Gene Symbol: ntrC
Description: fused DNA-binding response regulator in two-component regulatory system with GlnL: response regulator/sigma54 interaction protein
Alias: ECK3861, JW3839, glnT, ntrC
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Reitzer L, Schneider B. Metabolic context and possible physiological themes of sigma(54)-dependent genes in Escherichia coli. Microbiol Mol Biol Rev. 2001;65:422-44, table of contents pubmed
    ..Such a relationship may limit the number of physiological themes of sigma(54)-dependent genes within a single organism and may partially account for the unique features of sigma(54) and sigma(54)-dependent gene expression. ..
  2. Jiang P, Peliska J, Ninfa A. Enzymological characterization of the signal-transducing uridylyltransferase/uridylyl-removing enzyme (EC of Escherichia coli and its interaction with the PII protein. Biochemistry. 1998;37:12782-94 pubmed
    ..Our kinetic data were consistent with the hypothesis that both transferase and uridylyl-removal reactions occurred at a single active center on the enzyme. ..
  3. Reitzer L, Magasanik B. Expression of glnA in Escherichia coli is regulated at tandem promoters. Proc Natl Acad Sci U S A. 1985;82:1979-83 pubmed
  4. De Carlo S, Chen B, Hoover T, Kondrashkina E, Nogales E, Nixon B. The structural basis for regulated assembly and function of the transcriptional activator NtrC. Genes Dev. 2006;20:1485-95 pubmed
    ..solution scattering and electron microscopy structures of the activated, full-length nitrogen-regulatory protein C (NtrC) showing a novel mechanism for regulation of AAA+ ATPase assembly via the juxtaposition of the receiver domains and ..
  5. Sanders D, Gillece Castro B, Burlingame A, Koshland D. Phosphorylation site of NtrC, a protein phosphatase whose covalent intermediate activates transcription. J Bacteriol. 1992;174:5117-22 pubmed
    The NtrC transcription factor is a member of a family of homologous prokaryotic regulatory proteins that participate in the transduction of extracellular and nutritional signals...
  6. Jiang P, Ninfa A. Regulation of autophosphorylation of Escherichia coli nitrogen regulator II by the PII signal transduction protein. J Bacteriol. 1999;181:1906-11 pubmed
    The nitrogen regulator II (NRII or NtrB)-NRI (NtrC) two-component signal transduction system regulates the transcription of nitrogen-regulated genes in Escherichia coli...
  7. Atkinson M, Kamberov E, Weiss R, Ninfa A. Reversible uridylylation of the Escherichia coli PII signal transduction protein regulates its ability to stimulate the dephosphorylation of the transcription factor nitrogen regulator I (NRI or NtrC). J Biol Chem. 1994;269:28288-93 pubmed
    ..This signal transduction system consists of four proteins: the transcription factor NRI (NtrC), which activates glnA transcription when it is phosphorylated, the kinase/phosphatase protein NRII (NtrB) that ..
  8. Ueno Nishio S, Mango S, Reitzer L, Magasanik B. Identification and regulation of the glnL operator-promoter of the complex glnALG operon of Escherichia coli. J Bacteriol. 1984;160:379-84 pubmed
    ..We also observed in the intercistronic region a potential rho-independent terminator preceding glnLp and a sequence previously found in other intercistronic regions...
  9. Pahel G, Rothstein D, Magasanik B. Complex glnA-glnL-glnG operon of Escherichia coli. J Bacteriol. 1982;150:202-13 pubmed
    ..The lower level of glnG product originating from transcription initiated at the glnA-distal promoter is not sufficient to activate histidase synthesis, but is sufficient to activate fully and to repress glnA expression. ..

More Information


  1. Sasse Dwight S, Gralla J. Probing the Escherichia coli glnALG upstream activation mechanism in vivo. Proc Natl Acad Sci U S A. 1988;85:8934-8 pubmed
    ..These observations place interesting restrictions on models describing the mechanism by which NRI activates transcription from glnAp2 at a distance. ..
  2. Pioszak A, Jiang P, Ninfa A. 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. 2000;39:13450-61 pubmed
    ..These results indicate that PII controls NRII by interaction with the conserved kinase domain of the transmitter module. ..
