TSA1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Tsa1 is the major cytosolic peroxiredoxin of budding yeast; the cytosol is where it executes its peroxidase, redox-signaling and chaperone functions. Consistent with IDA evidence (PMID:18271751) and falcon synthesis. Reason: Core localization. Tsa1 is one of the most abundant cytosolic proteins and acts as the primary cytosolic peroxide sink. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000073874 · PANTHER:PTN000073874 SUPPORTS TRANSFER Current PTHR10681 PAINT places cytosol at this ancestral node. Its experimental seeds span bacterial, fungal, fly, mouse and human peroxiredoxins; SGD:S000004490 (TSA1) is itself a valid direct seed. Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md Tsa1 is repeatedly described as the major cytosolic peroxiredoxin in yeast.
GO:0006979 response to oxidative stress	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Response to oxidative stress is a true but high-level process for TSA1. The more specific child terms (cellular response to oxidative stress, hydrogen peroxide catabolic process) better capture the core function. Reason: Correct but general parent term; retained as non-core because more specific annotations represent the precise antioxidant function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000073874 · PANTHER:PTN000073874 SUPPORTS TRANSFER Current PTHR10681 PAINT places this broad stress-response term at the same ancestral peroxiredoxin node. The diverse experimental seed set includes TSA1 and its yeast paralog TSA2, so transfer is sound but less informative than the peroxide-specific processes. Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md Tsa1 reduces H2O2 and organic hydroperoxides; in typical 2‑Cys Prxs this occurs via CP attack on the peroxide bond, generating water/alcohol products.
GO:0008379 thioredoxin peroxidase activity	IBA GO_REF:0000033	ACCEPT	Summary: Core molecular function. Tsa1 is a thioredoxin-dependent peroxidase that reduces H2O2 and organic hydroperoxides via the typical 2-Cys peroxiredoxin cycle (peroxidatic Cys48, resolving Cys171), with the disulfide reduced by thioredoxin (Trx1/Trx2). Directly supported by IDA evidence (PMID:7961686). Reason: Defining enzymatic activity of TSA1, well supported across phylogenetic inference, biochemistry and structural data. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000073874 · PANTHER:PTN000073874 SUPPORTS TRANSFER Current PTHR10681 PAINT retains thioredoxin peroxidase activity at this node. The seed set includes TSA1, TSA2, fission-yeast Tpx1 and experimentally characterized metazoan/protist peroxiredoxins; TSA1's own biochemical evidence correctly grounds the ancestral assertion. Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md Tsa1’s primary biochemical role is as a thioredoxin-dependent peroxidase that reduces peroxides (especially H2O2) via the typical 2‑Cys Prx redox cycle centered on Cys48/Cys171.
GO:0042744 hydrogen peroxide catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Core biological process. As the major abundant cytosolic peroxiredoxin, Tsa1 is responsible for decomposing the bulk of cellular H2O2. Reason: Direct downstream process of the peroxidase activity; central to TSA1 function. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000073874 · PANTHER:PTN000073874 SUPPORTS TRANSFER Current PTHR10681 PAINT retains hydrogen peroxide catabolism at this node using broad experimental support across peroxiredoxins. TSA1 is not listed as a seed for this particular call, but its conserved catalytic mechanism and direct assays independently support transfer. Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md Reviews also emphasize that Prxs decompose >90% of cellular hydroperoxides and can detoxify up to ~90% of cytosolic H2O2 due to abundance and fast reaction rates (general Prx second-order rates ~10^6–10^8 M−1 s−1).
GO:0045454 cell redox homeostasis	IBA GO_REF:0000033	ACCEPT	Summary: Core process. Beyond peroxide scavenging, Tsa1 buffers the redox state of the proteome by forming and resolving mixed disulfides with client proteins (via thioredoxin), maintaining cellular thiol redox balance. Reason: Well supported as a core function; Tsa1 is a central node of the cytosolic thioredoxin-peroxiredoxin redox network. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000073874 · PANTHER:PTN000073874 SUPPORTS TRANSFER Current PTHR10681 PAINT retains cell redox homeostasis at this node. The GOA seed identifiers for the two Arabidopsis loci use older TAIR syntax than current PAINT, but the node and biological evidence are unchanged; TSA1 is also an experimental seed. Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md This provides a mechanistic route for Tsa1 to act not only as a sink for H2O2 but also as a regulator/buffer of protein thiol redox state.
