cAMP-activated global transcriptional regulator CRP

Details

Name
cAMP-activated global transcriptional regulator CRP
Synonyms
  • cAMP receptor protein
  • cAMP regulatory protein
  • cap
  • Catabolite activator protein
  • Catabolite gene activator
  • CRP
  • csm
Gene Name
crp
Organism
Escherichia coli (strain K12)
Amino acid sequence
>lcl|BSEQ0011452|cAMP-activated global transcriptional regulator CRP
MVLGKPQTDPTLEWFLSHCHIHKYPSKSTLIHQGEKAETLYYIVKGSVAVLIKDEEGKEM
ILSYLNQGDFIGELGLFEEGQERSAWVRAKTACEVAEISYKKFRQLIQVNPDILMRLSAQ
MARRLQVTSEKVGNLAFLDVTGRIAQTLLNLAKQPDAMTHPDGMQIKITRQEIGQIVGCS
RETVGRILKMLEDQNLISAHGKTIVVYGTR
Number of residues
210
Molecular Weight
23640.275
Theoretical pI
8.46
GO Classification
Functions
cAMP binding / DNA binding / transcription factor activity, sequence-specific DNA binding
Processes
carbon catabolite repression of transcription / negative regulation of transcription, DNA-templated / positive regulation of transcription, DNA-templated / transcription, DNA-templated
Components
cytosol
General Function
Transcription factor activity, sequence-specific dna binding
Specific Function
A global transcription regulator. Complexes with cyclic AMP (cAMP) which allosterically activates DNA binding (to consensus sequence 5'-AAATGTGATCTAGATCACATTT-3') to directly regulate the transcription of about 300 genes in about 200 operons and indirectly regulate the expression of about half the genome. There are 3 classes of CRP promoters; class I promoters have a single CRP-binding site upstream of the RNA polymerase (RNAP)-binding site, whereas in class II promoters the single CRP- and RNAP-binding site overlap, CRP making multiple contacts with RNAP. Class III promoters require multiple activator molecules, including at least one CRP dimer. It can act as an activator, repressor, coactivator or corepressor. Induces a severe bend in DNA (about 87 degrees), bringing upstream promoter elements into contact with RNAP. Acts as a negative regulator of its own synthesis as well as for adenylate cyclase (cyaA), which generates cAMP. High levels of active CRP are detrimental to growth (PubMed:16260780). Plays a major role in carbon catabolite repression (CCR). CCR involves cAMP, adenylate cyclase (cyaA), CRP and the EIIA-Glc component of the PTS (crr). In the presence of glucose EIIA-Glc is dephosphorylated, and does not activate adenylate cyclase, leading to reduced cAMP and thus decreased CRP activity. Also plays a role in many other processes (see PubMed:22573269).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasmic
Gene sequence
>lcl|BSEQ0011453|cAMP-activated global transcriptional regulator CRP (crp)
ATGGTGCTTGGCAAACCGCAAACAGACCCGACTCTCGAATGGTTCTTGTCTCATTGCCAC
ATTCATAAGTACCCATCCAAGAGCAAGCTTATTCACCAGGGTGAAAAAGCGGAAACGCTG
TACTACATCGTTAAAGGCTCTGTGGCAGTGCTGATCAAAGACGAAGAGGGTAAAGAAATG
ATCCTCTCCTATCTGAATCAGGGTGATTTTATTGGCGAACTGGGCCTGTTTGAAGAGGGC
CAGGAACGTAGCGCATGGGTACGTGCGAAAACCGCCTGTGAAGTGGCTGAAATTTCGTAC
AAAAAATTTCGCCAATTGATTCAGGTAAACCCGGACATTCTGATGCGTTTGTCTGCACAG
ATGGCGCGTCGTCTGCAAGTCACTTCAGAGAAAGTGGGCAACCTGGCGTTCCTCGACGTG
ACGGGCCGCATTGCACAGACTCTGCTGAATCTGGCAAAACAACCAGACGCTATGACTCAC
CCGGACGGTATGCAAATCAAAATTACCCGTCAGGAAATTGGTCAGATTGTCGGCTGTTCT
CGTGAAACCGTGGGACGCATTCTGAAGATGCTGGAAGATCAGAACCTGATCTCCGCACAC
GGTAAAACCATCGTCGTTTACGGCACTCGTTAA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP0ACJ8
UniProtKB Entry NameCRP_ECOLI
GenBank Protein ID145594
GenBank Gene IDJ01598
General References
  1. Aiba H, Fujimoto S, Ozaki N: Molecular cloning and nucleotide sequencing of the gene for E. coli cAMP receptor protein. Nucleic Acids Res. 1982 Feb 25;10(4):1345-61. [Article]
  2. Cossart P, Gicquel-Sanzey B: Cloning and sequence of the crp gene of Escherichia coli K 12. Nucleic Acids Res. 1982 Feb 25;10(4):1363-78. [Article]
  3. Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. [Article]
  4. Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, Ohtsubo E, Baba T, Wanner BL, Mori H, Horiuchi T: Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. Epub 2006 Feb 21. [Article]
