CPXR_ECOLI
ID CPXR_ECOLI Reviewed; 232 AA.
AC P0AE88; P16244; P76777; Q2M8K9;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Transcriptional regulatory protein CpxR;
GN Name=cpxR; Synonyms=yiiA; OrderedLocusNames=b3912, JW3883;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=L547;
RX PubMed=8294007; DOI=10.1016/0378-1119(93)90469-j;
RA Dong J., Iuchi S., Kwan H.-S., Lu Z., Lin E.;
RT "The deduced amino-acid sequence of the cloned cpxR gene suggests the
RT protein is the cognate regulator for the membrane sensor, CpxA, in a two-
RT component signal transduction system of Escherichia coli.";
RL Gene 136:227-230(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=8346018; DOI=10.1093/nar/21.15.3391;
RA Plunkett G. III, Burland V., Daniels D.L., Blattner F.R.;
RT "Analysis of the Escherichia coli genome. III. DNA sequence of the region
RT from 87.2 to 89.2 minutes.";
RL Nucleic Acids Res. 21:3391-3398(1993).
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 128-232.
RC STRAIN=K12;
RX PubMed=3058985; DOI=10.1016/0022-2836(88)90013-7;
RA Weber R.F., Silverman P.M.;
RT "The cpx proteins of Escherichia coli K12. Structure of the cpxA
RT polypeptide as an inner membrane component.";
RL J. Mol. Biol. 203:467-478(1988).
RN [6]
RP FUNCTION AS A TRANSCRIPTIONAL ACTIVATOR, ACTIVITY REGULATION,
RP PHOSPHORYLATION BY CPXA, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MC4100;
RX PubMed=7883164; DOI=10.1101/gad.9.4.387;
RA Danese P.N., Snyder W.B., Cosma C.L., Davis L.J., Silhavy T.J.;
RT "The Cpx two-component signal transduction pathway of Escherichia coli
RT regulates transcription of the gene specifying the stress-inducible
RT periplasmic protease, DegP.";
RL Genes Dev. 9:387-398(1995).
RN [7]
RP ACTIVITY REGULATION.
RX PubMed=9351822; DOI=10.1093/emboj/16.21.6394;
RA Jones C.H., Danese P.N., Pinkner J.S., Silhavy T.J., Hultgren S.J.;
RT "The chaperone-assisted membrane release and folding pathway is sensed by
RT two signal transduction systems.";
RL EMBO J. 16:6394-6406(1997).
RN [8]
RP FUNCTION, PHOSPHORYLATION BY CPXA, AND DNA-BINDING.
RC STRAIN=K12 / MC4100;
RX PubMed=9401031; DOI=10.1128/jb.179.24.7724-7733.1997;
RA Raivio T.L., Silhavy T.J.;
RT "Transduction of envelope stress in Escherichia coli by the Cpx two-
RT component system.";
RL J. Bacteriol. 179:7724-7733(1997).
RN [9]
RP FUNCTION, ACTIVITY REGULATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MC4100;
RX PubMed=9473036; DOI=10.1128/jb.180.4.831-839.1998;
RA Danese P.N., Silhavy T.J.;
RT "CpxP, a stress-combative member of the Cpx regulon.";
RL J. Bacteriol. 180:831-839(1998).
RN [10]
RP ACTIVITY REGULATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MC4100;
RX PubMed=10972835; DOI=10.1046/j.1365-2958.2000.02074.x;
RA Raivio T.L., Laird M.W., Joly J.C., Silhavy T.J.;
RT "Tethering of CpxP to the inner membrane prevents spheroplast induction of
RT the cpx envelope stress response.";
RL Mol. Microbiol. 37:1186-1197(2000).
RN [11]
RP FUNCTION IN BIOFILM FORMATION, INDUCTION BY ADHESION, AND DISRUPTION
RP PHENOTYPE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=11830644; DOI=10.1073/pnas.042521699;
RA Otto K., Silhavy T.J.;
RT "Surface sensing and adhesion of Escherichia coli controlled by the Cpx-
RT signaling pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:2287-2292(2002).
RN [12]
RP FUNCTION, AND ACTIVITY REGULATION.