GO:0098869 cellular oxidant detoxification	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: This combined IEA parent term is correct because TSA1 enzymatically removes hydroperoxides. Reason: Retained as a broad non-core parent of the more precise hydrogen peroxide catabolism annotation.
GO:0004601 peroxidase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Peroxidase activity is correct but is a general parent of the more specific thioredoxin-dependent peroxiredoxin activity that defines TSA1. Reason: True but general; the specific term thioredoxin-dependent peroxiredoxin activity (GO:0140824) better represents the core function. (Note: GO_REF:0000043 SPKW keyword annotations are being retired upstream.) Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md Tsa1’s primary biochemical role is as a thioredoxin-dependent peroxidase that reduces peroxides (especially H2O2) via the typical 2‑Cys Prx redox cycle centered on Cys48/Cys171.
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: UniProt subcellular-location mapping agrees with multiple direct cytosol/cytoplasm experiments. Reason: Correct core localization; GO:0005829 cytosol supplies the more precise child term.
GO:0008379 thioredoxin peroxidase activity	IEA GO_REF:0000117	ACCEPT	Summary: The ARBA prediction matches TSA1's directly measured thioredoxin-dependent peroxide reductase activity. Reason: Correct core molecular function, independently grounded by PMID:7961686.
GO:0016209 antioxidant activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: InterPro/keyword mapping correctly captures TSA1's antioxidant role but is less specific than peroxiredoxin activity. Reason: Broad umbrella activity retained as non-core because catalytic child terms are available.
GO:0016491 oxidoreductase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Oxidoreductase activity is chemically correct but very broad for a characterized thioredoxin-dependent peroxiredoxin. Reason: Retain as a non-core parent rather than obscuring the precise catalytic function.
GO:0034599 cellular response to oxidative stress	IEA GO_REF:0000117	ACCEPT	Summary: Core process. Tsa1 is the principal cytosolic effector of the cellular response to oxidative stress, both detoxifying peroxides and relaying H2O2 signals (e.g. to Yap1 and via redox modulation of PKA). Also supported by multiple IDA/IMP annotations. Reason: Central process for TSA1; redundantly supported by experimental evidence. Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md A major mechanistic insight from authoritative work is that Tsa1’s contribution to stress resistance and longevity can occur not simply by scavenging H2O2, but through redox modulation of nutrient signaling.
GO:0034605 cellular response to heat	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Tsa1 contributes to the heat-stress response via its chaperone/holdase switch: heat shock drives formation of high-MW oligomers that bind misfolded proteins and enhance heat-shock resistance (PMID:15163410). Reason: Genuine but downstream of the chaperone moonlighting function; the holdase MF and protein folding process capture the mechanism more directly. Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md At higher oxidant loads, Tsa1’s peroxidatic cysteine can become hyperoxidized (sulfinic/sulfonic states), which inactivates peroxidase activity and promotes formation of higher-order oligomers associated with molecular chaperone/holdase activity.
GO:0045454 cell redox homeostasis	IEA GO_REF:0000117	ACCEPT	Summary: ARBA inference is concordant with extensive direct evidence for TSA1-dependent peroxide/redox control. Reason: Correct core process of the thioredoxin-peroxiredoxin system.
GO:0050821 protein stabilization	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA captures the aggregation-prevention consequence of TSA1's stress-activated chaperone state. Reason: Correct but less mechanistically informative than protein folding chaperone activity.
GO:0051920 peroxiredoxin activity	IEA GO_REF:0000002	ACCEPT	Summary: Peroxiredoxin activity is correct for TSA1, the major 2-Cys peroxiredoxin of yeast. The thioredoxin-dependent child term (GO:0140824) is the most precise MF. Reason: Accurate MF supported by domain/family (AhpC/Prx1) inference and direct biochemistry. Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md The research target is the budding yeast (Saccharomyces cerevisiae) protein Tsa1, consistently described across primary and review sources as the major cytosolic typical 2‑Cys peroxiredoxin (Prx) with canonical active-site cysteines Cys48 (peroxidatic, CP) and Cys171 (resolving, CR).
