CPXP_ECOLI
ID CPXP_ECOLI Reviewed; 166 AA.
AC P0AE85; O65939; P32158; Q2M8L0;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Periplasmic protein CpxP {ECO:0000303|PubMed:9473036};
DE AltName: Full=ORF_o167 {ECO:0000303|PubMed:8346018};
DE AltName: Full=Periplasmic accessory protein CpxP;
DE Flags: Precursor;
GN Name=cpxP {ECO:0000303|PubMed:9473036}; Synonyms=yiiO;
GN OrderedLocusNames=b4484, JW5558;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
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 [2]
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 [3]
RP SEQUENCE REVISION.
RX PubMed=16397293; DOI=10.1093/nar/gkj405;
RA Riley M., Abe T., Arnaud M.B., Berlyn M.K.B., Blattner F.R.,
RA Chaudhuri R.R., Glasner J.D., Horiuchi T., Keseler I.M., Kosuge T.,
RA Mori H., Perna N.T., Plunkett G. III, Rudd K.E., Serres M.H., Thomas G.H.,
RA Thomson N.R., Wishart D., Wanner B.L.;
RT "Escherichia coli K-12: a cooperatively developed annotation snapshot
RT -- 2005.";
RL Nucleic Acids Res. 34:1-9(2006).
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 INDUCTION.
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, 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 [7]
RP INDUCTION.
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 [8]
RP FUNCTION, SUBUNIT, INDUCTION BY ALKALI, DOMAIN, DEGRADATION BY DEGP, AND
RP MUTAGENESIS OF GLN-55; MET-59; ARG-60; ASP-61 AND GLN-128.
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 [9]
RP FUNCTION, DEGRADATION BY DEGP, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MC4100;
RX PubMed=16303867; DOI=10.1073/pnas.0508936102;
RA Isaac D.D., Pinkner J.S., Hultgren S.J., Silhavy T.J.;
RT "The extracytoplasmic adaptor protein CpxP is degraded with substrate by
RT DegP.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:17775-17779(2005).
RN [10]
RP INDUCTION IN PERSISTER CELLS.
RC STRAIN=K12;
RX PubMed=16768798; DOI=10.1186/1471-2180-6-53;
RA Shah D., Zhang Z., Khodursky A., Kaldalu N., Kurg K., Lewis K.;
RT "Persisters: a distinct physiological state of E. coli.";
RL BMC Microbiol. 6:53-53(2006).
RN [11]
RP FUNCTION.
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 [12]
RP FUNCTION.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=21317898; DOI=10.1038/nsmb.2016;
RA Quan S., Koldewey P., Tapley T., Kirsch N., Ruane K.M., Pfizenmaier J.,
RA Shi R., Hofmann S., Foit L., Ren G., Jakob U., Xu Z., Cygler M.,
RA Bardwell J.C.;
RT "Genetic selection designed to stabilize proteins uncovers a chaperone
RT called Spy.";
RL Nat. Struct. Mol. Biol. 18:262-269(2011).
RN [13]
RP FUNCTION, INTERACTION WITH CPXA AND PAPE, SUBUNIT, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF ARG-56 AND ALA-108.
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 [14]
RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 40-151, FUNCTION, SUBUNIT, AND
RP MUTAGENESIS OF GLN-55 AND GLN-128.
RC STRAIN=K12 / MC4100;
RX PubMed=21317318; DOI=10.1128/jb.01296-10;
RA Thede G.L., Arthur D.C., Edwards R.A., Buelow D.R., Wong J.L., Raivio T.L.,
RA Glover J.N.;
RT "Structure of the periplasmic stress response protein CpxP.";
RL J. Bacteriol. 193:2149-2157(2011).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 21-150, FUNCTION, SUBUNIT,
RP DOMAIN, AND MUTAGENESIS OF ALA-103; ILE-107 AND ALA-108.
