CRP_ECOLI
ID CRP_ECOLI Reviewed; 210 AA.
AC P0ACJ8; P03020; Q2M723;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=cAMP-activated global transcriptional regulator CRP;
DE AltName: Full=Catabolite activator protein;
DE Short=CAP;
DE AltName: Full=Catabolite gene activator;
DE AltName: Full=cAMP receptor protein;
DE Short=CRP;
DE AltName: Full=cAMP regulatory protein;
GN Name=crp; Synonyms=cap, csm; OrderedLocusNames=b3357, JW5702;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND CAMP-BINDING.
RC STRAIN=K12;
RX PubMed=6280140; DOI=10.1093/nar/10.4.1345;
RA Aiba H., Fujimoto S., Ozaki N.;
RT "Molecular cloning and nucleotide sequencing of the gene for E. coli cAMP
RT receptor protein.";
RL Nucleic Acids Res. 10:1345-1361(1982).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=6280141; DOI=10.1093/nar/10.4.1363;
RA Cossart P., Gicquel-Sanzey B.;
RT "Cloning and sequence of the crp gene of Escherichia coli K 12.";
RL Nucleic Acids Res. 10:1363-1378(1982).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP PROTEIN SEQUENCE OF 2-10.
RC STRAIN=K12;
RX PubMed=17895580; DOI=10.1266/ggs.82.291;
RA Otsuka Y., Koga M., Iwamoto A., Yonesaki T.;
RT "A role of RnlA in the RNase LS activity from Escherichia coli.";
RL Genes Genet. Syst. 82:291-299(2007).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=164435; DOI=10.1128/jb.122.1.338-340.1975;
RA Sabourin D., Beckwith J.;
RT "Deletion of the Escherichia coli crp gene.";
RL J. Bacteriol. 122:338-340(1975).
RN [7]
RP INDUCTION, NEGATIVE AUTOREGULATION, AND DNA-BINDING.
RX PubMed=6297782; DOI=10.1016/0092-8674(83)90504-4;
RA Aiba H.;
RT "Autoregulation of the Escherichia coli crp gene: CRP is a transcriptional
RT repressor for its own gene.";
RL Cell 32:141-149(1983).
RN [8]
RP FUNCTION AS A TRANSCRIPTIONAL REPRESSOR, AUTOREGULATION, AND DNA-BINDING.
RX PubMed=2982847; DOI=10.1016/s0021-9258(18)89473-x;
RA Aiba H.;
RT "Transcription of the Escherichia coli adenylate cyclase gene is negatively
RT regulated by cAMP-cAMP receptor protein.";
RL J. Biol. Chem. 260:3063-3070(1985).
RN [9]
RP DNA-BINDING, AND MUTAGENESIS OF SER-129; ARG-181 AND ARG-186.
RX PubMed=3333845; DOI=10.1093/protein/1.3.201;
RA Gent M.E., Gartner S., Gronenborn A.M., Sandulache R., Clore G.M.;
RT "Site-directed mutants of the cAMP receptor protein -- DNA binding of five
RT mutant proteins.";
RL Protein Eng. 1:201-203(1987).
RN [10]
RP CAMP-BINDING, AND MUTAGENESIS OF SER-63; ARG-83; SER-84; THR-128 AND
RP SER-129.
RX PubMed=2845936; DOI=10.1042/bj2530801;
RA Gronenborn A.M., Sandulache R., Clore G.M.;
RT "Mutations in the cyclic AMP binding site of the cyclic AMP receptor
RT protein of Escherichia coli.";
RL Biochem. J. 253:801-807(1988).
RN [11]
RP CAMP-BINDING, INTERACTION WITH RNA POLYMERASE, AND SUBUNIT.
RC STRAIN=MRE-600;
RX PubMed=2839152; DOI=10.1042/bj2500897;
RA Pinkney M., Hoggett J.G.;
RT "Binding of the cyclic AMP receptor protein of Escherichia coli to RNA
RT polymerase.";
RL Biochem. J. 250:897-902(1988).
RN [12]
RP FUNCTION AS AN ACTIVATOR, FUNCTION AS A REPRESSOR, PROBABLE INTERACTION
RP WITH RPOA, AND SUBUNIT.
RX PubMed=1646077; DOI=10.1016/0092-8674(91)90553-b;
RA Igarashi K., Ishihama A.;
RT "Bipartite functional map of the E. coli RNA polymerase alpha subunit:
RT involvement of the C-terminal region in transcription activation by cAMP-
RT CRP.";
RL Cell 65:1015-1022(1991).
RN [13]
RP INDUCTION, AND POSITIVE AUTOREGULATION.
RX PubMed=1328816; DOI=10.1111/j.1365-2958.1992.tb01425.x;
RA Hanamura A., Aiba H.;
RT "A new aspect of transcriptional control of the Escherichia coli crp gene:
RT positive autoregulation.";
RL Mol. Microbiol. 6:2489-2497(1992).
RN [14]
RP MUTAGENESIS OF ASP-139.
RX PubMed=8380500; DOI=10.1073/pnas.90.1.75;
RA Ryu S., Kim J., Adhya S., Garges S.;
RT "Pivotal role of amino acid at position 138 in the allosteric hinge
RT reorientation of cAMP receptor protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:75-79(1993).
