Gene Symbol: cpxR
Description: response regulator in two-component regulatory system with CpxA
Alias: ECK3905, JW3883, yiiA
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Dorel C, Lejeune P, Rodrigue A. The Cpx system of Escherichia coli, a strategic signaling pathway for confronting adverse conditions and for settling biofilm communities?. Res Microbiol. 2006;157:306-14 pubmed
    ..Current knowledge of the regulatory mechanisms of the CpxR response (transcriptional and post-transcriptional) and the interactions between CpxR and the other bacterial ..
  2. Fleischer R, Heermann R, Jung K, Hunke S. Purification, reconstitution, and characterization of the CpxRAP envelope stress system of Escherichia coli. J Biol Chem. 2007;282:8583-93 pubmed
    ..It consists of the membrane-anchored sensor kinase CpxA, the response regulator CpxR, and the periplasmic protein CpxP...
  3. Hirakawa H, Inazumi Y, Masaki T, Hirata T, Yamaguchi A. Indole induces the expression of multidrug exporter genes in Escherichia coli. Mol Microbiol. 2005;55:1113-26 pubmed
    ..BaeR and CpxR directly bound to different sequences of the acrD and mdtA promoter regions...
  4. Jubelin G, Vianney A, Beloin C, Ghigo J, Lazzaroni J, Lejeune P, et al. CpxR/OmpR interplay regulates curli gene expression in response to osmolarity in Escherichia coli. J Bacteriol. 2005;187:2038-49 pubmed
    ..OmpR was shown to activate csgD expression, resulting in curli production. The CpxR regulator was shown to negatively affect curli gene expression when binding to its recognition site that overlaps ..
  5. Wolfe A, Parikh N, Lima B, Zemaitaitis B. Signal integration by the two-component signal transduction response regulator CpxR. J Bacteriol. 2008;190:2314-22 pubmed publisher
    ..pathway, can activate the transcription of cpxP in a CpxA-independent manner by donating its phosphoryl group to CpxR. We tested this hypothesis by measuring the transcription of cpxP using mutants with mutations in the CpxAR pathway,..
  6. DiGiuseppe P, Silhavy T. Signal detection and target gene induction by the CpxRA two-component system. J Bacteriol. 2003;185:2432-40 pubmed
    ..CpxA resides in the inner membrane and has both kinase and phosphatase activities. CpxR, the response regulator, mediates a response by activating transcription of stress-combative genes...
  7. Otto K, Silhavy T. Surface sensing and adhesion of Escherichia coli controlled by the Cpx-signaling pathway. Proc Natl Acad Sci U S A. 2002;99:2287-92 pubmed
    ..The defects in adhesion exhibited by the cpxR and nlpE mutants were strikingly similar to those of wild-type cells in which protein synthesis was inhibited, ..
  8. Pogliano J, Lynch A, Belin D, Lin E, Beckwith J. Regulation of Escherichia coli cell envelope proteins involved in protein folding and degradation by the Cpx two-component system. Genes Dev. 1997;11:1169-82 pubmed
    We show that the two-component signal transduction system of Escherichia coli, CpxA-CpxR, controls the expression of genes encoding cell envelope proteins involved in protein folding and degradation...
  9. Price N, Raivio T. Characterization of the Cpx regulon in Escherichia coli strain MC4100. J Bacteriol. 2009;191:1798-815 pubmed publisher
    ..Moderately Cpx-regulated gene clusters encode products implicated in biofilm formation. An analysis of CpxR binding sites in strongly regulated genes indicates that while neither a consensus match nor their orientation ..

More Information


  1. De Wulf P, Kwon O, Lin E. The CpxRA signal transduction system of Escherichia coli: growth-related autoactivation and control of unanticipated target operons. J Bacteriol. 1999;181:6772-8 pubmed
    ..We show that CpxR-P (the phosphorylated form of the cognate response regulator) activates cpxRA expression in conjunction with RpoS, ..
  2. Cuny C, Lesbats M, Dukan S. Induction of a global stress response during the first step of Escherichia coli plate growth. Appl Environ Microbiol. 2007;73:885-9 pubmed
    ..Our results indicate that in order to grow on plates, bacteria must not only adapt to new conditions but also perceive a real stress. ..
  3. De Wulf P, Lin E. Cpx two-component signal transduction in Escherichia coli: excessive CpxR-P levels underlie CpxA* phenotypes. J Bacteriol. 2000;182:1423-6 pubmed
    In Escherichia coli, the CpxA-CpxR two-component signal transduction system and the sigma(E) and sigma(32) response pathways jointly regulate gene expression in adaptation to adverse conditions...
