Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Sensor histidine kinase CpxA

Gene

cpxA

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Histidine kinase member of the two-component regulatory system CpxA/CpxR which responds to envelope stress response by activating expression of downstream genes including cpxP, degP, dsbA and ppiA (PubMed:7883164, PubMed:9401031, PubMed:9473036). Activates CpxR by phosphorylation; has autokinase, phosphotransferase and (in the presence of Mg2+ and/or ATP or ADP) phosphatase activity (PubMed:9401031, PubMed:17259177, PubMed:24492262). The kinase activity is inhibited by periplasmic accessory protein CpxP; proteolysis of CpxP relieves inhibition (PubMed:16166523, PubMed:17259177, PubMed:25207645). Involved in several diverse cellular processes, including the functioning of acetohydroxyacid synthetase I, the biosynthesis of isoleucine and valine, the TraJ protein activation activity for tra gene expression in F plasmid (PubMed:8432716), and the synthesis, translocation, or stability of cell envelope proteins (PubMed:7883164). Activates transcription of periplasmic protease degP, probably by phosphorylating the cognate response protein CpxR; overexpression of an outer membrane lipoprotein NlpE also leads to transcription of degP via CpxRA (PubMed:7883164). Required for efficient binding of stationary phase cells to hydrophobic surfaces, part of the process of biofilm formation (PubMed:11830644).1 Publication8 Publications

Catalytic activityi

ATP + protein L-histidine = ADP + protein N-phospho-L-histidine.1 Publication

Cofactori

Mg2+1 PublicationNote: Phosphotransfer to CpxR is stimulated by Mg2+ and/or Mn2+.1 Publication

Enzyme regulationi

The two-component system is activated by envelope stress such as overexpression of some (misfolded) periplasmic proteins (PubMed:7883164, PubMed:9351822). Activated by spheroplasting (which removes the periplasm) in an autoregulatory cpxA-cpxR-dependent fashion (PubMed:10972835). Cpx two-component system is induced at pH 8.0; in a degP deletion mutant induction is halved (PubMed:9473036, PubMed:16166523). The kinase activity is inhibited by periplasmic accessory protein CpxP; proteolysis of CpxP relieves inhibition (PubMed:16166523, PubMed:17259177, PubMed:25207645). Autokinase activity reconstituted in liposomes is 50% inhibited by periplasmic accessory protein CpxP, but CpxP has no effect on phosphatase activity; autokinase stimulated by KCl, NH4Cl, RbCl, pH 7.5 and 8.0, inhibited by sensor kinase inhibitors tetrachlorosalicylanilid and ethodin (PubMed:17259177).7 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei248Nucleophile1 Publication1
Binding sitei248ATP1 Publication1
Binding sitei386ATP1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi248 – 251ATP1 Publication4
Nucleotide bindingi359 – 364ATP1 Publication6
Nucleotide bindingi405 – 406ATP1 Publication2
Nucleotide bindingi416 – 421ATP1 Publication6

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • phosphorelay sensor kinase activity Source: EcoCyc

GO - Biological processi

  • cell adhesion involved in biofilm formation Source: CACAO
  • phosphorelay signal transduction system Source: EcoCyc
  • protein autophosphorylation Source: EcoCyc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Biological processi

Cell adhesion, Two-component regulatory system

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciEcoCyc:CPXA-MONOMER.
ECOL316407:JW3882-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Sensor histidine kinase CpxA (EC:2.7.13.31 Publication)
Gene namesi
Name:cpxA
Synonyms:ecfB, eup, ssd
Ordered Locus Names:b3911, JW3882
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10163. cpxA.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 7Cytoplasmic1 Publication7
Transmembranei8 – 29HelicalCuratedAdd BLAST22
Topological domaini30 – 163Periplasmic2 PublicationsAdd BLAST134
Transmembranei164 – 184HelicalCuratedAdd BLAST21
Topological domaini185 – 457Cytoplasmic2 PublicationsAdd BLAST273

GO - Cellular componenti

  • integral component of membrane Source: EcoCyc
  • intracellular Source: GOC
  • plasma membrane Source: EcoCyc
Complete GO annotation...

