| Functional aspect | Key findings | Representative evidence with year and URL |
|---|---|---|
| Identity / aliases | • **TSA1 / YML028W** in *Saccharomyces cerevisiae* encodes the **major cytosolic typical 2-Cys peroxiredoxin**  • Historical aliases include **thiol-specific antioxidant protein 1**, **thioredoxin peroxidase**, and **cytoplasmic thiol peroxidase**  • Orthologous to mammalian **PRDX1/Prdx1-like** enzymes (pqac-00000017, pqac-00000018, pqac-00000020) | **2018** West et al., *Antioxidants* — https://doi.org/10.3390/antiox7120177 (pqac-00000018) ; **2017** Santos et al. — https://doi.org/10.5772/intechopen.70401 (pqac-00000017) |
| Enzymatic reaction | • Functions as a **thioredoxin-dependent peroxidase** reducing **H2O2 and hydroperoxides** to water/alcohol  • Peroxidatic Cys attacks peroxide, forming **Cys-SOH**; typical 2-Cys cycle proceeds via inter-subunit disulfide  • Peroxiredoxins can remove **>90% of cytosolic/cellular hydroperoxides** because of high abundance and fast kinetics (~10^6–10^8 M^-1 s^-1 for Prxs generally) (pqac-00000017, pqac-00000018, pqac-00000019) | **2018** West et al. — https://doi.org/10.3390/antiox7120177 (pqac-00000018) ; **2017** Santos et al. — https://doi.org/10.5772/intechopen.70401 (pqac-00000017) ; **2023** Seisenbacher et al. — https://doi.org/10.1101/2023.12.13.571451 (pqac-00000019) |
| Catalytic residues | • **Cys48** is the **peroxidatic cysteine (CP)**; **Cys171** is the **resolving cysteine (CR)**  • C48 is essential for peroxide reaction, H2O2 resistance, and many redox-regulatory outputs  • Hyperoxidation of C48 to sulfinic/sulfonic states inactivates peroxidase function and promotes noncanonical activities (pqac-00000016, pqac-00000018, pqac-00000021) | **2017** Hanzén thesis — no URL available in source set (pqac-00000016) ; **2018** West et al. — https://doi.org/10.3390/antiox7120177 (pqac-00000018) ; **2023** Seisenbacher et al. — https://doi.org/10.1101/2023.12.13.571451 (pqac-00000021) |
| Redox cycle partners | • Oxidized Tsa1 disulfide is reduced by **thioredoxins Trx1/Trx2**; oxidized thioredoxin is recycled by **thioredoxin reductase (Trr)** using **NADPH**  • Tsa1 is a major substrate of the cytosolic thioredoxin system  • Thioredoxins also directly resolve Tsa1 mixed-disulfide adducts with client proteins (pqac-00000018, pqac-00000021, pqac-00000022) | **2018** West et al. — https://doi.org/10.3390/antiox7120177 (pqac-00000018) ; **2023** Seisenbacher et al. — https://doi.org/10.1101/2023.12.13.571451 (pqac-00000021) |
| Localization | • Tsa1 is the **major cytosolic** peroxiredoxin in budding yeast  • Also reported as present **associated with translating ribosomes** in addition to free cytosolic pool  • Cytosolic abundance estimated at **~10–50 µM** and about **~1% of cytosolic protein** (pqac-00000016, pqac-00000018, pqac-00000020) | **2018** West et al. — https://doi.org/10.3390/antiox7120177 (pqac-00000018) ; **2016** Hanzén et al., *Cell* — https://doi.org/10.1016/j.cell.2016.05.006 (pqac-00000020) |
| Redox signaling targets / pathways | • Tsa1 mediates **redox repression of Ras–cAMP–PKA signaling**, not just peroxide detoxification  • Promotes oxidative modification of **PKA catalytic subunits**; **Cys243** redox control blocks **Thr241** activation-loop phosphorylation  • This mechanism explains improved **H2O2 resistance** and longevity control beyond scavenging alone (pqac-00000008, pqac-00000009, pqac-00000010) | **2020** Roger et al., *eLife* — https://doi.org/10.7554/elife.60346 (pqac-00000008) ; **2019 preprint data underlying 2020 paper** — https://doi.org/10.1101/676270 (pqac-00000010) |
| Proteostasis / chaperone switch | • Hyperoxidized Tsa1 forms higher-order assemblies and switches from peroxidase to **molecular chaperone / holdase**  • Recruits **Hsp70 (Ssa1/2)** and **Hsp104** to oxidatively damaged aggregates; Tsa1 appears early at aggregates  • Mild Tsa1 overexpression extends lifespan by **~40%** in yeast; Tsa1 overproduction lowers age-related aggregate burden without increasing scavenging (pqac-00000004, pqac-00000008, pqac-00000014, pqac-00000015) | **2016** Hanzén et al., *Cell* — https://doi.org/10.1016/j.cell.2016.05.006 (pqac-00000014) ; **2020** Roger et al., *eLife* — https://doi.org/10.7554/elife.60346 (pqac-00000008) |
| Genome stability / rDNA | • **tsa1Δ** cells show a **~5–10-fold increase in mutation rates**, establishing Tsa1 as a major anti-mutator oxidant-defense factor  • Tsa1 suppresses genome instability partly through C48-dependent functions; full canonical peroxidase activity may not be strictly required for mutation suppression  • **2024** work links Tsa1 to **rDNA stability**: tsa1Δ causes reduced rDNA origin firing, increased recombination, increased E-pro transcription, and shortened lifespan; many defects are suppressed by **fob1** mutation (pqac-00000005, pqac-00000003, pqac-00000012) | **2018** West et al. — https://doi.org/10.3390/antiox7120177 (pqac-00000005) ; **2024** Ohira et al. — https://doi.org/10.1101/2024.03.14.585068 (pqac-00000012) |
| Peroxiredoxinylation | • **2023–2024 priority finding:** Tsa1 forms widespread **Tsa1-induced mixed disulfide intermediates (TIMDIs)** with client proteins; authors term this **peroxiredoxinylation**  • TIMDIs rise to **>20% of the Tsa1 pool** under low H2O2 stress and up to **~60%** in **trx1Δ trx2Δ** cells  • Proteomics identified **211 WT** interactors and **599 C171S** interactors; validated targets include **Cdc19** and **Gnd1**; Y78A reduces TIMDI formation (pqac-00000006, pqac-00000021, pqac-00000025, pqac-00000026, pqac-00000027) | **2023** Seisenbacher et al. — https://doi.org/10.1101/2023.12.13.571451 (pqac-00000006) ; **2023** same study, mechanistic/quantitative pages (pqac-00000021, pqac-00000026) |
| Industrial / real-world applications | • In wine and biomass-propagation strains, **TSA1 deletion alters trehalose/glycogen metabolism**, stress performance, and fermentation-associated outputs  • tsa1Δ reduces growth in **molasses** and lowers **fermentative capacity**; it also changes acetic acid/acetaldehyde production  • These data support Tsa1 as a target for optimizing **industrial yeast robustness**, stress tolerance, and biomass production (pqac-00000011) | **2020** Garrigós et al., *Microorganisms* — https://doi.org/10.3390/microorganisms8101537 (pqac-00000011) |


*Table: This table summarizes the main experimentally supported functional annotation points for yeast TSA1/P34760, emphasizing enzymatic mechanism, localization, signaling, proteostasis, genome stability, and recent 2023–2024 developments. It is useful as a compact evidence map for downstream gene-function annotation.*