CbrA (PA4725) is the sensor histidine kinase of the CbrA-CbrB two-component system of Pseudomonas aeruginosa. The 983-residue protein has an N-terminal domain of 12-13 transmembrane helices belonging to the solute:sodium symporter (SLC5/SSSF) family, followed by a PAS domain and a C-terminal HisKA/HATPase kinase core of the NtrB type. With the NtrC-family, sigma-54 dependent response regulator CbrB it controls the use of many carbon and nitrogen sources (arginine, histidine, proline, polyamines), carbon catabolite repression through the small RNAs CrcZ and CrcY, and in P. aeruginosa also swarming, biofilm formation, cytotoxicity and antibiotic resistance. In P. putida and P. fluorescens the orthologous CbrA autophosphorylates, phosphorylates CbrB, and its SLC5 domain transports L-histidine.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000155 phosphorelay sensor kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN009166588 (seeds Mak3, PprA, AtoS, PdtaS). Reason: Sound node with four experimentally seeded members; agrees with the P. putida ortholog biochemistry. Supporting Evidence: PMID:32214184 we show that CbrA and CbrAΞSLC5 can autophosphorylate at His766 and transfer the phosphoryl group to CbrB |
| GO:0000155 phosphorelay sensor kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from the HisKA dimerisation/phosphoacceptor domain. Reason: CbrA has the full kinase core; the purified P. putida ortholog autophosphorylates at His766 and phosphotransfers to CbrB. No direct kinase assay on P. aeruginosa CbrA is cached. Supporting Evidence: PMID:11401699 The cbrA and cbrB genes encode a sensor/histidine kinase (Mr 108 379, 983 residues) and a cognate response regulator PMID:32214184 we show that CbrA and CbrAΞSLC5 can autophosphorylate at His766 and transfer the phosphoryl group to CbrB |
| GO:0000160 phosphorelay signal transduction system | IDA PMID:11401699 The CbrA-CbrB two-component regulatory system controls the u... | ACCEPT | Summary: PseudoCAP IDA (IBD seed for GO:0007165 at PTN009166588). The paper cloned cbrA/cbrB and characterised cbrA and cbrB mutants (catabolic growth phenotypes, aot-argR induction, primer extension). Reason: The process is right: CbrA is the sensor kinase of the CbrA-CbrB pair and the orthologous protein phosphorylates CbrB. The abstract (full text not available) describes sequence analysis, mutant phenotypes, complementation and primer extension, which would support IMP/IGI rather than IDA. Because that call rests on what the abstract does not say, the evidence code is queried at SUSPECTED. Supporting Evidence: PMID:11401699 The cbrA and cbrB genes encode a sensor/histidine kinase (Mr 108 379, 983 residues) and a cognate response regulator PMID:11401699 the CbrA-CbrB system controls the expression of several catabolic pathways PMID:32214184 we show that CbrA and CbrAΞSLC5 can autophosphorylate at His766 and transfer the phosphoryl group to CbrB |
| GO:0004673 protein histidine kinase activity | IEA GO_REF:0000003 | TOO GENERAL | Summary: EC 2.7.13.3 mapping (EC from ARBA). Reason: Entailed by the accepted GO:0000155. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA, plasma membrane. Reason: CbrA has 12-13 predicted transmembrane helices and its kinase domain is cytoplasmic; an inner-membrane location is the only sensible one in a Gram-negative bacterium. Supporting Evidence: PMID:11401699 The amino-terminal half (490 residues) of CbrA appears to be a sensor membrane domain, as predicted by 12 possible transmembrane helices |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: InterPro2GO mapping (from a PAS-fold signature) to regulation of DNA-templated transcription. Reason: CbrA is a membrane sensor kinase; the transcriptional control of catabolic genes is exerted by its response regulator CbrB (and the CrcZ/CrcY sRNAs downstream). The kinase acts upstream of, not in, transcription regulation; GO captures its role with the phosphorelay terms, as for parS and KinB. Supporting Evidence: PMID:11401699 the CbrA-CbrB system controls the expression of several catabolic pathways |