Keywords - Cellular componenti

Cell inner membrane, Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Loss of the Cpx envelope stress response (PubMed:10972835). Decreased resistance to the antibiotic amnikacin (PubMed:2185221). Single cpxA and double cpxR-cpxA mutant decrease transcription of degP (PubMed:7883164). Decreased transcription of cpxP (PubMed:9473036). Hypersensitive to alkaline pH (greater than pH 8.8) (PubMed:9473036). Decreased numbers of stationary phase cells bind to hydrophobic surfaces (PubMed:11830644). Greatly increased resistance to hydroxyurea, probably due to decreased recognition of mis-folded proteins which eventually leads to decreased OH radical formation (PubMed:20005847).6 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi33R → C in cpxA104; a cpxA gain of function mutant, constitutively active. 1 Publication1
Mutagenesisi93 – 124Missing in cpxA24; a cpxA gain of function mutant, constitutively active, up-regulation of the Cpx regulon members. 1 PublicationAdd BLAST32
Mutagenesisi185S → R: Nearly complete loss of response to excess periplasmic protein. 1 Publication1
Mutagenesisi186L → Q: 30% decrease in response to excess periplasmic protein. 1 Publication1
Mutagenesisi197A → V: Slight decrease in response to excess periplasmic protein. 1 Publication1
Mutagenesisi204N → Y: 80% decrease in response to excess periplasmic protein. 1 Publication1
Mutagenesisi222G → D: 90% decrease in response to excess periplasmic protein. 1 Publication1
Mutagenesisi222G → R: 75% decrease in response to excess periplasmic protein. 1 Publication1
Mutagenesisi228M → V: No response to excess periplasmic protein, decreased autophosphorylation, no phosphotransfer to CpxR, no tetramer formation of the C-terminal domain in solution. 1 Publication1
Mutagenesisi252T → P in cpxA101; a cpxA gain of function mutant, decreased autophosphorylation, decreased phosphotransfer to CpxR, loss of phosphatase activity, responds to periplasmic protein overproduction. 1 Publication1
Mutagenesisi356N → Y: Nearly complete loss of response to excess periplasmic protein. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000747391 – 457Sensor histidine kinase CpxAAdd BLAST457

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei248Phosphohistidine; by autocatalysisPROSITE-ProRule annotation2 Publications1

Post-translational modificationi

Autophosphorylated (PubMed:9401031, PubMed:24492262). Maximal phosphorylation of the dimeric isolated cytoplasmic domain (residues 188-457) is about 70%, suggesting the protein may be hemiphosphorylated in vivo; probably occurs via a trans-autophosphorylation mechanism, i.e. one subunit phopshorylates the other (PubMed:24492262).2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP0AE82.
PRIDEiP0AE82.

PTM databases

iPTMnetiP0AE82.

Interactioni

Subunit structurei

The isolated cytoplasmic domain (residues 188-457) crystallizes as a homodimer, and forms dimers of dimers in solution which may be catalytically important (PubMed:24492262). Interacts with periplasmic accessory protein CpxP (PubMed:16166523, PubMed:21317318, PubMed:21239493, PubMed:25207645); interaction with CpxP 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). Interacts with cognate response regulator CpxR (PubMed:25207645).1 Publication2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
paaXP760863EBI-9141330,EBI-544692

Protein-protein interaction databases

BioGridi4262644. 12 interactors.
DIPiDIP-48358N.
IntActiP0AE82. 2 interactors.
STRINGi511145.b3911.

Structurei

Secondary structure

1457
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi189 – 200Combined sources12
Turni201 – 203Combined sources3
Helixi209 – 212Combined sources4
Beta strandi214 – 216Combined sources3
Helixi217 – 220Combined sources4
Helixi221 – 249Combined sources29
Helixi251 – 267Combined sources17
Helixi272 – 296Combined sources25
Beta strandi299 – 301Combined sources3
Beta strandi306 – 309Combined sources4
Helixi310 – 328Combined sources19
Beta strandi331 – 336Combined sources6
Beta strandi342 – 345Combined sources4
Helixi347 – 364Combined sources18
Beta strandi366 – 375Combined sources10
Beta strandi377 – 386Combined sources10
Helixi393 – 395Combined sources3
Helixi398 – 400Combined sources3
Helixi407 – 412Combined sources6
Helixi421 – 430Combined sources10
Beta strandi434 – 439Combined sources6
Beta strandi443 – 452Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BIUX-ray3.65A/B/C/D/E/F188-457[»]
4BIVX-ray3.40A/B188-457[»]
4BIWX-ray2.85A/B188-457[»]
4BIXX-ray2.00A/B188-457[»]
4BIYX-ray3.30A/B/C/D188-457[»]
4BIZX-ray2.65A/B/C/D/E/F188-457[»]
4CB0X-ray3.30A/B188-457[»]
ProteinModelPortaliP0AE82.
SMRiP0AE82.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini185 – 237HAMPPROSITE-ProRule annotationAdd BLAST53
Domaini245 – 455Histidine kinasePROSITE-ProRule annotationAdd BLAST211

