tsaA

UniProt ID: Q88NW9
Organism: Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440)
Review Status: COMPLETE
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Gene Description

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).

Proposed New Ontology Terms

holdase chaperone activity

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:

Existing Annotations Review

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 directly supported by the UniProt subcellular-location statement and corroborated by a PSORTb cytoplasmic prediction for KT2440 PP_1084 in the falcon report.
Reason: The protein is annotated as cytoplasmic and has no evidence for another compartment; a PSORTb prediction independently places PP_1084/PpPrx in the cytoplasm.
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: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 		MARK AS OVER ANNOTATED
Summary: Cellular response to stress is too broad for an enzyme whose direct role is peroxide reduction.
Reason: Use peroxide detoxification and oxidative-stress annotations rather than this generic stress-response process.
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 		ACCEPT
Summary: Peroxiredoxin activity is a specific and supported molecular function for this AhpC/Prx1-family protein. The falcon report confirms the directly studied KT2440 protein PP_1084 (PpPrx) is a 21 kDa AhpC/Tsa-family typical 2-Cys peroxiredoxin, matching the UniProt subfamily assignment.
Reason: UniProt identifies the protein as a thioredoxin peroxidase/peroxiredoxin family member that reduces peroxides, and the KT2440-specific study confirms typical 2-Cys peroxiredoxin classification.
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-uniprot.txt
Belongs to the peroxiredoxin family
file:PSEPK/PP_1084/PP_1084-deep-research-falcon.md
identifying it as a **21 kDa AhpC/Tsa family peroxiredoxin** (typical 2-Cys), which aligns with the UniProt description and subfamily assignment
GO:0098869 cellular oxidant detoxification
IEA
GO_REF:0000120 		ACCEPT
Summary: Cellular oxidant detoxification captures the biological process consequence of peroxide reduction. The falcon report documents that in KT2440 the protein was found among disulfide-bonded proteins enriched after oxidative treatments and detoxifies intracellular peroxides.
Reason: The protein detoxifies hydrogen peroxide and organic hydroperoxides, protecting cells from oxidative stress, and KT2440 evidence directly links it to intracellular peroxide detoxification.
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: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

Core Functions

Redox-dependent in-situ holdase activity. PpPrx high-molecular-weight oligomers suppress thermal aggregation of malate dehydrogenase and citrate synthase without detectable foldase activity. The HMW fraction has substantially greater chaperone activity than the LMW fraction. GO has no term yet for this in-situ holdase activity (GO:0051082 is obsolete).

Molecular Function:
holdase chaperone activity (proposed)
Cellular Locations:
cytoplasm
Supporting Evidence:
  • PMID:21104173
    PpPrx suppressed the thermal aggregation of the model substrate MDH at 43°C in a concentration-dependent manner (Fig.2B). At a subunit molar ratio of PpPrx to MDH of 0.5 vs. 1, MDH aggregation was completely suppressed. PpPrx can also efficiently protect the thermal aggregation of CS (Fig.2C), suggesting that PpPrx can indeed act as an efficient molecular chaperone. However, foldase activity as another chaperone activity was not detected (data not shown).
  • PMID:21104173
    The HMW complex fraction (F-1) exhibited high chaperone activity about fivefold compare to LMW fraction (F-2) and total protein fraction (Fig.3E), indicating that the chaperone activity of PpPrx was significantly affected by the structural composition.

Thioredoxin-dependent peroxiredoxin activity in the lower-molecular-weight state, reducing hydrogen peroxide and contributing to cellular oxidant detoxification. Directly measured H2O2 peroxidase activity was lower than that of the yeast thioredoxin-dependent peroxiredoxin control, while UniProt additionally infers reduction of organic hydroperoxides. This is a core biochemical activity, but the available comparative assay does not establish that it is physiologically dominant.

Molecular Function:
thioredoxin peroxidase activity
Directly Involved In:
hydrogen peroxide catabolic process cellular oxidant detoxification
Cellular Locations:
cytoplasm
Supporting Evidence:
  • 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.
  • 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-uniprot.txt
    SUBCELLULAR LOCATION: Cytoplasm

References

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Suggested Questions for Experts

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

Suggested Experiments

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

Deep Research

Falcon

(PP_1084-deep-research-falcon.md)

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📚 Additional Documentation

Notes

(PP_1084-notes.md)

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