cyclic amp receptor protein


Summary: A transcriptional regulator in prokaryotes which, when activated by binding cyclic AMP, acts at several promoters. Cyclic AMP receptor protein was originally identified as a catabolite gene activator protein. It was subsequently shown to regulate several functions unrelated to catabolism, and to be both a negative and a positive regulator of transcription. Cell surface cyclic AMP receptors are not included (CYCLIC AMP RECEPTORS), nor are the eukaryotic cytoplasmic cyclic AMP receptor proteins, which are the regulatory subunits of CYCLIC AMP-DEPENDENT PROTEIN KINASES.

Top Publications

  1. Landis L, Xu J, Johnson R. The cAMP receptor protein CRP can function as an osmoregulator of transcription in Escherichia coli. Genes Dev. 1999;13:3081-91 pubmed
    ..These findings suggest that CRP functions in certain contexts to regulate gene expression in response to osmotic changes, in addition to its role in catabolite control. ..
  2. Balsalobre C, Johansson J, Uhlin B. Cyclic AMP-dependent osmoregulation of crp gene expression in Escherichia coli. J Bacteriol. 2006;188:5935-44 pubmed
    ..Our findings suggest that the fine-tuning of the CRP activity may be critical for bacterial viability and adaptability to changing osmotic conditions. ..
  3. Xu M, Su Z. Computational prediction of cAMP receptor protein (CRP) binding sites in cyanobacterial genomes. BMC Genomics. 2009;10:23 pubmed publisher
    b>Cyclic AMP receptor protein (CRP), also known as catabolite gene activator protein (CAP), is an important transcriptional regulator widely distributed in many bacteria...
  4. Richet E. Synergistic transcription activation: a dual role for CRP in the activation of an Escherichia coli promoter depending on MalT and CRP. EMBO J. 2000;19:5222-32 pubmed
  5. Blokesch M. Chitin colonization, chitin degradation and chitin-induced natural competence of Vibrio cholerae are subject to catabolite repression. Environ Microbiol. 2012;14:1898-912 pubmed publisher
    ..These findings highlight the complex regulatory circuit of chitin-induced natural competence in V.cholerae. ..
  6. Perrenoud A, Sauer U. Impact of global transcriptional regulation by ArcA, ArcB, Cra, Crp, Cya, Fnr, and Mlc on glucose catabolism in Escherichia coli. J Bacteriol. 2005;187:3171-9 pubmed
    ..coli. This control goes well beyond the previously known ArcA-dependent regulation of the TCA cycle during microaerobiosis. ..
  7. Tomlinson S, Tutar Y, Harman J. CRP subunit association and hinge conformation changes in response to cAMP binding: analysis of C-helix cysteine-substituted CRP. Biochemistry. 2006;45:13438-46 pubmed
    ..cAMP complex. ..
  8. Popovych N, Tzeng S, Tonelli M, Ebright R, Kalodimos C. Structural basis for cAMP-mediated allosteric control of the catabolite activator protein. Proc Natl Acad Sci U S A. 2009;106:6927-32 pubmed publisher
  9. Suh S, Runyen Janecky L, Maleniak T, Hager P, MacGregor C, Zielinski Mozny N, et al. Effect of vfr mutation on global gene expression and catabolite repression control of Pseudomonas aeruginosa. Microbiology. 2002;148:1561-9 pubmed
    ..aeruginosa crc gene. Thus, although Vfr is structurally similar to CRP, and is a global regulator of gene expression in P. aeruginosa, Vfr is not required for catabolite repression control in this bacterium. ..

More Information


  1. Wickstrum J, Skredenske J, Balasubramaniam V, Jones K, Egan S. The AraC/XylS family activator RhaS negatively autoregulates rhaSR expression by preventing cyclic AMP receptor protein activation. J Bacteriol. 2010;192:225-32 pubmed publisher
    ..We found that RhaS autoregulation required the cyclic AMP receptor protein (CRP) binding site at rhaSR and that RhaS was able to bind to the RhaR binding site at rhaSR...
