PprA (PA4293) is the sensor histidine kinase of the PprA-PprB two-component system of Pseudomonas aeruginosa. It is a 922-residue protein without a signal peptide or transmembrane segments, so it is thought to be cytoplasmic; it carries several N-terminal PAS/PAC sensory modules and a C-terminal HisKA/HATPase kinase core. Purified PprA autophosphorylates and transfers the phosphoryl group to its cognate response regulator PprB (PA4296). PprB controls membrane permeability to aminoglycosides and, in later work, a biofilm regulon that includes Flp type IVb pili, the BapA adhesin and CupE fimbriae.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000155 phosphorelay sensor kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN009166588 (PTHR43065 sensor histidine kinases), for which PprA is one of four seeds. Reason: PprA has its own direct evidence for the term (autophosphorylation and phosphotransfer to PprB with purified proteins), so the IBA agrees with experiment. Its appearance in the WITH/FROM is the expected self-seed. The node is also seeded by E. coli AtoS (IDA), M. tuberculosis PdtaS (IDA) and S. pombe Mak3 (EXP), so the IBD does not rest on PprA. Supporting Evidence: PMID:12499175 PprA alone underwent active autophosphorylation, while PprB did not PMID:12499175 in the presence of PprA, PprB is highly phosphorylated; thus, PprA functions as a specific kinase for PprB |
| GO:0000155 phosphorelay sensor kinase activity | IDA PMID:12499175 Regulation of membrane permeability by a two-component regul... | ACCEPT | Summary: PseudoCAP IDA (IBD seed). Purified His-tagged PprA autophosphorylates with [gamma-32P]ATP and phosphorylates purified PprB. Reason: Full text read. This is a direct biochemical demonstration of the histidine-kinase and phosphotransfer activities that define phosphorelay sensor kinase activity. The seed is sound. Supporting Evidence: PMID:12499175 PprA alone underwent active autophosphorylation, while PprB did not PMID:12499175 in the presence of PprA, PprB is highly phosphorylated; thus, PprA functions as a specific kinase for PprB file:PSEAE/pprA/pprA-uniprot.txt Functions as a heme sensor histidine kinase which is autophosphorylated at a histidine residue and transfers its phosphate group to PprB |
| GO:0000155 phosphorelay sensor kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from the HisKA dimerisation/phosphoacceptor domain. Reason: Consistent with the direct assay on PprA. Supporting Evidence: PMID:12499175 PprA alone underwent active autophosphorylation, while PprB did not |
| GO:0000160 phosphorelay signal transduction system | IEA GO_REF:0000108 | ACCEPT | Summary: Inferred from the phosphorelay sensor kinase MF by inter-ontology link. Reason: PprA and PprB form a cognate two-component pair, shown by specific phosphotransfer and by the shared aminoglycoside-sensitivity phenotype on overexpression. Supporting Evidence: PMID:12499175 in the presence of PprA, PprB is highly phosphorylated; thus, PprA functions as a specific kinase for PprB PMID:12499175 the phosphorylation results strongly suggest a sensor-response regulator relationship between PprA and PprB |
| GO:0004673 protein histidine kinase activity | IEA GO_REF:0000003 | TOO GENERAL | Summary: EC 2.7.13.3 mapping. Reason: True, but GO:0000155 phosphorelay sensor kinase activity, accepted here, is_a protein histidine kinase activity. |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | TOO GENERAL | Summary: PAINT IBA from PTN009166588; PprA is not a seed of this IBD (seeds include FleS and CbrA). Reason: The node term suits the clade and the IBD is well seeded, but for PprA the more specific GO:0000160 is accepted and entails it. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO, signal transduction. Reason: Entailed by GO:0000160 phosphorelay signal transduction system, accepted here (same call as on parS and KinB). |
| GO:0016772 transferase activity, transferring phosphorus-containing groups | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO, transferase activity transferring phosphorus-containing groups. Reason: Entailed by the accepted GO:0000155. |
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Experiment: Ligand-binding and kinase assays with purified PprA in the presence of candidate ligands (heme, redox state), with PAS-domain point mutants.
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