PA5376 (CbcV) is the nucleotide-binding (ATPase) subunit of the Cbc (choline/betaine/carnitine) ABC importer, encoded in the cbcXWV operon (PA5378-PA5376) with the periplasmic substrate-binding protein CbcX and the integral membrane permease CbcW. It belongs to the ProV/ChoV family of osmolyte-uptake ABC ATPases (NCBIfam TIGR03415) and hydrolyses ATP to power substrate translocation through CbcW. The CbcWV core works with several separately encoded binding proteins that set substrate specificity. With CbcX it takes up choline (and betaine), with BetX glycine betaine, and with CaiX L-carnitine and short-chain acylcarnitines. Cbc imports these quaternary ammonium compounds mainly for use as carbon and nitrogen sources, and a PA5376 transposon mutant cannot grow on choline, glycine betaine or carnitine as sole carbon source. Expression of cbcXWV is induced by glycine betaine through the activator GbdR.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000166 nucleotide binding | IEA GO_REF:0000104 | TOO GENERAL | Summary: UniRule transfer of nucleotide binding. Reason: True but uninformative. ATP binding (GO:0005524), kept in this review, is a descendant and already entails it. Supporting Evidence: file:PSEAE/PA5376/PA5376-uniprot.txt ABC_transporter-like_ATP-bd |
| GO:0005275 amine transmembrane transporter activity | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA from PTN002466744 (ProV/ChoV-type ABC ATPases, 14 leaf IBAs in 12 taxa), seeded by PA5376 (PseudoCAP IDA, PMID:19919675) and E. coli ProV (P14175, EcoCyc IDA). Reason: The transport is real, but the term is on the wrong branch. GO defines amine transmembrane transporter activity for weakly basic amino or substituted-amino compounds. Choline, glycine betaine and carnitine (and ProU's glycine betaine and proline betaine) are quaternary ammonium compounds, which GO places under GO:0015651 and GO:0015418, not under amine transporter activity. Neither seed supports the amine term, so the IBD does not stand on ProV alone either. The right MF for the clade is ABC-type quaternary ammonium compound transporting activity. For the ATPase subunit this is a complex-level activity, recorded as contributes_to in core_functions. Same correction as for the permease PA5377 at PTN000766131. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002466744 · PTN002466744 SUPPORTS TRANSFER PTHR43869 node of ProV/ChoV-type QAC uptake ATPases. A QAC ABC transporter term suits it, but the amine term does not. UniProtKB:Q9HTI8 · PA5376 (self) SUPPORTS TRANSFER The target's own PseudoCAP IDA is a seed, which is expected, not circular. The evidence supports QAC transport, not amine transport. UniProtKB:P14175 · ProV (E. coli) SUPPORTS TRANSFER ProU imports glycine betaine and proline betaine, which are also QACs; its own GO:0005275 IDA (EcoCyc) has the same branch problem. Proposed replacements: ABC-type quaternary ammonium compound transporting activity Supporting Evidence: PMID:19919675 The PA5376::tn, PA5377::tn and PA5378::tn mutants all failed to grow on choline (Fig. 3A) and betaine (Fig. S2) as sole C sources PMID:19919675 Interestingly, cells of MKH13 transformed with pME6041 expressing cbcXWV from PAO1, pCbcPAO1, accumulated choline and betaine but little to no carnitine. |
| GO:0005275 amine transmembrane transporter activity | IDA PMID:19919675 The ATP-binding cassette transporter Cbc (choline/betaine/ca... | MODIFY | Summary: PseudoCAP IDA, a co-seed of the PTN002466744 amine transporter IBD. Reason: The paper shows Cbc-dependent uptake of choline, betaine and carnitine (quaternary ammonium compounds), with PA5376 required. The right GO branch is quaternary ammonium compound transport, not amine transport. Proposed replacements: ABC-type quaternary ammonium compound transporting activity Supporting Evidence: PMID:19919675 the deficiencies in choline uptake by PA14 mutants with insertions in individual cbc loci were complemented by cbcXWV from either PAO1 or B728a |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Combined IEA from the ABC transporter ATP-binding domain. Reason: CbcV is the nucleotide-binding domain of the importer, so it binds ATP. The informative activity is ATP hydrolysis coupled to transport; ATP binding is a component of that, as precise as needed for a binding term. Supporting Evidence: PMID:19919675 two nucleotide-binding domains (NBDs, or ATPases) that power the translocation |
