| IED ID | IndEnz0002004805 |
| Enzyme Type ID | protease004805 |
| Protein Name |
Sensor histidine kinase CpxA EC 2.7.13.3 |
| Gene Name | cpxA ecfB eup ssd b3911 JW3882 |
| Organism | Escherichia coli (strain K12) |
| Taxonomic Lineage | cellular organisms Bacteria Proteobacteria Gammaproteobacteria Enterobacterales Enterobacteriaceae Escherichia Escherichia coli Escherichia coli (strain K12) |
| Enzyme Sequence | MIGSLTARIFAIFWLTLALVLMLVLMLPKLDSRQMTELLDSEQRQGLMIEQHVEAELANDPPNDLMWWRRLFRAIDKWAPPGQRLLLVTTEGRVIGAERSEMQIIRNFIGQADNADHPQKKKYGRVELVGPFSVRDGEDNYQLYLIRPASSSQSDFINLLFDRPLLLLIVTMLVSTPLLLWLAWSLAKPARKLKNAADEVAQGNLRQHPELEAGPQEFLAAGASFNQMVTALERMMTSQQRLLSDISHELRTPLTRLQLGTALLRRRSGESKELERIETEAQRLDSMINDLLVMSRNQQKNALVSETIKANQLWSEVLDNAAFEAEQMGKSLTVNFPPGPWPLYGNPNALESALENIVRNALRYSHTKIEVGFAVDKDGITITVDDDGPGVSPEDREQIFRPFYRTDEARDRESGGTGLGLAIVETAIQQHRGWVKAEDSPLGGLRLVIWLPLYKRS |
| Enzyme Length | 457 |
| Uniprot Accession Number | P0AE82 |
| Absorption | |
| Active Site | ACT_SITE 248; /note=Nucleophile; /evidence=ECO:0000269|PubMed:24492262 |
| Activity Regulation | ACTIVITY REGULATION: 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, NH(4)Cl, RbCl, pH 7.5 and 8.0, inhibited by sensor kinase inhibitors tetrachlorosalicylanilid and ethodin (PubMed:17259177). {ECO:0000269|PubMed:10972835, ECO:0000269|PubMed:16166523, ECO:0000269|PubMed:17259177, ECO:0000269|PubMed:25207645, ECO:0000269|PubMed:7883164, ECO:0000269|PubMed:9351822, ECO:0000269|PubMed:9473036}. |
| Binding Site | BINDING 248; /note=ATP; /evidence=ECO:0000269|PubMed:24492262; BINDING 386; /note=ATP; /evidence=ECO:0000269|PubMed:24492262 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + protein L-histidine = ADP + protein N-phospho-L-histidine.; EC=2.7.13.3; Evidence={ECO:0000269|PubMed:9401031}; |
| DNA Binding | |
| EC Number | 2.7.13.3 |
| Enzyme Function | FUNCTION: 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 Mg(2+) 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). {ECO:0000269|PubMed:16166523, ECO:0000269|PubMed:17259177, ECO:0000269|PubMed:24492262, ECO:0000269|PubMed:25207645, ECO:0000269|PubMed:7883164, ECO:0000269|PubMed:8432716, ECO:0000269|PubMed:9401031, ECO:0000269|PubMed:9473036, ECO:0000305|PubMed:11830644}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 248..251; /note=ATP; /evidence=ECO:0000269|PubMed:24492262; NP_BIND 359..364; /note=ATP; /evidence=ECO:0000269|PubMed:24492262; NP_BIND 405..406; /note=ATP; /evidence=ECO:0000269|PubMed:24492262; NP_BIND 416..421; /note=ATP; /evidence=ECO:0000269|PubMed:24492262 |
| Features | Active site (1); Beta strand (9); Binding site (2); Chain (1); Domain (2); Erroneous initiation (1); Helix (12); Modified residue (1); Mutagenesis (11); Nucleotide binding (4); Sequence conflict (5); Topological domain (3); Transmembrane (2); Turn (1) |
| Keywords | 3D-structure;ATP-binding;Cell adhesion;Cell inner membrane;Cell membrane;Kinase;Membrane;Nucleotide-binding;Phosphoprotein;Reference proteome;Transferase;Transmembrane;Transmembrane helix;Two-component regulatory system |
| Interact With | Itself; P0AE88; P76086 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:15919996, ECO:0000269|PubMed:25207645, ECO:0000269|PubMed:3058985}; Multi-pass membrane protein {ECO:0000305|PubMed:15919996, ECO:0000305|PubMed:3058985}. |
| Modified Residue | MOD_RES 248; /note="Phosphohistidine; by autocatalysis"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00107, ECO:0000305|PubMed:24492262, ECO:0000305|PubMed:9401031" |
| Post Translational Modification | PTM: 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 phosphorylates the other (PubMed:24492262). {ECO:0000269|PubMed:24492262, ECO:0000269|PubMed:9401031}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (8) |
| Cross Reference PDB | 4BIU; 4BIV; 4BIW; 4BIX; 4BIY; 4BIZ; 4CB0; 5LFK; |
| Mapped Pubmed ID | 15522865; 24561554; 28552574; |
| Motif | |
| Gene Encoded By | |
| Mass | 51,624 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |