Escherichia coli K-12 substr. MG1655 Polypeptide: CpxA sensory histidine kinase

Gene: cpxA Accession Numbers: EG10163 (EcoCyc), b3911, ECK3904

Synonyms: rssE, ecfB, eup, ssd, ecf

Regulation Summary Diagram: ?

Regulation summary diagram for cpxA

Alternative forms of CpxA sensory histidine kinase: CpxA sensory histidine kinase - phosphorylated (summary available)

CpxA is the sensor kinase of the CpxAR two-component signal transduction system [Dong93]. The Cpx system is believed to be a stress response pathway that activates proteases and folding proteins in response to cell envelope damage [Pogliano97]. CpxA autophosphorylates and transfers a phosphate group to the response regulator, CpxR [Raivio97]. Autophosphorylation of CpxA is stimulated by diverse conditions such as alkaline pH, altered membrane lipid composition, interaction with hydrophobic surfaces and high osmolarity, however the exact nature of the ligand interacting with CpxA is not known [Dorel06]. CpxA can also dephosphorylate CpxR-P and this may be the default status of CpxA in the absence of stress signals [Wolfe08, Fleischer07]. The periplasmic protein CpxP binds to CpxA and inhibits the autokinase activity of CpxA [Fleischer07]. CpxA interacts directly with CpxP in vivo and this interaction is disrupted by high salt concentration (300mM NaCl) and the presence of misfolded P pilus subunit (from uropathogenic E. coli), PapE [Tschauner14].

By analogy to other sensor kinases autophosphorylation of CpxA is believed to occur intermolecularly between the subunits of a homodimer [Stock00].

cpxA: conjugative pilus expression [McEwen80a].

Locations: inner membrane

Map Position: [4,101,625 <- 4,102,998] (88.4 centisomes, 318°)
Length: 1374 bp / 457 aa

Molecular Weight of Polypeptide: 51.624 kD (from nucleotide sequence)

pI: 5.88

Unification Links: ASAP:ABE-0012772 , CGSC:908 , DIP:DIP-48358N , EchoBASE:EB0161 , EcoGene:EG10163 , EcoliWiki:b3911 , ModBase:P0AE82 , OU-Microarray:b3911 , PortEco:cpxA , PR:PRO_000022324 , Protein Model Portal:P0AE82 , RegulonDB:EG10163 , SMR:P0AE82 , String:511145.b3911 , UniProt:P0AE82

Relationship Links: InterPro:IN-FAMILY:IPR003594 , InterPro:IN-FAMILY:IPR003660 , InterPro:IN-FAMILY:IPR003661 , InterPro:IN-FAMILY:IPR004358 , InterPro:IN-FAMILY:IPR005467 , InterPro:IN-FAMILY:IPR009082 , PDB:Structure:4BIU , PDB:Structure:4BIV , PDB:Structure:4BIW , PDB:Structure:4BIX , PDB:Structure:4BIY , PDB:Structure:4BIZ , PDB:Structure:4CB0 , Pfam:IN-FAMILY:PF00512 , Pfam:IN-FAMILY:PF00672 , Pfam:IN-FAMILY:PF02518 , Prints:IN-FAMILY:PR00344 , Prosite:IN-FAMILY:PS50109 , Prosite:IN-FAMILY:PS50885 , Smart:IN-FAMILY:SM00304 , Smart:IN-FAMILY:SM00387 , Smart:IN-FAMILY:SM00388

In Paralogous Gene Group: 122 (29 members)

Reactions known to consume the compound:

CpxAR Two-Component Signal Transduction System :
CpxA + ATP → CpxA sensory histidine kinase - phosphorylated + ADP

Reactions known to produce the compound:

CpxAR Two-Component Signal Transduction System :
CpxR + CpxA sensory histidine kinase - phosphorylated → b3912 + CpxA

Genetic Regulation Schematic: ?

