PirA (PA0931) is a TonB-dependent outer-membrane receptor of Pseudomonas aeruginosa PAO1 for catecholate siderophores. It is a second ferric-enterobactin receptor, redundant with PfeA: only the pfeA pirA double mutant fails to use ferric enterobactin and several synthetic catecholate analogues. PirA also takes up iron chelated by host catecholamine neurotransmitters, with a preference for l-DOPA and norepinephrine, and its transcription is induced by catecholamines. It carries the plug domain and 22-strand beta-barrel of the TonB-dependent receptor family, and its crystal structure has been determined. PirA is also an entry route for siderophore-conjugated monobactam antibiotics.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006826 iron ion transport | IMP PMID:33350053 Opportunistic use of catecholamine neurotransmitters as side... | TOO GENERAL | Summary: UniProt IMP; pirA mutants are impaired in using catecholamines (l-DOPA, norepinephrine) as iron carriers under iron restriction. Reason: True but entailed by GO:0033214 siderophore-iron import into cell, accepted on this gene (is_a descendant of iron ion transport). Supporting Evidence: PMID:33350053 Bacterial growth assays under strong iron-restricted conditions and with numerous mutants showed that the TBDTs involved are PiuA and PirA. PMID:33350053 whereas PirA specificity appeared to be higher for l-DOPA and norepinephrine |
| GO:0009279 cell outer membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Cell outer membrane from PAINT node PTN002824128, seeded by E. coli TonB-dependent receptors with direct localization (FepA P05825, BtuB P06129, CirA P17315 and YncD P76115). Reason: TonB-dependent receptors are 22-strand outer-membrane beta-barrels with an N-terminal plug; the family membership and the cleavable signal peptide agree with outer-membrane location. Supporting Evidence: file:PSEAE/pirA/pirA-uniprot.txt PF00593; TonB_dep_Rec_b-barrel file:PSEAE/pirA/pirA-uniprot.txt FT SIGNAL 1..28 |
| GO:0009279 cell outer membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Cell outer membrane from the UniProt subcellular location and family rule. Reason: Consistent with the IBA row; a TonB-dependent receptor barrel. Supporting Evidence: file:PSEAE/pirA/pirA-uniprot.txt PF00593; TonB_dep_Rec_b-barrel |
| GO:0015343 siderophore-iron transmembrane transporter activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO siderophore-iron transmembrane transporter activity. Reason: True but entailed by GO:0015344 siderophore uptake transmembrane transporter activity, accepted on this gene (is_a descendant of GO:0015343). Supporting Evidence: PMID:15899402 Hence, we confirmed that pirA represents a second P. aeruginosa ferric-enterobactin receptor. |
| GO:0015344 siderophore uptake transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Siderophore uptake transmembrane transporter activity from PAINT node PTN004738955 (PTHR30069 TonB-dependent siderophore receptor clade, 142 leaves in 21 taxa). Its four IBD seeds are the PAO1 receptors PfeA, ChtA (PA4675), FvbA (PA4156) and PirA, each through a PseudoCAP IMP row; the node is assessed in the PA4675 notes. Reason: Core function. The gene product is itself a seed of this IBD through an experimental row on its own ferric-siderophore uptake, which is expected, not circular; the node is grounded in four independently characterized PAO1 receptors and sits within a TonB-dependent siderophore receptor clade where ferric-siderophore uptake is the established function. Supporting Evidence: 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. PMID:15899402 Hence, we confirmed that pirA represents a second P. aeruginosa ferric-enterobactin receptor. |
| GO:0015344 siderophore uptake transmembrane transporter activity | IEA GO_REF:0000120 | ACCEPT | Summary: Siderophore uptake transmembrane transporter activity from the PirA/FepA/PfeA family signature. Reason: Consistent with the IMP and IBA rows. Supporting Evidence: file:PSEAE/pirA/pirA-uniprot.txt IPR058134; PirA/FepA/PfeA PMID:15899402 Hence, we confirmed that pirA represents a second P. aeruginosa ferric-enterobactin receptor. |
| GO:0015344 siderophore uptake transmembrane transporter activity | IMP PMID:15899402 The Pseudomonas aeruginosa pirA gene encodes a second recept... | ACCEPT | Summary: PseudoCAP IMP seed for the IBD at PTN004738955. In a pyoverdine- and pyochelin-deficient background, ferric enterobactin and four synthetic catecholate siderophores fail to stimulate growth of the pfeA pirA double mutant, although they stimulate both single mutants. Reason: Seed verdict SOUND. This is double-mutant evidence, because PfeA and PirA are redundant for ferric enterobactin, but with the single-mutant controls it shows that PirA alone suffices for ferric-enterobactin uptake; the abstract states that PirA is a second ferric-enterobactin receptor. Later work adds catecholamine-iron uptake through PirA and a crystal structure of the receptor. Supporting Evidence: 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. PMID:15899402 Hence, we confirmed that pirA represents a second P. aeruginosa ferric-enterobactin receptor. PMID:33350053 Bacterial growth assays under strong iron-restricted conditions and with numerous mutants showed that the TBDTs involved are PiuA and PirA. |