GO:0140824 thioredoxin-dependent peroxiredoxin activity	IEA GO_REF:0000120	ACCEPT	Summary: This is the most precise molecular function term for TSA1: catalysis of hydroperoxide reduction using thioredoxin as the electron donor. Matches the experimentally characterized thioredoxin-coupled peroxidase activity (PMID:7961686, PMID:9888818) and is selected as the core MF. Reason: Most specific and accurate MF term; designated the core molecular function. Supporting Evidence: PMID:9888818 Kinetic characterization of the reactions catalyzed by type I and II TPxs revealed that type I preferentially reduces H2O2 rather than alkyl hydroperoxides, whereas type II shows the reverse specificity. file:yeast/TSA1/TSA1-deep-research-falcon.md Reduction of oxidized Tsa1 is primarily driven by the cytosolic thioredoxin system: Trx1/Trx2 reduce the Tsa1 disulfide, and oxidized thioredoxin is recycled by thioredoxin reductase using NADPH.
GO:0005515 protein binding	IPI PMID:16272220 A yeast two-hybrid knockout strain to explore thioredoxin-in...	MARK AS OVER ANNOTATED	Summary: The yeast two-hybrid study directly detected TSA1 as a thioredoxin target; GOA identifies the partner as TRX2 (P22803). This validates the physical interaction but not generic protein binding as a useful function. Reason: Uninformative generic binding term; the underlying interactions reflect redox-relay/chaperone biology better described by specific MF terms. Supporting Evidence: PMID:16272220 We demonstrate here that, in the CY306 strain, yeast TRX1 and TRX2, as well as Arabidopsis TRX introduced as bait, interact with known TRX targets or putative partners such as yeast peroxiredoxins AHP1 and TSA1, whereas the same interactions cannot be detected in classical Y2H strains.
GO:0005515 protein binding	IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom...	MARK AS OVER ANNOTATED	Summary: The high-throughput complex map reports association with TSA2 (Q04120), consistent with peroxiredoxin oligomerization, but GO:0005515 does not distinguish this structural association from TSA1's catalytic activity. Reason: Retain the interaction evidence while flagging the generic binding term as mechanistically uninformative.
GO:0005515 protein binding	IPI PMID:18719252 High-quality binary protein interaction map of the yeast int...	MARK AS OVER ANNOTATED	Summary: This binary-interactome row also records TSA2 (Q04120) as partner. The interaction can be valid while the generic binding MF remains unsuitable as a representation of TSA1's evolved function. Reason: Preserve the experimental interaction but do not elevate generic protein binding to a core function.
GO:0005515 protein binding	IPI PMID:37968396 The social and structural architecture of the yeast protein ...	MARK AS OVER ANNOTATED	Summary: Two physical GOA rows collapse to this signature, with TRX2 (P22803) and TSA2 (Q04120) as distinct partners. Both are biologically plausible, but GO:0005515 obscures the redox-cycle and oligomerization mechanisms. Reason: Retain both physical observations while treating the generic MF as over-annotated.
GO:0019207 kinase regulator activity	IMP PMID:27634403 Redox-dependent Regulation of Gluconeogenesis by a Novel Mec...	KEEP AS NON CORE	Summary: Tsa1 directly regulates the metabolic kinase Pyk1 (pyruvate kinase / Cdc19): it physically interacts with and suppresses Pyk1 activity via a peroxidatic-cysteine (Cys48)-dependent mechanism, and these interactions are augmented during the glycolysis-to-gluconeogenesis shift (PMID:27634403, Irokawa et al. 2016). This is a genuine but specialized, non-peroxidase target-modulator role distinct from the core peroxidase function. (Note: a separate, mechanistically distinct redox repression of the Ras-cAMP-PKA pathway is reported in Roger et al. 2020, eLife, which is not part of this GOA annotation.) Reason: Real direct kinase-regulation function (suppression of pyruvate kinase Pyk1), but peripheral to the core antioxidant/chaperone activities. Supporting Evidence: PMID:27634403 We found that the suppression of pyruvate kinase (Pyk1) via the interaction with Tsa1 contributes in part to gluconeogenic enhancement. PMID:27634403 a peroxidatic cysteine in the catalytic center of Tsa1 played an important role in the physical Tsa1-Pyk1 interactions.
GO:0005737 cytoplasm	HDA PMID:22842922 Dissecting DNA damage response pathways by analysing protein...	ACCEPT	Summary: Cytoplasmic localization, consistent with Tsa1 being the major cytosolic peroxiredoxin. Redundant with more precise cytosol (GO:0005829) annotations. Reason: Correct localization; the cytosol child term is preferred but cytoplasm is accurate. Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md Tsa1 is repeatedly described as the major cytosolic peroxiredoxin in yeast.
GO:0006111 regulation of gluconeogenesis	IMP PMID:27634403 Redox-dependent Regulation of Gluconeogenesis by a Novel Mec...	KEEP AS NON CORE	Summary: Tsa1 promotes efficient gluconeogenic flux via a direct, peroxidatic-cysteine (Cys48)-dependent physical interaction with and suppression of pyruvate kinase (Pyk1); the Tsa1-Pyk1 interaction is augmented during the glycolysis-to-gluconeogenesis shift (PMID:27634403, Irokawa et al. 2016). A specialized, context-specific metabolic output rather than a core function. Reason: Genuine but peripheral metabolic regulation arising from direct suppression of pyruvate kinase (Pyk1), not from PKA redox signaling. Supporting Evidence: PMID:27634403 we discovered that Tsa1, a major peroxiredoxin of budding yeast cells, is required for the efficient flux of gluconeogenesis. PMID:27634403 We found that the suppression of pyruvate kinase (Pyk1) via the interaction with Tsa1 contributes in part to gluconeogenic enhancement.
GO:0006457 protein folding	IDA PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	ACCEPT	Summary: Core moonlighting process. Upon oxidative/heat stress Tsa1 switches to a high-MW chaperone (holdase) that assists protein folding/prevents aggregation (PMID:15163410). Selected as one of the core functions. Reason: Well-supported chaperone function central to TSA1's dual-function biology. Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md At higher oxidant loads, Tsa1’s peroxidatic cysteine can become hyperoxidized (sulfinic/sulfonic states), which inactivates peroxidase activity and promotes formation of higher-order oligomers associated with molecular chaperone/holdase activity.
GO:0006457 protein folding	IMP PMID:16251355 The thioredoxin system protects ribosomes against stress-ind...	ACCEPT	Summary: tsa1 deletion causes accumulation of aggregated, predominantly ribosomal proteins, and the cached abstract attributes protection to Tsa1's chaperone rather than peroxidase function (PMID:16251355). Reason: Direct genetic evidence supports a core role in protein-folding proteostasis.
GO:0034599 cellular response to oxidative stress	IDA PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	ACCEPT	Summary: The paper directly shows oxidative stress drives Tsa1's structural and functional switch (PMID:15163410). Reason: Oxidative stress is both substrate context for peroxidase activity and trigger for the chaperone switch.
GO:0034605 cellular response to heat	IDA PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	KEEP AS NON CORE	Summary: Heat shock induces high-MW chaperone complexes and Tsa1 enhances heat resistance (PMID:15163410). Reason: Correct stress context, but secondary to the molecular chaperone function it elicits.
GO:0051082 unfolded protein binding	IDA PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	MODIFY	Summary: The paper directly demonstrates a stress-induced peroxiredoxin-to-chaperone switch. GO:0051082 is now obsolete; GO:0044183 accurately captures binding that assists protein folding, whereas GO:0140309 is inappropriate because Tsa1 prevents aggregation in situ and does not escort clients to a destination. Reason: Replace the obsolete binding term with protein folding chaperone. The experimental annotation is not rejected: its underlying chaperone/holdase biology is sound and is represented by the current activity term. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:15163410 We show here that two cytosolic yeast Prxs, cPrxI and II, which display diversity in structure and apparent molecular weights (MW), can act alternatively as peroxidases and molecular chaperones.