RC STRAIN=K12 / MC4100;
RX PubMed=16166523; DOI=10.1128/jb.187.19.6622-6630.2005;
RA Buelow D.R., Raivio T.L.;
RT "Cpx signal transduction is influenced by a conserved N-terminal domain in
RT the novel inhibitor CpxP and the periplasmic protease DegP.";
RL J. Bacteriol. 187:6622-6630(2005).
RN [13]
RP ACTIVITY REGULATION, AND PHOSPHORYLATION BY CPXA.
RX PubMed=17259177; DOI=10.1074/jbc.m605785200;
RA Fleischer R., Heermann R., Jung K., Hunke S.;
RT "Purification, reconstitution, and characterization of the CpxRAP envelope
RT stress system of Escherichia coli.";
RL J. Biol. Chem. 282:8583-8593(2007).
RN [14]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=23416055; DOI=10.1016/j.celrep.2013.01.026;
RA Dorsey-Oresto A., Lu T., Mosel M., Wang X., Salz T., Drlica K., Zhao X.;
RT "YihE kinase is a central regulator of programmed cell death in bacteria.";
RL Cell Rep. 3:528-537(2013).
RN [15]
RP ACTIVITY REGULATION, INTERACTION WITH CPXA, AND SUBUNIT.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=25207645; DOI=10.1371/journal.pone.0107383;
RA Tschauner K., Hoernschemeyer P., Mueller V.S., Hunke S.;
RT "Dynamic interaction between the CpxA sensor kinase and the periplasmic
RT accessory protein CpxP mediates signal recognition in E. coli.";
RL PLoS ONE 9:E107383-E107383(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) OF 131-231.
RA Mechaly A.E., Alzari P.M.A.;
RT "Structure of the response regulator CpxR.";
RL Submitted (MAR-2015) to the PDB data bank.
CC -!- FUNCTION: Response regulator member of the two-component regulatory
CC system CpxA/CpxR which responds to envelope stress response by
CC activating expression of downstream genes including cpxP, degP, dsbA
CC and ppiA (PubMed:7883164, PubMed:9401031). Required for efficient
CC binding of stationary phase cells to hydrophobic surfaces, part of the
CC process of biofilm formation (PubMed:11830644). Induced upon cell
CC surface binding, subsequently induces genes it controls (cpxP, dsbA and
CC spy, degP is only partially induced) (PubMed:11830644). Binds and
CC activates transcription from the degP promoter (PubMed:7883164);
CC binding is enhanced by phosphorylation (PubMed:9401031). This system
CC combats a variety of extracytoplasmic protein-mediated toxicities by
CC increasing the transcription of the periplasmic protease, DegP in
CC concert with sigma factor E (PubMed:7883164), as well as that of CpxP
CC protein. Other downstream effectors may include SrkA (PubMed:23416055).
CC {ECO:0000269|PubMed:11830644, ECO:0000269|PubMed:23416055,
CC ECO:0000269|PubMed:7883164, ECO:0000269|PubMed:9401031}.
CC -!- ACTIVITY REGULATION: The two-component system is activated by envelope
CC stress such as overexpression of some (misfolded) periplasmic proteins
CC (PubMed:7883164, PubMed:9351822). Activated by spheroplasting (which
CC removes the periplasm) in an autoregulatory cpxA-cpxR-dependent fashion
CC (PubMed:10972835). Cpx two-component system is activated at pH 8.0; in
CC a degP deletion mutant activation is halved (PubMed:9473036,
CC PubMed:16166523). The CpxA kinase activity is inhibited by periplasmic
CC accessory protein CpxP; proteolysis of CpxP relieves inhibition
CC (PubMed:16166523, PubMed:17259177, PubMed:25207645).
CC {ECO:0000269|PubMed:10972835, ECO:0000269|PubMed:16166523,
CC ECO:0000269|PubMed:7883164, ECO:0000269|PubMed:9351822,
CC ECO:0000269|PubMed:9473036}.
CC -!- SUBUNIT: Interacts with cognate sensor kinase CpxA.
CC {ECO:0000269|PubMed:25207645}.
