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Gene Review

TSA1  -  thioredoxin peroxidase TSA1

Saccharomyces cerevisiae S288c

Synonyms: Cytoplasmic thiol peroxidase 1, PRP, Peroxiredoxin TSA1, TPX1, TSA, ...
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Disease relevance of TSA1

  • The roles of Cys-47 and Cys-170 in yeast TSA were investigated by replacing them individually with serine and expressing the mutant TSA proteins (RC47S and RC170S, respectively), as well as wild-type TSA (RWT), in Escherichia coli [1].
  • We propose that Tsa1 normally functions to chaperone misassembled ribosomal proteins, preventing the toxicity that arises from their aggregation [2].
  • Except for the AhpC protein identified in Salmonella typhimurium, none of the TSA-like proteins is associated with known cellular functions [3].
  • Finally TSA medium supplemented with 0.05% yeast extract, 5% bovine blood, 0.01% DTT, 400 micrograms spectinomycin, and 250 micrograms/ml vancomycin, appeared to be optimal selective medium for intestinal Treponema sp. isolation [4].

Psychiatry related information on TSA1


High impact information on TSA1

  • We have analyzed the functions of several pre-mRNA processing (PRP) proteins in yeast spliceosome formation [6].
  • Defects in recombinational DNA double strand break repair, Rad6-mediated postreplicative repair, and DNA damage and replication checkpoints caused growth defects or lethality in the absence of Tsa1 [7].
  • In addition, the mutator phenotypes caused by a tsa1 mutation were significantly aggravated by defects in Ogg1, mismatch repair, or checkpoints [7].
  • Thiol-specific antioxidant (TSA) from yeast contains cysteine residues at amino acid positions 47 and 170 but is not associated with obvious redox cofactors [1].
  • The antioxidant activity of the various TSA proteins was evaluated from their ability to protect glutamine synthetase against the dithiothreitol/Fe3+/O2 oxidation system [1].

Chemical compound and disease context of TSA1


Biological context of TSA1


Anatomical context of TSA1

  • We report here that TSA1 confers resistance towards oxidative stress as well as is involved in the correct composition of hyphal cell walls [14].
  • However, when the functional state of the mitochondria was compromised, the necessity of TSA1 in cell protection against this oxidant was much more evident [15].
  • We have identified Tsa1p, a protein that is differentially localized to the cell wall of C. albicans in hyphal cells but remains in the cytosol and nucleus in yeast-form cells [14].
  • Human T cell cyclophilin18 binds to thiol-specific antioxidant protein Aop1 and stimulates its activity [16].
  • In contrast, S. cerevisiae spheroblasts lacking the TPx gene and/or treated with ATZ suffered a decrease in mitochondrial membrane potential, generated higher amounts of hydrogen peroxide and had decreased viability under these conditions [17].

Associations of TSA1 with chemical compounds

  • Therefore, de novo synthesis and recycling of glutathione were increased in the tsa1Delta mutant to maintain the catalytic cycle of glutathione peroxidase reaction efficiently as a backup system for thioredoxin peroxidase [18].
  • Unlike other TPx null mutants, cTPx I null mutant was hypersensitive to various oxidants except for 4-nitroquinoline N-oxide [12].
  • Cells lacking TSA1 were found to accumulate aggregated proteins, and this was exacerbated by exposure to DTT [2].
  • TPx exists as a dimer of identical 25-kDa subunits that contain 2 cysteine residues, Cys47 and Cys170 [19].
  • This 25-kDa protein acts as a peroxidase but requires a NADPH-dependent thioredoxin system or a thiol-containing intermediate, and was thus named thioredoxin peroxidase (TPx) [20].

Physical interactions of TSA1

  • The primary regulator of the PHR1 damage response is a 39-bp sequence called URS(PHR1) which is the binding site for a protein(s) that constitutes the damage-responsive repressor PRP [21].

Enzymatic interactions of TSA1

  • Conversely, loss of Srx1 prevents the reduction of oxidized Tpx1 and prolongs the inhibition of Pap1 activation [22].