RN [15]
RP FUNCTION, CHARACTERIZATION OF ACTIVATING REGION 1 (AR1), DNA-BINDING, AND
RP MUTAGENESIS OF ALA-157; THR-159; HIS-160 AND GLY-163.
RX PubMed=8392187; DOI=10.1073/pnas.90.13.6081;
RA Zhou Y., Zhang X., Ebright R.H.;
RT "Identification of the activating region of catabolite gene activator
RT protein (CAP): isolation and characterization of mutants of CAP
RT specifically defective in transcription activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:6081-6085(1993).
RN [16]
RP FUNCTION, CHARACTERIZATION OF ACTIVATING REGION 1 (AR1), DNA-BINDING, AND
RP MUTAGENESIS OF ALA-157; THR-159; HIS-160 AND GLY-163.
RC STRAIN=K12;
RX PubMed=7966284; DOI=10.1016/0022-2836(94)90034-5;
RA Niu W., Zhou Y., Dong Q., Ebright Y.W., Ebright R.H.;
RT "Characterization of the activating region of Escherichia coli catabolite
RT gene activator protein (CAP). I. Saturation and alanine-scanning
RT mutagenesis.";
RL J. Mol. Biol. 243:595-602(1994).
RN [17]
RP FUNCTION, CHARACTERIZATION OF ACTIVATING REGION 2 (AR2), INTERACTION WITH
RP RPOA, DNA-BINDING, DNA-BENDING, AND MUTAGENESIS OF HIS-20; HIS-22; LYS-53;
RP GLU-97; LYS-102; THR-159; HIS-160 AND GLY-163.
RX PubMed=8978616; DOI=10.1016/s0092-8674(00)81806-1;
RA Niu W., Kim Y., Tau G., Heyduk T., Ebright R.H.;
RT "Transcription activation at class II CAP-dependent promoters: two
RT interactions between CAP and RNA polymerase.";
RL Cell 87:1123-1134(1996).
RN [18]
RP IDENTIFICATION BY 2D-GEL.
RX PubMed=9298644; DOI=10.1002/elps.1150180805;
RA VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.;
RT "Escherichia coli proteome analysis using the gene-protein database.";
RL Electrophoresis 18:1243-1251(1997).
RN [19]
RP FUNCTION, CHARACTERIZATION OF ACTIVATING REGION 3 (AR3), AND MUTAGENESIS OF
RP 54-ASP--GLU-56 AND GLU-59.
RX PubMed=10860739; DOI=10.1006/jmbi.2000.3736;
RA Rhodius V.A., Busby S.J.;
RT "Transcription activation by the Escherichia coli cyclic AMP receptor
RT protein: determinants within activating region 3.";
RL J. Mol. Biol. 299:295-310(2000).
RN [20]
RP FUNCTION, CHARACTERIZATION OF ACTIVATING REGION 3 (AR3), PROBABLE
RP INTERACTION WITH SIGMA-70 (RPOD), AND MUTAGENESIS OF GLU-59.
RX PubMed=10860740; DOI=10.1006/jmbi.2000.3737;
RA Rhodius V.A., Busby S.J.;
RT "Interactions between activating region 3 of the Escherichia coli cyclic
RT AMP receptor protein and region 4 of the RNA polymerase sigma(70) subunit:
RT application of suppression genetics.";
RL J. Mol. Biol. 299:311-324(2000).
RN [21]
RP MUTAGENESIS OF ASP-139.
RX PubMed=15096034; DOI=10.1021/bi0362166;
RA Yu S., Lee J.C.;
RT "Role of residue 138 in the interdomain hinge region in transmitting
RT allosteric signals for DNA binding in Escherichia coli cAMP receptor
RT protein.";
RL Biochemistry 43:4662-4669(2004).
RN [22]
RP FUNCTION, REGULON, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-102 AND
RP HIS-160.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=15520470; DOI=10.1093/nar/gkh908;
RA Zheng D., Constantinidou C., Hobman J.L., Minchin S.D.;
RT "Identification of the CRP regulon using in vitro and in vivo
RT transcriptional profiling.";
RL Nucleic Acids Res. 32:5874-5893(2004).
RN [23]
RP FUNCTION, AND REGULON.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=16301522; DOI=10.1073/pnas.0506687102;
RA Grainger D.C., Hurd D., Harrison M., Holdstock J., Busby S.J.;
RT "Studies of the distribution of Escherichia coli cAMP-receptor protein and
RT RNA polymerase along the E. coli chromosome.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:17693-17698(2005).
RN [24]
RP FUNCTION, AND MUTAGENESIS OF 128-THR-SER-129.
RX PubMed=16260780; DOI=10.1074/jbc.m509421200;
RA Youn H., Kerby R.L., Conrad M., Roberts G.P.;
RT "Study of highly constitutively active mutants suggests how cAMP activates
RT cAMP receptor protein.";
RL J. Biol. Chem. 281:1119-1127(2006).
RN [25]
RP INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12;
RX PubMed=19019153; DOI=10.1111/j.1365-2958.2008.06504.x;
RA Iwamoto A., Lemire S., Yonesaki T.;
RT "Post-transcriptional control of Crp-cAMP by RNase LS in Escherichia
RT coli.";
RL Mol. Microbiol. 70:1570-1578(2008).