| GO:0006970 response to osmotic stress | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: ARBA prediction, presumably from the osmoprotectant-transporter family. Reason: ProU-type systems are osmoprotectant importers in E. coli, but in P. aeruginosa Cbc is characterised as a catabolic uptake system. Malek et al. found CbcXWV among the main choline transporters under hypo-osmolar conditions, with BetT3 dominant under hyperosmolar conditions. No osmotic-stress role for PA5376 has been shown. Supporting Evidence: PMID:21478341 BetT1 and CbcXWV were the primary choline transporters under hypo-osmolar conditions whereas BetT3 was the major choline transporter under hyperosmolar conditions |
| GO:0015220 choline transmembrane transporter activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the choline ABC transporter ATP-binding family. Reason: True, but ABC-type choline transporter activity (GO:0033266), accepted in this review from PMID:19919675, is a descendant and entails it. Supporting Evidence: file:PSEAE/PA5376/PA5376-uniprot.txt ABC_trnsptr_Choline_ATP-bd |
| GO:0015226 carnitine transmembrane transporter activity | IDA PMID:19919675 The ATP-binding cassette transporter Cbc (choline/betaine/ca... | MODIFY | Summary: PseudoCAP IDA for carnitine transporter activity. Reason: PAO1 CbcWV supports carnitine uptake only with the trans-encoded CaiX SBP; CbcXWV alone in E. coli takes up choline and betaine but not carnitine. Carnitine is one SBP-defined substrate. For the ATPase, the accurate MF is the QAC ABC transport activity it contributes to. Same action as on the permease PA5377. Proposed replacements: ABC-type quaternary ammonium compound transporting activity Supporting Evidence: PMID:19919675 These findings provide compelling evidence that Psyr_2916 and PA5388, hereafter referred to as CaiX, enable Cbc-mediated carnitine uptake in P. syringae and P. aeruginosa respectively. |
| GO:0015418 ABC-type quaternary ammonium compound transporting activity | IDA PMID:19919675 The ATP-binding cassette transporter Cbc (choline/betaine/ca... | ACCEPT | Summary: PseudoCAP IDA for ABC-type QAC transporting activity. Reason: The right level for a multi-substrate core transporter whose specificity is set by interchangeable SBPs. The choline and glycine betaine descendants also accepted here do not cover the CaiX-dependent carnitine mode, so this umbrella term is not redundant. For the ATPase subunit the activity is complex-level (contributes_to in core_functions). Supporting Evidence: PMID:19919675 In addition to the core transporter comprised of a transmembrane protein (CbcW) and an ATPase (CbcV), the Cbc transporter system interacts with at least three SBPs PMID:19919675 These transposon mutants also failed to grow on L-carnitine (Fig. S2), suggesting that carnitine is an additional substrate for this transporter. |
| GO:0015419 ABC-type sulfate transporter activity | IDA PMID:23763788 The widespread plant-colonizing bacterial species Pseudomona... | UNDECIDED | Summary: PseudoCAP IDA citing a P. syringae bioreporter paper (abstract only in cache). Reason: Inorganic sulfate is not a plausible substrate for a ProV/ChoV-type QAC importer, and the abstract mentions neither sulfate nor PA5376. The curator may have coded a sulfur-containing QAC such as choline-O-sulfate as sulfate. The full text could not be read, so the row is left undecided with a suspected wrong-term defect. The permease PA5377 carries a parallel sulfur compound row from the same paper, also UNDECIDED. Supporting Evidence: PMID:23763788 Whole-cell bacterial bioreporters of the phytopathogen Pseudomonas syringae were constructed that couple a QAC-responsive transcriptional fusion with well-characterized bacterial QAC transporters. |