Genetic regulation schematic for cpxA

GO Terms:

Biological Process: GO:0000160 - phosphorelay signal transduction system Inferred from experiment Inferred by computational analysis [UniProtGOA11, Danese95, Yamamoto05]
GO:0023014 - signal transduction by phosphorylation Inferred from experiment Inferred by computational analysis [GOA01, Danese95, Yamamoto05]
GO:0043708 - cell adhesion involved in biofilm formation Inferred from experiment [Dorel99]
GO:0046777 - protein autophosphorylation Inferred from experiment [Yamamoto05]
GO:0007165 - signal transduction Inferred by computational analysis [GOA01]
GO:0016310 - phosphorylation Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0018106 - peptidyl-histidine phosphorylation Inferred by computational analysis [Gaudet10]
Molecular Function: GO:0000155 - phosphorelay sensor kinase activity Inferred from experiment Inferred by computational analysis [GOA01, Danese95, Yamamoto05]
GO:0005515 - protein binding Inferred from experiment [Tschauner14, Rajagopala14]
GO:0000166 - nucleotide binding Inferred by computational analysis [UniProtGOA11]
GO:0004673 - protein histidine kinase activity Inferred by computational analysis [GOA01a]
GO:0004871 - signal transducer activity Inferred by computational analysis [GOA01]
GO:0005524 - ATP binding Inferred by computational analysis [UniProtGOA11]
GO:0016301 - kinase activity Inferred by computational analysis [UniProtGOA11]
GO:0016740 - transferase activity Inferred by computational analysis [UniProtGOA11]
GO:0016772 - transferase activity, transferring phosphorus-containing groups Inferred by computational analysis [GOA01]
Cellular Component: GO:0005886 - plasma membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, DiazMejia09, Zhang07, Daley05, Weber88, Arutyunov10]
GO:0016021 - integral component of membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, Weber88]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11, GOA01]

MultiFun Terms: cell processes protection detoxification
cell structure membrane
information transfer protein related posttranslational modification
metabolism degradation of macromolecules proteins/peptides/glycopeptides
regulation type of regulation posttranscriptional covalent modification, demodification, maturation
regulation type of regulation transcriptional level complex regulation two component regulatory systems (external signal)

Essentiality data for cpxA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 1]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 2]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 1]

Sequence Features

Protein sequence of CpxA sensory histidine kinase with features indicated

Feature Class Location Citations Comment State
Transmembrane-Region 8 -> 29
UniProt: Helical;; Non-Experimental Qualifier: probable;
Sequence-Conflict 68
[Weber88, Albin86, UniProt10]
UniProt: (in Ref. 1; AAA23600 and 2; CAA31687);
Transmembrane-Region 164 -> 184
UniProt: Helical;; Non-Experimental Qualifier: probable;
Conserved-Region 185 -> 237
UniProt: HAMP;
Conserved-Region 245 -> 455
UniProt: Histidine kinase;
Phosphorylation-Modification 248
UniProt: Phosphohistidine; by autocatalysis; Non-Experimental Qualifier: by similarity.
Sequence-Conflict 330
[Weber88, Albin86, UniProt10]
UniProt: (in Ref. 1; AAA23600/AAA72540 and 2; CAA31687);

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b3911 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10163; confirmed by SwissProt match.


Albin86: Albin R, Weber R, Silverman PM (1986). "The Cpx proteins of Escherichia coli K12. Immunologic detection of the chromosomal cpxA gene product." J Biol Chem 1986;261(10);4698-705. PMID: 3007473

Arutyunov10: Arutyunov D, Arenson B, Manchak J, Frost LS (2010). "F plasmid TraF and TraH are components of an outer membrane complex involved in conjugation." J Bacteriol 192(6);1730-4. PMID: 20081027

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Daley05: Daley DO, Rapp M, Granseth E, Melen K, Drew D, von Heijne G (2005). "Global topology analysis of the Escherichia coli inner membrane proteome." Science 308(5726);1321-3. PMID: 15919996

Danese95: Danese PN, Snyder WB, Cosma CL, Davis LJ, Silhavy TJ (1995). "The Cpx two-component signal transduction pathway of Escherichia coli regulates transcription of the gene specifying the stress-inducible periplasmic protease, DegP." Genes Dev 1995;9(4);387-98. PMID: 7883164

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Dong93: Dong J, Iuchi S, Kwan HS, Lu Z, Lin EC (1993). "The deduced amino-acid sequence of the cloned cpxR gene suggests the protein is the cognate regulator for the membrane sensor, CpxA, in a two-component signal transduction system of Escherichia coli." Gene 1993;136(1-2);227-30. PMID: 8294007