GO:0072721 cellular response to dithiothreitol	IMP PMID:16251355 The thioredoxin system protects ribosomes against stress-ind...	KEEP AS NON CORE	Summary: tsa1 mutants are DTT-sensitive and accumulate ribosomal-protein aggregates under DTT stress (PMID:16251355). Reason: Experimentally supported reductive-stress context, not a defining core function.
GO:0006457 protein folding	IMP PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	ACCEPT	Summary: High-MW Tsa1 complexes display molecular-chaperone activity during oxidative or heat stress (PMID:15163410). Reason: This CAFA-assigned IMP signature is biologically consistent with the paper's direct chaperone evidence.
GO:0008379 thioredoxin peroxidase activity	IMP PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	ACCEPT	Summary: The paper demonstrates the low-MW Tsa1 state is the peroxidase-dominant form (PMID:15163410). Reason: Core catalytic activity independently established by direct biochemical studies.
GO:0034605 cellular response to heat	IMP PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	KEEP AS NON CORE	Summary: Heat shock triggers the peroxidase-to-chaperone switch and Tsa1-dependent resistance (PMID:15163410). Reason: Valid contextual phenotype, subordinate to the core chaperone activity.
GO:0042802 identical protein binding	IMP PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	MARK AS OVER ANNOTATED	Summary: Tsa1 forms high-MW homo-oligomeric assemblies during the stress-induced chaperone switch, but the generic binding term does not express that mechanism. Reason: Oligomerization is real, yet this generic MF binding term and its IMP assignment do not capture the chaperone switch. The corresponding GO:0051258 protein polymerization BP is retained as non-core because it directly describes formation of the high-MW assembly, whereas GO:0042802 only restates that identical subunits contact one another.
GO:0045454 cell redox homeostasis	IMP PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	ACCEPT	Summary: Tsa1's peroxide-sensing catalytic cysteine couples redox state to a reversible functional switch (PMID:15163410). Reason: Consistent with TSA1's core role in the thioredoxin-peroxiredoxin redox network.
GO:0050821 protein stabilization	IMP PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	KEEP AS NON CORE	Summary: The stress-induced high-MW chaperone state stabilizes aggregation-prone proteins (PMID:15163410). Reason: Valid downstream consequence of holdase activity, but less mechanistically specific.
GO:0051082 unfolded protein binding	IMP PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	MODIFY	Summary: The genetic evidence supports Tsa1's aggregation-preventing chaperone role, but GO:0051082 is obsolete. GO:0044183 is the current evidence-matched activity term; GO:0140309 would incorrectly imply carrier-mediated escort. Reason: Preserve the experimentally supported chaperone biology while replacing the obsolete binding term with protein folding chaperone. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:15163410 The chaperone function of these proteins enhances yeast resistance to heat shock.
GO:0051258 protein polymerization	IMP PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	KEEP AS NON CORE	Summary: Oxidative stress and heat drive formation of high-MW Tsa1 complexes (PMID:15163410). Reason: Describes the regulatory oligomerization state rather than TSA1's core catalytic or chaperone activity.
GO:0071447 cellular response to hydroperoxide	IMP PMID:15163410 Two enzymes in one; two yeast peroxiredoxins display oxidati...	KEEP AS NON CORE	Summary: The peroxidatic cysteine acts as an H2O2 sensor that drives Tsa1's stress-dependent switch (PMID:15163410). Reason: Correct peroxide-specific stress response, but subordinate to peroxidase and chaperone functions.
GO:0006457 protein folding	IMP PMID:24022485 Peroxiredoxin chaperone activity is critical for protein hom...	ACCEPT	Summary: A chaperone-only Tsa1 allele rescues zinc-deficient growth, and holdase overexpression phenocopies rescue (PMID:24022485 abstract). Reason: Direct physiological genetic evidence supports the core chaperone/proteostasis role.
GO:0000077 DNA damage checkpoint signaling	IGI PMID:19851444 Loss of yeast peroxiredoxin Tsa1p induces genome instability...	KEEP AS NON CORE	Summary: tsa1 loss activates the DNA-damage checkpoint and alters dNTP homeostasis (PMID:19851444). Reason: Valid downstream consequence of genome instability, not a direct checkpoint activity of Tsa1.
