ParC (PA4964) is the A subunit of DNA topoisomerase IV of Pseudomonas aeruginosa, a type IIA topoisomerase made of two ParC and two ParE subunits. ParC is the GyrA-like subunit: it binds DNA and carries the catalytic tyrosine that cleaves both strands and forms the transient covalent DNA gate, while ParE (PA4967) supplies the ATPase. The reconstituted P. aeruginosa ParC-ParE enzyme decatenates and relaxes DNA in an ATP- and Mg2+-dependent manner and, unlike gyrase, does not introduce negative supercoils; neither subunit is active alone. By homology to E. coli topoisomerase IV, its cellular role is unlinking of replicated daughter chromosomes for segregation. Topoisomerase IV is a secondary target of fluoroquinolones in P. aeruginosa, and parC mutations contribute to high-level quinolone resistance.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003677 DNA binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from PTN001607041 (seeds E. coli GyrA and ParC). Reason: True: the A subunit binds the gate DNA segment. No more specific DNA-binding term is better supported; the core activity is captured by GO:0003918, which does not entail DNA binding in GO. Supporting Evidence: PMID:10049263 GyrA is responsible for the DNA strand binding, cleavage, and rejoining, and GyrB is responsible for ATPase activity. |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Automated mapping; agrees with the IBA. Reason: As for the IBA row. Supporting Evidence: PMID:10049263 GyrA is responsible for the DNA strand binding, cleavage, and rejoining, and GyrB is responsible for ATPase activity. |
| GO:0003916 DNA topoisomerase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro mapping to generic topoisomerase activity. Reason: Entailed by GO:0003918 type II (ATP-hydrolyzing) topoisomerase activity, accepted here. |
| GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity | IDA PMID:10049263 Cloning, expression, and enzymatic characterization of Pseud... | ACCEPT | Summary: PseudoCAP IDA row. The reconstituted ParC-ParE enzyme decatenates and relaxes DNA ATP-dependently; ParC alone is inactive. Reason: Directly shown for the holoenzyme of which ParC is the catalytic (DNA-cleaving) subunit. Strictly the subunit contributes_to this activity; recorded as such in core_functions. Not a PAINT seed for this term. Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. PMID:10049263 Enzymatic activity was dependent on ATP, Mg 2+ (data not shown), and the presence of both subunits |
| GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity | IEA GO_REF:0000120 | ACCEPT | Summary: UniRule/InterPro/EC mapping; agrees with the IDA. Reason: Same claim as the IDA row. Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. |
| GO:0005524 ATP binding | IBA GO_REF:0000033 | REMOVE | Summary: IBA from PTN001607041, seeded only by M. tuberculosis GyrA (P9WG47) and P. falciparum apicoplast gyrase A (Q8I0X3). Reason: In type IIA topoisomerases the ATP-binding GHKL domain is in the B subunit (GyrB, ParE); the A subunit (GyrA, ParC) has no ATP site. ATP binding is a property of the holoenzyme, not of ParC, and the term does not suit a GyrA/ParC clade node. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN001607041 · PTN001607041 SOURCE WEAK OR INFERRED GyrA/ParC (type IIA A-subunit) node. ATP binding is a B-subunit property, so an ATP-binding IBD at this node transfers a complex-level property to the A subunit across the clade. UniProtKB:P9WG47 · M. tuberculosis GyrA SUPPORTS SOURCE BUT NOT TARGET Its ATP-binding annotation most likely reflects assays of the reconstituted gyrase; not checked in full text. UniProtKB:Q8I0X3 · P. falciparum gyrase A UNRESOLVED Apicoplast gyrase A; ATP-binding evidence not checked. Supporting Evidence: PMID:10049263 GyrA is responsible for the DNA strand binding, cleavage, and rejoining, and GyrB is responsible for ATPase activity. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | REMOVE | Summary: InterPro2GO mapping from type IIA topoisomerase domain entries to ATP binding. Reason: As for the IBA row: the A-subunit domains (IPR002205 DNA_topo_IIA and related) do not bind ATP; the mapping fits holoenzyme-level entries or B subunits, not ParC. Supporting Evidence: PMID:10049263 GyrA is responsible for the DNA strand binding, cleavage, and rejoining, and GyrB is responsible for ATPase activity. |
