arcD (PA5170) encodes the arginine:ornithine antiporter of Pseudomonas aeruginosa, a polytopic inner-membrane protein of the APC superfamily (basic amino acid/polyamine antiporter family, TC 2.A.3.2) with 13 predicted hydrophobic segments, a cytoplasmic N terminus and a periplasmic C terminus. ArcD catalyses electroneutral exchange of external L-arginine for internal L-ornithine, the substrate and end product of the arginine deiminase (ADI) pathway, and can also mediate slower proton motive force-driven uptake of arginine and ornithine; lysine can replace arginine in the exchange. It is encoded by the first gene of the arcDABC operon, induced by oxygen limitation, with arginine deiminase (ArcA), catabolic ornithine carbamoyltransferase (ArcB) and carbamate kinase (ArcC). By coupling arginine import to ornithine export without energy cost, ArcD lets the ADI pathway yield net ATP, and arcD mutants cannot use external arginine for anaerobic energy generation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | EXP PMID:1311296 arcD, the first gene of the arc operon for anaerobic arginin... | ACCEPT | Summary: UniProt EXP: ArcD activity in membrane vesicles of E. coli expressing arcD. Reason: Heterologous, but consistent with the native inner-membrane localization shown in P. aeruginosa (PMID:8449902). This is where the core activity acts. Supporting Evidence: PMID:1311296 The arcD gene encodes a hydrophobic polytopic membrane protein. |
| GO:0005886 plasma membrane | EXP PMID:8449902 Characterization of the arcD arginine:ornithine exchanger of... | ACCEPT | Summary: UniProt EXP: epitope-tagged ArcD detected in the inner membrane of P. aeruginosa; PhoA fusions define the topology. Reason: Direct localization of the native host protein to the inner (plasma) membrane. Supporting Evidence: PMID:8449902 permitted the localization, by immunoblotting, of the hybrid protein in the inner membrane of P. aeruginosa |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (is_active_in) from PTN008675589, an APC-superfamily node seeded by ArcD and ten E. coli APC transporters with experimental membrane locations. Reason: ArcD is shown experimentally to sit in the P. aeruginosa inner membrane, where it transports; the inherited location agrees with the direct evidence. Supporting Evidence: PMID:8449902 permitted the localization, by immunoblotting, of the hybrid protein in the inner membrane of P. aeruginosa |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: UniProt subcellular location / InterPro ArcD-family mapping to plasma membrane. Reason: Same correct location as the experimental rows. Supporting Evidence: file:PSEAE/arcD/arcD-uniprot.txt SUBCELLULAR LOCATION: Cell inner membrane |
| GO:0006091 generation of precursor metabolites and energy | IMP PMID:2158926 The arc operon for anaerobic arginine catabolism in Pseudomo... | KEEP AS NON CORE | Summary: UniProt IMP: arcD mutants cannot use extracellular arginine as an energy source under oxygen limitation. Reason: The phenotype is real, and ArcD's exchange is what makes the ADI pathway energetically efficient. ArcD contributes by moving substrate and product, not by generating ATP itself, so the term is kept as non-core context. Supporting Evidence: PMID:2158926 Mutations in arcD rendered the cells unable to utilize extracellular arginine as an energy source. PMID:1311296 an electroneutral exchange between arginine and ornithine to allow high-efficiency energy conversion in the arginine deiminase pathway |
| GO:0006527 L-arginine catabolic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO (IPR022461, ArcD family) mapping to L-arginine catabolic process. Reason: ArcD is an operon partner of the ADI pathway and supplies its substrate, but it catalyses no catabolic step; the catabolic chemistry is done by ArcA, ArcB and ArcC. As the transporter dedicated to this pathway it is kept as non-core context rather than removed; its core process is arginine and ornithine transmembrane transport. Supporting Evidence: PMID:2158926 Mutations in arcD rendered the cells unable to utilize extracellular arginine as an energy source. |
| GO:0006527 L-arginine catabolic process | IMP PMID:2158926 The arc operon for anaerobic arginine catabolism in Pseudomo... | KEEP AS NON CORE | Summary: UniProt IMP from the arcD mutant phenotype. Reason: Consistent with the IEA row: ArcD is required for catabolism of external arginine via the ADI pathway but does none of the catabolic chemistry. Kept as non-core pathway context. Supporting Evidence: PMID:2158926 Mutations in arcD rendered the cells unable to utilize extracellular arginine as an energy source. |