RN [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-101, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=K12 / JW1106, and K12 / MG1655 / ATCC 47076;
RX PubMed=18723842; DOI=10.1074/mcp.m800187-mcp200;
RA Zhang J., Sprung R., Pei J., Tan X., Kim S., Zhu H., Liu C.F.,
RA Grishin N.V., Zhao Y.;
RT "Lysine acetylation is a highly abundant and evolutionarily conserved
RT modification in Escherichia coli.";
RL Mol. Cell. Proteomics 8:215-225(2009).
RN [27]
RP REVIEW.
RX PubMed=8394684; DOI=10.1146/annurev.bi.62.070193.003533;
RA Kolb A., Busby S., Buc H., Garges S., Adhya S.;
RT "Transcriptional regulation by cAMP and its receptor protein.";
RL Annu. Rev. Biochem. 62:749-795(1993).
RN [28]
RP REVIEW.
RX PubMed=10550204; DOI=10.1006/jmbi.1999.3161;
RA Busby S., Ebright R.H.;
RT "Transcription activation by catabolite activator protein (CAP).";
RL J. Mol. Biol. 293:199-213(1999).
RN [29]
RP REVIEW.
RX PubMed=19439203; DOI=10.1016/j.bbapap.2009.04.015;
RA Won H.S., Lee Y.S., Lee S.H., Lee B.J.;
RT "Structural overview on the allosteric activation of cyclic AMP receptor
RT protein.";
RL Biochim. Biophys. Acta 1794:1299-1308(2009).
RN [30]
RP REVIEW ON ROLE IN CARBON CATABOLITE REPRESSION AND OTHER PROCESSES.
RX PubMed=22573269; DOI=10.1007/s00253-012-4101-5;
RA Escalante A., Salinas Cervantes A., Gosset G., Bolivar F.;
RT "Current knowledge of the Escherichia coli phosphoenolpyruvate-carbohydrate
RT phosphotransferase system: peculiarities of regulation and impact on growth
RT and product formation.";
RL Appl. Microbiol. Biotechnol. 94:1483-1494(2012).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH CAMP, SUBUNIT, AND
RP DOMAIN.
RX PubMed=6286624; DOI=10.1016/s0021-9258(18)34101-2;
RA McKay D.B., Weber I.T., Steitz T.A.;
RT "Structure of catabolite gene activator protein at 2.9-A resolution.
RT Incorporation of amino acid sequence and interactions with cyclic AMP.";
RL J. Biol. Chem. 257:9518-9524(1982).
RN [32]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH CAMP, SUBUNIT, AND
RP DOMAIN.
RX PubMed=2828639; DOI=10.1016/0022-2836(87)90315-9;
RA Weber I.T., Steitz T.A.;
RT "Structure of a complex of catabolite gene activator protein and cyclic AMP
RT refined at 2.5-A resolution.";
RL J. Mol. Biol. 198:311-326(1987).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 2-206 IN COMPLEX WITH CAMP AND
RP DNA, SUBUNIT, DNA-BINDING, AND DNA-BENDING.
RX PubMed=1653449; DOI=10.1126/science.1653449;
RA Schultz S., Shields G., Steitz T.A.;
RT "Crystal structure of a CAP-DNA complex: the DNA is bent by 90 degrees.";
RL Science 253:1001-1007(1991).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 2-210 IN COMPLEX WITH CAMP AND
RP DNA, SUBUNIT, DNA-BINDING, AND DNA-BENDING.
RX PubMed=8757802; DOI=10.1006/jmbi.1996.0409;
RA Parkinson G., Wilson C., Gunasekera A., Ebright Y.W., Ebright R.H.,
RA Berman H.M.;
RT "Structure of the CAP-DNA complex at 2.5 angstroms resolution: a complete
RT picture of the protein-DNA interface.";
RL J. Mol. Biol. 260:395-408(1996).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH 2 CAMP PER MONOMER
RP AND DNA, SUBUNIT, AND DNA-BINDING.
RX PubMed=9096308; DOI=10.1073/pnas.94.7.2843;
RA Passner J.M., Steitz T.A.;
RT "The structure of a CAP-DNA complex having two cAMP molecules bound to each
RT monomer.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2843-2847(1997).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH CAMP, AND SUBUNIT.
RX PubMed=11124031; DOI=10.1006/jmbi.2000.4231;
RA Passner J.M., Schultz S.C., Steitz T.A.;
RT "Modeling the cAMP-induced allosteric transition using the crystal
RT structure of CAP-cAMP at 2.1 A resolution.";
RL J. Mol. Biol. 304:847-859(2000).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 2-210 IN COMPLEX WITH CAMP; DNA
RP AND RNAP, INTERACTION WITH RPOA, DNA-BINDING, AND SUBUNIT.
RX PubMed=12202833; DOI=10.1126/science.1076376;
RA Benoff B., Yang H., Lawson C.L., Parkinson G., Liu J., Blatter E.,
RA Ebright Y.W., Berman H.M., Ebright R.H.;
RT "Structural basis of transcription activation: the CAP-alpha CTD-DNA
RT complex.";
RL Science 297:1562-1566(2002).