| GO:0015837 amine transport | IEA GO_REF:0000108 | MODIFY | Summary: Inter-ontology inference from the amine transmembrane transporter activity rows. Reason: This row inherits the wrong-branch amine term. The substrates are quaternary ammonium compounds, and the corresponding process is quaternary ammonium group transport. Proposed replacements: quaternary ammonium group transport Supporting Evidence: PMID:19919675 These transposon mutants also failed to grow on L-carnitine (Fig. S2), suggesting that carnitine is an additional substrate for this transporter. |
| GO:0015838 amino-acid betaine transport | IDA PMID:19919675 The ATP-binding cassette transporter Cbc (choline/betaine/ca... | MODIFY | Summary: PseudoCAP IDA to the parent of glycine betaine and carnitine transport. Reason: Correct but general. Both specific descendants are supported in the same paper and already carried by the gene, glycine betaine transport and carnitine transmembrane transport. Proposed replacements: glycine betaine transport carnitine transmembrane transport Supporting Evidence: PMID:19919675 These transposon mutants also failed to grow on L-carnitine (Fig. S2), suggesting that carnitine is an additional substrate for this transporter. |
| GO:0015871 choline transport | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from the choline ABC transporter ATP-binding family. Reason: Consistent with family membership (TIGR03415 ChoXWV ATPase) and with the mutant and complementation evidence. Supporting Evidence: file:PSEAE/PA5376/PA5376-uniprot.txt ABC_choXWV_ATP |
| GO:0015871 choline transport | IMP PMID:19919675 The ATP-binding cassette transporter Cbc (choline/betaine/ca... | ACCEPT | Summary: PseudoCAP IMP from the PA14 PA5376::tn mutant. Reason: Direct mutant evidence. PA5376::tn fails to grow on choline as sole carbon source, and choline uptake by the cbc mutants is restored by PAO1 cbcXWV. Supporting Evidence: PMID:19919675 The PA5376::tn, PA5377::tn and PA5378::tn mutants all failed to grow on choline (Fig. 3A) and betaine (Fig. S2) as sole C sources PMID:19919675 the deficiencies in choline uptake by PA14 mutants with insertions in individual cbc loci were complemented by cbcXWV from either PAO1 or B728a |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from the ABC transporter ATPase domain. Reason: The subunit-level activity of an ABC importer NBD. CbcV is the ATPase that powers Cbc translocation. Supporting Evidence: PMID:19919675 two nucleotide-binding domains (NBDs, or ATPases) that power the translocation file:PSEAE/PA5376/PA5376-uniprot.txt ABC_transporter-like_ATP-bd |
| GO:0031457 glycine betaine catabolic process | IDA PMID:19919675 The ATP-binding cassette transporter Cbc (choline/betaine/ca... | MARK AS OVER ANNOTATED | Summary: PseudoCAP IDA to glycine betaine catabolism, based on the inability of the cbc mutants to grow on betaine as a carbon source. Reason: PA5376 is a transporter ATPase. It powers betaine import but performs no step of betaine demethylation (GbcAB and downstream enzymes). Loss of growth on betaine is an indirect phenotype of lost uptake, captured by glycine betaine transport. Same action as on PA5377. Supporting Evidence: PMID:19919675 The PA5376::tn, PA5377::tn and PA5378::tn mutants all failed to grow on choline (Fig. 3A) and betaine (Fig. S2) as sole C sources |
| GO:0031459 ABC-type glycine betaine transporter activity | IDA PMID:19919675 The ATP-binding cassette transporter Cbc (choline/betaine/ca... | ACCEPT | Summary: PseudoCAP IDA for ABC-type glycine betaine transporter activity. Reason: PAO1 CbcXWV confers betaine uptake on transporter-deficient E. coli MKH13, and the PA5376 mutant cannot grow on betaine. Betaine is carried with CbcX (low affinity) and BetX (high affinity). For the ATPase subunit this is a complex-level activity. Supporting Evidence: PMID:19919675 Interestingly, cells of MKH13 transformed with pME6041 expressing cbcXWV from PAO1, pCbcPAO1, accumulated choline and betaine but little to no carnitine. |