| GO:0006865 amino acid transport | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IPR004754, amino acid antiporter) mapping to amino acid transport. Reason: Correct but general. The substrates are known: L-arginine (GO:1903826, already on the gene) and L-ornithine (GO:1903352, proposed as NEW), both is_a descendants. Proposed replacements: L-arginine transmembrane transport L-ornithine transmembrane transport Supporting Evidence: PMID:1311296 These proteoliposomes mediate a stoichiometric exchange between arginine and ornithine. |
| GO:0015171 amino acid transmembrane transporter activity | IEA GO_REF:0000117 | MODIFY | Summary: ARBA prediction of amino acid transmembrane transporter activity. Reason: Correct but general; the specific activity, arginine:ornithine antiporter activity (GO:0043858), is an is_a descendant that the gene already carries with experimental support. Proposed replacements: arginine:ornithine antiporter activity Supporting Evidence: PMID:1311296 These proteoliposomes mediate a stoichiometric exchange between arginine and ornithine. |
| GO:0015297 antiporter activity | IEA GO_REF:0000117 | MODIFY | Summary: ARBA prediction of antiporter activity. Reason: Correct but general; replace with the experimentally supported is_a descendant GO:0043858, already on the gene. Proposed replacements: arginine:ornithine antiporter activity Supporting Evidence: PMID:1311296 It is concluded that the ArcD protein is a transport system that catalyzes an electroneutral exchange between arginine and ornithine |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping to membrane. Reason: Correct but general; ArcD is an inner (plasma) membrane protein, a term the gene already carries with experimental support. Proposed replacements: plasma membrane Supporting Evidence: PMID:8449902 permitted the localization, by immunoblotting, of the hybrid protein in the inner membrane of P. aeruginosa |
| GO:0022857 transmembrane transporter activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IPR002293, APC permease) mapping to transmembrane transporter activity. Reason: Correct but general; replace with GO:0043858, the experimentally supported is_a descendant already on the gene. Proposed replacements: arginine:ornithine antiporter activity Supporting Evidence: PMID:1311296 These proteoliposomes mediate a stoichiometric exchange between arginine and ornithine. |
| GO:0043858 arginine:ornithine antiporter activity | EXP PMID:2158926 The arc operon for anaerobic arginine catabolism in Pseudomo... | ACCEPT | Summary: UniProt EXP for arginine:ornithine antiporter activity citing the arcD discovery paper. That paper sequenced arcD, showed a membrane-located product and an arcD mutant phenotype, and proposed the antiport. Reason: The activity is correct and directly demonstrated elsewhere (PMID:1311296, PMID:8449902). The cited paper itself only proposes it from the mutant phenotype and the coupling of arginine uptake to ornithine release, so it is weak support for an EXP row. UniProt's own FUNCTION comment cites the two later papers instead. Flagged for checking rather than removed, since the full text was not available. Supporting Evidence: PMID:2158926 it is proposed that arcD specifies an arginine: ornithine antiporter or a part thereof PMID:1311296 These proteoliposomes mediate a stoichiometric exchange between arginine and ornithine. |
| GO:0043858 arginine:ornithine antiporter activity | EXP PMID:8449902 Characterization of the arcD arginine:ornithine exchanger of... | ACCEPT | Summary: UniProt EXP: ArcD arginine:ornithine exchange activity; tagged hybrids retained arginine transport. Reason: Direct support for the core activity of the P. aeruginosa protein. Supporting Evidence: PMID:8449902 The arcD gene specifies a 53-kDa protein with arginine: ornithine exchange activity. |
| GO:0043858 arginine:ornithine antiporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000208945, an ArcD-type subclade (16 leaf IBAs, 11 taxa) whose IBD has a single seed, this protein. The target appearing in its own WITH/FROM is expected, not circular. Reason: The seed is sound: arginine:ornithine exchange by ArcD was measured directly in reconstituted proteoliposomes and in P. aeruginosa. PA5170 is the founding member of the clade. One leaf of the node, C. trachomatis AaxC, is probably an arginine:agmatine exchanger instead; that concerns another leaf (PTN000926691, which attaches directly to the node; tree checked 2026-11-05) and is flagged for checking. Supporting Evidence: PMID:1311296 It is concluded that the ArcD protein is a transport system that catalyzes an electroneutral exchange between arginine and ornithine file:PSEAE/arcD/arcD-uniprot.txt Catalyzes electroneutral exchange between arginine and ornithine to allow high-efficiency energy conversion in the arginine deiminase pathway |
| GO:0043858 arginine:ornithine antiporter activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR022461, Arg/Orn antiporter ArcD) mapping. Reason: Same correct core claim as the experimental and IBA rows. Supporting Evidence: file:PSEAE/arcD/arcD-uniprot.txt InterPro; IPR022461; Arg/Orn_antiprt_ArcD. |