RN [38]
RP STRUCTURE BY NMR OF 2-210 OF APO-CRP, ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=19359484; DOI=10.1073/pnas.0900595106;
RA Popovych N., Tzeng S.R., Tonelli M., Ebright R.H., Kalodimos C.G.;
RT "Structural basis for cAMP-mediated allosteric control of the catabolite
RT activator protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:6927-6932(2009).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF APO-CRP, ACTIVITY REGULATION,
RP SUBUNIT, AND MUTAGENESIS OF ASP-139.
RX PubMed=19805344; DOI=10.1073/pnas.0908380106;
RA Sharma H., Yu S., Kong J., Wang J., Steitz T.A.;
RT "Structure of apo-CAP reveals that large conformational changes are
RT necessary for DNA binding.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:16604-16609(2009).
RN [40]
RP STRUCTURE BY ELECTRON MICROSCOPY (19.80 ANGSTROMS) OF 2-210 IN COMPLEX WITH
RP RPOA; RPOB; RPOC; RPOD; RPOZ AND DNA, INTERACTION WITH ROPA, DNA-BINDING,
RP AND SUBUNIT.
RX PubMed=19903881; DOI=10.1073/pnas.0908782106;
RA Hudson B.P., Quispe J., Lara-Gonzalez S., Kim Y., Berman H.M., Arnold E.,
RA Ebright R.H., Lawson C.L.;
RT "Three-dimensional EM structure of an intact activator-dependent
RT transcription initiation complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19830-19835(2009).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 2-210 IN COMPLEX WITH 2 CAMP PER
RP MONOMER, AND SUBUNIT.
RA Kumarevel T.S., Tanaka T., Shinkai A., Yokoyama S.;
RT "Crystal structure of activated CRP protein from E.coli.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [42]
RP STRUCTURE BY NMR OF 2-210 OF APO-CRP, AND MUTAGENESIS OF 128-THR-SER-129.
RX PubMed=23644478; DOI=10.1038/nchembio.1250;
RA Tzeng S.R., Kalodimos C.G.;
RT "Allosteric inhibition through suppression of transient conformational
RT states.";
RL Nat. Chem. Biol. 9:462-465(2013).
CC -!- FUNCTION: A global transcription regulator. Complexes with cyclic AMP
CC (cAMP) which allosterically activates DNA binding (to consensus
CC sequence 5'-AAATGTGATCTAGATCACATTT-3') to directly regulate the
CC transcription of about 300 genes in about 200 operons and indirectly
CC regulate the expression of about half the genome. There are 3 classes
CC of CRP promoters; class I promoters have a single CRP-binding site
CC upstream of the RNA polymerase (RNAP)-binding site, whereas in class II
CC promoters the single CRP- and RNAP-binding site overlap, CRP making
CC multiple contacts with RNAP. Class III promoters require multiple
CC activator molecules, including at least one CRP dimer. It can act as an
CC activator, repressor, coactivator or corepressor. Induces a severe bend
CC in DNA (about 87 degrees), bringing upstream promoter elements into
CC contact with RNAP. Acts as a negative regulator of its own synthesis as
CC well as for adenylate cyclase (cyaA), which generates cAMP. High levels
CC of active CRP are detrimental to growth (PubMed:16260780). Plays a
CC major role in carbon catabolite repression (CCR). CCR involves cAMP,
CC adenylate cyclase (cyaA), CRP and the EIIA-Glc component of the PTS
CC (crr). In the presence of glucose EIIA-Glc is dephosphorylated, and
CC does not activate adenylate cyclase, leading to reduced cAMP and thus
CC decreased CRP activity. Also plays a role in many other processes (see
CC PubMed:22573269). {ECO:0000269|PubMed:10860739,
CC ECO:0000269|PubMed:10860740, ECO:0000269|PubMed:15520470,
CC ECO:0000269|PubMed:16260780, ECO:0000269|PubMed:16301522,
CC ECO:0000269|PubMed:1646077, ECO:0000269|PubMed:2982847,
CC ECO:0000269|PubMed:7966284, ECO:0000269|PubMed:8392187,
CC ECO:0000269|PubMed:8978616}.
CC -!- ACTIVITY REGULATION: In the apo-form the DNA-binding helices form a
CC rigid body in which their DNA recognitions helices are buried. cAMP
CC binding causes a coil-to helix transition, stabilizing the active DNA
CC binding conformation by reorienting and elongating these helices, which
CC precludes a return to the inactive state. {ECO:0000269|PubMed:19359484,
CC ECO:0000269|PubMed:19805344}.
CC -!- SUBUNIT: Homodimer, which upon binding cAMP is able to bind DNA. AR1 of
CC the upstream subunit binds to the C-terminus of RNAP subunit RpoA, AR2
CC of the downstream subunit binds to the N-terminus of RpoA while AR3
CC binds to sigma-70 (RpoD). {ECO:0000269|PubMed:11124031,
CC ECO:0000269|PubMed:12202833, ECO:0000269|PubMed:1646077,
CC ECO:0000269|PubMed:1653449, ECO:0000269|PubMed:19359484,
CC ECO:0000269|PubMed:19805344, ECO:0000269|PubMed:19903881,
CC ECO:0000269|PubMed:2828639, ECO:0000269|PubMed:2839152,
CC ECO:0000269|PubMed:6286624, ECO:0000269|PubMed:8757802,
CC ECO:0000269|PubMed:8978616, ECO:0000269|PubMed:9096308,
CC ECO:0000269|Ref.41}.