| GO:0031460 glycine betaine transport | IDA PMID:19919675 The ATP-binding cassette transporter Cbc (choline/betaine/ca... | ACCEPT | Summary: PseudoCAP IDA from heterologous uptake assays with PAO1 cbcXWV. Reason: PAO1 CbcXWV confers betaine uptake on transporter-deficient E. coli MKH13, and the PA5376 mutant cannot grow on betaine. Supporting Evidence: PMID:19919675 Interestingly, cells of MKH13 transformed with pME6041 expressing cbcXWV from PAO1, pCbcPAO1, accumulated choline and betaine but little to no carnitine. |
| GO:0031460 glycine betaine transport | IDA PMID:21478341 Roles of three transporters, CbcXWV, BetT1, and BetT3, in Ps... | ACCEPT | Summary: PseudoCAP IDA citing Malek et al. 2011 (abstract only in cache). Reason: The claim is well supported by PMID:19919675. The abstract of PMID:21478341 concerns choline uptake and GbdR/betaine induction of cbcXWV; the betaine data the curator used cannot be seen, so this is deferred to the curator. Supporting Evidence: PMID:19919675 Interestingly, cells of MKH13 transformed with pME6041 expressing cbcXWV from PAO1, pCbcPAO1, accumulated choline and betaine but little to no carnitine. |
| GO:0033266 ABC-type choline transporter activity | IDA PMID:19919675 The ATP-binding cassette transporter Cbc (choline/betaine/ca... | ACCEPT | Summary: PseudoCAP IDA for ABC-type choline transporter activity. Reason: Choline is the principal substrate of CbcXWV (CbcX binds choline with high affinity). PAO1 cbcXWV restores choline uptake to the PA14 cbc mutants and confers choline uptake on E. coli MKH13. For the ATPase subunit the activity is complex-level. Supporting Evidence: PMID:19919675 the deficiencies in choline uptake by PA14 mutants with insertions in individual cbc loci were complemented by cbcXWV from either PAO1 or B728a |
| GO:0042426 choline catabolic process | IDA PMID:19919675 The ATP-binding cassette transporter Cbc (choline/betaine/ca... | MARK AS OVER ANNOTATED | Summary: PseudoCAP IDA to choline catabolism, from the growth defect of cbc mutants on choline. Reason: The transporter imports choline for catabolism but does not oxidise it (BetA and BetB do). The growth defect on choline is an indirect consequence of lost uptake, already captured by choline transport. Supporting Evidence: PMID:19919675 The PA5376::tn, PA5377::tn and PA5378::tn mutants all failed to grow on choline (Fig. 3A) and betaine (Fig. S2) as sole C sources |
| GO:0042426 choline catabolic process | IDA PMID:21478341 Roles of three transporters, CbcXWV, BetT1, and BetT3, in Ps... | MARK AS OVER ANNOTATED | Summary: PseudoCAP IDA to choline catabolism citing Malek et al. 2011. Reason: The abstract frames the paper as about choline uptake transporters that support growth on choline, an indirect phenotype for a catabolic-process term. The transporter does not catabolise choline. See the defect on the PMID:19919675 row. Supporting Evidence: PMID:21478341 BetT3 and CbcXWV, but not BetT1, were sufficient to support growth on choline. |
| GO:0043190 ATP-binding cassette (ABC) transporter complex | IBA GO_REF:0000033 | TOO GENERAL | Summary: PAINT IBA from PTN002466744, seeded by PA5376 (PseudoCAP IDA) and E. coli ProV (part of the ProU complex, ComplexPortal). Reason: The claim is sound and suits the whole clade of ABC importer NBDs, and the IBD stands on ProV alone. For this gene, the more specific descendant GO:0055052 (substrate-binding subunit-containing ABC complex), accepted in this review, entails it: Cbc is a binding protein-dependent importer. Supporting Evidence: PMID:19919675 In addition to the core transporter comprised of a transmembrane protein (CbcW) and an ATPase (CbcV), the Cbc transporter system interacts with at least three SBPs |