  3. Reitzer L, Magasanik B. Transcription of glnA in E. coli is stimulated by activator bound to sites far from the promoter. Cell. 1986;45:785-92 pubmed
    ..promoter glnAp2 requires sigma 60, the product of rpoN (glnF, ntrA), and NRI, the product of glnG (ntrC)...
  4. Weiss V, Magasanik B. Phosphorylation of nitrogen regulator I (NRI) of Escherichia coli. Proc Natl Acad Sci U S A. 1988;85:8919-23 pubmed
    ..In turn, NRII-phosphate transfers its phosphate reversibly to an aspartic residue of NRI. NRI-phosphate is hydrolyzed to NRI and inorganic phosphate in a divalent cation-requiring autocatalytic reaction. ..
  5. Schumacher J, Behrends V, Pan Z, Brown D, Heydenreich F, Lewis M, et al. Nitrogen and carbon status are integrated at the transcriptional level by the nitrogen regulator NtrC in vivo. MBio. 2013;4:e00881-13 pubmed publisher
    ..glutamine as a sole nitrogen source is assumed to be nitrogen limiting, inferred from slow growth and strong NtrB/NtrC-dependent gene activation...
  6. Jiang P, Ninfa A. Alpha-ketoglutarate controls the ability of the Escherichia coli PII signal transduction protein to regulate the activities of NRII (NrB but does not control the binding of PII to NRII. Biochemistry. 2009;48:11514-21 pubmed publisher
    ..Thus, PII control of NRII activities could be dissected into distinct binding and regulation steps, and when present in its physiological concentration range, alpha-ketoglutarate apparently played a role in only the latter step. ..
  7. MacNeil T, MacNeil D, Tyler B. Fine-structure deletion map and complementation analysis of the glnA-glnL-glnG region in Escherichia coli. J Bacteriol. 1982;150:1302-13 pubmed
    ..Results indicate that mutations in 12 and 15 examined strains clearly map outside of glnA, probably in glnL. ..
  8. Reitzer L. Nitrogen assimilation and global regulation in Escherichia coli. Annu Rev Microbiol. 2003;57:155-76 pubmed
    ..Guanosine tetraphosphate appears to control Lrp synthesis. In summary, a network of interacting global regulators that senses different aspects of metabolism integrates nitrogen assimilation with other metabolic processes. ..
  9. Mao X, Huo Y, Buck M, Kolb A, Wang Y. Interplay between CRP-cAMP and PII-Ntr systems forms novel regulatory network between carbon metabolism and nitrogen assimilation in Escherichia coli. Nucleic Acids Res. 2007;35:1432-40 pubmed
    ..5 upstream of glnAp2. CRP-induced DNA-bending prevents the nitrogen regulation protein C (NtrC) activator from approaching the activator-accessible face of the promoter-bound Esigma(54) closed complex, and ..
  10. Schneider B, Kiupakis A, Reitzer L. Arginine catabolism and the arginine succinyltransferase pathway in Escherichia coli. J Bacteriol. 1998;180:4278-86 pubmed
    ..We conclude that the AST pathway is necessary for aerobic arginine catabolism in E. coli and that at least one enzyme of this pathway contributes to ornithine catabolism. ..
  11. Atkinson M, Ninfa A. Role of the GlnK signal transduction protein in the regulation of nitrogen assimilation in Escherichia coli. Mol Microbiol. 1998;29:431-47 pubmed
    ..from Ntr promoters, apparently by regulating the phosphorylation state of the transcriptional activator NRI-P (NtrC-P, the phosphorylated form of the glnG (ntrC) product)...
  12. Magasanik B. Regulation of transcription of the glnALG operon of Escherichia coli by protein phosphorylation. Biochimie. 1989;71:1005-12 pubmed
    ..The signal is transduced to the modulator by means of 2 additional proteins: uridylytransferase and PII. ..
