pfeA

UniProt ID: Q05098
Organism: Pseudomonas aeruginosa PAO1
Review Status: COMPLETE
πŸ“ Provide Detailed Feedback

Gene Description

pfeA (PA2688) encodes PfeA, the ferric-enterobactin receptor of Pseudomonas aeruginosa, a TonB-dependent outer membrane receptor orthologous to E. coli FepA (more than 60% identity). It has an N-terminal TonB box, a plug domain and a 22-stranded beta-barrel embedded in the outer membrane. PfeA binds ferric enterobactin, a catecholate siderophore made by enteric bacteria but not by P. aeruginosa, and uses energy delivered by the TonB-ExbB-ExbD system to transport it across the outer membrane into the periplasm. This lets P. aeruginosa take up iron with a xenosiderophore under iron limitation. pfeA expression is induced by iron limitation and by enterobactin. The second receptor PirA is partly redundant with PfeA, so only the double mutant fails to use ferric enterobactin. PfeA also recognises synthetic catecholate siderophore analogues.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0009279 cell outer membrane
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from the TonB-dependent receptor node PTN002824128, seeded by E. coli TBDRs.
Reason: PfeA is a TBDR beta-barrel made in the outer membrane, as shown for the cloned protein. Correct and core location.
Supporting Evidence:
PMID:8419284
direct the synthesis of high levels of a protein of the same molecular weight in the outer membranes of Escherichia coli fepA strains MT912 and IR20
file:PSEAE/pfeA/pfeA-uniprot.txt
Belongs to the TonB-dependent receptor family.
GO:0009279 cell outer membrane
IEA
GO_REF:0000120
ACCEPT
Summary: InterPro/UniProt subcellular-location mapping to cell outer membrane.
Reason: Same correct claim as the IBA row; consistent with outer-membrane expression.
Supporting Evidence:
PMID:8419284
direct the synthesis of high levels of a protein of the same molecular weight in the outer membranes of Escherichia coli fepA strains MT912 and IR20
GO:0015343 siderophore-iron transmembrane transporter activity
IEA
GO_REF:0000002
MODIFY
Summary: InterPro TonB-dependent siderophore receptor mapping.
Reason: Correct but general. The gene already carries two supported descendants: enterobactin transmembrane transporter activity (its specific substrate) and siderophore uptake transmembrane transporter activity.
Supporting Evidence:
PMID:8419284
Moreover, the fragment complemented the fepA mutation in MT912, restoring both growth in EDDHA-containing medium and enterobactin-dependent uptake of 55Fe3+.
GO:0015344 siderophore uptake transmembrane transporter activity
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN004738955 (142 leaf IBAs), seeded by PfeA and three other PAO1 TBDRs. PfeA in its own WITH/FROM is expected, not circular.
Reason: PfeA is a TonB-dependent siderophore receptor with genetic evidence for ferric-enterobactin uptake. The node is a TBDR clade for which siderophore uptake is the expected function, so the IBD is sound.
Supporting Evidence:
PMID:8419284
Moreover, the fragment complemented the fepA mutation in MT912, restoring both growth in EDDHA-containing medium and enterobactin-dependent uptake of 55Fe3+.
GO:0015344 siderophore uptake transmembrane transporter activity
IEA
GO_REF:0000120
ACCEPT
Summary: ARBA/InterPro (PirA/FepA/PfeA family) mapping.
Reason: Same correct claim as the IBA and IMP rows.
Supporting Evidence:
file:PSEAE/pfeA/pfeA-uniprot.txt
InterPro; IPR058134; PirA/FepA/PfeA.
GO:0015344 siderophore uptake transmembrane transporter activity
IMP
PMID:8419284
Cloning and characterization of the ferric enterobactin rece...
ACCEPT
Summary: PseudoCAP IMP; one of four seeds of the PTN004738955 IBD. The receptor-less mutant K407 grows poorly on ferric enterobactin, and the cloned gene restores enterobactin-dependent iron uptake in E. coli fepA.
Reason: The mutant lacks the receptor protein itself, and complementation restores both the protein and siderophore-dependent 55Fe uptake. This is specific evidence for transport, not an indirect phenotype.
Supporting Evidence:
PMID:8419284
Pseudomonas aeruginosa K407, a mutant lacking a high-affinity 80,000-molecular-weight ferric enterobactin receptor protein (80K protein), exhibited poor growth (small colonies) on iron-deficient succinate minimal medium containing ethylenediamine-di(o-hydroxyphenylacetic acid) (EDDHA) and enterobactin.
PMID:8419284
Moreover, the fragment complemented the fepA mutation in MT912, restoring both growth in EDDHA-containing medium and enterobactin-dependent uptake of 55Fe3+.
GO:0015891 siderophore transport
IEA
GO_REF:0000002
MODIFY
Summary: InterPro mapping to siderophore transport.
Reason: Correct but general. The specific substrate is ferric enterobactin, and the gene already carries the descendant enterobactin transport.
Proposed replacements: enterobactin transport
Supporting Evidence:
PMID:8419284
Moreover, the fragment complemented the fepA mutation in MT912, restoring both growth in EDDHA-containing medium and enterobactin-dependent uptake of 55Fe3+.
GO:0015891 siderophore transport
IMP
PMID:8419284
Cloning and characterization of the ferric enterobactin rece...
MODIFY
Summary: PseudoCAP IMP from the same mutant and complementation data.
Reason: Correct but general. The same paper also supports, and PseudoCAP also annotated, the descendant enterobactin transport.
Proposed replacements: enterobactin transport
Supporting Evidence:
PMID:8419284
Moreover, the fragment complemented the fepA mutation in MT912, restoring both growth in EDDHA-containing medium and enterobactin-dependent uptake of 55Fe3+.
GO:0019867 outer membrane
IDA
PMID:8419284
Cloning and characterization of the ferric enterobactin rece...
MODIFY
Summary: PseudoCAP IDA. The 80 kDa protein was detected in outer membranes of P. aeruginosa and E. coli carrying the clone.
Reason: Correct but general. For a bacterial protein the specific child is cell outer membrane, which the gene already carries by IBA and IEA.
Proposed replacements: cell outer membrane
Supporting Evidence:
PMID:8419284
direct the synthesis of high levels of a protein of the same molecular weight in the outer membranes of Escherichia coli fepA strains MT912 and IR20
GO:0033214 siderophore-iron import into cell
IEA
GO_REF:0000120
MODIFY
Summary: Inferred from the siderophore-iron transporter MF terms.
Reason: Correct but general. PfeA performs the outer-membrane step of ferric-enterobactin import, so the specific descendant is ferric-enterobactin import into cell.