Other interactions of TSA1

  • Here we report on the functional characterization of yeast tsa2Delta mutants and the comparison of TSA1 with TSA2 [10].
  • Similar to yeast Tsa1p, Ahp1p forms a disulfide-linked homodimer upon oxidation and in vivo requires the presence of the thioredoxin system but not of glutathione to perform its antioxidant protective function [13].
  • Taken together, these results suggest that cTPx II is a target of Msn2p/Msn4p transcription factors under negative control of the Ras-protein kinase A and target of rapamycin signaling pathways [11].
  • It has been suggested that both transcription-activating proteins, Yap1p and Skn7p, regulate the transcription of cTPx II upon exposure to oxidative stress [11].
  • Thus, Tsa1, a ubiquitous thioredoxin peroxidase, is required for the activation of Yap1 in yeast strain Y700, which is derived from W303 [23].

Analytical, diagnostic and therapeutic context of TSA1

  • Analysis of the transcriptional activity of site-directed mutagenesis of the putative STREs (STRE1 and STRE2) and YREs (TRE1 and YRE2) in terms of the activity of a lacZ reporter gene under control of the cTPx II promoter indicates that STRE2 acts as a principal binding element essential for transactivation of the cTPx II promoter [11].
  • We investigated the mechanism by which TSA protects biomolecules from oxidative damage caused by the thiol-containing oxidation system using the spin trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) [24].
  • Southern blot analysis of petite yeast DNA, studies with protein synthesis inhibitors, and protein immunoblot analyses of cytosolic and mitochondrial proteins suggest that TSA is a cytosolic protein encoded by nuclear DNA (chromosome XIII) [25].
  • The selective interaction of the dimer form of cTPx II (the oxidized form) with SFH2p was also confirmed by glutathione S-transferase pull-down and immunoprecipitation assays [26].
  • Radiolabeled orotidine 5'-phosphate (OMP), generated in situ from [7-(14)C]-orotate and alpha-d-5-phoshorylribose 1-diphosphate (PRPP), binds tightly enough to OPRTase (a dimer composed of identical subunits) that the complex survives gel-filtration chromatography [27].


