pprA / PA4293 (Q9HWA7) review notes

Summary of the literature

PprA is a 922-residue sensor histidine kinase of P. aeruginosa. UniProt (reviewed,
PPRA_PSEAE) places several PAS/PAC modules in the N-terminal half (DOMAIN 506-684
and others) and a HisKA/HATPase kinase core at the C-terminus. There is no signal
peptide and no transmembrane segment.

Primary data, Wang et al. 2003 PMID:12499175, full text read (PMC149007):

A spontaneous aminoglycoside-resistant PAK mutant (PAK1-3) with reduced membrane
permeability was complemented by a genomic clone carrying PA4293, named pprA
PMID:12499175.
PprA has no signal sequence or TM segment and is predicted cytoplasmic, with
N-terminal PAS and PAC motifs PMID:12499175.
In vitro kinase assay with purified His-tagged proteins: "PprA alone underwent
active autophosphorylation, while PprB did not" and "in the presence of PprA, PprB is
highly phosphorylated; thus, PprA functions as a specific kinase for PprB"
PMID:12499175.
The pprA insertion mutant itself showed no change in antibiotic resistance
(the effect was seen on overexpression), so the permeability phenotype is not a
loss-of-function phenotype of pprA.

UniProt adds later work (PubMed:21091863, 23209420, 31492668 — not cached here) in which
PprA/PprB control a biofilm regulon (Flp type IVb pilin, BapA adhesin, CupE fimbriae) and
describes PprA as a heme sensor histidine kinase.

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:0000155 phosphorelay sensor kinase activity	4	268 (41 taxa)	GO:0000155, IDA, PMID:12499175 (PseudoCAP)	SOUND	Full text read: purified PprA autophosphorylates with [γ-32P]ATP and transfers phosphate to purified PprB. This is exactly the activity the term denotes, measured directly on this protein.	S. pombe Mak3 (O74539, EXP GO:0000155), E. coli AtoS (Q06067, IDA GO:0000155), M. tuberculosis PdtaS (P9WGL5, IDA GO:0000155) — all verified by live QuickGO query 2026-11-05	Yes, comfortably: three of the four seeds have independent direct kinase evidence. No GO_CENTRAL defect.

PprA is not a seed of the second IBD on the same node (GO:0007165 signal transduction);
FleS and CbrA in this batch are (see their notes). The node is PTHR43065 "sensor histidine
kinase", an appropriate home for a generic kinase/signalling term.

Node-level note for PTN009166588 (recorded once, here)

The three P. aeruginosa genes in this batch that sit under PTN009166588 — pprA, fleS, cbrA —
receive the same pair of IBAs (GO:0000155, GO:0007165). Both IBDs are soundly seeded (see the
seed lists above and in fleS-notes.md), the node term suits a histidine-kinase clade, and
no GO_CENTRAL defect is filed for this node. The existing reviews of the other PAO1 sensor
kinases, genes/PSEAE/parS and genes/PSEAE/PA5484 (KinB), reached the same conclusion for the
GO:0000155 IBA, and the TOO_GENERAL treatment of GO:0007165, GO:0016772, GO:0004673 and
GO:0016301/GO:0016740 is kept consistent with them.

Annotation decisions

GO:0000155 (IDA, IBA, IEA): ACCEPT. Direct biochemistry, agreeing IBA from a well-seeded node.
GO:0000160 (IEA GO_REF:0000108, from the MF): ACCEPT — PprA/PprB are a cognate pair.
GO:0004673, GO:0016772, GO:0007165 (IEA), GO:0007165 (IBA): TOO_GENERAL, each entailed by an
accepted more specific term (GO:0000155 or GO:0000160).

No source defects: the single PseudoCAP row on this gene is a correct IDA.