  2. Sheoran A, Timoney J, Tinge S, Sundaram P, Curtiss R. Intranasal immunogenicity of a Delta cya Delta crp-pabA mutant of Salmonella enterica serotype Typhimurium for the horse. Vaccine. 2001;19:3787-95 pubmed
    ..The results indicate that a S. typhimurium Deltacya Deltacrp-pabA mutant has potential as an intranasal vaccine against salmonellosis in the horse. ..
  3. Feng Y, Cronan J. Overlapping repressor binding sites result in additive regulation of Escherichia coli FadH by FadR and ArcA. J Bacteriol. 2010;192:4289-99 pubmed publisher
    ..fatty acid degradation FadR repressor, the oxygen-responsive ArcA-ArcB two-component system, and the cyclic AMP receptor protein-cyclic AMP (CRP-cAMP) complex...
  4. Passner J, Schultz S, Steitz T. Modeling the cAMP-induced allosteric transition using the crystal structure of CAP-cAMP at 2.1 A resolution. J Mol Biol. 2000;304:847-59 pubmed publisher
    ..Additionally, cAMP binding may cause a further rearrangement of the DNA-binding and cAMP-binding domains of CAP via a flap consisting of beta-strands 4 and 5 which lies over the cAMP...
  5. Tian Z, Li Q, Buck M, Kolb A, Wang Y. The CRP-cAMP complex and downregulation of the glnAp2 promoter provides a novel regulatory linkage between carbon metabolism and nitrogen assimilation in Escherichia coli. Mol Microbiol. 2001;41:911-24 pubmed
    ..A novel regulatory linkage between carbon and nitrogen regulons is proposed. ..
  6. Zheng D, Constantinidou C, Hobman J, Minchin S. Identification of the CRP regulon using in vitro and in vivo transcriptional profiling. Nucleic Acids Res. 2004;32:5874-93 pubmed
    The Escherichia coli cyclic AMP receptor protein (CRP) is a global regulator that controls transcription initiation from more than 100 promoters by binding to a specific DNA sequence within cognate promoters...
  7. Chahla M, Wooll J, Laue T, Nguyen N, Senear D. Role of protein-protein bridging interactions on cooperative assembly of DNA-bound CRP-CytR-CRP complex and regulation of the Escherichia coli CytR regulon. Biochemistry. 2003;42:3812-25 pubmed
    ..Instead, cytidine binding must induce a CytR conformation that is more rigid or in some other way less tolerant of the variation in the geometric arrangement of operator sites between different promoters. ..
  8. Shin D, Cho N, Heu S, Ryu S. Selective regulation of ptsG expression by Fis. Formation of either activating or repressing nucleoprotein complex in response to glucose. J Biol Chem. 2003;278:14776-81 pubmed
    ..The regulation of ptsG P1 transcription is also under positive control by cyclic AMP receptor protein and cyclic AMP complex (CRP.cAMP) as observed in other Mlc regulon...
  9. Soutourina O, Kolb A, Krin E, Laurent Winter C, Rimsky S, Danchin A, et al. Multiple control of flagellum biosynthesis in Escherichia coli: role of H-NS protein and the cyclic AMP-catabolite activator protein complex in transcription of the flhDC master operon. J Bacteriol. 1999;181:7500-8 pubmed
  10. Zhang H, Chong H, Ching C, Jiang R. Random mutagenesis of global transcription factor cAMP receptor protein for improved osmotolerance. Biotechnol Bioeng. 2012;109:1165-72 pubmed publisher
    ..Scanning electron microscopy images confirmed the elongation of both WT and MT6 when exposed to NaCl but the cell surface of MT6 was relatively smooth. ..
  11. Li J, Cheng X, Lee J. Structure and dynamics of the modular halves of Escherichia coli cyclic AMP receptor protein. Biochemistry. 2002;41:14771-8 pubmed
    E. coli cyclic AMP receptor protein, CRP, is a modular protein that consists of a covalent linkage of two common structural domains...