  5. Otsuka Y, Koga M, Iwamoto A, Yonesaki T: A role of RnlA in the RNase LS activity from Escherichia coli. Genes Genet Syst. 2007 Aug;82(4):291-9. [Article]
  6. Sabourin D, Beckwith J: Deletion of the Escherichia coli crp gene. J Bacteriol. 1975 Apr;122(1):338-40. [Article]
  7. Aiba H: Autoregulation of the Escherichia coli crp gene: CRP is a transcriptional repressor for its own gene. Cell. 1983 Jan;32(1):141-9. [Article]
  8. Aiba H: Transcription of the Escherichia coli adenylate cyclase gene is negatively regulated by cAMP-cAMP receptor protein. J Biol Chem. 1985 Mar 10;260(5):3063-70. [Article]
  9. Gent ME, Gartner S, Gronenborn AM, Sandulache R, Clore GM: Site-directed mutants of the cAMP receptor protein--DNA binding of five mutant proteins. Protein Eng. 1987 Jun;1(3):201-3. [Article]
  10. Gronenborn AM, Sandulache R, Gartner S, Clore GM: Mutations in the cyclic AMP binding site of the cyclic AMP receptor protein of Escherichia coli. Biochem J. 1988 Aug 1;253(3):801-7. [Article]
  11. Pinkney M, Hoggett JG: Binding of the cyclic AMP receptor protein of Escherichia coli to RNA polymerase. Biochem J. 1988 Mar 15;250(3):897-902. [Article]
  12. Igarashi K, Ishihama A: Bipartite functional map of the E. coli RNA polymerase alpha subunit: involvement of the C-terminal region in transcription activation by cAMP-CRP. Cell. 1991 Jun 14;65(6):1015-22. [Article]
  13. Hanamura A, Aiba H: A new aspect of transcriptional control of the Escherichia coli crp gene: positive autoregulation. Mol Microbiol. 1992 Sep;6(17):2489-97. [Article]
  14. Ryu S, Kim J, Adhya S, Garges S: Pivotal role of amino acid at position 138 in the allosteric hinge reorientation of cAMP receptor protein. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):75-9. [Article]
  15. Zhou Y, Zhang X, Ebright RH: Identification of the activating region of catabolite gene activator protein (CAP): isolation and characterization of mutants of CAP specifically defective in transcription activation. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6081-5. [Article]
  16. Niu W, Zhou Y, Dong Q, Ebright YW, Ebright RH: Characterization of the activating region of Escherichia coli catabolite gene activator protein (CAP). I. Saturation and alanine-scanning mutagenesis. J Mol Biol. 1994 Nov 4;243(4):595-602. [Article]
  17. Niu W, Kim Y, Tau G, Heyduk T, Ebright RH: Transcription activation at class II CAP-dependent promoters: two interactions between CAP and RNA polymerase. Cell. 1996 Dec 13;87(6):1123-34. [Article]
  18. VanBogelen RA, Abshire KZ, Moldover B, Olson ER, Neidhardt FC: Escherichia coli proteome analysis using the gene-protein database. Electrophoresis. 1997 Aug;18(8):1243-51. [Article]
  19. Rhodius VA, Busby SJ: Transcription activation by the Escherichia coli cyclic AMP receptor protein: determinants within activating region 3. J Mol Biol. 2000 Jun 2;299(2):295-310. [Article]
  20. Rhodius VA, Busby SJ: Interactions between activating region 3 of the Escherichia coli cyclic AMP receptor protein and region 4 of the RNA polymerase sigma(70) subunit: application of suppression genetics. J Mol Biol. 2000 Jun 2;299(2):311-24. [Article]
  21. Yu S, Lee JC: Role of residue 138 in the interdomain hinge region in transmitting allosteric signals for DNA binding in Escherichia coli cAMP receptor protein. Biochemistry. 2004 Apr 27;43(16):4662-9. [Article]
  22. Zheng D, Constantinidou C, Hobman JL, Minchin SD: Identification of the CRP regulon using in vitro and in vivo transcriptional profiling. Nucleic Acids Res. 2004 Nov 1;32(19):5874-93. Print 2004. [Article]
  23. Grainger DC, Hurd D, Harrison M, Holdstock J, Busby SJ: Studies of the distribution of Escherichia coli cAMP-receptor protein and RNA polymerase along the E. coli chromosome. Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17693-8. Epub 2005 Nov 21. [Article]