| GO:0043858 arginine:ornithine antiporter activity | IMP PMID:1311296 arcD, the first gene of the arc operon for anaerobic arginin... | ACCEPT | Summary: PseudoCAP row; it supports the sole-seed IBD at PTN000208945 and one of the seven seeds of the PTN008675589 transmembrane transporter activity IBD. The paper measures arginine/ornithine exchange in vesicles from E. coli expressing arcD and in proteoliposomes with reconstituted ArcD. Reason: Sound seed: the paper directly demonstrates stoichiometric arginine:ornithine exchange by the ArcD protein. The abstract describes only direct assays of the gene product (vesicles and proteoliposomes), so IDA looks the better code, although the full text (not read) could include a mutant experiment; this does not affect the claim or the IBD. Supporting Evidence: PMID:1311296 These proteoliposomes mediate a stoichiometric exchange between arginine and ornithine. |
| GO:0046943 carboxylic acid transmembrane transporter activity | IEA GO_REF:0000117 | MODIFY | Summary: ARBA prediction of carboxylic acid transmembrane transporter activity. Reason: True in the formal sense (arginine and ornithine are carboxylic acids) but general; GO:0043858 is an is_a descendant already on the gene. Proposed replacements: arginine:ornithine antiporter activity Supporting Evidence: PMID:1311296 These proteoliposomes mediate a stoichiometric exchange between arginine and ornithine. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping to transmembrane transport. Reason: Correct but general; the transported substrates are known, so the specific descendants L-arginine and L-ornithine transmembrane transport apply. Proposed replacements: L-arginine transmembrane transport L-ornithine transmembrane transport Supporting Evidence: PMID:1311296 These proteoliposomes mediate a stoichiometric exchange between arginine and ornithine. |
| GO:1903826 L-arginine transmembrane transport | EXP PMID:2158926 The arc operon for anaerobic arginine catabolism in Pseudomo... | ACCEPT | Summary: UniProt EXP for L-arginine transmembrane transport from the arcD mutant phenotype (no use of external arginine). Reason: Correct core process. The mutant phenotype (external arginine not used, polar effects aside) supports a role in arginine uptake; it would be better coded IMP, but direct transport assays confirm the claim. Supporting Evidence: PMID:2158926 Mutations in arcD rendered the cells unable to utilize extracellular arginine as an energy source. PMID:1311296 Arginine and ornithine uptake was coupled to the proton motive force with a bias toward the transmembrane electrical potential. |
| GO:1903826 L-arginine transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO (IPR022461) mapping to L-arginine transmembrane transport. Reason: Correct core process; ArcD moves arginine across the inner membrane. Supporting Evidence: PMID:1311296 Arginine and ornithine uptake was coupled to the proton motive force with a bias toward the transmembrane electrical potential. |
| GO:1903352 L-ornithine transmembrane transport | IDA PMID:1311296 arcD, the first gene of the arc operon for anaerobic arginin... | NEW | Summary: ArcD exports L-ornithine in exchange for L-arginine across the inner membrane. Reason: ArcD itself moves ornithine across the membrane, as shown in vesicles and reconstituted proteoliposomes, so the gene product does the work of this process. The gene carries L-arginine transmembrane transport but no ornithine counterpart, and GO:0043858 is not under an ornithine-specific process. Not redundant with any existing row. Supporting Evidence: PMID:1311296 Accumulated ornithine was readily exchangeable for external arginine or lysine. PMID:1311296 These proteoliposomes mediate a stoichiometric exchange between arginine and ornithine. |
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Download this section (compressed HTML)Q: Does Chlamydia trachomatis AaxC (O84379) exchange ornithine at all? Its C. pneumoniae ortholog is an arginine:agmatine exchanger insensitive to ornithine, so the arginine:ornithine antiporter IBA from PTN000208945 may need a NOT at the AaxC leaf PTN000926691 (the tree has no chlamydial subclade and no alternative node to move the IBD to).
Q: Should GO:0043858 arginine:ornithine antiporter activity be annotated with the EXP rows citing PMID:1311296 and PMID:8449902 instead of PMID:2158926, which proposes the antiport only from a mutant phenotype?
Experiment: Assay the PAO1 paralog PA1194 (Q9I4E4, same subfamily and node) and C. trachomatis AaxC in proteoliposomes for arginine/ornithine versus arginine/agmatine exchange, to define which leaves of PTN000208945 truly share the ArcD activity.
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