GO:0005737 cytoplasm	IDA PMID:10681558 Distinct physiological functions of thiol peroxidase isoenzy...	ACCEPT	Summary: The isoenzyme study explicitly identifies TSA1/cTPxI as a cytoplasmic thiol peroxidase (PMID:10681558). Reason: Direct localization evidence supports the core cytoplasmic compartment.
GO:0005737 cytoplasm	IDA PMID:8344960 Cloning, sequencing, and mutation of thiol-specific antioxid...	ACCEPT	Summary: Cytosolic and mitochondrial fractionation identifies TSA1 as cytosolic (PMID:8344960). Reason: Direct experimental localization agrees with UniProt and the cytosol IBA.
GO:0005829 cytosol	IDA PMID:18271751 The yeast Tsa1 peroxiredoxin is a ribosome-associated antiox...	ACCEPT	Summary: Tsa1 is present in the cytosol and additionally associates with actively translating ribosomes (PMID:18271751). Reason: Core localization supported by direct fractionation/localization work.
GO:0008379 thioredoxin peroxidase activity	IDA PMID:7961686 Thioredoxin-dependent peroxide reductase from yeast.	ACCEPT	Summary: Purified TSA1 reduces H2O2 and alkyl hydroperoxides using thioredoxin, thioredoxin reductase and NADPH (PMID:7961686). Reason: Direct biochemical demonstration of TSA1's defining molecular function.
GO:0008379 thioredoxin peroxidase activity	IMP PMID:7961686 Thioredoxin-dependent peroxide reductase from yeast.	ACCEPT	Summary: Loss-of-function catalytic-cysteine analysis complements the purified-enzyme evidence for thioredoxin peroxidase activity (PMID:7961686). Reason: Mutant phenotype/mechanism supports the same core catalytic function.
GO:0008379 thioredoxin peroxidase activity	IDA PMID:9799566 Thermosensitive phenotype of yeast mutant lacking thioredoxi...	ACCEPT	Summary: The study characterizes TSA1 as an NADPH/thioredoxin-dependent peroxidase in cellular heat-stress defense (PMID:9799566). Reason: Experimental enzymology and phenotype support the core activity.
GO:0008379 thioredoxin peroxidase activity	IMP PMID:9799566 Thermosensitive phenotype of yeast mutant lacking thioredoxi...	ACCEPT	Summary: tsa1 disruption causes thermosensitivity and excess peroxide/protein oxidation, supporting its peroxidase role (PMID:9799566). Reason: Genetic evidence independently supports the core enzymatic function.
GO:0033194 response to hydroperoxide	IMP PMID:15210711 Cytosolic thioredoxin peroxidase I and II are important defe...	KEEP AS NON CORE	Summary: tsa1 deletion is sensitive to both organic hydroperoxide and H2O2, and purified Tsa1 removes both substrates (PMID:15210711). Reason: Correct general stress response, but less specific than peroxide catabolism and cellular response to oxidative stress.
GO:0034599 cellular response to oxidative stress	IGI PMID:15051715 Peroxiredoxin-null yeast cells are hypersensitive to oxidati...	ACCEPT	Summary: Peroxiredoxin-null cells are oxidant-sensitive, and TSA1 rescues the mutator phenotype in a catalytic-site-dependent manner (PMID:15051715). Reason: Direct genetic evidence supports TSA1 as a core oxidative-stress effector.
GO:0034599 cellular response to oxidative stress	IMP PMID:18271751 The yeast Tsa1 peroxiredoxin is a ribosome-associated antiox...	ACCEPT	Summary: Tsa1 protects cytosol and active ribosomes from endogenous ROS and shifts toward chaperone function under peroxide stress (PMID:18271751). Reason: Central experimentally supported oxidative-stress role.
GO:0034599 cellular response to oxidative stress	IDA PMID:8344960 Cloning, sequencing, and mutation of thiol-specific antioxid...	ACCEPT	Summary: tsa1 disruption impairs aerobic growth and peroxide resistance, demonstrating an antioxidant-stress role (PMID:8344960). Reason: Foundational direct evidence for TSA1's core oxidative-stress function.