| GO:0043190 ATP-binding cassette (ABC) transporter complex | IDA PMID:19919675 The ATP-binding cassette transporter Cbc (choline/betaine/ca... | TOO GENERAL | Summary: PseudoCAP IDA to the ABC transporter complex; co-seed of the PTN002466744 IBD. Seed verdict SOUND. Reason: CbcWV acts as a core transporter with interchangeable SBPs. The complex was inferred from function rather than isolated, but the claim is true. The accepted descendant GO:0055052 entails it. Supporting Evidence: PMID:19919675 A plasmid expressing only the core transporter, pNcbcWV, was constructed by deleting cbcX from pNcb-cXWV; it restored carnitine uptake to BT (Fig. 5), consistent with an association between the native CaiX SBP and the core transporter. |
| GO:0055052 ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO for the binding protein-dependent ABC importer complex. Reason: Cbc is a binding protein-dependent importer: the CbcWV core works with the SBPs CbcX, BetX and CaiX. Supporting Evidence: PMID:19919675 In addition to the core transporter comprised of a transmembrane protein (CbcW) and an ATPase (CbcV), the Cbc transporter system interacts with at least three SBPs |
| GO:1901682 sulfur compound transmembrane transporter activity | IDA PMID:23763788 The widespread plant-colonizing bacterial species Pseudomona... | UNDECIDED | Summary: PseudoCAP IDA citing a P. syringae bioreporter paper (abstract only in cache). Reason: The abstract describes P. syringae QAC bioreporters and plant choline. It mentions neither sulfur compounds nor PA5376, and no full text is available. The sulfur compound may be choline-O-sulfate transported by Cbc, but this cannot be verified. Same action as on PA5377. Supporting Evidence: PMID:23763788 Whole-cell bacterial bioreporters of the phytopathogen Pseudomonas syringae were constructed that couple a QAC-responsive transcriptional fusion with well-characterized bacterial QAC transporters. |
| GO:1902358 sulfate transmembrane transport | IEA GO_REF:0000108 | UNDECIDED | Summary: Inter-ontology inference from the ABC-type sulfate transporter IDA. Reason: Follows the GO:0015419 row, which is itself undecided (suspected mis-coding of a sulfur-containing QAC as sulfate). Inorganic sulfate transport by a ProV/ChoV-type QAC importer is not otherwise supported. Supporting Evidence: PMID:23763788 Whole-cell bacterial bioreporters of the phytopathogen Pseudomonas syringae were constructed that couple a QAC-responsive transcriptional fusion with well-characterized bacterial QAC transporters. |
| GO:1902603 carnitine transmembrane transport | IDA PMID:21478341 Roles of three transporters, CbcXWV, BetT1, and BetT3, in Ps... | ACCEPT | Summary: PseudoCAP IDA citing Malek et al. 2011. Reason: True for Cbc with the CaiX SBP (PMID:19919675, PMID:29517479). The cited abstract concerns only choline uptake and its full text could not be retrieved, so the reference is flagged for checking, as on PA5377. Supporting Evidence: PMID:19919675 These transposon mutants also failed to grow on L-carnitine (Fig. S2), suggesting that carnitine is an additional substrate for this transporter. PMID:29517479 Short-chain acylcarnitines are imported by the ABC transporter CaiX-CbcWV. |
Loading supporting content…
Download this section (compressed HTML)Q: Should the PTN002466744 amine transporter IBD (seeded by PA5376 and E. coli ProV) be repointed to GO:0015418, given that both seeds move quaternary ammonium compounds and GO does not class these as amines?
Q: What sulfur compound underlies the PseudoCAP GO:0015419 and GO:1901682 IDAs from PMID:23763788 (for example choline-O-sulfate), and was PAO1 cbcXWV used in that study?
Experiment: Test whether PAO1 CbcWV with each of its SBPs (CbcX, BetX, CaiX) takes up 35S-sulfate or choline-O-sulfate in a QAC transporter-deficient host, to resolve the sulfate and sulfur compound transporter claims.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)