tsaA (locus PP_1084) encodes the cytoplasmic AhpC/Prx1-family typical 2-Cys peroxiredoxin PpPrx, with two directly supported biochemical states. Its thioredoxin-dependent low-molecular-weight state reduces hydrogen peroxide, while high-molecular-weight oligomers act as in-situ holdases that suppress protein aggregation without detectable foldase activity. In direct comparisons, purified PpPrx had relatively low H2O2 peroxidase activity, substantially greater chaperone activity than the yeast peroxiredoxin control, and predominantly formed the HMW chaperone-associated complex. These measurements establish a redox-regulated peroxidase/holdase switch but do not by themselves rank the two activities under physiological KT2440 growth conditions (PMID:21104173; PMID:26278368).
Definition: Binding to an unfolded or misfolded protein to prevent its aggregation without actively catalyzing refolding. The holdase maintains the client protein in a soluble, folding-competent state.
Justification: Purified PpPrx directly suppresses thermal aggregation of MDH and citrate synthase, while foldase activity was not detected. This is an in-situ holdase activity. The obsolete GO:0051082 lacks a suitable replacement: GO:0044183 implies assistance with folding, and carrier-specific GO:0140309 requires escort to an acceptor or location. A general holdase activity term is therefore required (go-ontology#30552; projects/UNFOLDED_PROTEIN_BINDING.md).
Parent term: molecular_function
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004601 peroxidase activity | IEA GO_REF:0000117 | ACCEPT | Summary: Peroxidase activity is correct for this thiol-specific peroxidase, although the peroxiredoxin/thioredoxin peroxidase terms are more informative. Reason: UniProt describes reduction of hydrogen peroxide and organic hydroperoxides, supporting peroxidase activity. Supporting Evidence: file:PSEPK/PP_1084/PP_1084-uniprot.txt Thiol-specific peroxidase that catalyzes the reduction of file:PSEPK/PP_1084/PP_1084-uniprot.txt Plays a role in cell protection against oxidative stress PMID:21104173 PpPrx exhibited low H2O2catabolic peroxidase activity (Fig.2D), substantially lower than that of yeast Trx-dependent Prx (yTPx), but PpPrx exhibited five times higher the chaperone activity than yTPx, used as a positive control. |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: Cytoplasm is supported by the PSORTb cytoplasmic prediction reported for PP_1084/PpPrx in the KT2440 characterization study and by the absence of export or membrane features. Reason: The KT2440 PpPrx study (PMID:21104173) reports a PSORTb cytoplasmic prediction for PP1084; this is a computational call made in a paper on this gene, not a fractionation result. The UniProt FT table has no SIGNAL or TRANSMEM feature (only DOMAIN and ACT_SITE), and AhpC/Prx1 family membership (PIRSF000239) is consistent with a soluble intracellular peroxidase. The UniProt cytoplasm line is ARBA-only and is not used as support. The evidence resolves the location to the cytoplasm, not to the cytosol specifically. Supporting Evidence: PMID:21104173 The PSORTb tool predicted that PP1084 which we renamed PpPrx is a cytoplasmic protein file:PSEPK/PP_1084/PP_1084-uniprot.txt DR PIRSF; PIRSF000239; AHPC; 1. |
| GO:0005829 cytosol | IEA GO_REF:0000118 | KEEP AS NON CORE | Summary: Cytosol is compatible with the cytoplasmic location, but it is not the core function. A PSORTb cytoplasmic prediction for KT2440 PP_1084 in the falcon report is consistent with this assignment. Reason: Retain as a non-core location annotation in the bacterial cytoplasm/cytosol context. Supporting Evidence: file:PSEPK/PP_1084/PP_1084-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm file:PSEPK/PP_1084/PP_1084-deep-research-falcon.md PSORTb-based prediction placed PP1084/PpPrx in the **cytoplasm**, aligning with expected localization for a thioredoxin-coupled peroxide detox enzyme operating on intracellular peroxides and protein thiol redox balance |
| GO:0006979 response to oxidative stress | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Response to oxidative stress is supported but broad relative to direct peroxide detoxification. The falcon report notes the protein was enriched after oxidative treatments (H2O2, gamma rays) in KT2440. Reason: The protein protects against oxidative stress through peroxidase activity; the direct detoxification process terms are more specific. Supporting Evidence: file:PSEPK/PP_1084/PP_1084-uniprot.txt Thiol-specific peroxidase that catalyzes the reduction of file:PSEPK/PP_1084/PP_1084-uniprot.txt Plays a role in cell protection against oxidative stress file:PSEPK/PP_1084/PP_1084-deep-research-falcon.md PP1084/PpPrx was discovered among **disulfide-bonded proteins** enriched after **oxidative treatments (H2O2, gamma rays)** in KT2440, consistent with involvement in oxidative-stress response and thiol redox homeostasis |