  12. Chen S, Gunasekera A, Zhang X, Kunkel T, Ebright R, Berman H. Indirect readout of DNA sequence at the primary-kink site in the CAP-DNA complex: alteration of DNA binding specificity through alteration of DNA kinking. J Mol Biol. 2001;314:75-82 pubmed
    ..The Glu181-->Asp substitution does not eliminate hydrogen-bond formation with G:C(7), and thus does not eliminate direct-readout-based specificity for G:C(7). ..
  13. Napoli A, Lawson C, Ebright R, Berman H. Indirect readout of DNA sequence at the primary-kink site in the CAP-DNA complex: recognition of pyrimidine-purine and purine-purine steps. J Mol Biol. 2006;357:173-83 pubmed
  14. Green J, Scott C, Guest J. Functional versatility in the CRP-FNR superfamily of transcription factors: FNR and FLP. Adv Microb Physiol. 2001;44:1-34 pubmed
    ..And, at the level of RNA-polymerase-interaction, different combinations of three discrete regions contacting the polymerase (the activating regions) are used for polymerase recruitment and promoting transcription...
  15. Dixit S, Andrews D, Beveridge D. Induced fit and the entropy of structural adaptation in the complexation of CAP and lambda-repressor with cognate DNA sequences. Biophys J. 2005;88:3147-57 pubmed
    ..The entropy arising from protein DNA cross-correlations, a contribution not previously discussed, is surprisingly large. ..
  16. Cooper T, Rozen D, Lenski R. Parallel changes in gene expression after 20,000 generations of evolution in Escherichiacoli. Proc Natl Acad Sci U S A. 2003;100:1072-7 pubmed
    ..Our study demonstrates the utility of expression arrays for addressing evolutionary issues including the quantitative measurement of parallel evolution in independent lineages and the identification of beneficial mutations. ..
  17. Tanaka Y, Kimata K, Inada T, Tagami H, Aiba H. Negative regulation of the pts operon by Mlc: mechanism underlying glucose induction in Escherichia coli. Genes Cells. 1999;4:391-9 pubmed
    ..We propose that glucose induces the pts transcription by modulating the Mlc activity. The mechanism by which glucose modulates the Mlc action remains to be studied. ..
  18. Popovych N, Sun S, Ebright R, Kalodimos C. Dynamically driven protein allostery. Nat Struct Mol Biol. 2006;13:831-8 pubmed
    ..The results provide strong support for the existence of purely dynamics-driven allostery. ..
  19. Plumbridge J, Pellegrini O. Expression of the chitobiose operon of Escherichia coli is regulated by three transcription factors: NagC, ChbR and CAP. Mol Microbiol. 2004;52:437-49 pubmed
  20. Cameron A, Volar M, Bannister L, Redfield R. RNA secondary structure regulates the translation of sxy and competence development in Haemophilus influenzae. Nucleic Acids Res. 2008;36:10-20 pubmed
    ..Thus, mRNA secondary structure is responsive to conditions where DNA uptake will be favorable, and transcription of sxy is simultaneously enhanced if CRP activation signals that energy supplies are limited. ..
  21. Desai T, Rodionov D, Gelfand M, Alm E, Rao C. Engineering transcription factors with novel DNA-binding specificity using comparative genomics. Nucleic Acids Res. 2009;37:2493-503 pubmed publisher
    ..Collectively, these results in this work demonstrate that comparative genomics can inform the design of bacterial transcription factors. ..
  22. Fuchs E, Brutinel E, Jones A, Fulcher N, Urbanowski M, Yahr T, et al. The Pseudomonas aeruginosa Vfr regulator controls global virulence factor expression through cyclic AMP-dependent and -independent mechanisms. J Bacteriol. 2010;192:3553-64 pubmed publisher
    ..aeruginosa to fine-tune its virulence program in response to specific host cues or environments. ..