RX PubMed=21239493; DOI=10.1074/jbc.m110.194092;
RA Zhou X., Keller R., Volkmer R., Krauss N., Scheerer P., Hunke S.;
RT "Structural basis for two-component system inhibition and pilus sensing by
RT the auxiliary CpxP protein.";
RL J. Biol. Chem. 286:9805-9814(2011).
CC -!- FUNCTION: Acts as an auxiliary protein in the Cpx two-component
CC envelope stress response system, helping modulate the Cpx response
CC systems response to some inducers (PubMed:25207645, PubMed:16303867).
CC Binds the periplasmic domain of sensor histidine kinase CpxA,
CC inhibiting induction of the Cpx envelope stress response in the absence
CC of inducer; overexpression decreases Cpx pathway activity
CC (PubMed:16166523, PubMed:21317318). Some periplasmic stimulii (shown
CC for P pili subunit PapE and probably 0.3 M NaCl) increase CpxP's
CC susceptibility to DegP, leading to CpxP degradation, inducing the Cpx
CC pathway (PubMed:16166523, PubMed:16303867). Aids in combating
CC extracytoplasmic protein-mediated toxicity (PubMed:9473036,
CC PubMed:16303867, PubMed:21239493). Overexpression leads to degradation
CC by DegP of misfolded P pili subunits in the periplasm (tested using
CC PapE) (PubMed:21239493). Inhibits autophosphorylation of CpxA in
CC reconstituted liposomes by 50% but has no effect on phosphatase
CC activity of CpxA (PubMed:17259177, PubMed:21239493). Has mild protein
CC chaperone activity (PubMed:21317898, PubMed:21239493).
CC {ECO:0000269|PubMed:16166523, ECO:0000269|PubMed:16303867,
CC ECO:0000269|PubMed:17259177, ECO:0000269|PubMed:21239493,
CC ECO:0000269|PubMed:21317318, ECO:0000269|PubMed:21317898,
CC ECO:0000269|PubMed:25207645, ECO:0000269|PubMed:9473036}.
CC -!- SUBUNIT: Homodimer; it might alter shape slightly at pH 8.0 when Cpx is
CC induced (PubMed:21317318, PubMed:21239493). Binds the periplasmic
CC sensor domain of CpxA (PubMed:16166523, PubMed:21317318,
CC PubMed:21239493, PubMed:25207645). Interaction with CpxA is not seen in
CC vivo when cells are grown in 0.3 M NaCl, or if the misfolded P pili
CC protein PapE is overexpressed (PubMed:25207645).
CC {ECO:0000269|PubMed:21239493, ECO:0000269|PubMed:21317318,
CC ECO:0000269|PubMed:25207645, ECO:0000305|PubMed:16166523}.
CC -!- INTERACTION:
CC P0AE85; P0AE85: cpxP; NbExp=2; IntAct=EBI-6413881, EBI-6413881;
CC -!- SUBCELLULAR LOCATION: Periplasm {ECO:0000269|PubMed:25207645,
CC ECO:0000269|PubMed:9473036}.
CC -!- INDUCTION: Induced by envelope stress such as overexpression of
CC misfolded periplasmic proteins (PubMed:9351822). Induced by alkaine pH
CC (tested up to pH 8.4) (PubMed:9473036, PubMed:16166523). Induction is
CC decreased in a degP deletion (PubMed:16166523). Transcription is
CC stimulated by the Cpx two-component signal transduction pathway; sigma
CC factor E (rpoE) is not involved (PubMed:9351822, PubMed:9473036,
CC PubMed:10972835). Transcription induced by spheroplasting, which
CC removes the periplasm and thus this protein; if the protein is anchored
CC to the outer surface of the inner membrane induction does not occur
CC (PubMed:10972835). Induced in persister cells (PubMed:16768798).