Supporting Evidence:
PMID:8419284
Moreover, the fragment complemented the fepA mutation in MT912, restoring both growth in EDDHA-containing medium and enterobactin-dependent uptake of 55Fe3+.
GO:0038023 signaling receptor activity
IEA
GO_REF:0000002
REMOVE
Summary: InterPro2GO mapping of the TonB-dependent siderophore receptor signature.
Reason: "Receptor" here means a ligand-binding transporter, not a signal transducer. TonB-dependent transducers carry an N-terminal signalling domain before the TonB box; PfeA has none (signal peptide 1-25, TonB box 39-44, plug from 47). Enterobactin-dependent induction of pfeA works through a separate two-component system. The InterPro2GO mapping over-generalises from the transducer subset of the family.
Supporting Evidence:
file:PSEAE/pfeA/pfeA-uniprot.txt
MOTIF 39..44
file:PSEAE/pfeA/pfeA-uniprot.txt
DOMAIN 47..174
GO:0042912 colicin transmembrane transporter activity
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: IBA from PTN000763909, seeded by E. coli FepA, which is also the receptor for colicins B and D.
Reason: Colicin uptake through FepA is an E. coli parasitism of the receptor. No evidence was found that PfeA admits colicins, and colicins B and D are not known to act on P. aeruginosa. The property is lineage-specific and is not safely inherited by the Pseudomonas leaf.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: LINEAGE OR TAXON MISMATCH
Sources checked:
UniProtKB:P05825 SUPPORTS SOURCE BUT NOT TARGET
E. coli FepA is a colicin B/D receptor; nothing shows PfeA has that property.
Supporting Evidence:
PMID:8419284
The PfeA protein showed more than 60% homology to the E. coli FepA protein.
GO:0042930 enterobactin transport
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN000763909, whose enterobactin transport IBD is seeded only by this gene's own PseudoCAP IMP row (3 leaf IBAs: PfeA, E. coli and Salmonella FepA). The target in its own WITH/FROM is expected.
Reason: Ferric-enterobactin transport is PfeA's core function, and the other leaves are the canonical FepA ferric-enterobactin receptors. The IBD is sound.
Supporting Evidence:
PMID:8419284
Moreover, the fragment complemented the fepA mutation in MT912, restoring both growth in EDDHA-containing medium and enterobactin-dependent uptake of 55Fe3+.
PMID:15899402
Ferric-enterobactin also failed to stimulate growth of the double pfeA-pirA mutant although, like its synthetic analogues, it stimulated growth of the corresponding single mutants.
GO:0042930 enterobactin transport
IMP
PMID:8419284
Cloning and characterization of the ferric enterobactin rece...
ACCEPT
Summary: PseudoCAP IMP; sole seed of the PTN000763909 enterobactin transport IBD.
Reason: The receptor-less mutant is defective in growth on ferric enterobactin, and the gene restores enterobactin-dependent 55Fe uptake. Sound.
Supporting Evidence:
PMID:8419284
Pseudomonas aeruginosa K407, a mutant lacking a high-affinity 80,000-molecular-weight ferric enterobactin receptor protein (80K protein), exhibited poor growth (small colonies) on iron-deficient succinate minimal medium containing ethylenediamine-di(o-hydroxyphenylacetic acid) (EDDHA) and enterobactin.
GO:0042931 enterobactin transmembrane transporter activity
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN000763909, seeded only by this gene's own PseudoCAP IMP row.
Reason: Correct and core. The FepA/PfeA clade transports ferric enterobactin across the outer membrane. GO:0015620 ferric-enterobactin transmembrane transporter activity would name the iron-loaded substrate more exactly, but this term sits under siderophore-iron transmembrane transporter activity and is acceptable.
Supporting Evidence:
PMID:8419284
Moreover, the fragment complemented the fepA mutation in MT912, restoring both growth in EDDHA-containing medium and enterobactin-dependent uptake of 55Fe3+.
GO:0042931 enterobactin transmembrane transporter activity
IEA
GO_REF:0000117
ACCEPT
Summary: ARBA machine-learning prediction.
Reason: Same correct claim as the IMP and IBA rows, independently supported by the experimental data.
Supporting Evidence:
PMID:8419284
Moreover, the fragment complemented the fepA mutation in MT912, restoring both growth in EDDHA-containing medium and enterobactin-dependent uptake of 55Fe3+.
GO:0042931 enterobactin transmembrane transporter activity
IMP
PMID:8419284
Cloning and characterization of the ferric enterobactin rece...
ACCEPT
Summary: PseudoCAP IMP; sole seed of the PTN000763909 enterobactin transmembrane transporter activity IBD.
Reason: The mutation removes the receptor protein, and complementation restores enterobactin-dependent iron uptake, which ties the transport activity to this gene product. Sound seed.
Supporting Evidence:
PMID:8419284
Moreover, the fragment complemented the fepA mutation in MT912, restoring both growth in EDDHA-containing medium and enterobactin-dependent uptake of 55Fe3+.
GO:0043213 bacteriocin transport
IEA
GO_REF:0000108
MARK AS OVER ANNOTATED
Summary: Inferred from the colicin transmembrane transporter activity IBA.
Reason: Follows only from the colicin transporter IBA, which is over-propagated from E. coli FepA. No bacteriocin transport is known for PfeA.
Supporting Evidence:
PMID:8419284
The PfeA protein showed more than 60% homology to the E. coli FepA protein.
GO:0044718 siderophore transmembrane transport
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN004738955, seeded by E. coli Cir (P17315).
Reason: PfeA moves a ferric siderophore across the outer membrane. GO has no enterobactin-specific child of this term, so it is as precise as available.
Supporting Evidence:
PMID:8419284
Moreover, the fragment complemented the fepA mutation in MT912, restoring both growth in EDDHA-containing medium and enterobactin-dependent uptake of 55Fe3+.
GO:1903981 enterobactin binding
IDA
PMID:35101443
Fluorescent sensors of siderophores produced by bacterial pa...
KEEP AS NON CORE
Summary: UniProt IDA. A fluorescently labelled PfeA sensor bound ferric enterobactin with the same ligand preference as E. coli FepA.
Reason: Correct direct binding evidence. Ligand binding is part of the receptor's transport cycle and is captured by the core transporter activity, so this term is kept as non-core.
Supporting Evidence:
PMID:35101443
First, the EcoFepA orthologs KpnFepA1658 (82% identity) and PaePfeA (61% identity) had the same ligand preferences as EcoFepA (FeEnt > FeEntβˆ— > FeGEnt).