| GO:0015891 siderophore transport | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO siderophore transport. Reason: True but entailed by GO:0044718 siderophore transmembrane transport, accepted on this gene (is_a descendant). Supporting Evidence: PMID:15899402 Hence, we confirmed that pirA represents a second P. aeruginosa ferric-enterobactin receptor. |
| GO:0015891 siderophore transport | IMP PMID:15899402 The Pseudomonas aeruginosa pirA gene encodes a second recept... | TOO GENERAL | Summary: PseudoCAP IMP; pfeA pirA double mutant cannot use ferric enterobactin. Reason: True but entailed by GO:0044718 siderophore transmembrane transport, accepted on this gene (is_a descendant). Supporting Evidence: 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:0015891 siderophore transport | IMP PMID:28137795 Structure and Function of the PiuA and PirA Siderophore-Drug... | TOO GENERAL | Summary: UniProt IMP; P. aeruginosa pirA deletion lowers susceptibility to siderophore-monobactam conjugates (UniProt disruption phenotype). Reason: True but entailed by GO:0044718 siderophore transmembrane transport, accepted on this gene (is_a descendant). Supporting Evidence: PMID:28137795 The crystal structures of PiuA and PirA from A. baumannii and their orthologues from P. aeruginosa were determined. |
| GO:0015891 siderophore transport | IMP PMID:33350053 Opportunistic use of catecholamine neurotransmitters as side... | TOO GENERAL | Summary: UniProt IMP; pirA mutants impaired in catecholamine-mediated iron uptake. Reason: True but entailed by GO:0044718 siderophore transmembrane transport, accepted on this gene (is_a descendant). Supporting Evidence: PMID:33350053 Bacterial growth assays under strong iron-restricted conditions and with numerous mutants showed that the TBDTs involved are PiuA and PirA. |
| GO:0033214 siderophore-iron import into cell | IEA GO_REF:0000120 | ACCEPT | Summary: Siderophore-iron import into cell, inferred from the molecular function rows. Reason: PirA imports iron complexed with enterobactin, synthetic catecholates and host catecholamines, so the broad siderophore-iron import term fits better than a ferric-enterobactin-only term. Supporting Evidence: 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. PMID:33350053 Bacterial growth assays under strong iron-restricted conditions and with numerous mutants showed that the TBDTs involved are PiuA and PirA. |
| GO:0038023 signaling receptor activity | IEA GO_REF:0000002 | REMOVE | Summary: InterPro2GO signaling receptor activity from the TonB-dependent siderophore receptor signature. Reason: The mapping is wrong for this member. Signalling TonB-dependent receptors (transducers such as FpvA or FecA) carry an N-terminal signalling extension of about 70 residues before the plug, which contacts an anti-sigma factor in the periplasm; this protein has only a signal peptide followed directly by the plug domain, so it is a receptor-transporter, not a signalling receptor. Same decision as for PfeA. Supporting Evidence: file:PSEAE/pirA/pirA-uniprot.txt FT SIGNAL 1..28 file:PSEAE/pirA/pirA-uniprot.txt PF07715; Plug |
| GO:0042930 enterobactin transport | IMP PMID:15899402 The Pseudomonas aeruginosa pirA gene encodes a second recept... | ACCEPT | Summary: PseudoCAP IMP; ferric enterobactin does not support growth of the pfeA pirA double mutant. Reason: Core process; PirA is a ferric-enterobactin receptor, redundant with PfeA. Supporting Evidence: 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. PMID:15899402 Hence, we confirmed that pirA represents a second P. aeruginosa ferric-enterobactin receptor. |
| GO:0042931 enterobactin transmembrane transporter activity | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA enterobactin transmembrane transporter activity. Reason: Consistent with the IMP row and with the curated UniProt function. Supporting Evidence: PMID:15899402 Hence, we confirmed that pirA represents a second P. aeruginosa ferric-enterobactin receptor. |
| GO:0042931 enterobactin transmembrane transporter activity | IMP PMID:15899402 The Pseudomonas aeruginosa pirA gene encodes a second recept... | ACCEPT | Summary: PseudoCAP IMP; PirA mediates ferric-enterobactin use in the absence of PfeA. Reason: Core activity; the substrate-specific counterpart of GO:0015344 for the canonical ligand. GO:0015620 ferric-enterobactin transmembrane transporter activity would name the iron-loaded form more exactly, as noted for PfeA. Supporting Evidence: 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. PMID:15899402 Hence, we confirmed that pirA represents a second P. aeruginosa ferric-enterobactin receptor. file:PSEAE/pirA/pirA-uniprot.txt Specific receptor for the siderophore ferric enterobactin |
| GO:0044718 siderophore transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: Siderophore transmembrane transport from PAINT node PTN004738955, seeded by E. coli CirA (P17315, IMP). Reason: Core process; TonB-dependent ferric-siderophore uptake across the outer membrane, shown for this receptor by its mutant phenotype. Supporting Evidence: 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. PMID:33350053 Bacterial growth assays under strong iron-restricted conditions and with numerous mutants showed that the TBDTs involved are PiuA and PirA. |
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Download this section (compressed HTML)Experiment: Measure radiolabelled ferric-enterobactin uptake and binding by purified PirA, and compare catecholamine-iron uptake kinetics of pirA and piuA single and double mutants, to separate the two receptors contributions.
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