CC {ECO:0000269|PubMed:10972835, ECO:0000269|PubMed:16166523,
CC ECO:0000269|PubMed:16768798, ECO:0000269|PubMed:9351822,
CC ECO:0000269|PubMed:9473036}.
CC -!- DOMAIN: A region in the N-terminus (residues 55-61) probably interacts
CC with the periplasmic sensor domain of CpxA to inhibit its kinase
CC activity and is also important for CpxP stability (PubMed:16166523).
CC The homodimer has an elongated cradle shape; a hydrophobic cleft on the
CC convex face may interact with periplasmic protein PapE
CC (PubMed:21239493). {ECO:0000269|PubMed:16166523,
CC ECO:0000269|PubMed:21239493}.
CC -!- PTM: Degraded by DegP; some CpxP mutant proteins are more susceptible
CC to the protease than others (PubMed:16166523). Degradation probably
CC occurs when CpxP is associated with some misfolded proteins;
CC overexpression of PapE leads to DegP-mediated degradation of CpxP and
CC PapE, which requires the N-terminus of PapE. Overexpression of NlpE
CC does not induce this degradation however (PubMed:16303867).
CC {ECO:0000269|PubMed:16166523, ECO:0000269|PubMed:16303867}.
CC -!- DISRUPTION PHENOTYPE: Hypersensitive to alkaline pH (greater than pH
CC 8.8) (PubMed:9473036). Increased accumulation and toxicity of
CC overexpressed, misfolded periplasmic proteins (PubMed:16303867).
CC {ECO:0000269|PubMed:16303867, ECO:0000269|PubMed:9473036}.
CC -!- SIMILARITY: Belongs to the CpxP/Spy family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB03046.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; L19201; AAB03046.1; ALT_INIT; Genomic_DNA.
DR EMBL; U00096; AAT48235.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77396.1; -; Genomic_DNA.
DR RefSeq; WP_001223800.1; NZ_STEB01000017.1.
DR RefSeq; YP_026277.1; NC_000913.3.
DR PDB; 3ITF; X-ray; 1.45 A; A/B=21-150.
DR PDB; 3QZC; X-ray; 2.85 A; A/B=40-151.
DR PDBsum; 3ITF; -.
DR PDBsum; 3QZC; -.
DR AlphaFoldDB; P0AE85; -.
DR SMR; P0AE85; -.
DR BioGRID; 4262646; 127.
DR DIP; DIP-47937N; -.
DR IntAct; P0AE85; 4.
DR STRING; 511145.b4484; -.
DR jPOST; P0AE85; -.
DR PaxDb; P0AE85; -.
DR PRIDE; P0AE85; -.
DR EnsemblBacteria; AAT48235; AAT48235; b4484.
DR EnsemblBacteria; BAE77396; BAE77396; BAE77396.
DR GeneID; 2847688; -.
DR GeneID; 66672178; -.
DR KEGG; ecj:JW5558; -.
DR KEGG; eco:b4484; -.
DR PATRIC; fig|1411691.4.peg.2791; -.
DR EchoBASE; EB1818; -.
DR eggNOG; COG3678; Bacteria.
DR HOGENOM; CLU_124352_2_1_6; -.
DR InParanoid; P0AE85; -.
DR OMA; NERMQEC; -.
DR PhylomeDB; P0AE85; -.
DR BioCyc; EcoCyc:G7816-MON; -.
DR EvolutionaryTrace; P0AE85; -.
DR PRO; PR:P0AE85; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0030288; C:outer membrane-bounded periplasmic space; IDA:EcoCyc.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0051082; F:unfolded protein binding; IDA:EcoCyc.
DR CDD; cd09916; CpxP_like; 1.
DR InterPro; IPR012899; LTXXQ.
DR Pfam; PF07813; LTXXQ; 1.