CC -!- INTERACTION:
CC P0AE88; P0AE82: cpxA; NbExp=3; IntAct=EBI-550918, EBI-9141330;
CC P0AE88; P00861: lysA; NbExp=4; IntAct=EBI-550918, EBI-553837;
CC P0AE88; P0AG86: secB; NbExp=3; IntAct=EBI-550918, EBI-555877;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- INDUCTION: Induced about 3-fold when stationary phase cells bind to
CC hydrophobic surfaces; requires direct contact with hydrophobic surfaces
CC for up-regulation of Cpx activity (PubMed:11830644).
CC {ECO:0000269|PubMed:11830644}.
CC -!- PTM: Phosphorylated by CpxA. {ECO:0000269|PubMed:17259177,
CC ECO:0000269|PubMed:9401031, ECO:0000305|PubMed:7883164}.
CC -!- DISRUPTION PHENOTYPE: Loss of the Cpx envelope stress response
CC (PubMed:10972835). A double cpxR-cpxA mutant decreases transcription of
CC degP (PubMed:7883164). Cells are less sensitive to killing by nalidixic
CC acid; double cpxR-srkA disruption mutants are as sensitive to killing
CC as single srkA mutants, suggesting the SrkA protein kinase is partially
CC regulated by CpxR. Hypersensitive to alkaline pH (greater than pH 8.8)
CC (PubMed:9473036). Decreased numbers of stationary phase cells bind to
CC hydrophobic surfaces, cellular adhesion has altered dynamic properties;
CC no induction of cpxR when cells bind to hydrophobic surfaces
CC (PubMed:11830644). {ECO:0000269|PubMed:10972835,
CC ECO:0000269|PubMed:11830644, ECO:0000269|PubMed:23416055,
CC ECO:0000269|PubMed:7883164, ECO:0000269|PubMed:9473036}.
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DR EMBL; L14579; AAC36868.1; -; Unassigned_DNA.
DR EMBL; L19201; AAB03045.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76894.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77397.1; -; Genomic_DNA.
DR EMBL; X13307; CAA31686.1; -; Genomic_DNA.
DR EMBL; M36795; AAA23599.1; -; Genomic_DNA.
DR PIR; C65197; C65197.
DR RefSeq; NP_418348.1; NC_000913.3.
DR RefSeq; WP_001033722.1; NZ_STEB01000017.1.
DR PDB; 4UHJ; X-ray; 1.90 A; A/B/C=1-123.
DR PDB; 4UHK; X-ray; 2.60 A; A/B/C=1-123.
DR PDB; 4UHS; X-ray; 5.00 A; A/B/C=1-123.
DR PDB; 4UHT; X-ray; 1.15 A; A/B=131-231.
DR PDBsum; 4UHJ; -.
DR PDBsum; 4UHK; -.
DR PDBsum; 4UHS; -.
DR PDBsum; 4UHT; -.
DR AlphaFoldDB; P0AE88; -.
DR SMR; P0AE88; -.
DR BioGRID; 4262645; 290.
DR BioGRID; 852701; 2.
DR DIP; DIP-47991N; -.
DR IntAct; P0AE88; 11.
DR STRING; 511145.b3912; -.
DR jPOST; P0AE88; -.
DR PaxDb; P0AE88; -.
DR PRIDE; P0AE88; -.
DR EnsemblBacteria; AAC76894; AAC76894; b3912.
DR EnsemblBacteria; BAE77397; BAE77397; BAE77397.
DR GeneID; 67417576; -.
DR GeneID; 948404; -.
DR KEGG; ecj:JW3883; -.
DR KEGG; eco:b3912; -.
DR PATRIC; fig|1411691.4.peg.2792; -.
DR EchoBASE; EB0019; -.
DR eggNOG; COG0745; Bacteria.
DR HOGENOM; CLU_000445_30_4_6; -.
DR InParanoid; P0AE88; -.
DR OMA; LAEVWDW; -.
DR PhylomeDB; P0AE88; -.
DR BioCyc; EcoCyc:CPXR-MON; -.
DR BioCyc; MetaCyc:CPXR-MON; -.
DR PHI-base; PHI:4523; -.
DR PHI-base; PHI:8273; -.