Core Functions

TonB-dependent outer-membrane receptor that binds the xenosiderophore ferric enterobactin and transports it into the periplasm, the outer-membrane step of enterobactin-mediated iron acquisition.

Supporting Evidence:
  • PMID:8419284
    Moreover, the fragment complemented the fepA mutation in MT912, restoring both growth in EDDHA-containing medium and enterobactin-dependent uptake of 55Fe3+.
  • PMID:15899402
    Ferric-enterobactin also failed to stimulate growth of the double pfeA-pirA mutant although, like its synthetic analogues, it stimulated growth of the corresponding single mutants.

References

Loading supporting content…

Download this section (compressed HTML)

Suggested Questions for Experts

Q: Should the PfeA/FepA enterobactin rows use GO:0015620 ferric-enterobactin transmembrane transporter activity rather than GO:0042931, given that the receptors transport the iron-loaded siderophore?

Q: Is the colicin transmembrane transporter IBD at PTN000763909 meant to reach the Pseudomonas leaf?

Suggested Experiments

Experiment: Test whether colicin B or D kills P. aeruginosa, or an E. coli fepA mutant expressing pfeA, to settle whether PfeA can act as a colicin receptor.

πŸ“š Additional Documentation

Notes

(pfeA-notes.md)

Loading supporting content…

Download this section (compressed HTML)

πŸ“„ View Raw YAML

Loading supporting content…

Download this section (compressed HTML)