CPXA_ECOLI
ID CPXA_ECOLI Reviewed; 457 AA.
AC P0AE82; P08336; Q2M8K8;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Sensor histidine kinase CpxA;
DE EC=2.7.13.3 {ECO:0000269|PubMed:9401031};
GN Name=cpxA; Synonyms=ecfB, eup, ssd; OrderedLocusNames=b3911, JW3882;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, AND TOPOLOGY.
RC STRAIN=K12;
RX PubMed=3007473; DOI=10.1016/s0021-9258(17)38558-7;
RA Albin R., Weber R.F., Silverman P.M.;
RT "The Cpx proteins of Escherichia coli K12. Immunologic detection of the
RT chromosomal cpxA gene product.";
RL J. Biol. Chem. 261:4698-4705(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 [3]
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 [4]
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 [5]
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 [6]
RP CHARACTERIZATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / AE2000;
RX PubMed=2185221; DOI=10.1128/jb.172.5.2456-2461.1990;
RA Rainwater S., Silverman P.M.;
RT "The Cpx proteins of Escherichia coli K-12: evidence that cpxA, ecfB, ssd,
RT and eup mutations all identify the same gene.";
RL J. Bacteriol. 172:2456-2461(1990).
RN [7]
RP FUNCTION.
RC STRAIN=K12;
RX PubMed=8432716; DOI=10.1128/jb.175.4.921-925.1993;
RA Silverman P.M., Tran L., Harris R., Gaudin H.M.;
RT "Accumulation of the F plasmid TraJ protein in cpx mutants of Escherichia
RT coli.";
RL J. Bacteriol. 175:921-925(1993).
RN [8]
RP FUNCTION, ACTIVITY REGULATION, 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 [9]
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 [10]
RP FUNCTION AS A KINASE AND PHOSPHATASE, CATALYTIC ACTIVITY, COFACTOR, DOMAIN,
RP PHOSPHORYLATION AT HIS-248, AND MUTAGENESIS OF ARG-33; 93-ARG--GLY-124 AND
RP THR-252.
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 [11]
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 [12]
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 [13]
RP FUNCTION IN BIOFILM FORMATION, AND DISRUPTION 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 [14]
RP SUBCELLULAR LOCATION, AND TOPOLOGY [LARGE SCALE ANALYSIS].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=15919996; DOI=10.1126/science.1109730;
RA Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.;
RT "Global topology analysis of the Escherichia coli inner membrane
RT proteome.";
RL Science 308:1321-1323(2005).
RN [15]
RP FUNCTION, ACTIVITY REGULATION, AND PROBABLE SUBUNIT.
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 [16]
RP FUNCTION, AND ACTIVITY REGULATION.
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 [17]
RP ROLE IN HYDROXYUREA RESISTANCE, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / MC4100 / ATCC 35695 / DSM 6574;
RX PubMed=20005847; DOI=10.1016/j.molcel.2009.11.024;
RA Davies B.W., Kohanski M.A., Simmons L.A., Winkler J.A., Collins J.J.,
RA Walker G.C.;
RT "Hydroxyurea induces hydroxyl radical-mediated cell death in Escherichia
RT coli.";
RL Mol. Cell 36:845-860(2009).
RN [18]
RP SUBUNIT.
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 [19]
RP SUBUNIT.
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).
RN [20]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH CPXP AND CPXR, AND
RP SUBCELLULAR LOCATION.
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 [21]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 188-457 IN COMPLEX WITH ADP; ATP
RP AND ATP ANALOG, FUNCTION, SUBUNIT, ACTIVE SITE, REACTION MECHANISM, DOMAIN,
RP PHOSPHORYLATION AT HIS-248, AND MUTAGENESIS OF SER-185; LEU-186; ALA-197;
RP ASN-204; GLY-222; MET-228 AND ASN-356.
RX PubMed=24492262; DOI=10.1371/journal.pbio.1001776;
RA Mechaly A.E., Sassoon N., Betton J.M., Alzari P.M.;
RT "Segmental helical motions and dynamical asymmetry modulate histidine
RT kinase autophosphorylation.";
RL PLoS Biol. 12:E1001776-E1001776(2014).