| GO:0007165 signal transduction | IBA GO_REF:0000033 | TOO GENERAL | Summary: PAINT IBA from PTN009166588; CbrA is one of seven seeds (via its GO:0000160 row). Reason: The IBD stands without CbrA (AtoS, ZraS and PdtaS have IDA signalling annotations; Mak3 IGI). For CbrA, GO:0000160 is accepted and entails it. |
| GO:0007165 signal transduction | IEA GO_REF:0000120 | TOO GENERAL | Summary: Combined IEA, signal transduction. Reason: Entailed by the accepted GO:0000160. |
| GO:0016020 membrane | IEA GO_REF:0000120 | TOO GENERAL | Summary: Combined IEA, membrane. Reason: Entailed by GO:0005886 plasma membrane, accepted here (same call as on parS and KinB). |
| GO:0016301 kinase activity | IEA GO_REF:0000104 | TOO GENERAL | Summary: Kinase activity (rule-based transfer). Reason: Entailed by the accepted GO:0000155. |
| GO:0016740 transferase activity | IEA GO_REF:0000104 | TOO GENERAL | Summary: Transferase activity (rule-based transfer). Reason: Entailed by the accepted GO:0000155. |
| 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. |
| GO:0022857 transmembrane transporter activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO from the Na+/solute symporter (SSSF, SLC5) domain. Reason: The N-terminal SLC5 domain is a genuine transporter in the orthologs: CbrA of P. putida KT2440 binds and transports L-histidine specifically, and CbrA of P. fluorescens SBW25 mediates histidine uptake. The general transporter term should be refined to the substrate shown in the orthologs. This rests on ortholog data; transport by P. aeruginosa CbrA itself has not been measured. Proposed replacements: L-histidine transmembrane transporter activity Supporting Evidence: PMID:32214184 It is demonstrated that CbrA can bind and transport L-histidine. PMID:32214184 We demonstrated that the SLC5 domain of CbrA transports L-histidine PMID:26148710 implicated CbrA in histidine uptake |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO from the SSSF domain, transmembrane transport. Reason: True in the orthologs, where CbrA imports L-histidine; refine to the specific process. Based on P. putida and P. fluorescens data, not on P. aeruginosa CbrA itself. Proposed replacements: L-histidine import across plasma membrane Supporting Evidence: PMID:32214184 It is demonstrated that CbrA can bind and transport L-histidine. PMID:26148710 implicated CbrA in histidine uptake |
| GO:1900232 negative regulation of single-species biofilm formation on inanimate substrate | IMP PMID:21169488 The sensor kinase CbrA is a global regulator that modulates ... | KEEP AS NON CORE | Summary: PseudoCAP IMP; the PA14 cbrA deletion mutant forms more biofilm. Reason: A pleiotropic downstream phenotype of a global metabolic regulator (abstract read; full text not cached). The abstract states the observation; it is plausible as a regulatory output via CbrB and CrcZ, but not the kinase's core role. Supporting Evidence: PMID:21169488 The cbrA deletion mutant was completely unable to swarm while exhibiting an increase in biofilm formation |
| GO:2000147 positive regulation of cell motility | IMP PMID:21169488 The sensor kinase CbrA is a global regulator that modulates ... | KEEP AS NON CORE | Summary: PseudoCAP IMP; the cbrA deletion mutant cannot swarm. Reason: Downstream phenotype of a global regulator. GO has no term for regulation of swarming motility, so the general motility term is as precise as available. Supporting Evidence: PMID:21169488 The cbrA deletion mutant was completely unable to swarm while exhibiting an increase in biofilm formation |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Is histidine transport by P. aeruginosa CbrA coupled to its kinase output, and what is the signal (C/N ratio, histidine) sensed?
Experiment: Radiolabelled L-histidine uptake into P. aeruginosa cells or proteoliposomes with CbrA versus SLC5-domain mutants, to test whether the transporter function is conserved in P. aeruginosa.
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)