  23. Mazon H, Gabor K, Leys D, Heck A, van der Oost J, van den Heuvel R. Transcriptional activation by CprK1 is regulated by protein structural changes induced by effector binding and redox state. J Biol Chem. 2007;282:11281-90 pubmed
  24. Won H, Seo M, Ko H, Choi W, Lee B. Interdomain interaction of cyclic AMP receptor protein in the absence of cyclic AMP. J Biochem. 2008;143:163-7 pubmed
    Interdomain interaction of apo-cyclic AMP receptor protein (apo-CRP) was qualified using its isolated domains...
  25. Ferrell E, Carty N, Colmer Hamood J, Hamood A, West S. Regulation of Pseudomonas aeruginosa ptxR by Vfr. Microbiology. 2008;154:431-9 pubmed publisher
    ..Our results suggest that Vfr modulates toxA and lasB expression in PAO1 through PtxR. A model defining the relationships between these different genes is presented. ..
  26. Davinic M, Carty N, Colmer Hamood J, San Francisco M, Hamood A. Role of Vfr in regulating exotoxin A production by Pseudomonas aeruginosa. Microbiology. 2009;155:2265-73 pubmed publisher
  27. Gao H, Wang X, Yang Z, Chen J, Liang Y, Chen H, et al. Physiological roles of ArcA, Crp, and EtrA and their interactive control on aerobic and anaerobic respiration in Shewanella oneidensis. PLoS ONE. 2010;5:e15295 pubmed publisher
    ..This extensive survey demonstrated that all these three global regulators are functional in S. oneidensis. In addition, the reporter system constructed in this study will facilitate in vivo transcriptional analysis of targeted promoters...
  28. Spreadbury C, Pallen M, Overton T, Behr M, Mostowy S, Spiro S, et al. Point mutations in the DNA- and cNMP-binding domains of the homologue of the cAMP receptor protein (CRP) in Mycobacterium bovis BCG: implications for the inactivation of a global regulator and strain attenuation. Microbiology. 2005;151:547-56 pubmed
    ..bovis BCG strains. This raises the possibility that a contributing factor to the attenuation of BCG strains may be an inability of this global regulator to control the expression of genes required for in vivo survival and persistence. ..
  29. Yu S, Lee J. Role of residue 138 in the interdomain hinge region in transmitting allosteric signals for DNA binding in Escherichia coli cAMP receptor protein. Biochemistry. 2004;43:4662-9 pubmed
    ..All these correlations indicate the importance of structural stability and dynamics in the ability of CRP to manifest its intrinsic allosteric properties. ..
  30. Holcroft C, Egan S. Interdependence of activation at rhaSR by cyclic AMP receptor protein, the RNA polymerase alpha subunit C-terminal domain, and rhaR. J Bacteriol. 2000;182:6774-82 pubmed
    ..assays of various rhaS-lacZ promoter fusions combined with mobility shift assays indicated that a cyclic AMP receptor protein (CRP) site located at -111.5 is also required for full activation of rhaSR expression...
  31. Ma Z, Richard H, Foster J. pH-Dependent modulation of cyclic AMP levels and GadW-dependent repression of RpoS affect synthesis of the GadX regulator and Escherichia coli acid resistance. J Bacteriol. 2003;185:6852-9 pubmed
    ..The presence of multiple pH control pathways governing expression of this acid resistance system is thought to reflect different environmental routes to a low pH...
  32. Dyckman D, Fried M. The Escherichia coli cyclic AMP receptor protein forms a 2:2 complex with RNA polymerase holoenzyme, in vitro. J Biol Chem. 2002;277:19064-70 pubmed
    Sedimentation equilibrium studies show that the Escherichia coli cyclic AMP receptor protein (CAP) and RNA polymerase holoenzyme associate to form a 2:2 complex in vitro...
  33. Lin S, Lee J. Communications between the high-affinity cyclic nucleotide binding sites in E. coli cyclic AMP receptor protein: effect of single site mutations. Biochemistry. 2002;41:11857-67 pubmed
    ..Instead, these results are more consistent with the concept that CRP exists as an ensemble of native states, the distribution of which can be altered by these mutations. ..
  34. Basak S, Jiang R. Enhancing E. coli tolerance towards oxidative stress via engineering its global regulator cAMP receptor protein (CRP). PLoS ONE. 2012;7:e51179 pubmed publisher
    ..The positive outcome of this approach may suggest that engineering CRP can be successfully implemented as an efficient strain engineering alternative for E. coli. ..
  35. Traxler M, Chang D, Conway T. Guanosine 3',5'-bispyrophosphate coordinates global gene expression during glucose-lactose diauxie in Escherichia coli. Proc Natl Acad Sci U S A. 2006;103:2374-9 pubmed
  36. Antonova E, Bernardy E, Hammer B. Natural competence in Vibrio cholerae is controlled by a nucleoside scavenging response that requires CytR-dependent anti-activation. Mol Microbiol. 2012;86:1215-31 pubmed publisher
    ..Thus, a nucleoside scavenging mechanism couples nutrient stress and cell-cell signalling to natural transformation in V.?cholerae as described in other bacterial pathogens. ..
  37. Belyaeva T, Wade J, Webster C, Howard V, Thomas M, Hyde E, et al. Transcription activation at the Escherichia coli melAB promoter: the role of MelR and the cyclic AMP receptor protein. Mol Microbiol. 2000;36:211-22 pubmed
    ..This activation is dependent on MelR and melibiose. These studies also show that the cyclic AMP receptor protein (CRP) interacts with the melAB promoter and increases MelR-dependent transcription activation...
  38. McLeod S, Xu J, Johnson R. Coactivation of the RpoS-dependent proP P2 promoter by fis and cyclic AMP receptor protein. J Bacteriol. 2000;182:4180-7 pubmed
    ..Efficient transcription in vitro requires that both activators must be preincubated with the DNA prior to addition of RNA polymerase. ..
  39. Kapanidis A, Ebright Y, Ludescher R, Chan S, Ebright R. Mean DNA bend angle and distribution of DNA bend angles in the CAP-DNA complex in solution. J Mol Biol. 2001;312:453-68 pubmed
    ..The methods used here will permit mutational analysis of CAP-induced DNA bending and the role of CAP-induced DNA bending in transcriptional activation. ..
  40. Stapleton M, Haq I, Hunt D, Arnvig K, Artymiuk P, Buxton R, et al. Mycobacterium tuberculosis cAMP receptor protein (Rv3676) differs from the Escherichia coli paradigm in its cAMP binding and DNA binding properties and transcription activation properties. J Biol Chem. 2010;285:7016-27 pubmed publisher
    ..Thus, M. tuberculosis CRP has evolved several distinct characteristics, compared with the Escherichia coli CRP paradigm, to allow it to regulate gene expression against a background of high concentrations of cAMP. ..
  41. Husnain S, Busby S, Thomas M. Downregulation of the Escherichia coli guaB promoter by upstream-bound cyclic AMP receptor protein. J Bacteriol. 2009;191:6094-104 pubmed publisher
    ..nucleoid-associated protein FIS, and putative binding sites for the regulatory proteins DnaA, PurR, and cyclic AMP receptor protein (CRP)...
  42. Wickstrum J, Egan S. Ni+-affinity purification of untagged cAMP receptor protein. Biotechniques. 2002;33:728-30 pubmed
  43. Wolfgang M, Lee V, Gilmore M, Lory S. Coordinate regulation of bacterial virulence genes by a novel adenylate cyclase-dependent signaling pathway. Dev Cell. 2003;4:253-63 pubmed
    ..Transcriptome analysis of mutants lacking the ability to synthesize cAMP or the cAMP binding protein Vfr implicated this pathway in the global regulation of host-directed virulence determinants, including the TTSS. ..