CC -!- FUNCTION: Histidine kinase 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, PubMed:9473036). Activates
CC CpxR by phosphorylation; has autokinase, phosphotransferase and (in the
CC presence of Mg(2+) and/or ATP or ADP) phosphatase activity
CC (PubMed:9401031, PubMed:17259177, PubMed:24492262). The kinase activity
CC is inhibited by periplasmic accessory protein CpxP; proteolysis of CpxP
CC relieves inhibition (PubMed:16166523, PubMed:17259177,
CC PubMed:25207645). Involved in several diverse cellular processes,
CC including the functioning of acetohydroxyacid synthetase I, the
CC biosynthesis of isoleucine and valine, the TraJ protein activation
CC activity for tra gene expression in F plasmid (PubMed:8432716), and the
CC synthesis, translocation, or stability of cell envelope proteins
CC (PubMed:7883164). Activates transcription of periplasmic protease degP,
CC probably by phosphorylating the cognate response protein CpxR;
CC overexpression of an outer membrane lipoprotein NlpE also leads to
CC transcription of degP via CpxRA (PubMed:7883164). Required for
CC efficient binding of stationary phase cells to hydrophobic surfaces,
CC part of the process of biofilm formation (PubMed:11830644).
CC {ECO:0000269|PubMed:16166523, ECO:0000269|PubMed:17259177,
CC ECO:0000269|PubMed:24492262, ECO:0000269|PubMed:25207645,
CC ECO:0000269|PubMed:7883164, ECO:0000269|PubMed:8432716,
CC ECO:0000269|PubMed:9401031, ECO:0000269|PubMed:9473036,
CC ECO:0000305|PubMed:11830644}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + protein L-histidine = ADP + protein N-phospho-L-
CC histidine.; EC=2.7.13.3; Evidence={ECO:0000269|PubMed:9401031};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:9401031};
CC Note=Phosphotransfer to CpxR is stimulated by Mg(2+) and/or Mn(2+).
CC {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 induced at pH 8.0; in a
CC degP deletion mutant induction is halved (PubMed:9473036,
CC PubMed:16166523). The kinase activity is inhibited by periplasmic
CC accessory protein CpxP; proteolysis of CpxP relieves inhibition
CC (PubMed:16166523, PubMed:17259177, PubMed:25207645). Autokinase
CC activity reconstituted in liposomes is 50% inhibited by periplasmic
CC accessory protein CpxP, but CpxP has no effect on phosphatase activity;
CC autokinase stimulated by KCl, NH(4)Cl, RbCl, pH 7.5 and 8.0, inhibited
CC by sensor kinase inhibitors tetrachlorosalicylanilid and ethodin
CC (PubMed:17259177). {ECO:0000269|PubMed:10972835,
CC ECO:0000269|PubMed:16166523, ECO:0000269|PubMed:17259177,
CC ECO:0000269|PubMed:25207645, ECO:0000269|PubMed:7883164,
CC ECO:0000269|PubMed:9351822, ECO:0000269|PubMed:9473036}.
CC -!- SUBUNIT: The isolated cytoplasmic domain (residues 188-457)
CC crystallizes as a homodimer, and forms dimers of dimers in solution
CC which may be catalytically important (PubMed:24492262). Interacts with
CC periplasmic accessory protein CpxP (PubMed:16166523, PubMed:21317318,
CC PubMed:21239493, PubMed:25207645); interaction with CpxP 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). Interacts with cognate
CC response regulator CpxR (PubMed:25207645).
CC {ECO:0000269|PubMed:24492262, ECO:0000269|PubMed:25207645,
CC ECO:0000305|PubMed:16166523}.
CC -!- INTERACTION:
CC P0AE82; P0AE82: cpxA; NbExp=3; IntAct=EBI-9141330, EBI-9141330;
CC P0AE82; P0AE88: cpxR; NbExp=3; IntAct=EBI-9141330, EBI-550918;
CC P0AE82; P76086: paaX; NbExp=3; IntAct=EBI-9141330, EBI-544692;
CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:15919996,
CC ECO:0000269|PubMed:25207645, ECO:0000269|PubMed:3058985}; Multi-pass
CC membrane protein {ECO:0000305|PubMed:15919996,
CC ECO:0000305|PubMed:3058985}.
CC -!- DOMAIN: The periplasmic segment (residues 30-163) defines the sensory
CC domain (PubMed:9401031). Conformational changes in the cytoplasmic HAMP
CC domain modulate the mobility of the central alpha-helices (which bend
CC at Ser-238 and Pro-253) that allows formation of 1 kinase-active state.
CC {ECO:0000269|PubMed:24492262, ECO:0000269|PubMed:9401031}.