  13. Jiang P, Peliska J, Ninfa A. The regulation of Escherichia coli glutamine synthetase revisited: role of 2-ketoglutarate in the regulation of glutamine synthetase adenylylation state. Biochemistry. 1998;37:12802-10 pubmed
    ..regulation of GS adenylylation state to the regulation of phosphorylation state of the transcription factor NRI (NtrC) in a reconstituted bicyclic system containing NRI, the bifunctional kinase/phosphatase NRII (NtrB), PII, and the ..
  14. Schumacher J, Joly N, Rappas M, Zhang X, Buck M. Structures and organisation of AAA+ enhancer binding proteins in transcriptional activation. J Struct Biol. 2006;156:190-9 pubmed
    ..Parallels with the substrate binding elements near the central pore of other AAA+ members are drawn. We propose a structural model of EBPs in complex with a sigma(54)-RNAP-promoter complex. ..
  15. Ninfa A, Selinsky S, Perry N, Atkins S, Xiu Song Q, Mayo A, et al. Using two-component systems and other bacterial regulatory factors for the fabrication of synthetic genetic devices. Methods Enzymol. 2007;422:488-512 pubmed
    ..transduction systems for synthetic biology applications and describes our use of the Escherichia coli NRI/NRII (NtrC/NtrB) two-component system for the construction of a synthetic genetic oscillator and toggle switch for E. coli...
  16. Lee S, De La Torre A, Yan D, Kustu S, Nixon B, Wemmer D. Regulation of the transcriptional activator NtrC1: structural studies of the regulatory and AAA+ ATPase domains. Genes Dev. 2003;17:2552-63 pubmed publisher
    ..The extended, structured loops from the subunits of the heptamer localize to a pore in the center of the ring and form a surface that could contact sigma54...
  17. Brown D, Barton G, Pan Z, Buck M, Wigneshweraraj S. Nitrogen stress response and stringent response are coupled in Escherichia coli. Nat Commun. 2014;5:4115 pubmed publisher
    ..Escherichia coli to scavenge for alternative nitrogen sources and requires the global transcriptional regulator NtrC. In addition, nitrogen-starved E...
  18. Verhamme D, Arents J, Postma P, Crielaard W, Hellingwerf K. Investigation of in vivo cross-talk between key two-component systems of Escherichia coli. Microbiology. 2002;148:69-78 pubmed
    ..Cross-talk towards NtrC did occur, however, in a ntrB deletion strain, upon joint activation of Pho, Ntr and Uhp...
  19. Zhang X, Chaney M, Wigneshweraraj S, Schumacher J, Bordes P, Cannon W, et al. Mechanochemical ATPases and transcriptional activation. Mol Microbiol. 2002;45:895-903 pubmed
    ..In particular, interprotomer ATP interactions rely upon the use of an arginine finger, a situation reminiscent of GTPase-activating proteins. ..
  20. Weiss V, Claverie Martin F, Magasanik B. Phosphorylation of nitrogen regulator I of Escherichia coli induces strong cooperative binding to DNA essential for activation of transcription. Proc Natl Acad Sci U S A. 1992;89:5088-92 pubmed
    ..We propose that not the phosphorylation of NRI itself but rather the tetramerization of NRI-phosphate on DNA binding induces the conformational change of the central domain to the active conformation. ..
  21. Miranda Rios J, Sanchez Pescador R, Urdea M, Covarrubias A. The complete nucleotide sequence of the glnALG operon of Escherichia coli K12. Nucleic Acids Res. 1987;15:2757-70 pubmed
    The nucleotide sequence of the E. coli glnALG operon has been determined. The glnL (ntrB) and glnG (ntrC) genes present a high homology, at the nucleotide and aminoacid levels, with the corresponding genes of Klebsiella pneumoniae...
  22. Lilja A, Jenssen J, Kahn J. Geometric and dynamic requirements for DNA looping, wrapping and unwrapping in the activation of E.coli glnAp2 transcription by NtrC. J Mol Biol. 2004;342:467-78 pubmed
    Transcriptional activation by the E.coli NtrC protein can occur via DNA looping between a DNA-bound activator and the target sigma(54) RNA polymerase. NtrC forms an octamer on DNA that is capable of binding two DNA molecules...
  23. Pahel G, Tyler B. A new glnA-linked regulatory gene for glutamine synthetase in Escherichia coli. Proc Natl Acad Sci U S A. 1979;76:4544-8 pubmed
    ..An analysis of the evidence accumulated to date makes it unlikely that glnG is the only gene in the glnA region involved in the complex system of nitrogen regulation. ..
  24. Schulz A, Langowski J, Rippe K. The effect of the DNA conformation on the rate of NtrC activated transcription of Escherichia coli RNA polymerase.sigma(54) holoenzyme. J Mol Biol. 2000;300:709-25 pubmed
    The transcription activator protein NtrC (nitrogen regulatory protein C) can catalyze the transition of Escherichia coli RNA polymerase complexed with the sigma 54 factor (RNAP.sigma(54)) from the closed complex (RNAP...
  25. Backman K, Chen Y, Magasanik B. Physical and genetic characterization of the glnA--glnG region of the Escherichia coli chromosome. Proc Natl Acad Sci U S A. 1981;78:3743-7 pubmed
    ..A region of DNA between glnA and glnG contains genetic information whose loss may result in the inability to reduce expression of glnA and other operons in response to ammonia (the GlnC phenotype). ..
  26. Magasanik B. The regulation of nitrogen utilization in enteric bacteria. J Cell Biochem. 1993;51:34-40 pubmed
  27. Pioszak A, Ninfa A. Mutations altering the N-terminal receiver domain of NRI (NtrC) That prevent dephosphorylation by the NRII-PII complex in Escherichia coli. J Bacteriol. 2004;186:5730-40 pubmed
    ..The properties of these altered proteins are consistent with the hypothesis that the NRII-PII complex is not a true phosphatase but rather collaborates with NRI approximately P to bring about its dephosphorylation. ..
  28. Feng J, Atkinson M, McCleary W, Stock J, Wanner B, Ninfa A. Role of phosphorylated metabolic intermediates in the regulation of glutamine synthetase synthesis in Escherichia coli. J Bacteriol. 1992;174:6061-70 pubmed
    Transcription of the Ntr regulon is controlled by the two-component system consisting of the response regulator NRI (NtrC) and the kinase/phosphatase NRII (NtrB), which both phosphorylates and dephosphorylates NRI...
  29. MacNeil D. General method, using Mu-Mud1 dilysogens, to determine the direction of transcription of and generate deletions in the glnA region of Escherichia coli. J Bacteriol. 1981;146:260-8 pubmed
    ..In Escherichia coli, the glnA and glnG genes are transcribed in the same direction. ..
  30. Mutalik V, Venkatesh K. A theoretical steady state analysis indicates that induction of Escherichia coli glnALG operon can display all-or-none behavior. Biosystems. 2007;90:1-19 pubmed
    ..coli glnALG operon to nutrient starvation prevents the premature initiation of transcription and may represent the desperate attempt by the cell to survive in limiting conditions. ..
  31. Salinas P, Contreras A. Identification and analysis of Escherichia coli proteins that interact with the histidine kinase NtrB in a yeast two-hybrid system. Mol Genet Genomics. 2003;269:574-81 pubmed
  32. McFarland N, McCarter L, Artz S, Kustu S. 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. 1981;78:2135-9 pubmed
    ..of Escherichia coli and Salmonella typhimurium is composed of two cistrons, which we propose to call ntrB and ntrC (nitrogen regulation B and C)...
  33. Blauwkamp T, Ninfa A. Physiological role of the GlnK signal transduction protein of Escherichia coli: survival of nitrogen starvation. Mol Microbiol. 2002;46:203-14 pubmed
    ..The specific roles of GlnK during nitrogen starvation were not the result of a distinct function of the protein, as expression of PII from the glnK promoter in cells lacking GlnK restored the wild-type phenotypes. ..
  34. Gyaneshwar P, Paliy O, McAuliffe J, Popham D, Jordan M, Kustu S. Sulfur and nitrogen limitation in Escherichia coli K-12: specific homeostatic responses. J Bacteriol. 2005;187:1074-90 pubmed
    ..As predicted from the fact that the ddp operon is activated by NtrC, synthesis of cross-links between diaminopimelate residues in the murein layer was increased under N-limiting ..