DR PIRSF; PIRSF034445; CpxP_Spy; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Periplasm; Reference proteome; Signal; Stress response.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..166
FT /note="Periplasmic protein CpxP"
FT /id="PRO_0000020992"
FT REGION 55..61
FT /note="Important for protein stability, probably interacts
FT with CpxA"
FT /evidence="ECO:0000269|PubMed:16166523"
FT REGION 151..166
FT /note="Not required for activation of CpxA or to induce
FT degradation of misfolded P pili subunits"
FT /evidence="ECO:0000269|PubMed:21239493"
FT MUTAGEN 55
FT /note="Q->P: No longer inhibits Cpx pathway, protein more
FT susceptible to DegP."
FT /evidence="ECO:0000269|PubMed:16166523,
FT ECO:0000269|PubMed:21317318"
FT MUTAGEN 56
FT /note="R->Q: No longer interacts with CpxA."
FT /evidence="ECO:0000269|PubMed:25207645"
FT MUTAGEN 59
FT /note="M->T: No longer inhibits Cpx pathway, protein more
FT susceptible to DegP."
FT /evidence="ECO:0000269|PubMed:16166523"
FT MUTAGEN 60
FT /note="R->Q: No longer inhibits Cpx pathway."
FT /evidence="ECO:0000269|PubMed:16166523"
FT MUTAGEN 61
FT /note="D->E,V: No longer inhibits Cpx pathway."
FT /evidence="ECO:0000269|PubMed:16166523"
FT MUTAGEN 103
FT /note="A->D,G: Decreased protein stability, significantly
FT reduced degradation of PapE."
FT /evidence="ECO:0000269|PubMed:21239493"
FT MUTAGEN 107
FT /note="I->D: Decreased protein stability, significantly
FT reduced degradation of PapE."
FT /evidence="ECO:0000269|PubMed:21239493"
FT MUTAGEN 107
FT /note="I->G,N: Decreased protein stability, wild-type
FT degradation of PapE."
FT /evidence="ECO:0000269|PubMed:21239493"
FT MUTAGEN 108
FT /note="A->D: Decreased protein stability, significantly
FT reduced degradation of PapE."
FT /evidence="ECO:0000269|PubMed:21239493"
FT MUTAGEN 108
FT /note="A->G: Decreased protein stability, wild-type
FT degradation of PapE."
FT /evidence="ECO:0000269|PubMed:21239493"
FT MUTAGEN 108
FT /note="A->V: Decreased protein stability, significantly
FT reduced degradation of PapE, retains most Cpx inhibition
FT activity."
FT /evidence="ECO:0000269|PubMed:21239493,
FT ECO:0000269|PubMed:25207645"
FT MUTAGEN 128
FT /note="Q->H: No longer inhibits Cpx pathway in wild-type
FT cells, protein more susceptible to DegP, in the absence of
FT DegP protease partially inhibits Cpx."
FT /evidence="ECO:0000269|PubMed:16166523,
FT ECO:0000269|PubMed:21317318"
FT TURN 45..48
FT /evidence="ECO:0007829|PDB:3ITF"
FT HELIX 53..69
FT /evidence="ECO:0007829|PDB:3ITF"
FT HELIX 75..85
FT /evidence="ECO:0007829|PDB:3ITF"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:3QZC"
FT HELIX 92..121
FT /evidence="ECO:0007829|PDB:3ITF"
FT HELIX 126..142
FT /evidence="ECO:0007829|PDB:3ITF"
FT HELIX 146..149
FT /evidence="ECO:0007829|PDB:3ITF"
SQ SEQUENCE 166 AA; 18965 MW; BD517D2D14D90209 CRC64;
MRIVTAAVMA STLAVSSLSH AAEVGSGDNW HPGEELTQRS TQSHMFDGIS LTEHQRQQMR
DLMQQARHEQ PPVNVSELET MHRLVTAENF DENAVRAQAE KMANEQIARQ VEMAKVRNQM
YRLLTPEQQA VLNEKHQQRM EQLRDVTQWQ KSSSLKLLSS SNSRSQ