CC -!- INTERACTION:
CC P0ACJ8; P0ACJ8: crp; NbExp=5; IntAct=EBI-547513, EBI-547513;
CC P0ACJ8; P0AFG0: nusG; NbExp=2; IntAct=EBI-547513, EBI-369628;
CC P0ACJ8; P23862: priC; NbExp=2; IntAct=EBI-547513, EBI-1117383;
CC P0ACJ8; P0A7K2: rplL; NbExp=2; IntAct=EBI-547513, EBI-543702;
CC P0ACJ8; P0A8E5: yacL; NbExp=4; IntAct=EBI-547513, EBI-554965;
CC -!- INDUCTION: Constitutively expressed, levels decrease in stationary
CC phase; more strongly induced in an rnlA deletion mutant, levels remain
CC high even in stationary phase (at protein level). Both positively
CC (PubMed:1328816) and negatively autoregulated (PubMed:6297782).
CC {ECO:0000269|PubMed:1328816, ECO:0000269|PubMed:19019153,
CC ECO:0000269|PubMed:6297782}.
CC -!- DOMAIN: The N-terminal domain binds cAMP and is responsible for
CC homodimerization, while the C-terminal domain binds DNA when cAMP is
CC bound. {ECO:0000269|PubMed:2828639, ECO:0000269|PubMed:6286624}.
CC -!- DISRUPTION PHENOTYPE: Not essential (on rich medium), greatly increased
CC levels of cAMP. Eliminates the NaCl sensitivity of an rnlA deletion
CC mutant. {ECO:0000269|PubMed:15520470, ECO:0000269|PubMed:164435,
CC ECO:0000269|PubMed:19019153}.
CC -!- MISCELLANEOUS: Binds 2 cAMP; cAMP 1 is in the anti conformation, while
CC cAMP 2 is in the syn conformation. {ECO:0000305|PubMed:9096308}.
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DR EMBL; J01598; AAA23601.1; -; Genomic_DNA.
DR EMBL; U18997; AAA58154.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76382.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77933.1; -; Genomic_DNA.
DR PIR; A93416; QRECC.
DR RefSeq; NP_417816.1; NC_000913.3.
DR RefSeq; WP_000242755.1; NZ_STEB01000004.1.
DR PDB; 1CGP; X-ray; 3.00 A; A/B=2-206.
DR PDB; 1G6N; X-ray; 2.10 A; A/B=1-210.
DR PDB; 1HW5; X-ray; 1.82 A; A/B=1-210.
DR PDB; 1I5Z; X-ray; 1.90 A; A/B=2-210.
DR PDB; 1I6X; X-ray; 2.20 A; A/B=2-210.
DR PDB; 1J59; X-ray; 2.50 A; A/B=2-210.
DR PDB; 1LB2; X-ray; 3.10 A; A=2-210.
DR PDB; 1O3Q; X-ray; 3.00 A; A=9-208.
DR PDB; 1O3R; X-ray; 3.00 A; A=9-208.
DR PDB; 1O3S; X-ray; 3.00 A; A=9-208.
DR PDB; 1O3T; X-ray; 2.80 A; A/B=9-208.
DR PDB; 1RUN; X-ray; 2.70 A; A/B=2-210.
DR PDB; 1RUO; X-ray; 2.70 A; A/B=2-210.
DR PDB; 1ZRC; X-ray; 2.80 A; A/B=2-210.
DR PDB; 1ZRD; X-ray; 2.80 A; A/B=2-210.
DR PDB; 1ZRE; X-ray; 2.80 A; A/B=2-210.
DR PDB; 1ZRF; X-ray; 2.10 A; A/B=2-210.
DR PDB; 2CGP; X-ray; 2.20 A; A=1-210.
DR PDB; 2GZW; X-ray; 2.21 A; A/B/C/D=2-210.
DR PDB; 2WC2; NMR; -; A/B=2-210.
DR PDB; 3FWE; X-ray; 2.30 A; A/B=1-210.
DR PDB; 3HIF; X-ray; 3.59 A; A/B/C/D/E/F=1-210.
DR PDB; 3IYD; EM; -; G/H=2-210.
DR PDB; 3KCC; X-ray; 1.66 A; A/B=1-210.
DR PDB; 3N4M; X-ray; 2.99 A; A=2-210.
DR PDB; 3QOP; X-ray; 1.96 A; A/B=1-210.
DR PDB; 3RDI; X-ray; 2.95 A; A/B=1-210.
DR PDB; 3ROU; X-ray; 2.10 A; A/B=1-210.
DR PDB; 3RPQ; X-ray; 2.61 A; A/B=1-210.
DR PDB; 3RYP; X-ray; 1.60 A; A/B=1-210.
DR PDB; 3RYR; X-ray; 2.70 A; A/B=1-210.
DR PDB; 4BH9; NMR; -; A=2-210.