  35. Yang X, Ji Y, Schneider B, Reitzer L. 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. 2004;279:36708-14 pubmed
    The response regulator NtrC transcriptionally activates genes of the nitrogen-regulated (Ntr) response. Phosphorylation of its N-terminal receiver domain stimulates an essential oligomerization of the central domain...
  36. Morett E, Segovia L. The sigma 54 bacterial enhancer-binding protein family: mechanism of action and phylogenetic relationship of their functional domains. J Bacteriol. 1993;175:6067-74 pubmed
  37. Gao R, Tao Y, Stock A. System-level mapping of Escherichia coli response regulator dimerization with FRET hybrids. Mol Microbiol. 2008;69:1358-72 pubmed publisher
    ..Weak hetero-pair interactions were also identified between several different RRs, suggesting potential cross-regulation between distinct pathways. ..
  38. Jiang P, Ninfa A. Sensation and signaling of alpha-ketoglutarate and adenylylate energy charge by the Escherichia coli PII signal transduction protein require cooperation of the three ligand-binding sites within the PII trimer. Biochemistry. 2009;48:11522-31 pubmed publisher
  39. MacNeil T, Roberts G, MacNeil D, Tyler B. The products of glnL and glnG are bifunctional regulatory proteins. Mol Gen Genet. 1982;188:325-33 pubmed
  40. Samsonova N, Smirnov S, Altman I, Ptitsyn L. Molecular cloning and characterization of Escherichia coli K12 ygjG gene. BMC Microbiol. 2003;3:2 pubmed
    ..coli K12 ygjG coding region revealed sigma54-depended ORF which encodes a 459-amino acid protein with putrescine:2-OG aminotransferase activity. The enzyme also was able to transaminate cadaverine and, in lower extent, spermidine. ..
  41. Huo Y, Nan B, You C, Tian Z, Kolb A, Wang Y. FIS activates glnAp2 in Escherichia coli: role of a DNA bend centered at -55, upstream of the transcription start site. FEMS Microbiol Lett. 2006;257:99-105 pubmed
    ..In vitro transcription assays indicated that all DNA bends centered at -55 activate transcriptional initiation of glnAp2, especially when linear templates were used. ..
  42. Lei M, Velos J, Gardino A, Kivenson A, Karplus M, Kern D. Segmented transition pathway of the signaling protein nitrogen regulatory protein C. J Mol Biol. 2009;392:823-36 pubmed publisher
    ..The targeted molecular dynamics pathway suggests that several transient nonnative hydrogen bonds may facilitate the transition. ..
  43. Harrod A, Yang X, Junker M, Reitzer L. Evidence for a second interaction between the regulatory amino-terminal and central output domains of the response regulator NtrC (nitrogen regulator I) in Escherichia coli. J Biol Chem. 2004;279:2350-9 pubmed
    Nitrogen limitation in Escherichia coli activates about 100 genes. Their expression requires the response regulator NtrC (also called nitrogen regulator I or NR(I))...
  44. Studholme D, Buck M. The biology of enhancer-dependent transcriptional regulation in bacteria: insights from genome sequences. FEMS Microbiol Lett. 2000;186:1-9 pubmed
    ..By scanning their genome sequences, new functions have been predicted for enhancer-dependent transcription in A. aeolicus, Chlamydia trachomatis, Escherichia coli, Treponema pallidum and B. burgdorferi. ..
  45. Lee J, Owens J, Hwang I, Meares C, Kustu S. Phosphorylation-induced signal propagation in the response regulator ntrC. J Bacteriol. 2000;182:5188-95 pubmed
    The bacterial enhancer-binding protein NtrC is a well-studied response regulator in a two-component regulatory system...
  46. Ueno Nishio S, Backman K, Magasanik B. Regulation at the glnL-operator-promoter of the complex glnALG operon of Escherichia coli. J Bacteriol. 1983;153:1247-51 pubmed
    ..We identified the portion of the glnALG operon that contains the promoter and operator of the glnLG suboperon and showed that the product of glnG represses transcription initiated at glnLp. ..