  24. Youn H, Kerby RL, Conrad M, Roberts GP: Study of highly constitutively active mutants suggests how cAMP activates cAMP receptor protein. J Biol Chem. 2006 Jan 13;281(2):1119-27. Epub 2005 Oct 31. [Article]
  25. Iwamoto A, Lemire S, Yonesaki T: Post-transcriptional control of Crp-cAMP by RNase LS in Escherichia coli. Mol Microbiol. 2008 Dec;70(6):1570-8. doi: 10.1111/j.1365-2958.2008.06504.x. Epub 2008 Oct 23. [Article]
  26. Zhang J, Sprung R, Pei J, Tan X, Kim S, Zhu H, Liu CF, Grishin NV, Zhao Y: Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli. Mol Cell Proteomics. 2009 Feb;8(2):215-25. doi: 10.1074/mcp.M800187-MCP200. Epub 2008 Aug 23. [Article]
  27. Kolb A, Busby S, Buc H, Garges S, Adhya S: Transcriptional regulation by cAMP and its receptor protein. Annu Rev Biochem. 1993;62:749-95. [Article]
  28. Busby S, Ebright RH: Transcription activation by catabolite activator protein (CAP). J Mol Biol. 1999 Oct 22;293(2):199-213. [Article]
  29. Won HS, Lee YS, Lee SH, Lee BJ: Structural overview on the allosteric activation of cyclic AMP receptor protein. Biochim Biophys Acta. 2009 Sep;1794(9):1299-308. doi: 10.1016/j.bbapap.2009.04.015. Epub 2009 May 9. [Article]
  30. Escalante A, Salinas Cervantes A, Gosset G, Bolivar F: Current knowledge of the Escherichia coli phosphoenolpyruvate-carbohydrate phosphotransferase system: peculiarities of regulation and impact on growth and product formation. Appl Microbiol Biotechnol. 2012 Jun;94(6):1483-94. doi: 10.1007/s00253-012-4101-5. Epub 2012 May 11. [Article]
  31. McKay DB, Weber IT, Steitz TA: Structure of catabolite gene activator protein at 2.9-A resolution. Incorporation of amino acid sequence and interactions with cyclic AMP. J Biol Chem. 1982 Aug 25;257(16):9518-24. [Article]
  32. Weber IT, Steitz TA: Structure of a complex of catabolite gene activator protein and cyclic AMP refined at 2.5 A resolution. J Mol Biol. 1987 Nov 20;198(2):311-26. [Article]
  33. Schultz SC, Shields GC, Steitz TA: Crystal structure of a CAP-DNA complex: the DNA is bent by 90 degrees. Science. 1991 Aug 30;253(5023):1001-7. [Article]
  34. Parkinson G, Wilson C, Gunasekera A, Ebright YW, Ebright RH, Berman HM: Structure of the CAP-DNA complex at 2.5 angstroms resolution: a complete picture of the protein-DNA interface. J Mol Biol. 1996 Jul 19;260(3):395-408. [Article]
  35. Passner JM, Steitz TA: The structure of a CAP-DNA complex having two cAMP molecules bound to each monomer. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):2843-7. [Article]
  36. Passner JM, Schultz SC, Steitz TA: Modeling the cAMP-induced allosteric transition using the crystal structure of CAP-cAMP at 2.1 A resolution. J Mol Biol. 2000 Dec 15;304(5):847-59. [Article]
  37. Benoff B, Yang H, Lawson CL, Parkinson G, Liu J, Blatter E, Ebright YW, Berman HM, Ebright RH: Structural basis of transcription activation: the CAP-alpha CTD-DNA complex. Science. 2002 Aug 30;297(5586):1562-6. [Article]
  38. Popovych N, Tzeng SR, Tonelli M, Ebright RH, Kalodimos CG: Structural basis for cAMP-mediated allosteric control of the catabolite activator protein. Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):6927-32. doi: 10.1073/pnas.0900595106. Epub 2009 Apr 9. [Article]
  39. Sharma H, Yu S, Kong J, Wang J, Steitz TA: Structure of apo-CAP reveals that large conformational changes are necessary for DNA binding. Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16604-9. doi: 10.1073/pnas.0908380106. Epub 2009 Sep 16. [Article]
  40. Hudson BP, Quispe J, Lara-Gonzalez S, Kim Y, Berman HM, Arnold E, Ebright RH, Lawson CL: Three-dimensional EM structure of an intact activator-dependent transcription initiation complex. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19830-5. doi: 10.1073/pnas.0908782106. Epub 2009 Nov 10. [Article]
  41. Tzeng SR, Kalodimos CG: Allosteric inhibition through suppression of transient conformational states. Nat Chem Biol. 2013 Jul;9(7):462-5. doi: 10.1038/nchembio.1250. Epub 2013 May 5. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02527Cyclic adenosine monophosphateexperimentalunknownDetails