UniProt functional annotation for P0AE85



	UniProt functional annotation for P0AE85

UniProt code: P0AE85.

Organism: Escherichia coli (strain K12).

Taxonomy: Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.

Function: Acts as an auxiliary protein in the Cpx two-component envelope stress response system, helping modulate the Cpx response systems response to some inducers (PubMed:25207645, PubMed:16303867). Binds the periplasmic domain of sensor histidine kinase CpxA, inhibiting induction of the Cpx envelope stress response in the absence of inducer; overexpression decreases Cpx pathway activity (PubMed:16166523, PubMed:21317318). Some periplasmic stimulii (shown for P pili subunit PapE and probably 0.3 M NaCl) increase CpxP's susceptibility to DegP, leading to CpxP degradation, inducing the Cpx pathway (PubMed:16166523, PubMed:16303867). Aids in combating extracytoplasmic protein-mediated toxicity (PubMed:9473036, PubMed:16303867, PubMed:21239493). Overexpression leads to degradation by DegP of misfolded P pili subunits in the periplasm (tested using PapE) (PubMed:21239493). Inhibits autophosphorylation of CpxA in reconstituted liposomes by 50% but has no effect on phosphatase activity of CpxA (PubMed:17259177, PubMed:21239493). Has mild protein chaperone activity (PubMed:21317898, PubMed:21239493). {ECO:0000269|PubMed:16166523, ECO:0000269|PubMed:16303867, ECO:0000269|PubMed:17259177, ECO:0000269|PubMed:21239493, ECO:0000269|PubMed:21317318, ECO:0000269|PubMed:21317898, ECO:0000269|PubMed:25207645, ECO:0000269|PubMed:9473036}.

Subunit: Homodimer; it might alter shape slightly at pH 8.0 when Cpx is induced (PubMed:21317318, PubMed:21239493). Binds the periplasmic sensor domain of CpxA (PubMed:16166523, PubMed:21317318, PubMed:21239493, PubMed:25207645). Interaction with CpxA is not seen in vivo when cells are grown in 0.3 M NaCl, or if the misfolded P pili protein PapE is overexpressed (PubMed:25207645). {ECO:0000269|PubMed:21239493, ECO:0000269|PubMed:21317318, ECO:0000269|PubMed:25207645, ECO:0000305|PubMed:16166523}.

Subcellular location: Periplasm {ECO:0000269|PubMed:25207645, ECO:0000269|PubMed:9473036}.

Induction: Induced by envelope stress such as overexpression of misfolded periplasmic proteins (PubMed:9351822). Induced by alkaine pH (tested up to pH 8.4) (PubMed:9473036, PubMed:16166523). Induction is decreased in a degP deletion (PubMed:16166523). Transcription is stimulated by the Cpx two-component signal transduction pathway; sigma factor E (rpoE) is not involved (PubMed:9351822, PubMed:9473036, PubMed:10972835). Transcription induced by spheroplasting, which removes the periplasm and thus this protein; if the protein is anchored to the outer surface of the inner membrane induction does not occur (PubMed:10972835). Induced in persister cells (PubMed:16768798). {ECO:0000269|PubMed:10972835, ECO:0000269|PubMed:16166523, ECO:0000269|PubMed:16768798, ECO:0000269|PubMed:9351822, ECO:0000269|PubMed:9473036}.

Domain: A region in the N-terminus (residues 55-61) probably interacts with the periplasmic sensor domain of CpxA to inhibit its kinase activity and is also important for CpxP stability (PubMed:16166523). The homodimer has an elongated cradle shape; a hydrophobic cleft on the convex face may interact with periplasmic protein PapE (PubMed:21239493). {ECO:0000269|PubMed:16166523, ECO:0000269|PubMed:21239493}.

Ptm: Degraded by DegP; some CpxP mutant proteins are more susceptible to the protease than others (PubMed:16166523). Degradation probably occurs when CpxP is associated with some misfolded proteins; overexpression of PapE leads to DegP-mediated degradation of CpxP and PapE, which requires the N-terminus of PapE. Overexpression of NlpE does not induce this degradation however (PubMed:16303867). {ECO:0000269|PubMed:16166523, ECO:0000269|PubMed:16303867}.

Disruption phenotype: Hypersensitive to alkaline pH (greater than pH 8.8) (PubMed:9473036). Increased accumulation and toxicity of overexpressed, misfolded periplasmic proteins (PubMed:16303867). {ECO:0000269|PubMed:16303867, ECO:0000269|PubMed:9473036}.

Similarity: Belongs to the CpxP/Spy family. {ECO:0000305}.

