cbrA / PA4725 (Q9HV74) review notes

Summary of the literature

CbrA is a 983-residue hybrid protein: an N-terminal solute:sodium symporter (SSSF/SLC5)
transporter domain of 12-13 predicted transmembrane helices (UniProt lists TRANSMEM features
through residue ~451), then a PAS domain and a C-terminal HisKA/HATPase kinase core of the NtrB
type. The UniProtKB entry is unreviewed, and its FUNCTION-level statements are ARBA-derived
(including, incorrectly for the whole protein, "Belongs to the sodium:solute symporter (SSF)
family"), so I did not use them as evidence.

Primary data:

Nishijyo, Haas & Itoh 2001 PMID:11401699, abstract only. Discovery of CbrA-CbrB:
PMID:11401699; architecture PMID:11401699; conclusion PMID:11401699. The experiments named in the abstract are mutant growth phenotypes,
aot-argR induction, histidase and proline dehydrogenase assays, complementation and primer
extension — i.e. genetics, not a phosphorylation assay.
Yeung, Bains & Hancock 2011 PMID:21169488, abstract only: PMID:21169488,
plus cytotoxicity and antibiotic-resistance phenotypes and a swarming microarray. These are
the two PseudoCAP IMP rows (GO:2000147, GO:1900232).
Ortholog biochemistry, full text cached: Wirtz et al. 2020 on P. putida KT2440
PMID:32214184 and PMID:32214184 / PMID:32214184. Zhang et al. 2015 on P. fluorescens SBW25 reach the same
conclusion genetically PMID:26148710, and find SSSF
mutations that separate transport from signalling. Monteagudo-Cascales et al. 2019
PMID:31235731 dissect the TM and PAS domains of P. putida CbrA in signalling.

So the kinase and transporter functions are established for the orthologs and inferred here;
neither has been assayed on the P. aeruginosa protein in anything I could read.

PseudoCAP IBA-seed assessment

PTN node	node term	n_seeds	leaf IBAs	seed annotation (term, evidence, PMID)	verdict	rationale	other seeds	IBD stands without this seed?
PTN009166588	GO:0007165 signal transduction	7	268 (41 taxa)	GO:0000160, IDA, PMID:11401699 (PseudoCAP)	INDIRECT-PHENOTYPE (process right, code queried)	CbrA really is the sensor kinase of the CbrA-CbrB pair, and the P. putida ortholog autophosphorylates and phosphorylates CbrB, so the claim is accepted. The cited paper, however, describes only sequence analysis, mutant growth phenotypes, complementation and primer extension in its abstract; IMP or IGI would fit. Confidence SUSPECTED: this rests on what the abstract does not say, and a 2001 two-component paper could well contain a phosphorylation gel in the full text.	E. coli NtrB (P0AFB5), E. coli ZraS (P14377, IDA GO:0007165), E. coli AtoS (Q06067, IDA GO:0007165), S. pombe Mak3 (O74539), M. tuberculosis PdtaS (P9WGL5, IDA GO:0000160), P. aeruginosa FleS (Q9I4N4) — verified by live QuickGO query 2026-11-05	Yes. Four seeds have independent experimental kinase/signalling annotations. No GO_CENTRAL defect for this node; see `genes/PSEAE/pprA/pprA-notes.md`, where the node-level assessment for PTN009166588 is recorded once for this batch (pprA, fleS, cbrA all sit under it).

Annotation decisions

GO:0000155 (IEA, IBA): ACCEPT — full kinase core, well-seeded node, ortholog biochemistry.
GO:0000160 (IDA, PMID:11401699): ACCEPT the claim, with a PSEUDOCAP WRONG_EVIDENCE_CODE
defect at SUSPECTED.
GO:0022857 / GO:0055085 (InterPro2GO from the SSSF domain): MODIFY to
GO:0005290 L-histidine transmembrane transporter activity and GO:1903810 L-histidine import
across plasma membrane. The transporter domain is real and its substrate is known in two
Pseudomonas orthologs; the generic terms are less precise than the evidence allows. Both
replacements rest on ortholog data, which is stated in the reasons.
GO:0006355 (InterPro2GO, regulation of DNA-templated transcription):
MARK_AS_OVER_ANNOTATED. The transcriptional work is done by CbrB and by the CrcZ/CrcY sRNAs;
the kinase acts upstream. This matches the treatment of the sensor kinases parS and KinB,
where regulation terms were not transferred to the kinase.
GO:1900232, GO:2000147 (IMP, PMID:21169488): KEEP_AS_NON_CORE — downstream phenotypes of a
global metabolic regulator. GO has no "regulation of swarming motility" term (only
GO:0071978 bacterial-type flagellum-dependent swarming motility), so GO:2000147 is as
precise as available.
GO:0005886 (IBA): ACCEPT, 12-13 TM helices. GO:0016020 (IEA): TOO_GENERAL.
GO:0004673, GO:0016301, GO:0016740, GO:0016772, GO:0007165 (IEA/IBA): TOO_GENERAL, entailed by
GO:0000155 or GO:0000160, consistent with parS, KinB, pprA and fleS.

Knowledge gap not filed

Whether P. aeruginosa CbrA itself transports histidine is unmeasured, but that is a question
for a wet-lab experiment on a known activity of the orthologs rather than a genuine unknown of
the family, so it is recorded as a suggested experiment, not a knowledge_gaps entry.