ParS (PA1798) is the membrane sensor histidine kinase of the ParR-ParS two-component system of Pseudomonas aeruginosa. The 428-residue protein has a transmembrane segment followed by a cytoplasmic HAMP linker and a HisKA/HATPase histidine kinase module with the conserved autophosphorylation site His218. In response to subinhibitory concentrations of polymyxins, colistin and cationic antimicrobial peptides it activates its cognate response regulator ParR (PA1799), which switches on the arnBCADTEF-ugd lipid A aminoarabinosylation operon and mexXY and represses the porin gene oprD, producing adaptive resistance to polymyxins and aminoglycosides.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000155 phosphorelay sensor kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core activity, inherited from a sensor kinase node grounded by biochemically characterised kinases. Reason: PTN001293174 is seeded by E. coli EnvZ and P. aeruginosa KinB (PA5484), both with IDA, so it stands without the ParS IMP; Q9I2U4 in its own WITH/FROM marks its seed, which is expected. ParS has the HisKA and HATPase_c domains and the conserved phospho-His. Supporting Evidence: file:PSEAE/parS/parS-uniprot.txt Pfam; PF00512; HisKA; 1. PMID:24034668 As is typical of TCST systems, the ParS/ParR system consists of a membrane-bound histidine sensor kinase (ParS) and a cytoplasmic response regulator (ParR). |
| GO:0000155 phosphorelay sensor kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Same core activity from the HisKA dimerisation/phosphoacceptor domain mapping. Reason: Consistent with the IBA row and the domain architecture. Supporting Evidence: file:PSEAE/parS/parS-uniprot.txt InterPro; IPR003661; HisK_dim/P_dom. |
| GO:0000155 phosphorelay sensor kinase activity | IMP PMID:20547815 Adaptive resistance to the "last hope" antibiotics polymyxin... | ACCEPT | Summary: Fernandez et al. 2010 identified ParR-ParS as the system needed for peptide-induced arn expression and adaptive polymyxin resistance. Reason: The function is right and is ParS's core activity, so the row is accepted. Its evidence code is questionable: the abstract reports mutant phenotypes (loss of arn induction and adaptive resistance), not a kinase, autophosphorylation or phosphotransfer assay, so the molecular function is inferred from phenotype plus domain architecture. Filed as a CHECK at SUSPECTED because the full text was not available, matching the parR GO:0000156 row from the same paper. Supporting Evidence: PMID:20547815 This system was required for activation of the arnBCADTEF LPS modification operon in the presence of subinhibitory concentrations of polymyxin, colistin, or the bovine peptide indolicidin, leading to increased resistance to various polycationic antibiotics, including aminoglycosides. |
| GO:0000160 phosphorelay signal transduction system | IEA GO_REF:0000108 | ACCEPT | Summary: ParS is the sensor kinase of the ParR-ParS two-component phosphorelay. Reason: Inferred from the sensor kinase MF and supported by genetics - parS and parR mutants change the transcriptome in the same way. Supporting Evidence: PMID:24034668 As shown in Figure 2, mutations in parS or parR caused similar changes in the PAO1 transcriptome at the mid log phase. |
| GO:0004673 protein histidine kinase activity | IEA GO_REF:0000003 | TOO GENERAL | Summary: True but entailed by the accepted phosphorelay sensor kinase activity. Reason: Phosphorelay sensor kinase activity (GO:0000155), accepted above, is_a protein histidine kinase activity. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Inner (plasma) membrane sensor kinase. Reason: Seeded by E. coli EnvZ and RstB (plasma membrane by experiment). ParS has a predicted TM helix ahead of its cytoplasmic HAMP and kinase domains, as in EnvZ-type sensors. Supporting Evidence: file:PSEAE/parS/parS-uniprot.txt TRANSMEM 133..154 /note="Helical" PMID:24034668 As is typical of TCST systems, the ParS/ParR system consists of a membrane-bound histidine sensor kinase (ParS) |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Same location from the subcellular location mapping. Reason: Consistent with the IBA row and the predicted topology. Supporting Evidence: file:PSEAE/parS/parS-uniprot.txt DOMAIN 155..207 /note="HAMP" |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | TOO GENERAL | Summary: True but entailed by the accepted phosphorelay signal transduction system. Reason: Phosphorelay signal transduction system (GO:0000160), accepted above, is_a intracellular signal transduction, is_a signal transduction. |
| GO:0016020 membrane | IEA GO_REF:0000002 | TOO GENERAL | Summary: True but entailed by the accepted plasma membrane. Reason: Plasma membrane (GO:0005886), accepted on the IBA and IEA rows, is_a membrane. |
| GO:0016301 kinase activity | IEA GO_REF:0000104 | TOO GENERAL | Summary: True but entailed by the accepted phosphorelay sensor kinase activity. Reason: GO:0000155 is_a protein histidine kinase activity, is_a protein kinase activity, is_a kinase activity. |
| GO:0016740 transferase activity | IEA GO_REF:0000104 | TOO GENERAL | Summary: True but uninformative; entailed by the accepted sensor kinase activity. Reason: GO:0000155 descends from transferase activity through protein histidine kinase activity. |
| GO:0016772 transferase activity, transferring phosphorus-containing groups | IEA GO_REF:0000002 | TOO GENERAL | Summary: True but entailed by the accepted sensor kinase activity. Reason: GO:0000155 is_a protein histidine kinase activity, is_a phosphotransferase activity with a nitrogenous group as acceptor, is_a this term. |
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