeaH nd nd [GEA] [7]
  NtrC-Phosphorylated activator yhdWp Sigma54 -126.0 -303.0 yhdW, yhdX, yhdY, yhdZ
gtaaatatttTGCGCCAAAATGTGGCGcatgtttcat
3418838 3418854 [AIBSCS], [GEA] [7]
  NtrC-Phosphorylated activator yhdWp Sigma54 -96.0 -273.0 yhdW, yhdX, yhdY, yhdZ
gtttcattttCGCACCATTGCGGGGCGctgtttttat
3418868 3418884 [AIBSCS], [GEA] [7]


Alignment and PSSM for NtrC TFBSs    

Position weight matrix (PWM).   
A	0	0	0	14	1	3	17	15	13	20	3	3	1	3	3	4	14	6
C	4	2	24	7	21	15	1	3	6	1	2	6	2	4	1	20	0	5
G	2	23	1	4	0	0	4	2	2	4	1	12	20	4	19	0	5	4
T	19	0	0	0	3	7	3	5	4	0	19	4	2	14	2	1	6	10

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

 [GEA] Gene expression analysis

 [IDA] Inferred from direct assay

 [IPI] Inferred from physical interaction

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [HIBSCS] Human inference based on similarity to consensus sequences

 [SM] Site mutation

 [IEP] Inferred from expression pattern



Reference(s)    

 [1] Chen P, Reitzer LJ., 1995, Active contribution of two domains to cooperative DNA binding of the enhancer-binding protein nitrogen regulator I (NtrC) of Escherichia coli: stimulation by phosphorylation and the binding of ATP., J Bacteriol.

 [2] De Carlo S., Chen B., Hoover TR., Kondrashkina E., Nogales E., Nixon BT., 2006, The structural basis for regulated assembly and function of the transcriptional activator NtrC., Genes Dev. 20(11):1485-95

 [3] Fiedler U, Weiss V., 1995, A common switch in activation of the response regulators NtrC and PhoB: phosphorylation induces dimerization of the receiver modules., EMBO J.

 [4] Nohaile M, Kern D, Wemmer D, Stedman K, Kustu S., 1997, Structural and functional analyses of activating amino acid substitutions in the receiver domain of NtrC: evidence for an activating surface., J Mol Biol.

 [5] Rippe K, M¿¿¿cke N, Schulz A., 1998, Association states of the transcription activator protein NtrC from E. coli determined by analytical ultracentrifugation., J Mol Biol.

 [6] 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

 [7] Zimmer DP., Soupene E., Lee HL., Wendisch VF., Khodursky AB., Peter BJ., Bender RA., Kustu S., 2000, Nitrogen regulatory protein C-controlled genes of Escherichia coli: scavenging as a defense against nitrogen limitation., Proc Natl Acad Sci U S A. 97(26):14674-9

 [8] Kiupakis AK., Reitzer L., 2002, ArgR-independent induction and ArgR-dependent superinduction of the astCADBE operon in Escherichia coli., J Bacteriol. 184(11):2940-50

 [9] Ninfa AJ., Reitzer LJ., Magasanik B., 1987, Initiation of transcription at the bacterial glnAp2 promoter by purified E. coli components is facilitated by enhancers., Cell. 50(7):1039-46

 [10] Reitzer LJ., Magasanik B., 1985, Expression of glnA in Escherichia coli is regulated at tandem promoters., Proc Natl Acad Sci U S A. 82(7):1979-83

 [11] Reitzer LJ., Magasanik B., 1986, Transcription of glnA in E. coli is stimulated by activator bound to sites far from the promoter., Cell. 45(6):785-92

 [12] Reitzer LJ., Movsas B., Magasanik B., 1989, Activation of glnA transcription by nitrogen regulator I (NRI)-phosphate in Escherichia coli: evidence for a long-range physical interaction between NRI-phosphate and RNA polymerase., J Bacteriol. 171(10):5512-22

 [13] Atkinson MR., Pattaramanon N., Ninfa AJ., 2002, Governor of the glnAp2 promoter of Escherichia coli., Mol Microbiol. 46(5):1247-57

 [14] Collado-Vides J., Magasanik B., Gralla JD., 1991, Control site location and transcriptional regulation in Escherichia coli., Microbiol Rev. 55(3):371-94

 [15] Claverie-Martin F., Magasanik B., 1991, Role of integration host factor in the regulation of the glnHp2 promoter of Escherichia coli., Proc Natl Acad Sci U S A. 88(5):1631-5

 [16] van Heeswijk WC., Hoving S., Molenaar D., Stegeman B., Kahn D., Westerhoff HV., 1996, An alternative PII protein in the regulation of glutamine synthetase in Escherichia coli., Mol Microbiol. 21(1):133-46

 [17] Rocha M., Vazquez M., Garciarrubio A., Covarrubias AA., 1985, Nucleotide sequence of the glnA-glnL intercistronic region of Escherichia coli., Gene. 37(1-3):91-9

 [18] Ueno-Nishio S., Mango S., Reitzer LJ., Magasanik B., 1984, Identification and regulation of the glnL operator-promoter of the complex glnALG operon of Escherichia coli., J Bacteriol. 160(1):379-84

 [19] Muse WB., Bender RA., 1998, The nac (nitrogen assimilation control) gene from Escherichia coli., J Bacteriol. 180(5):1166-73