Domaini

The periplasmic segment (residues 30-163) defines the sensory domain (PubMed:9401031). Conformational changes in the cytoplasmic HAMP domain modulate the mobility of the central alpha-helices (which bend at Ser-238 and Pro-253) that allows formation of 1 kinase-active state.2 Publications

Sequence similaritiesi

Contains 1 HAMP domain.PROSITE-ProRule annotation
Contains 1 histidine kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG4105E0F. Bacteria.
ENOG410XTWD. LUCA.
HOGENOMiHOG000269851.
InParanoidiP0AE82.
KOiK07640.
OMAiIPVEKAC.
PhylomeDBiP0AE82.

Family and domain databases

CDDicd06225. HAMP. 1 hit.
Gene3Di1.10.287.130. 1 hit.
3.30.565.10. 1 hit.
InterProiIPR032404. CpxA_peri.
IPR003660. HAMP_dom.
IPR003594. HATPase_C.
IPR005467. His_kinase_dom.
IPR003661. HisK_dim/P.
IPR004358. Sig_transdc_His_kin-like_C.
[Graphical view]
PfamiPF16527. CpxA_peri. 1 hit.
PF00672. HAMP. 1 hit.
PF02518. HATPase_c. 1 hit.
PF00512. HisKA. 1 hit.
[Graphical view]
PRINTSiPR00344. BCTRLSENSOR.
SMARTiSM00304. HAMP. 1 hit.
SM00387. HATPase_c. 1 hit.
SM00388. HisKA. 1 hit.
[Graphical view]
SUPFAMiSSF47384. SSF47384. 1 hit.
SSF55874. SSF55874. 1 hit.
PROSITEiPS50885. HAMP. 1 hit.
PS50109. HIS_KIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0AE82-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MIGSLTARIF AIFWLTLALV LMLVLMLPKL DSRQMTELLD SEQRQGLMIE
60 70 80 90 100
QHVEAELAND PPNDLMWWRR LFRAIDKWAP PGQRLLLVTT EGRVIGAERS
110 120 130 140 150
EMQIIRNFIG QADNADHPQK KKYGRVELVG PFSVRDGEDN YQLYLIRPAS
160 170 180 190 200
SSQSDFINLL FDRPLLLLIV TMLVSTPLLL WLAWSLAKPA RKLKNAADEV
210 220 230 240 250
AQGNLRQHPE LEAGPQEFLA AGASFNQMVT ALERMMTSQQ RLLSDISHEL
260 270 280 290 300
RTPLTRLQLG TALLRRRSGE SKELERIETE AQRLDSMIND LLVMSRNQQK
310 320 330 340 350
NALVSETIKA NQLWSEVLDN AAFEAEQMGK SLTVNFPPGP WPLYGNPNAL
360 370 380 390 400
ESALENIVRN ALRYSHTKIE VGFAVDKDGI TITVDDDGPG VSPEDREQIF
410 420 430 440 450
RPFYRTDEAR DRESGGTGLG LAIVETAIQQ HRGWVKAEDS PLGGLRLVIW

LPLYKRS
Length:457
Mass (Da):51,624
Last modified:December 6, 2005 - v1
Checksum:i720EE4A62885BA33
GO