| GO:0008379 thioredoxin peroxidase activity | IEA GO_REF:0000118 | ACCEPT | Summary: Thioredoxin peroxidase activity is the specific catalytic role of TsaA. The falcon report confirms that the directly characterized KT2440 protein (PpPrx) is a thioredoxin-dependent peroxidase assayed with a thioredoxin-coupled system, consistent with this term. Reason: The UniProt entry identifies the protein as a thiol-specific/thioredoxin peroxidase that reduces peroxides, and the directly studied KT2440 protein PpPrx (PP_1084) is experimentally a thioredoxin-dependent peroxidase. Supporting Evidence: file:PSEPK/PP_1084/PP_1084-uniprot.txt Thiol-specific peroxidase that catalyzes the reduction of file:PSEPK/PP_1084/PP_1084-uniprot.txt Plays a role in cell protection against oxidative stress file:PSEPK/PP_1084/PP_1084-deep-research-falcon.md locus **PP_1084** encodes a cytosolic **AhpC/Prx1-family (typical 2-Cys) peroxiredoxin**, experimentally characterized as a **thioredoxin-dependent peroxidase** that can also act as a **stress-responsive molecular chaperone** via oligomerization-dependent functional switching PMID:21104173 PpPrx exhibited low H2O2catabolic peroxidase activity (Fig.2D), substantially lower than that of yeast Trx-dependent Prx (yTPx), but PpPrx exhibited five times higher the chaperone activity than yTPx, used as a positive control. |
| GO:0016209 antioxidant activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Antioxidant activity is true in a broad sense but is less informative than peroxiredoxin and thioredoxin peroxidase activity. Reason: The annotation should prioritize the direct enzymatic activity rather than a generic antioxidant-function parent. Supporting Evidence: file:PSEPK/PP_1084/PP_1084-uniprot.txt Thiol-specific peroxidase that catalyzes the reduction of file:PSEPK/PP_1084/PP_1084-uniprot.txt Plays a role in cell protection against oxidative stress |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Oxidoreductase activity is a broad parent that adds little beyond the specific peroxiredoxin/peroxidase terms. Reason: The specific peroxide-reduction terms are available and should carry the functional interpretation. Supporting Evidence: file:PSEPK/PP_1084/PP_1084-uniprot.txt Thiol-specific peroxidase that catalyzes the reduction of file:PSEPK/PP_1084/PP_1084-uniprot.txt Plays a role in cell protection against oxidative stress |
| GO:0033554 cellular response to stress | IEA GO_REF:0000118 | KEEP AS NON CORE | Summary: Broad but true parent process for a peroxiredoxin; retained as non-core rather than rejected. Reason: GO:0033554 is defined as any process changing the state or activity of a cell as a result of a stimulus indicating the organism is under stress, which is what PpPrx does: UniProt records a thiol-specific peroxidase that plays a role in cell protection against oxidative stress, and the same PANTHER node supplies the more specific GO:0006979 and GO:0042744 terms this review accepts. GO:0006979 is not in fact a descendant of GO:0033554 (its only parents are GO:0006950 and GO:0050896), so the broader term is not strictly redundant with the oxidative terms, and the characterized holdase state of this protein - HMW oligomers that suppress protein aggregation - is a cellular stress response the peroxidase terms do not cover. Kept as non-core because it is uninformative beside the specific peroxide terms, not because it is unsupported. Supporting Evidence: file:PSEPK/PP_1084/PP_1084-uniprot.txt Thiol-specific peroxidase that catalyzes the reduction of file:PSEPK/PP_1084/PP_1084-uniprot.txt Plays a role in cell protection against oxidative stress |
| GO:0042744 hydrogen peroxide catabolic process | IEA GO_REF:0000118 | ACCEPT | Summary: Hydrogen peroxide catabolic process is directly supported by the peroxidase reaction described for TsaA. H2O2 is the best-supported, directly assayed substrate for the KT2440 protein per the falcon report. Reason: The UniProt function states that the enzyme reduces hydrogen peroxide to water, and KT2440 experiments directly assayed PP_1084/PpPrx against H2O2. Supporting Evidence: file:PSEPK/PP_1084/PP_1084-uniprot.txt Thiol-specific peroxidase that catalyzes the reduction of file:PSEPK/PP_1084/PP_1084-uniprot.txt Plays a role in cell protection against oxidative stress file:PSEPK/PP_1084/PP_1084-deep-research-falcon.md The best-supported primary substrate in KT2440 experiments is **H2O2**, with broader substrate scope (e.g., organic hydroperoxides, peroxynitrite) supported by strong family-level evidence for typical 2-Cys peroxiredoxins PMID:21104173 PpPrx exhibited low H2O2catabolic peroxidase activity (Fig.2D), substantially lower than that of yeast Trx-dependent Prx (yTPx), but PpPrx exhibited five times higher the chaperone activity than yTPx, used as a positive control. |