  4. Partridge J, Sanguinetti G, Dibden D, Roberts R, Poole R, Green J. Transition of Escherichia coli from aerobic to micro-aerobic conditions involves fast and slow reacting regulatory components. J Biol Chem. 2007;282:11230-7 pubmed
    ..Similarly, the cell envelope stress sensors RpoE and CpxR reacted rapidly and more slowly, respectively...
  5. Siryaporn A, Goulian M. Cross-talk suppression between the CpxA-CpxR and EnvZ-OmpR two-component systems in E. coli. Mol Microbiol. 2008;70:494-506 pubmed publisher
    ..mechanisms that suppress cross-talk between these two proteins, which depend on the corresponding cognate partners CpxR and EnvZ and on the bifunctional nature of the histidine kinases CpxA and EnvZ...
  6. Raffa R, Raivio T. A third envelope stress signal transduction pathway in Escherichia coli. Mol Microbiol. 2002;45:1599-611 pubmed
    ..BaeS and BaeR do not affect expression of other known Cpx-regulated genes, however, baeR cpxR double mutants show increased sensitivity to envelope stresses relative to either single mutant alone...
  7. Batchelor E, Walthers D, Kenney L, Goulian M. The Escherichia coli CpxA-CpxR envelope stress response system regulates expression of the porins ompF and ompC. J Bacteriol. 2005;187:5723-31 pubmed
    ..Subsequent genetic analysis revealed that this phenotype is dependent on phosphorylation of the response regulator CpxR and that activation of CpxA in wild-type cells results in similar regulation of porin expression...
  8. Raivio T, Popkin D, Silhavy T. The Cpx envelope stress response is controlled by amplification and feedback inhibition. J Bacteriol. 1999;181:5263-72 pubmed
    ..It is comprised of the histidine kinase CpxA and the response regulator CpxR. This response plays a role in protection from stresses, such as elevated pH, as well as in the biogenesis of ..
  9. Cosma C, Danese P, Carlson J, Silhavy T, Snyder W. Mutational activation of the Cpx signal transduction pathway of Escherichia coli suppresses the toxicity conferred by certain envelope-associated stresses. Mol Microbiol. 1995;18:491-505 pubmed
    ..A subset of these targets may constitute a regulon involved in relieving extracytoplasmic and/or secretion-related stress. ..
  10. Yamamoto K, Ishihama A. Characterization of copper-inducible promoters regulated by CpxA/CpxR in Escherichia coli. Biosci Biotechnol Biochem. 2006;70:1688-95 pubmed
    The copper stimulon in Escherichia coli consists of four regulons, the CueR-, CusS/CusR-, CpxA/CpxR-, and YedV/YedW regulons. E. coli mutants defective in cpxRA showed higher sensitivity to copper than the wild type...
  11. Lau Wong I, Locke T, Ellison M, Raivio T, Frost L. Activation of the Cpx regulon destabilizes the F plasmid transfer activator, TraJ, via the HslVU protease in Escherichia coli. Mol Microbiol. 2008;67:516-27 pubmed
    ..Thus, the CpxAR stress response indirectly controls the synthesis of the F mating apparatus, a complex transenvelope type IV secretion system, by degrading TraJ. ..
  12. Davidge K, Sanguinetti G, Yee C, Cox A, McLeod C, Monk C, et al. Carbon monoxide-releasing antibacterial molecules target respiration and global transcriptional regulators. J Biol Chem. 2009;284:4516-24 pubmed publisher
    ..modeling of transcriptomic data identified the global transcription regulators ArcA, CRP, Fis, FNR, Fur, BaeR, CpxR, and IHF as targets and potential CO sensors...
  13. Pao G, Saier M. Response regulators of bacterial signal transduction systems: selective domain shuffling during evolution. J Mol Evol. 1995;40:136-54 pubmed
    ..Sequence data were correlated with structure/function when such information was available.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  14. Vogt S, Evans A, Guest R, Raivio T. The Cpx envelope stress response regulates and is regulated by small noncoding RNAs. J Bacteriol. 2014;196:4229-38 pubmed publisher
    ..Here, we showed for the first time that sRNAs are members of the Cpx regulon. We found that CpxR binds to the promoter regions and regulates expression of two sRNA genes, cyaR and rprA...
  15. Dong J, Iuchi S, Kwan H, Lu Z, Lin E. The deduced amino-acid sequence of the cloned cpxR gene suggests the protein is the cognate regulator for the membrane sensor, CpxA, in a two-component signal transduction system of Escherichia coli. Gene. 1993;136:227-30 pubmed
    ..It showed high homology to the regulator elements of two-component transduction systems. The newly identified gene, designated as cpxR, may encode the cognate protein receiving signals from CpxA.
  16. Tapparel C, Monod A, Kelley W. The DNA-binding domain of the Escherichia coli CpxR two-component response regulator is constitutively active and cannot be fully attenuated by fused adjacent heterologous regulatory domains. Microbiology. 2006;152:431-41 pubmed
    ..This study focuses on the Escherichia coli CpxR response regulator that responds to periplasmic and outer-membrane stress...
  17. Gerken H, Charlson E, Cicirelli E, Kenney L, Misra R. MzrA: a novel modulator of the EnvZ/OmpR two-component regulon. Mol Microbiol. 2009;72:1408-22 pubmed publisher
    ..Furthermore, our data show that MzrA links the two-component envelope stress response regulators, CpxA/CpxR and EnvZ/OmpR.
  18. Kumar S, Tiwari V, Doerrler W. Cpx-dependent expression of YqjA requires cations at elevated pH. FEMS Microbiol Lett. 2017;364: pubmed publisher
    ..Increased activity of the yqjA promoter required both the transcriptional regulator CpxR, in agreement with previous results, and sodium or potassium salts at alkaline pH...
  19. Mechaly A, Soto Diaz S, Sassoon N, Buschiazzo A, Betton J, Alzari P. Structural Coupling between Autokinase and Phosphotransferase Reactions in a Bacterial Histidine Kinase. Structure. 2017;25:939-944.e3 pubmed publisher
    ..of the prototypical HK CpxA trapped as a hemi-phosphorylated dimer, and of the receiver domain from the RR partner, CpxR. Our results reveal that the two catalytic reactions can occur simultaneously, one in each protomer of the ..
  20. Nevesinjac A, Raivio T. The Cpx envelope stress response affects expression of the type IV bundle-forming pili of enteropathogenic Escherichia coli. J Bacteriol. 2005;187:672-86 pubmed
    ..The two-component regulatory system consisting of the sensor kinase CpxA and the response regulator CpxR senses and mediates adaptation to envelope insults believed to result in protein misfolding in this compartment...
  21. De Wulf P, Akerley B, Lin E. Presence of the Cpx system in bacteria. Microbiology. 2000;146 ( Pt 2):247-8 pubmed
  22. Langen G, Harper J, Silhavy T, Howard S. Absence of the outer membrane phospholipase A suppresses the temperature-sensitive phenotype of Escherichia coli degP mutants and induces the Cpx and sigma(E) extracytoplasmic stress responses. J Bacteriol. 2001;183:5230-8 pubmed
    ..These results suggest that the absence of OMPLA corrects the degP temperature-sensitive phenotype by inducing the Cpx and sigma(E) regulons rather than by inactivating the phospholipase per se. ..
  23. Macritchie D, Ward J, Nevesinjac A, Raivio T. Activation of the Cpx envelope stress response down-regulates expression of several locus of enterocyte effacement-encoded genes in enteropathogenic Escherichia coli. Infect Immun. 2008;76:1465-75 pubmed publisher
    ..Coupled with recent findings, our results suggest that Cpx-mediated down regulation of virulence is a conserved theme in a number of bacterial pathogens. ..
  24. Bury Moné S, Nomane Y, Reymond N, Barbet R, Jacquet E, Imbeaud S, et al. Global analysis of extracytoplasmic stress signaling in Escherichia coli. PLoS Genet. 2009;5:e1000651 pubmed publisher
    ..The extracytoplasmic stress signaling pathways in E. coli thus regulate mainly complementary functions whose discrete contributions are integrated to mount the full adaptive response. ..
  25. Groban E, Clarke E, Salis H, Miller S, Voigt C. Kinetic buffering of cross talk between bacterial two-component sensors. J Mol Biol. 2009;390:380-93 pubmed publisher
    ..In this work, we studied the EnvZ/OmpR and CpxA/CpxR systems from Escherichia coli, which have been shown previously to exhibit slow cross talk in vitro...
  26. Parkinson J. Signal transduction schemes of bacteria. Cell. 1993;73:857-71 pubmed
  27. Hirakawa H, Nishino K, Yamada J, Hirata T, Yamaguchi A. Beta-lactam resistance modulated by the overexpression of response regulators of two-component signal transduction systems in Escherichia coli. J Antimicrob Chemother. 2003;52:576-82 pubmed
    ..MICs were determined by the agar dilution method. Thirteen response regulators out of 32 genes, namely baeR, cheY, cpxR, creB, evgA, fimZ, narL, ompR, rcsB, rstA, yedW, yehT and dcuR, conferred increased beta-lactam resistance...
  28. 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. ..
  29. Danese P, Snyder W, Cosma C, Davis L, Silhavy T. The Cpx two-component signal transduction pathway of Escherichia coli regulates transcription of the gene specifying the stress-inducible periplasmic protease, DegP. Genes Dev. 1995;9:387-98 pubmed
    ..Defined null mutations in cpxA or the gene encoding its cognate response regulator, cpxR, decrease transcription from degP...
  30. Ma Q, Wood T. OmpA influences Escherichia coli biofilm formation by repressing cellulose production through the CpxRA two-component system. Environ Microbiol. 2009;11:2735-46 pubmed publisher
    ..CpxA phosphorylates CpxR and results in reduced csgD expression...
  31. Danese P, Silhavy T. The sigma(E) and the Cpx signal transduction systems control the synthesis of periplasmic protein-folding enzymes in Escherichia coli. Genes Dev. 1997;11:1183-93 pubmed
    ..signal transduction pathway, which consists of an inner-membrane sensor (CpxA) and a cognate response regulator (CpxR), is stimulated by overproduction of the outer-membrane lipoprotein, NlpE...
  32. Weber R, Silverman P. The cpx proteins of Escherichia coli K12. Structure of the cpxA polypeptide as an inner membrane component. J Mol Biol. 1988;203:467-78 pubmed
    ..Based on these structural data, we propose that CpxA functions as a trans-membrane sensory protein. The DNA sequence data also indicate that cpxA is the 3' gene of an operon...
  33. Stock J, Stock A, Mottonen J. Signal transduction in bacteria. Nature. 1990;344:395-400 pubmed publisher
    ..This phosphotransfer network couples environmental signals to an array of response elements that control cell motility and regulate gene expression...
  34. Ogasawara H, Teramoto J, Hirao K, Yamamoto K, Ishihama A, Utsumi R. Negative regulation of DNA repair gene (ung) expression by the CpxR/CpxA two-component system in Escherichia coli K-12 and induction of mutations by increased expression of CpxR. J Bacteriol. 2004;186:8317-25 pubmed
    In Escherichia coli K-12 overexpressing CpxR, transcription of the ung gene for uracil-DNA glycosylase was repressed, ultimately leading to the induction of mutation...
  35. Moreau P. Protective role of the RpoE (?E) and Cpx envelope stress responses against gentamicin killing of nongrowing Escherichia coli incubated under aerobic, phosphate starvation conditions. FEMS Microbiol Lett. 2014;357:151-6 pubmed publisher
  36. Bernal Cabas M, Ayala J, Raivio T. The Cpx envelope stress response modifies peptidoglycan cross-linking via the L,D-transpeptidase LdtD and the novel protein YgaU. J Bacteriol. 2015;197:603-14 pubmed publisher
    ..Phosphorylated CpxR binds to the upstream regions of these genes, which contain putative CpxR binding sites, suggesting that regulation ..
  37. Prigent Combaret C, Brombacher E, Vidal O, Ambert A, Lejeune P, Landini P, et al. Complex regulatory network controls initial adhesion and biofilm formation in Escherichia coli via regulation of the csgD gene. J Bacteriol. 2001;183:7213-23 pubmed
    ..propose that this negative regulation takes place via rpoS-dependent transcription of the transcription regulator cpxR; cpxR-mediated repression of csgB and csgD promoters is also triggered by osmolarity and by curli overproduction, ..
  38. Dorel C, Vidal O, Prigent Combaret C, Vallet I, Lejeune P. Involvement of the Cpx signal transduction pathway of E. coli in biofilm formation. FEMS Microbiol Lett. 1999;178:169-75 pubmed
    ..The effect of the cpxA mutation could not be observed in cpxR- mutants, suggesting that they affect the same regulatory pathway...
  39. Kinnersley M, Holben W, Rosenzweig F. E Unibus Plurum: genomic analysis of an experimentally evolved polymorphism in Escherichia coli. PLoS Genet. 2009;5:e1000713 pubmed publisher
    ..93% were exhibited by the majority clone, many of which are controlled by global regulators, CRP and CpxR. When transcriptional profiling was performed on adaptive clones cultured together, many expression differences ..
  40. Weatherspoon Griffin N, Yang D, Kong W, Hua Z, Shi Y. The CpxR/CpxA two-component regulatory system up-regulates the multidrug resistance cascade to facilitate Escherichia coli resistance to a model antimicrobial peptide. J Biol Chem. 2014;289:32571-82 pubmed publisher
    A genome-wide susceptibility assay was used to identify specific CpxR-dependent genes that facilitate Escherichia coli resistance to a model cationic antimicrobial peptide, protamine...