DR PRO; PR:P0AE88; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0032993; C:protein-DNA complex; IBA:GO_Central.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; IBA:GO_Central.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:EcoCyc.
DR GO; GO:0000156; F:phosphorelay response regulator activity; IDA:CACAO.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:EcoCyc.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:EcoCyc.
DR GO; GO:0010810; P:regulation of cell-substrate adhesion; IMP:UniProtKB.
DR CDD; cd00383; trans_reg_C; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR011006; CheY-like_superfamily.
DR InterPro; IPR001867; OmpR/PhoB-type_DNA-bd.
DR InterPro; IPR001789; Sig_transdc_resp-reg_receiver.
DR InterPro; IPR039420; WalR-like.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR PANTHER; PTHR48111; PTHR48111; 1.
DR Pfam; PF00072; Response_reg; 1.
DR Pfam; PF00486; Trans_reg_C; 1.
DR SMART; SM00448; REC; 1.
DR SMART; SM00862; Trans_reg_C; 1.
DR SUPFAM; SSF52172; SSF52172; 1.
DR PROSITE; PS51755; OMPR_PHOB; 1.
DR PROSITE; PS50110; RESPONSE_REGULATORY; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cell adhesion; Cytoplasm; DNA-binding;
KW Phosphoprotein; Reference proteome; Stress response; Transcription;
KW Transcription regulation; Two-component regulatory system.
FT CHAIN 1..232
FT /note="Transcriptional regulatory protein CpxR"
FT /id="PRO_0000081078"
FT DOMAIN 3..115
FT /note="Response regulatory"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT DNA_BIND 131..230
FT /note="OmpR/PhoB-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01091"
FT MOD_RES 51
FT /note="4-aspartylphosphate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00169"
FT STRAND 3..7
FT /evidence="ECO:0007829|PDB:4UHJ"
FT HELIX 11..23
FT /evidence="ECO:0007829|PDB:4UHJ"
FT STRAND 27..33
FT /evidence="ECO:0007829|PDB:4UHJ"
FT HELIX 34..40
FT /evidence="ECO:0007829|PDB:4UHJ"
FT STRAND 47..50
FT /evidence="ECO:0007829|PDB:4UHJ"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:4UHJ"
FT HELIX 59..66
FT /evidence="ECO:0007829|PDB:4UHJ"
FT TURN 67..69
FT /evidence="ECO:0007829|PDB:4UHJ"
FT STRAND 74..79
FT /evidence="ECO:0007829|PDB:4UHJ"
FT HELIX 83..91
FT /evidence="ECO:0007829|PDB:4UHJ"
FT STRAND 95..101
FT /evidence="ECO:0007829|PDB:4UHJ"
FT HELIX 104..123
FT /evidence="ECO:0007829|PDB:4UHJ"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:4UHT"
FT STRAND 139..142
FT /evidence="ECO:0007829|PDB:4UHT"
FT TURN 143..146
FT /evidence="ECO:0007829|PDB:4UHT"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:4UHT"
FT HELIX 159..170
FT /evidence="ECO:0007829|PDB:4UHT"
FT TURN 171..173
FT /evidence="ECO:0007829|PDB:4UHT"
FT HELIX 178..186
FT /evidence="ECO:0007829|PDB:4UHT"
FT HELIX 196..207
FT /evidence="ECO:0007829|PDB:4UHT"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:4UHT"
FT TURN 222..224
FT /evidence="ECO:0007829|PDB:4UHT"
FT STRAND 225..228
FT /evidence="ECO:0007829|PDB:4UHT"
SQ SEQUENCE 232 AA; 26312 MW; 667FC2B246082F46 CRC64;
MNKILLVDDD RELTSLLKEL LEMEGFNVIV AHDGEQALDL LDDSIDLLLL DVMMPKKNGI
DTLKALRQTH QTPVIMLTAR GSELDRVLGL ELGADDYLPK PFNDRELVAR IRAILRRSHW
SEQQQNNDNG SPTLEVDALV LNPGRQEASF DGQTLELTGT EFTLLYLLAQ HLGQVVSREH
LSQEVLGKRL TPFDRAIDMH ISNLRRKLPD RKDGHPWFKT LRGRGYLMVS AS