CC -!- PTM: Autophosphorylated (PubMed:9401031, PubMed:24492262). Maximal
CC phosphorylation of the dimeric isolated cytoplasmic domain (residues
CC 188-457) is about 70%, suggesting the protein may be hemiphosphorylated
CC in vivo; probably occurs via a trans-autophosphorylation mechanism,
CC i.e. one subunit phosphorylates the other (PubMed:24492262).
CC {ECO:0000269|PubMed:24492262, ECO:0000269|PubMed:9401031}.
CC -!- DISRUPTION PHENOTYPE: Loss of the Cpx envelope stress response
CC (PubMed:10972835). Decreased resistance to the antibiotic amnikacin
CC (PubMed:2185221). Single cpxA and double cpxR-cpxA mutant decrease
CC transcription of degP (PubMed:7883164). Decreased transcription of cpxP
CC (PubMed:9473036). Hypersensitive to alkaline pH (greater than pH 8.8)
CC (PubMed:9473036). Decreased numbers of stationary phase cells bind to
CC hydrophobic surfaces (PubMed:11830644). Greatly increased resistance to
CC hydroxyurea, probably due to decreased recognition of mis-folded
CC proteins which eventually leads to decreased OH radical formation
CC (PubMed:20005847). {ECO:0000269|PubMed:10972835,
CC ECO:0000269|PubMed:11830644, ECO:0000269|PubMed:20005847,
CC ECO:0000269|PubMed:2185221, ECO:0000269|PubMed:7883164,
CC ECO:0000269|PubMed:9473036}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA72540.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; M13493; AAA72540.1; ALT_INIT; Genomic_DNA.
DR EMBL; M36795; AAA23600.1; -; Genomic_DNA.
DR EMBL; X13307; CAA31687.1; -; Genomic_DNA.
DR EMBL; L19201; AAB03044.1; -; Genomic_DNA.
DR EMBL; U00096; AAC76893.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE77398.1; -; Genomic_DNA.
DR PIR; S40855; S40855.
DR RefSeq; NP_418347.1; NC_000913.3.
DR RefSeq; WP_000580417.1; NZ_STEB01000017.1.
DR PDB; 4BIU; X-ray; 3.65 A; A/B/C/D/E/F=188-457.
DR PDB; 4BIV; X-ray; 3.40 A; A/B=188-457.
DR PDB; 4BIW; X-ray; 2.85 A; A/B=188-457.
DR PDB; 4BIX; X-ray; 2.00 A; A/B=188-457.
DR PDB; 4BIY; X-ray; 3.30 A; A/B/C/D=188-457.
DR PDB; 4BIZ; X-ray; 2.65 A; A/B/C/D/E/F=188-457.
DR PDB; 4CB0; X-ray; 3.30 A; A/B=188-457.
DR PDB; 5LFK; X-ray; 3.09 A; A/B=188-457.
DR PDBsum; 4BIU; -.
DR PDBsum; 4BIV; -.
DR PDBsum; 4BIW; -.
DR PDBsum; 4BIX; -.
DR PDBsum; 4BIY; -.
DR PDBsum; 4BIZ; -.
DR PDBsum; 4CB0; -.
DR PDBsum; 5LFK; -.
DR AlphaFoldDB; P0AE82; -.
DR SMR; P0AE82; -.
DR BioGRID; 4262644; 15.
DR BioGRID; 852702; 2.
DR DIP; DIP-48358N; -.
DR IntAct; P0AE82; 2.
DR STRING; 511145.b3911; -.
DR iPTMnet; P0AE82; -.
DR jPOST; P0AE82; -.
DR PaxDb; P0AE82; -.
DR PRIDE; P0AE82; -.
DR EnsemblBacteria; AAC76893; AAC76893; b3911.
DR EnsemblBacteria; BAE77398; BAE77398; BAE77398.
DR GeneID; 66672180; -.
DR GeneID; 948405; -.
DR KEGG; ecj:JW3882; -.
DR KEGG; eco:b3911; -.
DR PATRIC; fig|1411691.4.peg.2793; -.
DR EchoBASE; EB0161; -.
DR eggNOG; COG2205; Bacteria.
DR HOGENOM; CLU_000445_89_27_6; -.
DR InParanoid; P0AE82; -.
DR OMA; ANDLLWW; -.
DR PhylomeDB; P0AE82; -.
DR BioCyc; EcoCyc:CPXA-MON; -.