  44. Akhter Y, Yellaboina S, Farhana A, Ranjan A, Ahmed N, Hasnain S. Genome scale portrait of cAMP-receptor protein (CRP) regulons in mycobacteria points to their role in pathogenesis. Gene. 2008;407:148-58 pubmed
    ..The conservation of the CRP regulated genes in pathogenic mycobacteria, as opposed to non-pathogenic ones, highlights the importance of CRP-regulated genes in pathogenesis. ..
  45. Smith R, Wolfgang M, Lory S. An adenylate cyclase-controlled signaling network regulates Pseudomonas aeruginosa virulence in a mouse model of acute pneumonia. Infect Immun. 2004;72:1677-84 pubmed
  46. Shinkai A, Kira S, Nakagawa N, Kashihara A, Kuramitsu S, Yokoyama S. Transcription activation mediated by a cyclic AMP receptor protein from Thermus thermophilus HB8. J Bacteriol. 2007;189:3891-901 pubmed
    ..thermophilus-specific proteins of unknown function. These results suggest a role for cAMP signal transduction in T. thermophilus and imply the T. thermophilus CRP is a cAMP-responsive regulator. ..
  47. Omagari K, Yoshimura H, Takano M, Hao D, Ohmori M, Sarai A, et al. Systematic single base-pair substitution analysis of DNA binding by the cAMP receptor protein in cyanobacterium Synechocystis sp. PCC 6803. FEBS Lett. 2004;563:55-8 pubmed
    ..The result is similar to that previously reported for CRP, whereas there were differences between SYCRP1 and CRP in the rank order of affinity for each substitution. ..
  48. Teplitski M, Goodier R, Ahmer B. Catabolite repression of the SirA regulatory cascade in Salmonella enterica. Int J Med Microbiol. 2006;296:449-66 pubmed
    ..Although SirA does not regulate csrA, this gene was also under crp/cya control. Supplementation of a rich medium with phosphate diminished the catabolite control of the csr portion but not the virulence portion of the SirA regulon. ..
  49. Benoff B, Yang H, Lawson C, Parkinson G, Liu J, Blatter E, et al. Structural basis of transcription activation: the CAP-alpha CTD-DNA complex. Science. 2002;297:1562-6 pubmed
    ..These findings are consistent with the proposal that activation involves a simple "recruitment" mechanism. ..
  50. De Lay N, Gottesman S. The Crp-activated small noncoding regulatory RNA CyaR (RyeE) links nutritional status to group behavior. J Bacteriol. 2009;191:461-76 pubmed publisher
    ..These results provide insight into the mechanisms by which Crp negatively regulates genes such as luxS and ompX and provide a link between catabolite repression, quorum sensing, and nitrogen assimilation in E. coli. ..
  51. Beatty C, Browning D, Busby S, Wolfe A. Cyclic AMP receptor protein-dependent activation of the Escherichia coli acsP2 promoter by a synergistic class III mechanism. J Bacteriol. 2003;185:5148-57 pubmed
    The cyclic AMP receptor protein (CRP) activates transcription of the Escherichia coli acs gene, which encodes an acetate-scavenging enzyme required for fitness during periods of carbon starvation...
  52. Fried M, Daugherty M. In vitro interaction of the Escherichia coli cyclic AMP receptor protein with the lactose repressor. J Biol Chem. 2001;276:11226-9 pubmed
    Sedimentation equilibrium studies show that the Escherichia coli cyclic AMP receptor protein (CAP) and lactose repressor associate to form a 2:1 complex in vitro...
  53. Tomás Gallardo L, Santero E, Floriano B. Involvement of a putative cyclic amp receptor protein (CRP)-like binding sequence and a CRP-like protein in glucose-mediated catabolite repression of thn genes in Rhodococcus sp. strain TFB. Appl Environ Microbiol. 2012;78:5460-2 pubmed publisher
    ..The protein was detected bound to putative CRP-like boxes localized at the promoters of the thnA1 and thnS genes...