DR PDB; 4BHP; NMR; -; A=2-210.
DR PDB; 4FT8; X-ray; 1.97 A; A/B=2-210.
DR PDB; 4HZF; X-ray; 1.48 A; A/B=1-210.
DR PDB; 4I01; X-ray; 2.30 A; A/B=1-210.
DR PDB; 4I02; X-ray; 1.75 A; A/B/C/D/E/F=1-210.
DR PDB; 4I09; X-ray; 2.05 A; A/B=1-210.
DR PDB; 4I0A; X-ray; 2.20 A; A/B=1-210.
DR PDB; 4I0B; X-ray; 1.50 A; A/B=1-210.
DR PDB; 4R8H; X-ray; 1.46 A; A/B=1-210.
DR PDB; 5CIZ; X-ray; 5.01 A; A=2-210.
DR PDBsum; 1CGP; -.
DR PDBsum; 1G6N; -.
DR PDBsum; 1HW5; -.
DR PDBsum; 1I5Z; -.
DR PDBsum; 1I6X; -.
DR PDBsum; 1J59; -.
DR PDBsum; 1LB2; -.
DR PDBsum; 1O3Q; -.
DR PDBsum; 1O3R; -.
DR PDBsum; 1O3S; -.
DR PDBsum; 1O3T; -.
DR PDBsum; 1RUN; -.
DR PDBsum; 1RUO; -.
DR PDBsum; 1ZRC; -.
DR PDBsum; 1ZRD; -.
DR PDBsum; 1ZRE; -.
DR PDBsum; 1ZRF; -.
DR PDBsum; 2CGP; -.
DR PDBsum; 2GZW; -.
DR PDBsum; 2WC2; -.
DR PDBsum; 3FWE; -.
DR PDBsum; 3HIF; -.
DR PDBsum; 3IYD; -.
DR PDBsum; 3KCC; -.
DR PDBsum; 3N4M; -.
DR PDBsum; 3QOP; -.
DR PDBsum; 3RDI; -.
DR PDBsum; 3ROU; -.
DR PDBsum; 3RPQ; -.
DR PDBsum; 3RYP; -.
DR PDBsum; 3RYR; -.
DR PDBsum; 4BH9; -.
DR PDBsum; 4BHP; -.
DR PDBsum; 4FT8; -.
DR PDBsum; 4HZF; -.
DR PDBsum; 4I01; -.
DR PDBsum; 4I02; -.
DR PDBsum; 4I09; -.
DR PDBsum; 4I0A; -.
DR PDBsum; 4I0B; -.
DR PDBsum; 4R8H; -.
DR PDBsum; 5CIZ; -.
DR AlphaFoldDB; P0ACJ8; -.
DR BMRB; P0ACJ8; -.
DR SMR; P0ACJ8; -.
DR BioGRID; 4262928; 15.
DR BioGRID; 852178; 31.
DR DIP; DIP-29232N; -.
DR IntAct; P0ACJ8; 42.
DR MINT; P0ACJ8; -.
DR STRING; 511145.b3357; -.
DR DrugBank; DB02527; Cyclic adenosine monophosphate.
DR iPTMnet; P0ACJ8; -.
DR jPOST; P0ACJ8; -.
DR PaxDb; P0ACJ8; -.
DR PRIDE; P0ACJ8; -.
DR EnsemblBacteria; AAC76382; AAC76382; b3357.
DR EnsemblBacteria; BAE77933; BAE77933; BAE77933.
DR GeneID; 67450219; -.
DR GeneID; 947867; -.
DR KEGG; ecj:JW5702; -.
DR KEGG; eco:b3357; -.
DR PATRIC; fig|1411691.4.peg.3373; -.
DR EchoBASE; EB0162; -.
DR eggNOG; COG0664; Bacteria.
DR HOGENOM; CLU_075053_3_5_6; -.
DR InParanoid; P0ACJ8; -.
DR OMA; VLCRDFG; -.
DR PhylomeDB; P0ACJ8; -.
DR BioCyc; EcoCyc:PD00257; -.
DR EvolutionaryTrace; P0ACJ8; -.
DR PRO; PR:P0ACJ8; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR CollecTF; EXPREG_00000850; -.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0032993; C:protein-DNA complex; IPI:CollecTF.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0008301; F:DNA binding, bending; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003680; F:minor groove of adenine-thymine-rich DNA binding; IDA:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IPI:CollecTF.
DR GO; GO:0045013; P:carbon catabolite repression of transcription; IMP:EcoCyc.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:EcoliWiki.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:EcoliWiki.
DR GO; GO:0006351; P:transcription, DNA-templated; IDA:EcoCyc.
DR CDD; cd00038; CAP_ED; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR018488; cNMP-bd_CS.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR012318; HTH_CRP.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR018335; Tscrpt_reg_HTH_Crp-type_CS.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00027; cNMP_binding; 1.
DR Pfam; PF13545; HTH_Crp_2; 1.
DR PRINTS; PR00034; HTHCRP.
DR SMART; SM00100; cNMP; 1.
DR SMART; SM00419; HTH_CRP; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR PROSITE; PS00888; CNMP_BINDING_1; 1.