DR BioCyc; MetaCyc:CPXA-MON; -.
DR BRENDA; 2.7.13.3; 2026.
DR PRO; PR:P0AE82; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:EcoCyc.
DR GO; GO:0030288; C:outer membrane-bounded periplasmic space; IDA:EcoCyc.
DR GO; GO:0005886; C:plasma membrane; IDA:EcoCyc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:EcoCyc.
DR GO; GO:0000155; F:phosphorelay sensor kinase activity; IDA:EcoCyc.
DR GO; GO:0043708; P:cell adhesion involved in biofilm formation; IMP:CACAO.
DR GO; GO:0036460; P:cellular response to cell envelope stress; TAS:EcoCyc.
DR GO; GO:0018106; P:peptidyl-histidine phosphorylation; ISM:EcoCyc.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:EcoCyc.
DR GO; GO:0009314; P:response to radiation; IMP:EcoCyc.
DR GO; GO:0007165; P:signal transduction; TAS:EcoCyc.
DR CDD; cd00082; HisKA; 1.
DR Gene3D; 3.30.450.210; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR032404; CpxA_peri.
DR InterPro; IPR038515; CpxA_peri_sf.
DR InterPro; IPR003660; HAMP_dom.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR005467; His_kinase_dom.
DR InterPro; IPR003661; HisK_dim/P.
DR InterPro; IPR036097; HisK_dim/P_sf.
DR InterPro; IPR004358; Sig_transdc_His_kin-like_C.
DR Pfam; PF16527; CpxA_peri; 1.
DR Pfam; PF00672; HAMP; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF00512; HisKA; 1.
DR PRINTS; PR00344; BCTRLSENSOR.
DR SMART; SM00304; HAMP; 1.
DR SMART; SM00387; HATPase_c; 1.
DR SMART; SM00388; HisKA; 1.
DR SUPFAM; SSF47384; SSF47384; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR PROSITE; PS50885; HAMP; 1.
DR PROSITE; PS50109; HIS_KIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Cell adhesion; Cell inner membrane;
KW Cell membrane; Kinase; Membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix;
KW Two-component regulatory system.
FT CHAIN 1..457
FT /note="Sensor histidine kinase CpxA"
FT /id="PRO_0000074739"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:15919996"
FT TRANSMEM 8..29
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 30..163
FT /note="Periplasmic"
FT /evidence="ECO:0000305|PubMed:15919996,
FT ECO:0000305|PubMed:3058985"
FT TRANSMEM 164..184
FT /note="Helical"
FT /evidence="ECO:0000305"
FT TOPO_DOM 185..457
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:15919996,
FT ECO:0000305|PubMed:3058985"
FT DOMAIN 185..237
FT /note="HAMP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00102"
FT DOMAIN 245..455
FT /note="Histidine kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107"
FT ACT_SITE 248
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:24492262"
FT BINDING 248..251
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24492262"
FT BINDING 248
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24492262"
FT BINDING 359..364
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24492262"
FT BINDING 386
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24492262"
FT BINDING 405..406
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24492262"
FT BINDING 416..421
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24492262"
FT MOD_RES 248
FT /note="Phosphohistidine; by autocatalysis"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00107,
FT ECO:0000305|PubMed:24492262, ECO:0000305|PubMed:9401031"
FT MUTAGEN 33
FT /note="R->C: In cpxA104; a cpxA gain of function mutant,
FT constitutively active."
FT /evidence="ECO:0000269|PubMed:9401031"
FT MUTAGEN 93..124
FT /note="Missing: In cpxA24; a cpxA gain of function mutant,
FT constitutively active, up-regulation of the Cpx regulon
FT members."
FT /evidence="ECO:0000269|PubMed:9401031"
FT MUTAGEN 185
FT /note="S->R: Nearly complete loss of response to excess
FT periplasmic protein."
FT /evidence="ECO:0000269|PubMed:24492262"
FT MUTAGEN 186
FT /note="L->Q: 30% decrease in response to excess periplasmic
FT protein."
FT /evidence="ECO:0000269|PubMed:24492262"
FT MUTAGEN 197
FT /note="A->V: Slight decrease in response to excess
FT periplasmic protein."
FT /evidence="ECO:0000269|PubMed:24492262"
FT MUTAGEN 204
FT /note="N->Y: 80% decrease in response to excess periplasmic
FT protein."
FT /evidence="ECO:0000269|PubMed:24492262"
FT MUTAGEN 222
FT /note="G->D: 90% decrease in response to excess periplasmic
FT protein."