GO:0034599 cellular response to oxidative stress	IMP PMID:8344960 Cloning, sequencing, and mutation of thiol-specific antioxid...	ACCEPT	Summary: The tsa1 mutant's oxidant-sensitive phenotype supports a required cellular response to oxidative stress (PMID:8344960). Reason: Core process directly linked to loss of TSA1.
GO:0042262 DNA protection	IMP PMID:19543365 Peroxiredoxin Tsa1 is the key peroxidase suppressing genome ...	KEEP AS NON CORE	Summary: Tsa1 is the strongest anti-mutator among yeast oxidant-defense genes; tsa1-null cells show a ~5-10-fold increased mutation rate and genome instability. This genome-protective role is partly peroxidase-dependent and partly via redox-network effects (e.g. thioredoxin/RNR), making it an important but non-core, indirect consequence of the antioxidant function. Reason: Well-documented but downstream/indirect protective effect rather than a direct molecular function of Tsa1 on DNA. Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md Yeast lacking TSA1 show a mutator phenotype, with reported ~5–10‑fold increased mutation rates, and Tsa1 is described as the strongest suppressor of mutations among oxidant-defense genes in yeast.
GO:0043022 ribosome binding	IDA PMID:18271751 The yeast Tsa1 peroxiredoxin is a ribosome-associated antiox...	KEEP AS NON CORE	Summary: Tsa1 associates with translating ribosomes, acting as a ribosome-associated antioxidant that protects nascent polypeptides from oxidative damage and misfolding (PMID:18271751). A specialized localization-linked function. Reason: Genuine ribosome-associated antioxidant role, but ancillary to the core cytosolic peroxidase/chaperone activities. Supporting Evidence: file:yeast/TSA1/TSA1-deep-research-falcon.md In addition to a free cytosolic pool, one source reports Tsa1 is also found associated with translating ribosomes, suggesting functional proximity to nascent polypeptides and translation-linked proteostasis.
GO:0045454 cell redox homeostasis	IDA PMID:8344960 Cloning, sequencing, and mutation of thiol-specific antioxid...	ACCEPT	Summary: TSA1 is a cytosolic thiol-specific antioxidant required for peroxide defense (PMID:8344960). Reason: Direct evidence is consistent with its core role in cellular redox homeostasis.
GO:0045454 cell redox homeostasis	IMP PMID:8344960 Cloning, sequencing, and mutation of thiol-specific antioxid...	ACCEPT	Summary: Disruption of TSA1 perturbs oxidant resistance, genetically supporting redox homeostasis (PMID:8344960). Reason: Core downstream process of the thioredoxin-dependent peroxidase reaction.
GO:0045454 cell redox homeostasis	IMP PMID:9799566 Thermosensitive phenotype of yeast mutant lacking thioredoxi...	ACCEPT	Summary: tsa1 mutants accumulate peroxide and oxidatively damaged proteins during heat stress (PMID:9799566). Reason: Genetic evidence supports the core redox-homeostasis process.
GO:0051082 unfolded protein binding	IMP PMID:16251355 The thioredoxin system protects ribosomes against stress-ind...	MODIFY	Summary: The cached abstract directly attributes aggregate prevention to Tsa1's chaperone function. Because GO:0051082 is obsolete, GO:0044183 is the best current activity term; the carrier-specific GO:0140309 does not fit. Reason: The experiment supports chaperone-assisted proteostasis, so retain the biological assertion through an evidence-matched same-aspect replacement. Proposed replacements: protein folding chaperone Supporting Evidence: PMID:16251355 We propose that Tsa1 normally functions to chaperone misassembled ribosomal proteins, preventing the toxicity that arises from their aggregation.
GO:0051920 peroxiredoxin activity	IDA PMID:17210445 Reactions of yeast thioredoxin peroxidases I and II with hyd...	ACCEPT	Summary: Competitive kinetics directly measure rapid Tsa1 reactions with H2O2 and peroxynitrite (PMID:17210445). Reason: Direct kinetic evidence supports peroxiredoxin activity as a core function.

Gene Description

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holdase chaperone activity

Existing Annotations Review

Core Functions

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