| GO:0045454 cell redox homeostasis | IEA GO_REF:0000118 | KEEP AS NON CORE | Summary: Cell redox homeostasis is consistent with peroxiredoxin function but broader than direct peroxide detoxification. The falcon report notes the thioredoxin system primarily guides the redox-dependent structural/functional switching of PP_1084. Reason: Retain as a supported non-core process because peroxide reduction contributes to redox balance. Supporting Evidence: file:PSEPK/PP_1084/PP_1084-uniprot.txt Thiol-specific peroxidase that catalyzes the reduction of file:PSEPK/PP_1084/PP_1084-uniprot.txt Plays a role in cell protection against oxidative stress file:PSEPK/PP_1084/PP_1084-deep-research-falcon.md Exposure to **H2O2** drives structural changes and a corresponding functional switch, and the thioredoxin system is described as a primary guide of this switching behavior |
| GO:0051920 peroxiredoxin activity | IEA GO_REF:0000002 | MODIFY | Summary: Peroxiredoxin activity is correct for this typical 2-Cys AhpC/Prx1-family protein but is less specific than the thioredoxin-dependent peroxidase activity directly shown for PpPrx, which the gene already carries as GO:0008379. Reason: PMID:21104173 measured PpPrx (PP1084) peroxidase activity with a yeast thioredoxin/thioredoxin reductase system and describes the LMW form as a Trx-dependent peroxidase. AhpC family membership (PIRSF000239) and the PIRSR-predicted peroxidatic cysteine (Cys51) are consistent. GO:0008379 thioredoxin peroxidase activity is a descendant of GO:0051920 and is accepted elsewhere in this review, so the general term is refined to it. The ARBA-only UniProt function and similarity lines are not used. Proposed replacements: thioredoxin peroxidase activity Supporting Evidence: PMID:21104173 Our genetic and biochemical studies revealed that PpPrx can act alternately as a Trx-dependent peroxidase and as a molecular chaperone. PMID:21104173 The LMW PpPrx function acts as a Trx-dependent peroxidase that catalyzes the removal of H2O2. file:PSEPK/PP_1084/PP_1084-uniprot.txt DR PIRSF; PIRSF000239; AHPC; 1. file:PSEPK/PP_1084/PP_1084-uniprot.txt Cysteine sulfenic acid (-SOH) intermediate; for |
| GO:0098869 cellular oxidant detoxification | IEA GO_REF:0000120 | ACCEPT | Summary: Cellular oxidant detoxification captures the biological process consequence of peroxide reduction by PpPrx, which the KT2440 study shows removes H2O2 as a thioredoxin-dependent peroxidase. Reason: PMID:21104173 shows that PpPrx (PP1084) reduces H2O2 with a thioredoxin system in vitro and that, in KT2440 cells exposed to H2O2, the thioredoxin system converts HMW PpPrx to the LMW peroxidase form that removes H2O2. This places the protein directly in intracellular peroxide detoxification. Organic hydroperoxide reduction rests only on the ARBA-backed UniProt function line and is not claimed here. Supporting Evidence: PMID:21104173 The LMW PpPrx function acts as a Trx-dependent peroxidase that catalyzes the removal of H2O2. PMID:21104173 In the H2O2-sensitive pathway, most HMW complexes are converted to LMW forms by the Trx system in vivo to remove the oxidative stress of H2O2. |
| GO:0042802 identical protein binding | IPI PMID:26278368 An additional cysteine in a typical 2-Cys peroxiredoxin of P... | KEEP AS NON CORE | Summary: Identical protein binding is supported by the IntAct self-interaction record and reflects the homo-oligomerization that is mechanistically central to TsaA/PpPrx function. The falcon report and PMID:26278368 show PP_1084/PpPrx self-associates into high-molecular-weight (HMW, chaperone-active) and low-molecular-weight (LMW, peroxidase-active) forms, so self-association underpins the redox-dependent peroxidase/chaperone switch. Reason: Retain as non-core self-association evidence; while peripheral to the catalytic chemistry itself, the homo-oligomerization it captures drives the functional switching between peroxidase and chaperone states. Supporting Evidence: file:PSEPK/PP_1084/PP_1084-uniprot.txt Q88NW9; Q88NW9: tsaA; NbExp=4 PMID:26278368 PpPrx and PaPrx can alternatively function as a peroxidase and chaperone file:PSEPK/PP_1084/PP_1084-deep-research-falcon.md PP_1084/PpPrx self-associates into high-molecular-weight (HMW) complexes and lower-molecular-weight (LMW) species |
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Download this section (compressed HTML)Q: Under which physiological oxidative-stress conditions in KT2440 does TsaA/PpPrx shift between the HMW chaperone-active and LMW peroxidase-active oligomeric states, and what is the in vivo balance of these two functions?
Suggested experts: Bacterial oxidative stress experts
Q: Does KT2440 TsaA reduce organic hydroperoxides and peroxynitrite in addition to H2O2, as predicted from AhpC/Prx1 subfamily membership?
Suggested experts: Peroxiredoxin enzymology experts
Experiment: Measure peroxide-reduction kinetics (H2O2 and organic hydroperoxides) and oligomeric state changes for purified TsaA under peroxide and thioredoxin/thioredoxin-reductase conditions, using size-exclusion chromatography to resolve HMW versus LMW species.
Type: redox enzyme assay
Experiment: Assess molecular chaperone (holdase) activity of purified TsaA by thermal- and chemical-aggregation suppression assays with model substrates, correlating activity with oligomeric state and redox conditions.
Type: chaperone aggregation-suppression assay
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