Dorel06: Dorel C, Lejeune P, Rodrigue A (2006). "The Cpx system of Escherichia coli, a strategic signaling pathway for confronting adverse conditions and for settling biofilm communities?." Res Microbiol 157(4);306-14. PMID: 16487683

Dorel99: Dorel C, Vidal O, Prigent-Combaret C, Vallet I, Lejeune P (1999). "Involvement of the Cpx signal transduction pathway of E. coli in biofilm formation." FEMS Microbiol Lett 178(1);169-75. PMID: 10483736

Fleischer07: Fleischer R, Heermann R, Jung K, Hunke S (2007). "Purification, reconstitution, and characterization of the CpxRAP envelope stress system of Escherichia coli." J Biol Chem 282(12);8583-93. PMID: 17259177

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

McEwen80a: McEwen J, Silverman P (1980). "Chromosomal mutations of Escherichia coli that alter expression of conjugative plasmid functions." Proc Natl Acad Sci U S A 77(1);513-7. PMID: 6102380

Pogliano97: Pogliano J, Lynch AS, Belin D, Lin EC, Beckwith J (1997). "Regulation of Escherichia coli cell envelope proteins involved in protein folding and degradation by the Cpx two-component system." Genes Dev 11(9);1169-82. PMID: 9159398

Raivio97: Raivio TL, Silhavy TJ (1997). "Transduction of envelope stress in Escherichia coli by the Cpx two-component system." J Bacteriol 179(24);7724-33. PMID: 9401031

Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554

Stock00: Stock AM, Robinson VL, Goudreau PN (2000). "Two-component signal transduction." Annu Rev Biochem 69;183-215. PMID: 10966457

Tschauner14: Tschauner K, Hornschemeyer P, Muller VS, Hunke S (2014). "Dynamic Interaction between the CpxA Sensor Kinase and the Periplasmic Accessory Protein CpxP Mediates Signal Recognition in E. coli." PLoS One 9(9);e107383. PMID: 25207645

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt13: UniProt Consortium (2013). "UniProt version 2013-08 released on 2013-08-01 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

Weber88: Weber RF, Silverman PM (1988). "The cpx proteins of Escherichia coli K12. Structure of the cpxA polypeptide as an inner membrane component." J Mol Biol 1988;203(2);467-78. PMID: 3058985

Wolfe08: Wolfe AJ, Parikh N, Lima BP, Zemaitaitis B (2008). "Signal integration by the two-component signal transduction response regulator CpxR." J Bacteriol 190(7);2314-22. PMID: 18223085

Yamamoto05: Yamamoto K, Hirao K, Oshima T, Aiba H, Utsumi R, Ishihama A (2005). "Functional characterization in vitro of all two-component signal transduction systems from Escherichia coli." J Biol Chem 280(2);1448-56. PMID: 15522865

Zhang07: Zhang N, Chen R, Young N, Wishart D, Winter P, Weiner JH, Li L (2007). "Comparison of SDS- and methanol-assisted protein solubilization and digestion methods for Escherichia coli membrane proteome analysis by 2-D LC-MS/MS." Proteomics 7(4);484-93. PMID: 17309111

Other References Related to Gene Regulation

BuryMone09: Bury-Mone S, Nomane Y, Reymond N, Barbet R, Jacquet E, Imbeaud S, Jacq A, Bouloc P (2009). "Global analysis of extracytoplasmic stress signaling in Escherichia coli." PLoS Genet 5(9);e1000651. PMID: 19763168

De99b: De Wulf P, Kwon O, Lin EC (1999). "The CpxRA signal transduction system of Escherichia coli: growth-related autoactivation and control of unanticipated target operons." J Bacteriol 1999;181(21);6772-8. PMID: 10542180

Holmqvist12: Holmqvist E, Unoson C, Reimegard J, Wagner EG (2012). "A mixed double negative feedback loop between the sRNA MicF and the global regulator Lrp." Mol Microbiol 84(3);414-27. PMID: 22324810

Raivio13: Raivio TL, Leblanc SK, Price NL (2013). "The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity." J Bacteriol 195(12);2755-67. PMID: 23564175

Yamamoto06: Yamamoto K, Ishihama A (2006). "Characterization of copper-inducible promoters regulated by CpxA/CpxR in Escherichia coli." Biosci Biotechnol Biochem 70(7);1688-95. PMID: 16861804

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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