DR PROSITE; PS00889; CNMP_BINDING_2; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
DR PROSITE; PS00042; HTH_CRP_1; 1.
DR PROSITE; PS51063; HTH_CRP_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; cAMP; cAMP-binding;
KW Direct protein sequencing; DNA-binding; Nucleotide-binding;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:17895580"
FT CHAIN 2..210
FT /note="cAMP-activated global transcriptional regulator CRP"
FT /id="PRO_0000100144"
FT DOMAIN 138..210
FT /note="HTH crp-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00387"
FT DNA_BIND 180..186
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00387"
FT REGION 20..22
FT /note="Activating region 2 (AR2); probably contacts the N-
FT terminus of RpoA"
FT REGION 53..59
FT /note="Activating region 3 (AR3); probably contacts sigma-
FT 70 (RpoD)"
FT REGION 154..163
FT /note="Activating region 1 (AR1); probably contacts the C-
FT terminus of RpoA"
FT BINDING 57..63
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:11124031,
FT ECO:0000269|PubMed:12202833, ECO:0000269|PubMed:1653449,
FT ECO:0000269|PubMed:2828639, ECO:0000269|PubMed:6286624,
FT ECO:0000269|PubMed:8757802"
FT BINDING 72..74
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:11124031,
FT ECO:0000269|PubMed:12202833, ECO:0000269|PubMed:1653449,
FT ECO:0000269|PubMed:2828639, ECO:0000269|PubMed:6286624,
FT ECO:0000269|PubMed:8757802"
FT BINDING 83..84
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:11124031,
FT ECO:0000269|PubMed:12202833, ECO:0000269|PubMed:1653449,
FT ECO:0000269|PubMed:2828639, ECO:0000269|PubMed:6286624,
FT ECO:0000269|PubMed:8757802"
FT BINDING 128..129
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:11124031,
FT ECO:0000269|PubMed:12202833, ECO:0000269|PubMed:1653449,
FT ECO:0000269|PubMed:2828639, ECO:0000269|PubMed:6286624,
FT ECO:0000269|PubMed:8757802"
FT BINDING 136..137
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11124031,
FT ECO:0000269|PubMed:12202833, ECO:0000269|PubMed:1653449,
FT ECO:0000269|PubMed:2828639, ECO:0000269|PubMed:6286624,
FT ECO:0000269|PubMed:8757802"
FT BINDING 171..181
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11124031,
FT ECO:0000269|PubMed:12202833, ECO:0000269|PubMed:1653449,
FT ECO:0000269|PubMed:2828639, ECO:0000269|PubMed:6286624,
FT ECO:0000269|PubMed:8757802"
FT SITE 97
FT /note="Activating region 2 (AR2); probably contacts the N-
FT terminus of RpoA"
FT SITE 102
FT /note="Activating region 2 (AR2); probably contacts the N-
FT terminus of RpoA"
FT MOD_RES 101
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:18723842"
FT MUTAGEN 20
FT /note="H->A,L,Y: Decreased transcription activation at
FT class II promoters, decreased interaction with RNAP, binds
FT DNA."
FT /evidence="ECO:0000269|PubMed:8978616"
FT MUTAGEN 22
FT /note="H->A,L: Decreased transcription activation at class
FT II promoters, decreased interaction with RNAP, binds DNA."
FT /evidence="ECO:0000269|PubMed:8978616"
FT MUTAGEN 53
FT /note="K->N: Increased activation at class II promoters,
FT increased interaction with RNAP."
FT /evidence="ECO:0000269|PubMed:8978616"
FT MUTAGEN 54..56
FT /note="DEE->AAA: 80% reduction in activation of class II
FT promoters; 95% loss when associated with A-59."
FT /evidence="ECO:0000269|PubMed:10860739"
FT MUTAGEN 59
FT /note="E->A: 45% reduction in activation of class II
FT promoters; 95% loss when associated with AAA-54-56."
FT /evidence="ECO:0000269|PubMed:10860739,
FT ECO:0000269|PubMed:10860740"
FT MUTAGEN 59
FT /note="E->G,K: Reduction in activation of class II
FT promoters."
FT /evidence="ECO:0000269|PubMed:10860739,
FT ECO:0000269|PubMed:10860740"
FT MUTAGEN 63
FT /note="S->A: Enhanced cAMP-binding, enhanced
FT transcription."
FT /evidence="ECO:0000269|PubMed:2845936"
FT MUTAGEN 83
FT /note="R->L: Loss of cAMP-binding."
FT /evidence="ECO:0000269|PubMed:2845936"
FT MUTAGEN 84
FT /note="S->A,K: No modification of cAMP-binding."
FT /evidence="ECO:0000269|PubMed:2845936"
FT MUTAGEN 97
FT /note="E->A: Increased transcription activation at class II
FT promoters, binds DNA."
FT /evidence="ECO:0000269|PubMed:8978616"
FT MUTAGEN 102
FT /note="K->E: Disrupts AR2. No activation of class II
FT promoters, decreased interaction with RNAP, binds DNA."
FT /evidence="ECO:0000269|PubMed:15520470,
FT ECO:0000269|PubMed:8978616"
FT MUTAGEN 128..129
FT /note="TS->LI: Constitutively active at class I and II
FT promoters in the absence of cAMP, binds DNA almost as well
FT in the absence as in the presence of cAMP. Binds cAMP
FT normally."