Sequence caution: Sequence=AAB03046.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Escherichia coli (strain K12).
Taxonomy:		Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.



Function:		Acts as an auxiliary protein in the Cpx two-component envelope stress response system, helping modulate the Cpx response systems response to some inducers (PubMed:25207645, PubMed:16303867). Binds the periplasmic domain of sensor histidine kinase CpxA, inhibiting induction of the Cpx envelope stress response in the absence of inducer; overexpression decreases Cpx pathway activity (PubMed:16166523, PubMed:21317318). Some periplasmic stimulii (shown for P pili subunit PapE and probably 0.3 M NaCl) increase CpxP's susceptibility to DegP, leading to CpxP degradation, inducing the Cpx pathway (PubMed:16166523, PubMed:16303867). Aids in combating extracytoplasmic protein-mediated toxicity (PubMed:9473036, PubMed:16303867, PubMed:21239493). Overexpression leads to degradation by DegP of misfolded P pili subunits in the periplasm (tested using PapE) (PubMed:21239493). Inhibits autophosphorylation of CpxA in reconstituted liposomes by 50% but has no effect on phosphatase activity of CpxA (PubMed:17259177, PubMed:21239493). Has mild protein chaperone activity (PubMed:21317898, PubMed:21239493). {ECO:0000269\|PubMed:16166523, ECO:0000269\|PubMed:16303867, ECO:0000269\|PubMed:17259177, ECO:0000269\|PubMed:21239493, ECO:0000269\|PubMed:21317318, ECO:0000269\|PubMed:21317898, ECO:0000269\|PubMed:25207645, ECO:0000269\|PubMed:9473036}.


Subunit:		Homodimer; it might alter shape slightly at pH 8.0 when Cpx is induced (PubMed:21317318, PubMed:21239493). Binds the periplasmic sensor domain of CpxA (PubMed:16166523, PubMed:21317318, PubMed:21239493, PubMed:25207645). Interaction with CpxA is not seen in vivo when cells are grown in 0.3 M NaCl, or if the misfolded P pili protein PapE is overexpressed (PubMed:25207645). {ECO:0000269\|PubMed:21239493, ECO:0000269\|PubMed:21317318, ECO:0000269\|PubMed:25207645, ECO:0000305\|PubMed:16166523}.
Subcellular location:		Periplasm {ECO:0000269\|PubMed:25207645, ECO:0000269\|PubMed:9473036}.
Induction:		Induced by envelope stress such as overexpression of misfolded periplasmic proteins (PubMed:9351822). Induced by alkaine pH (tested up to pH 8.4) (PubMed:9473036, PubMed:16166523). Induction is decreased in a degP deletion (PubMed:16166523). Transcription is stimulated by the Cpx two-component signal transduction pathway; sigma factor E (rpoE) is not involved (PubMed:9351822, PubMed:9473036, PubMed:10972835). Transcription induced by spheroplasting, which removes the periplasm and thus this protein; if the protein is anchored to the outer surface of the inner membrane induction does not occur (PubMed:10972835). Induced in persister cells (PubMed:16768798). {ECO:0000269\|PubMed:10972835, ECO:0000269\|PubMed:16166523, ECO:0000269\|PubMed:16768798, ECO:0000269\|PubMed:9351822, ECO:0000269\|PubMed:9473036}.
Domain:		A region in the N-terminus (residues 55-61) probably interacts with the periplasmic sensor domain of CpxA to inhibit its kinase activity and is also important for CpxP stability (PubMed:16166523). The homodimer has an elongated cradle shape; a hydrophobic cleft on the convex face may interact with periplasmic protein PapE (PubMed:21239493). {ECO:0000269\|PubMed:16166523, ECO:0000269\|PubMed:21239493}.
Ptm:		Degraded by DegP; some CpxP mutant proteins are more susceptible to the protease than others (PubMed:16166523). Degradation probably occurs when CpxP is associated with some misfolded proteins; overexpression of PapE leads to DegP-mediated degradation of CpxP and PapE, which requires the N-terminus of PapE. Overexpression of NlpE does not induce this degradation however (PubMed:16303867). {ECO:0000269\|PubMed:16166523, ECO:0000269\|PubMed:16303867}.
Disruption phenotype:		Hypersensitive to alkaline pH (greater than pH 8.8) (PubMed:9473036). Increased accumulation and toxicity of overexpressed, misfolded periplasmic proteins (PubMed:16303867). {ECO:0000269\|PubMed:16303867, ECO:0000269\|PubMed:9473036}.
Similarity:		Belongs to the CpxP/Spy family. {ECO:0000305}.
Sequence caution:		Sequence=AAB03046.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};