PA4521 is the P. aeruginosa AmpE homologue, a polytopic inner-membrane protein with five predicted transmembrane helices, encoded second in the ampDE operon after the cytoplasmic anhydromuropeptide amidase AmpD. AmpD limits induction of the chromosomal AmpC beta-lactamase by recycling the peptidoglycan fragments that activate the regulator AmpR. AmpE has been proposed to sense or relay the cell-wall signal in this pathway, but its role is unresolved: in enterobacteria one study found AmpE essential for beta-lactamase induction and another found it dispensable, and in P. aeruginosa clinical isolates it seems to contribute only indirectly to AmpC-mediated resistance. Its biochemical activity is unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN002214697, seeded by E. coli AmpE (P0AE14). Reason: E. coli AmpE is a cytoplasmic membrane protein, and PA4521 has five predicted TM helices. The location fits the whole AmpE clade. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P0AE14 · E. coli AmpE SUPPORTS TRANSFER Seed of the plasma membrane IBD; described as a cytoplasmic membrane protein (PMID:2607970). Supporting Evidence: PMID:2607970 whereas the ampE gene product is a cytoplasmic membrane protein file:PSEAE/PA4521/PA4521-uniprot.txt /evidence="ECO:0000256|SAM:Phobius" |
| GO:0046677 response to antibiotic | IBA GO_REF:0000033 | UNDECIDED | Summary: PAINT IBA from PTN002214697, sole seed the PseudoCAP IMP on this protein (expected self-reference for a seed). Reason: Kept consistent with the IMP row, whose paper cannot be read. The seed cannot be verified (the cited abstract reports no ampE phenotype) and AmpE's own role in beta-lactamase induction is contested. The node itself is a clean orthology group (7 AmpE orthologs, one per organism, no duplications; tree checked 2026-11-05), so the doubt is not about clade breadth but about the seed: in enterobacteria any AmpE effect on resistance runs through AmpR and an inducible AmpC, which E. coli, one of the leaves, lacks. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK GRANULARITY MISMATCH Sources checked: PANTHER:PTN002214697 · PTN002214697 SOURCE WEAK OR INFERRED PAINT leaf GAF (cached 2026-10-28) lists 7 GO:0046677 leaves (E. coli, Salmonella, Yersinia, Coxiella, Shewanella, Xanthomonas AmpE, PA4521). The tree (checked 2026-11-05) makes these a single SPECIATION clade of AmpE orthologs in PTHR38684:SF1, so the propagation path is sound and only the seed is in doubt. UniProtKB:G3XD69 · PA4521 SOURCE WEAK OR INFERRED Sole seed; PseudoCAP IMP on an abstract that reports only ampD complementation. Supporting Evidence: PMID:2691840 Since neither AmpD nor AmpE are needed for beta-lactam induction and since these proteins could not be covalently labelled by benzylpenicillin, they are not thought to act as beta-lactam-binding sensory transducers. PMID:2607970 although Escherichia coli has lost its ampR gene it has retained the second regulatory locus and that this comprises the bicistronic ampDE operon |
| GO:0046677 response to antibiotic | IMP PMID:9835532 An ampD gene in Pseudomonas aeruginosa encodes a negative re... | UNDECIDED | Summary: PseudoCAP IMP citing Langaee et al. 1998, the cloning of P. aeruginosa ampD and ampE; abstract only. Reason: The paper cannot be read (abstract only; PMC full text not retrievable). The abstract reports only that ampD complements E. coli ampD mutants and does not mention an ampE mutant, so the evidence for an ampE phenotype cannot be checked. Later P. aeruginosa work suggests AmpE plays at most an indirect role in AmpC-mediated resistance. Supporting Evidence: PMID:9835532 The ampD product transcomplemented Escherichia coli ampD mutants to wild-type beta-lactamase expression. PMID:16251318 our findings suggest that for certain types of mutations, AmpE plays an indirect role in resistance |
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Download this section (compressed HTML)Q: Does P. aeruginosa AmpE affect AmpC induction or basal expression on its own, independently of AmpD, and if so through which muropeptide or membrane signal?
Experiment: Construct a clean, non-polar in-frame ampE deletion in PAO1 and measure basal and cefoxitin-induced AmpC activity and beta-lactam MICs, with ampE complementation and an ampD ampE double mutant as controls.
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