  41. Parkinson J, Kofoid E. Communication modules in bacterial signaling proteins. Annu Rev Genet. 1992;26:71-112 pubmed
  42. Keller R, Ariöz C, Hansmeier N, Stenberg Bruzell F, Burstedt M, Vikström D, et al. The Escherichia coli Envelope Stress Sensor CpxA Responds to Changes in Lipid Bilayer Properties. Biochemistry. 2015;54:3670-6 pubmed publisher
    ..Moreover, the Cpx response was validated in vivo by monitoring expression of a PcpxP-gfp reporter in lipid-engineered strains of E. coli. Our combined data indicate that CpxA responds specifically to different lipid compositions. ..
  43. Raivio T, Silhavy T. Transduction of envelope stress in Escherichia coli by the Cpx two-component system. J Bacteriol. 1997;179:7724-33 pubmed
    ..pathways is a two-component regulatory system comprised of the histidine kinase CpxA and the response regulator, CpxR. In this study we characterized gain-of-function Cpx* mutants in order to learn more about Cpx signal transduction...
  44. Raivio T, Laird M, Joly J, Silhavy T. Tethering of CpxP to the inner membrane prevents spheroplast induction of the cpx envelope stress response. Mol Microbiol. 2000;37:1186-97 pubmed
    ..Because the sigmaE response is specifically affected by alterations in outer membrane protein biogenesis, we think it possible that Spy may be involved in this process. ..
  45. Lee Y, DiGiuseppe P, Silhavy T, Hultgren S. P pilus assembly motif necessary for activation of the CpxRA pathway by PapE in Escherichia coli. J Bacteriol. 2004;186:4326-37 pubmed
    ..Thus, the data presented in this study argue that PapE has features inherent in its structure or during its folding that act as specific inducers of Cpx signal transduction. ..
  46. Kurabayashi K, Hirakawa Y, Tanimoto K, Tomita H, Hirakawa H. Role of the CpxAR two-component signal transduction system in control of fosfomycin resistance and carbon substrate uptake. J Bacteriol. 2014;196:248-56 pubmed publisher
    ..cpxA mutant lacking its phosphatase activity results in constitutive activation of its cognate response regulator, CpxR, and fosfomycin resistance...
  47. Keller R, Hunke S. Misfolded maltose binding protein MalE219 induces the CpxRA envelope stress response by stimulating phosphoryl transfer from CpxA to CpxR. Res Microbiol. 2009;160:396-400 pubmed publisher
    ..and phosphatase activities of the reconstituted CpxA-6His protein remained unaffected, whereas phosphotransfer to CpxR became activated by MalE219...
  48. Lima B, Lennon C, Ross W, Gourse R, Wolfe A. In vitro evidence that RNA Polymerase acetylation and acetyl phosphate-dependent CpxR phosphorylation affect cpxP transcription regulation. FEMS Microbiol Lett. 2016;363:fnw011 pubmed publisher
    ..and demonstrate, using an in vitro transcription system, that acP-dependent phosphorylation of aspartate 51 of CpxR induces transcription of one of its regulon members in E. coli, cpxP...
  49. Delhaye A, Collet J, Laloux G. Fine-Tuning of the Cpx Envelope Stress Response Is Required for Cell Wall Homeostasis in Escherichia coli. MBio. 2016;7:e00047-16 pubmed publisher
    ..Thus, by contributing to PG homeostasis, the Cpx system lies at the crossroads between key processes of bacterial life, including cell shape, growth, division, and antibiotic resistance. ..
  50. Condemine G, Berrier C, Plumbridge J, Ghazi A. Function and expression of an N-acetylneuraminic acid-inducible outer membrane channel in Escherichia coli. J Bacteriol. 2005;187:1959-65 pubmed
    ..nanC expression is also activated by the regulators cyclic AMP-catabolite activator protein, OmpR, and CpxR. When the NanC protein was reconstituted into liposomes, it formed channels with a conductance of 450 pS at ..
  51. Shimohata N, Chiba S, Saikawa N, Ito K, Akiyama Y. The Cpx stress response system of Escherichia coli senses plasma membrane proteins and controls HtpX, a membrane protease with a cytosolic active site. Genes Cells. 2002;7:653-62 pubmed
    ..The pathway for this transmembrane signalling is mediated by the CpxR-CpxA two-component phospho-relay mechanism...