| GO:0005694 chromosome | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro mapping to chromosome. Reason: Topoisomerase IV acts on chromosomal DNA; acceptable but peripheral and not shown in P. aeruginosa. Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA (PTN000018855; seeds E. coli GyrA and ParC). Reason: A soluble enzyme acting on the nucleoid in the bacterial cytoplasm; true but generic location. Supporting Evidence: PMID:10049263 69 and 75% identity with that of E. coli ParC and ParE, respectively |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | TOO GENERAL | Summary: UniProt subcellular-location mapping (cell membrane, peripheral). Reason: Entailed by GO:0019897 extrinsic component of plasma membrane, kept here as non-core. |
| GO:0006259 DNA metabolic process | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro mapping to DNA metabolic process. Reason: Entailed by GO:0006265 DNA topological change, accepted here. |
| GO:0006265 DNA topological change | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN001607041, seeded by E. coli ParC and GyrA, M. tuberculosis GyrA, P. falciparum gyrase A and this gene's own PseudoCAP IDA row (expected self-seed). Reason: Directly supported by this gene's reconstitution data; the IBD stands on the other four seeds too. Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. |
| GO:0006265 DNA topological change | IDA PMID:10049263 Cloning, expression, and enzymatic characterization of Pseud... | ACCEPT | Summary: PseudoCAP IDA seed of PTN001607041: reconstituted ParC-ParE decatenates and relaxes DNA. Reason: Seed SOUND (full text read). Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. PMID:10049263 relaxing activity of superhelical DNA was detected with the combination of ParC and ParE |
| GO:0006265 DNA topological change | IEA GO_REF:0000120 | ACCEPT | Summary: Automated mapping; agrees with the IDA. Reason: Same claim as the IDA row. Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. |
| GO:0007059 chromosome segregation | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000018879 seeded by E. coli ParC. Reason: Decatenation of replicated chromosomes is the cellular role of topoisomerase IV (E. coli par mutants are segregation-defective); P. aeruginosa ParC decatenates in vitro and is a 69% identical ortholog. Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. PMID:10049263 69 and 75% identity with that of E. coli ParC and ParE, respectively |
| GO:0007059 chromosome segregation | IEA GO_REF:0000104 | ACCEPT | Summary: UniRule (HAMAP ParC) mapping; agrees with the IBA. Reason: As for the IBA row. Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. |
| GO:0009330 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex | IBA GO_REF:0000033 | TOO GENERAL | Summary: IBA from PTN001607041 seeded by E. coli ParC, A. aeolicus GyrA and this gene's own topo IV complex row. Reason: True but entailed by GO:0009340 DNA topoisomerase IV complex, accepted here (is_a GO:0009330). Node term suits the GyrA/ParC clade. |
| GO:0009330 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA prediction. Reason: Entailed by GO:0009340, accepted here. |
| GO:0009340 DNA topoisomerase IV complex | IDA PMID:10049263 Cloning, expression, and enzymatic characterization of Pseud... | ACCEPT | Summary: PseudoCAP IDA row, a seed of the PTN001607041 GO:0009330 IBD. Activity requires both ParC and ParE, which reconstitute the active enzyme. Reason: Seed SOUND (full text read): functional reconstitution from both subunits shows the ParC-ParE complex. Supporting Evidence: PMID:10049263 Enzymatic activity was dependent on ATP, Mg 2+ (data not shown), and the presence of both subunits |
| GO:0019897 extrinsic component of plasma membrane | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: UniRule (HAMAP ParC type 1) location: peripheral membrane protein. Reason: Rests on the HAMAP rule's E. coli basis (topoisomerase IV recovered with the membrane fraction); not tested in P. aeruginosa and peripheral to the function. Supporting Evidence: PMID:10049263 69 and 75% identity with that of E. coli ParC and ParE, respectively |
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Experiment: Deplete ParC in P. aeruginosa and image nucleoid segregation to confirm its chromosome decatenation role in vivo.
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