Sequence cautioni

The sequence AAA72540 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti68W → WW in AAA23600 (PubMed:3007473).Curated1
Sequence conflicti68W → WW in CAA31687 (PubMed:3058985).Curated1
Sequence conflicti330K → R in AAA23600 (PubMed:3007473).Curated1
Sequence conflicti330K → R in AAA72540 (PubMed:3007473).Curated1
Sequence conflicti330K → R in CAA31687 (PubMed:3058985).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13493 Genomic DNA. Translation: AAA72540.1. Different initiation.
M36795 Genomic DNA. Translation: AAA23600.1.
X13307 Genomic DNA. Translation: CAA31687.1.
L19201 Genomic DNA. Translation: AAB03044.1.
U00096 Genomic DNA. Translation: AAC76893.1.
AP009048 Genomic DNA. Translation: BAE77398.1.
PIRiS40855.
RefSeqiNP_418347.1. NC_000913.3.
WP_000580417.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC76893; AAC76893; b3911.
BAE77398; BAE77398; BAE77398.
GeneIDi948405.
KEGGiecj:JW3882.
eco:b3911.
PATRICi32123335. VBIEscCol129921_4028.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13493 Genomic DNA. Translation: AAA72540.1. Different initiation.
M36795 Genomic DNA. Translation: AAA23600.1.
X13307 Genomic DNA. Translation: CAA31687.1.
L19201 Genomic DNA. Translation: AAB03044.1.
U00096 Genomic DNA. Translation: AAC76893.1.
AP009048 Genomic DNA. Translation: BAE77398.1.
PIRiS40855.
RefSeqiNP_418347.1. NC_000913.3.
WP_000580417.1. NZ_LN832404.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BIUX-ray3.65A/B/C/D/E/F188-457[»]
4BIVX-ray3.40A/B188-457[»]
4BIWX-ray2.85A/B188-457[»]
4BIXX-ray2.00A/B188-457[»]
4BIYX-ray3.30A/B/C/D188-457[»]
4BIZX-ray2.65A/B/C/D/E/F188-457[»]
4CB0X-ray3.30A/B188-457[»]
ProteinModelPortaliP0AE82.
SMRiP0AE82.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4262644. 12 interactors.
DIPiDIP-48358N.
IntActiP0AE82. 2 interactors.
STRINGi511145.b3911.

PTM databases

iPTMnetiP0AE82.

Proteomic databases

PaxDbiP0AE82.
PRIDEiP0AE82.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC76893; AAC76893; b3911.
BAE77398; BAE77398; BAE77398.
GeneIDi948405.
KEGGiecj:JW3882.
eco:b3911.
PATRICi32123335. VBIEscCol129921_4028.

Organism-specific databases

EchoBASEiEB0161.
EcoGeneiEG10163. cpxA.

Phylogenomic databases

eggNOGiENOG4105E0F. Bacteria.
ENOG410XTWD. LUCA.
HOGENOMiHOG000269851.
InParanoidiP0AE82.
KOiK07640.
OMAiIPVEKAC.
PhylomeDBiP0AE82.

Enzyme and pathway databases

BioCyciEcoCyc:CPXA-MONOMER.
ECOL316407:JW3882-MONOMER.

Miscellaneous databases

PROiP0AE82.

Family and domain databases

CDDicd06225. HAMP. 1 hit.
Gene3Di1.10.287.130. 1 hit.
3.30.565.10. 1 hit.
InterProiIPR032404. CpxA_peri.
IPR003660. HAMP_dom.
IPR003594. HATPase_C.
IPR005467. His_kinase_dom.
IPR003661. HisK_dim/P.
IPR004358. Sig_transdc_His_kin-like_C.
[Graphical view]
PfamiPF16527. CpxA_peri. 1 hit.
PF00672. HAMP. 1 hit.
PF02518. HATPase_c. 1 hit.
PF00512. HisKA. 1 hit.
[Graphical view]
PRINTSiPR00344. BCTRLSENSOR.
SMARTiSM00304. HAMP. 1 hit.
SM00387. HATPase_c. 1 hit.
SM00388. HisKA. 1 hit.
[Graphical view]
SUPFAMiSSF47384. SSF47384. 1 hit.
SSF55874. SSF55874. 1 hit.
PROSITEiPS50885. HAMP. 1 hit.
PS50109. HIS_KIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCPXA_ECOLI
AccessioniPrimary (citable) accession number: P0AE82
Secondary accession number(s): P08336, Q2M8K8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: December 6, 2005
Last modified: November 2, 2016
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.