FT /evidence="ECO:0000269|PubMed:16260780,
FT ECO:0000269|PubMed:23644478"
FT MUTAGEN 128
FT /note="T->A: No modification of cAMP-binding."
FT /evidence="ECO:0000269|PubMed:2845936"
FT MUTAGEN 129
FT /note="S->A: Reduced DNA-binding; no modification of cAMP-
FT binding."
FT /evidence="ECO:0000269|PubMed:2845936,
FT ECO:0000269|PubMed:3333845"
FT MUTAGEN 139
FT /note="D->L: Some stabilization of an inactive (apo-) form.
FT Decreased affinity for DNA, normal subunit association."
FT /evidence="ECO:0000269|PubMed:15096034,
FT ECO:0000269|PubMed:19805344, ECO:0000269|PubMed:8380500"
FT MUTAGEN 157
FT /note="A->D,P: Decreased transcription activation (6-29%),
FT binds DNA."
FT /evidence="ECO:0000269|PubMed:7966284,
FT ECO:0000269|PubMed:8392187"
FT MUTAGEN 159
FT /note="T->A,I,N,S,V: Decreased transcription activation
FT (15-87%) at class I and II promoters, binds DNA."
FT /evidence="ECO:0000269|PubMed:7966284,
FT ECO:0000269|PubMed:8392187, ECO:0000269|PubMed:8978616"
FT MUTAGEN 160
FT /note="H->A,K,L,N,P,Q,R,Y: Disrupts AR1. Decreased
FT transcription activation (3-45%) at class I and II
FT promoters, binds DNA."
FT /evidence="ECO:0000269|PubMed:15520470,
FT ECO:0000269|PubMed:7966284, ECO:0000269|PubMed:8392187,
FT ECO:0000269|PubMed:8978616"
FT MUTAGEN 163
FT /note="G->A,C,D,R,S,V: Decreased transcription activation
FT (2-62%) at class I and II promoters, binds DNA."
FT /evidence="ECO:0000269|PubMed:7966284,
FT ECO:0000269|PubMed:8392187, ECO:0000269|PubMed:8978616"
FT MUTAGEN 181
FT /note="R->K: Suppresses DNA-binding."
FT /evidence="ECO:0000269|PubMed:3333845"
FT MUTAGEN 181
FT /note="R->L: Suppresses DNA-binding."
FT /evidence="ECO:0000269|PubMed:3333845"
FT MUTAGEN 186
FT /note="R->K: No modification of DNA-binding."
FT /evidence="ECO:0000269|PubMed:3333845"
FT MUTAGEN 186
FT /note="R->L: Marginally reduced DNA-binding."
FT /evidence="ECO:0000269|PubMed:3333845"
FT CONFLICT 29
FT /note="T -> K (in Ref. 4; BAE77933)"
FT /evidence="ECO:0000305"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:2WC2"
FT HELIX 10..16
FT /evidence="ECO:0007829|PDB:4R8H"
FT STRAND 19..24
FT /evidence="ECO:0007829|PDB:4R8H"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:2WC2"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:4R8H"
FT STRAND 33..36
FT /evidence="ECO:0007829|PDB:1O3T"
FT STRAND 39..45
FT /evidence="ECO:0007829|PDB:4R8H"
FT STRAND 47..53
FT /evidence="ECO:0007829|PDB:4R8H"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:1HW5"
FT STRAND 59..66
FT /evidence="ECO:0007829|PDB:4R8H"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:4R8H"
FT HELIX 74..77
FT /evidence="ECO:0007829|PDB:4R8H"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:1I5Z"
FT STRAND 85..91
FT /evidence="ECO:0007829|PDB:4R8H"
FT STRAND 93..99
FT /evidence="ECO:0007829|PDB:4R8H"
FT HELIX 100..109
FT /evidence="ECO:0007829|PDB:4R8H"
FT HELIX 112..137
FT /evidence="ECO:0007829|PDB:4R8H"
FT HELIX 140..152
FT /evidence="ECO:0007829|PDB:4R8H"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:1J59"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:4R8H"
FT STRAND 163..167
FT /evidence="ECO:0007829|PDB:4R8H"
FT HELIX 170..177
FT /evidence="ECO:0007829|PDB:4R8H"
FT HELIX 181..193
FT /evidence="ECO:0007829|PDB:4R8H"
FT STRAND 196..200
FT /evidence="ECO:0007829|PDB:4R8H"
FT STRAND 203..207
FT /evidence="ECO:0007829|PDB:4R8H"
SQ SEQUENCE 210 AA; 23640 MW; DCBC24FA46C61B3D CRC64;
MVLGKPQTDP TLEWFLSHCH IHKYPSKSTL IHQGEKAETL YYIVKGSVAV LIKDEEGKEM
ILSYLNQGDF IGELGLFEEG QERSAWVRAK TACEVAEISY KKFRQLIQVN PDILMRLSAQ
MARRLQVTSE KVGNLAFLDV TGRIAQTLLN LAKQPDAMTH PDGMQIKITR QEIGQIVGCS
RETVGRILKM LEDQNLISAH GKTIVVYGTR