 [20] Robison K., McGuire AM., Church GM., 1998, A comprehensive library of DNA-binding site matrices for 55 proteins applied to the complete Escherichia coli K-12 genome., J Mol Biol. 284(2):241-54

 [21] Samsonova NN., Smirnov SV., Altman IB., Ptitsyn LR., 2003, Molecular cloning and characterization of Escherichia coli K12 ygjG gene., BMC Microbiol. 3(1):2

 [22] Schneider BL., Hernandez VJ., Reitzer L., 2013, Putrescine catabolism is a metabolic response to several stresses in Escherichia coli., Mol Microbiol. 88(3):537-50

 [23] Brown DR., Barton G., Pan Z., Buck M., Wigneshweraraj S., 2014, Nitrogen stress response and stringent response are coupled in Escherichia coli., Nat Commun. 5:4115

 [24] Klein G., Stupak A., Biernacka D., Wojtkiewicz P., Lindner B., Raina S., 2016, Multiple transcriptional factors regulate transcription of the rpoE gene in Escherichia coli under different growth conditions and when the lipopolysaccharide biosynthesis is defective., J Biol Chem

 [25] Reitzer L., 2003, Nitrogen assimilation and global regulation in Escherichia coli., Annu Rev Microbiol. 57:155-76

 [26] Studholme DJ., Buck M., 2000, The biology of enhancer-dependent transcriptional regulation in bacteria: insights from genome sequences., FEMS Microbiol Lett. 186(1):1-9

 [27] Miranda-Rios J., Sanchez-Pescador R., Urdea M., Covarrubias AA., 1987, The complete nucleotide sequence of the glnALG operon of Escherichia coli K12., Nucleic Acids Res. 15(6):2757-70

 [28] Magasanik B., 1993, The regulation of nitrogen utilization in enteric bacteria., J Cell Biochem. 51(1):34-40

 [29] Weiss V., Magasanik B., 1988, Phosphorylation of nitrogen regulator I (NRI) of Escherichia coli., Proc Natl Acad Sci U S A. 85(23):8919-23

 [30] Feng J., Atkinson MR., McCleary W., Stock JB., Wanner BL., Ninfa AJ., 1992, Role of phosphorylated metabolic intermediates in the regulation of glutamine synthetase synthesis in Escherichia coli., J Bacteriol. 174(19):6061-70

 [31] Pioszak AA., Jiang P., Ninfa AJ., 2000, The Escherichia coli PII signal transduction protein regulates the activities of the two-component system transmitter protein NRII by direct interaction with the kinase domain of the transmitter module., Biochemistry. 39(44):13450-61

 [32] Pioszak AA., Ninfa AJ., 2004, Mutations altering the N-terminal receiver domain of NRI (NtrC) That prevent dephosphorylation by the NRII-PII complex in Escherichia coli., J Bacteriol. 186(17):5730-40

 [33] Jiang P., Ninfa AJ., 1999, Regulation of autophosphorylation of Escherichia coli nitrogen regulator II by the PII signal transduction protein., J Bacteriol. 181(6):1906-11

 [34] Atkinson MR., Ninfa AJ., 1998, Role of the GlnK signal transduction protein in the regulation of nitrogen assimilation in Escherichia coli., Mol Microbiol. 29(2):431-47

 [35] Jiang P., Peliska JA., Ninfa AJ., 1998, Enzymological characterization of the signal-transducing uridylyltransferase/uridylyl-removing enzyme (EC 2.7.7.59) of Escherichia coli and its interaction with the PII protein., Biochemistry. 37(37):12782-94

 [36] Lee SY., De La Torre A., Yan D., Kustu S., Nixon BT., Wemmer DE., 2003, Regulation of the transcriptional activator NtrC1: structural studies of the regulatory and AAA+ ATPase domains., Genes Dev. 17(20):2552-63

 [37] Sanders DA., Gillece-Castro BL., Burlingame AL., Koshland DE., 1992, Phosphorylation site of NtrC, a protein phosphatase whose covalent intermediate activates transcription., J Bacteriol. 174(15):5117-22

 [38] Morett E., Segovia L., 1993, The sigma 54 bacterial enhancer-binding protein family: mechanism of action and phylogenetic relationship of their functional domains., J Bacteriol. 175(19):6067-74

 [39] Zhang X., Chaney M., Wigneshweraraj SR., Schumacher J., Bordes P., Cannon W., Buck M., 2002, Mechanochemical ATPases and transcriptional activation., Mol Microbiol. 45(4):895-903

 [40] Yang XF., Ji Y., Schneider BL., Reitzer L., 2004, Phosphorylation-independent dimer-dimer interactions by the enhancer-binding activator NtrC of Escherichia coli: a third function for the C-terminal domain., J Biol Chem. 279(35):36708-14

 [41] Huo YX., Nan BY., You CH., Tian ZX., Kolb A., Wang YP., 2006, FIS activates glnAp2 in Escherichia coli: role of a DNA bend centered at -55, upstream of the transcription start site., FEMS Microbiol Lett. 257(1):99-105

 [42] McFarland N., McCarter L., Artz S., Kustu S., 1981, Nitrogen regulatory locus glnR of enteric bacteria is composed of cistrons ntrB and ntrC: identification of their protein products., Proc Natl Acad Sci U S A. 78(4):2135-9



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