  1. Dimerization of thiol-specific antioxidant and the essential role of cysteine 47. Chae, H.Z., Uhm, T.B., Rhee, S.G. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  2. The thioredoxin system protects ribosomes against stress-induced aggregation. Rand, J.D., Grant, C.M. Mol. Biol. Cell (2006) [Pubmed]
  3. A thiol-specific antioxidant and sequence homology to various proteins of unknown function. Chae, H.Z., Rhee, S.G. Biofactors (1994) [Pubmed]
  4. Evaluation of selective media for primary isolation of Treponema hyodysenteriae and Treponema innocens. Szynkiewicz, Z.M., Binek, M. Comp. Immunol. Microbiol. Infect. Dis. (1986) [Pubmed]
  5. Antioxidant defense mechanisms: a new thiol-specific antioxidant enzyme. Rhee, S.G., Kim, K.H., Chae, H.Z., Yim, M.B., Uchida, K., Netto, L.E., Stadtman, E.R. Ann. N. Y. Acad. Sci. (1994) [Pubmed]
  6. Four yeast spliceosomal proteins (PRP5, PRP9, PRP11, and PRP21) interact to promote U2 snRNP binding to pre-mRNA. Ruby, S.W., Chang, T.H., Abelson, J. Genes Dev. (1993) [Pubmed]
  7. A biological network in Saccharomyces cerevisiae prevents the deleterious effects of endogenous oxidative DNA damage. Huang, M.E., Kolodner, R.D. Mol. Cell (2005) [Pubmed]
  8. Yeast thioredoxin peroxidase expression enhances the resistance of Escherichia coli to oxidative stress induced by singlet oxygen. Kim, S.Y., Kim, E.J., Park, J.W. Redox Rep. (2002) [Pubmed]
  9. Possible function of SP-22, a substrate of mitochondrial ATP-dependent protease, as a radical scavenger. Watabe, S., Hasegawa, H., Takimoto, K., Yamamoto, Y., Takahashi, S.Y. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  10. Cooperation of yeast peroxiredoxins Tsa1p and Tsa2p in the cellular defense against oxidative and nitrosative stress. Wong, C.M., Zhou, Y., Ng, R.W., Kung Hf, H.F., Jin, D.Y. J. Biol. Chem. (2002) [Pubmed]
  11. Msn2p/Msn4p act as a key transcriptional activator of yeast cytoplasmic thiol peroxidase II. Hong, S.K., Cha, M.K., Choi, Y.S., Kim, W.C., Kim, I.H. J. Biol. Chem. (2002) [Pubmed]
  12. Distinct physiological functions of thiol peroxidase isoenzymes in Saccharomyces cerevisiae. Park, S.G., Cha, M.K., Jeong, W., Kim, I.H. J. Biol. Chem. (2000) [Pubmed]
  13. A new antioxidant with alkyl hydroperoxide defense properties in yeast. Lee, J., Spector, D., Godon, C., Labarre, J., Toledano, M.B. J. Biol. Chem. (1999) [Pubmed]
  14. The moonlighting protein Tsa1p is implicated in oxidative stress response and in cell wall biogenesis in Candida albicans. Urban, C., Xiong, X., Sohn, K., Schröppel, K., Brunner, H., Rupp, S. Mol. Microbiol. (2005) [Pubmed]
  15. Cytosolic thioredoxin peroxidase I is essential for the antioxidant defense of yeast with dysfunctional mitochondria. Demasi, A.P., Pereira, G.A., Netto, L.E. FEBS Lett. (2001) [Pubmed]
  16. Human T cell cyclophilin18 binds to thiol-specific antioxidant protein Aop1 and stimulates its activity. Jäschke, A., Mi, H., Tropschug, M. J. Mol. Biol. (1998) [Pubmed]
  17. Catalases and thioredoxin peroxidase protect Saccharomyces cerevisiae against Ca(2+)-induced mitochondrial membrane permeabilization and cell death. Kowaltowski, A.J., Vercesi, A.E., Rhee, S.G., Netto, L.E. FEBS Lett. (2000) [Pubmed]
  18. Genetic analysis of glutathione peroxidase in oxidative stress response of Saccharomyces cerevisiae. Inoue, Y., Matsuda, T., Sugiyama, K., Izawa, S., Kimura, A. J. Biol. Chem. (1999) [Pubmed]
  19. Thioredoxin-dependent peroxide reductase from yeast. Chae, H.Z., Chung, S.J., Rhee, S.G. J. Biol. Chem. (1994) [Pubmed]
  20. Thermosensitive phenotype of yeast mutant lacking thioredoxin peroxidase. Lee, S.M., Park, J.W. Arch. Biochem. Biophys. (1998) [Pubmed]
  21. RPH1 and GIS1 are damage-responsive repressors of PHR1. Jang, Y.K., Wang, L., Sancar, G.B. Mol. Cell. Biol. (1999) [Pubmed]
  22. Oxidation of a eukaryotic 2-Cys peroxiredoxin is a molecular switch controlling the transcriptional response to increasing levels of hydrogen peroxide. Bozonet, S.M., Findlay, V.J., Day, A.M., Cameron, J., Veal, E.A., Morgan, B.A. J. Biol. Chem. (2005) [Pubmed]
  23. Peroxiredoxin-mediated redox regulation of the nuclear localization of Yap1, a transcription factor in budding yeast. Okazaki, S., Naganuma, A., Kuge, S. Antioxid. Redox Signal. (2005) [Pubmed]
  24. On the protective mechanism of the thiol-specific antioxidant enzyme against the oxidative damage of biomacromolecules. Yim, M.B., Chae, H.Z., Rhee, S.G., Chock, P.B., Stadtman, E.R. J. Biol. Chem. (1994) [Pubmed]
  25. Cloning, sequencing, and mutation of thiol-specific antioxidant gene of Saccharomyces cerevisiae. Chae, H.Z., Kim, I.H., Kim, K., Rhee, S.G. J. Biol. Chem. (1993) [Pubmed]
  26. The protein interaction of Saccharomyces cerevisiae cytoplasmic thiol peroxidase II with SFH2p and its in vivo function. Cha, M.K., Hong, S.K., Oh, Y.M., Kim, I.H. J. Biol. Chem. (2003) [Pubmed]
  27. Half-of-sites binding of orotidine 5'-phosphate and alpha-D-5-phosphorylribose 1-diphosphate to orotate phosphoribosyltransferase from Saccharomyces cerevisiae supports a novel variant of the Theorell-Chance mechanism with alternating site catalysis. McClard, R.W., Holets, E.A., MacKinnon, A.L., Witte, J.F. Biochemistry (2006) [Pubmed]
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