FT /evidence="ECO:0000269|PubMed:24492262"
FT MUTAGEN 222
FT /note="G->R: 75% decrease in response to excess periplasmic
FT protein."
FT /evidence="ECO:0000269|PubMed:24492262"
FT MUTAGEN 228
FT /note="M->V: No response to excess periplasmic protein,
FT decreased autophosphorylation, no phosphotransfer to CpxR,
FT no tetramer formation of the C-terminal domain in
FT solution."
FT /evidence="ECO:0000269|PubMed:24492262"
FT MUTAGEN 252
FT /note="T->P: In cpxA101; a cpxA gain of function mutant,
FT decreased autophosphorylation, decreased phosphotransfer to
FT CpxR, loss of phosphatase activity, responds to periplasmic
FT protein overproduction."
FT /evidence="ECO:0000269|PubMed:9401031"
FT MUTAGEN 356
FT /note="N->Y: Nearly complete loss of response to excess
FT periplasmic protein."
FT /evidence="ECO:0000269|PubMed:24492262"
FT CONFLICT 68
FT /note="W -> WW (in Ref. 1; AAA23600 and 2; CAA31687)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="K -> R (in Ref. 1; AAA23600/AAA72540 and 2;
FT CAA31687)"
FT /evidence="ECO:0000305"
FT HELIX 189..200
FT /evidence="ECO:0007829|PDB:4BIV"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:4BIV"
FT HELIX 209..212
FT /evidence="ECO:0007829|PDB:4BIV"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:4BIV"
FT HELIX 217..220
FT /evidence="ECO:0007829|PDB:4BIW"
FT HELIX 221..249
FT /evidence="ECO:0007829|PDB:4BIX"
FT HELIX 251..267
FT /evidence="ECO:0007829|PDB:4BIX"
FT HELIX 272..296
FT /evidence="ECO:0007829|PDB:4BIX"
FT STRAND 299..301
FT /evidence="ECO:0007829|PDB:4BIW"
FT STRAND 306..309
FT /evidence="ECO:0007829|PDB:4BIX"
FT HELIX 310..328
FT /evidence="ECO:0007829|PDB:4BIX"
FT STRAND 331..336
FT /evidence="ECO:0007829|PDB:4BIX"
FT STRAND 342..345
FT /evidence="ECO:0007829|PDB:4BIX"
FT HELIX 347..364
FT /evidence="ECO:0007829|PDB:4BIX"
FT STRAND 366..375
FT /evidence="ECO:0007829|PDB:4BIX"
FT STRAND 377..386
FT /evidence="ECO:0007829|PDB:4BIX"
FT HELIX 393..395
FT /evidence="ECO:0007829|PDB:4BIX"
FT HELIX 398..400
FT /evidence="ECO:0007829|PDB:4BIX"
FT HELIX 407..412
FT /evidence="ECO:0007829|PDB:4BIZ"
FT HELIX 421..430
FT /evidence="ECO:0007829|PDB:4BIX"
FT STRAND 434..439
FT /evidence="ECO:0007829|PDB:4BIX"
FT STRAND 443..452
FT /evidence="ECO:0007829|PDB:4BIX"
SQ SEQUENCE 457 AA; 51624 MW; 720EE4A62885BA33 CRC64;
MIGSLTARIF AIFWLTLALV LMLVLMLPKL DSRQMTELLD SEQRQGLMIE QHVEAELAND
PPNDLMWWRR LFRAIDKWAP PGQRLLLVTT EGRVIGAERS EMQIIRNFIG QADNADHPQK
KKYGRVELVG PFSVRDGEDN YQLYLIRPAS SSQSDFINLL FDRPLLLLIV TMLVSTPLLL
WLAWSLAKPA RKLKNAADEV AQGNLRQHPE LEAGPQEFLA AGASFNQMVT ALERMMTSQQ
RLLSDISHEL RTPLTRLQLG TALLRRRSGE SKELERIETE AQRLDSMIND LLVMSRNQQK
NALVSETIKA NQLWSEVLDN AAFEAEQMGK SLTVNFPPGP WPLYGNPNAL ESALENIVRN
ALRYSHTKIE VGFAVDKDGI TITVDDDGPG VSPEDREQIF RPFYRTDEAR DRESGGTGLG
LAIVETAIQQ HRGWVKAEDS PLGGLRLVIW LPLYKRS
