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Gene Review

TXN  -  thioredoxin

Bos taurus

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Disease relevance of TXN

  • Escherichia coli MsrA and MsrB and bovine MsrA efficiently use either Trx or DTT as reducing agents [1].
  • Disulfide formation in reduced tetanus toxin by thioredoxin: the pharmacological role of interchain covalent and noncovalent bonds [2].

High impact information on TXN

  • A heat-stable protein has been detected in bovine liver that, in the presence of EDTA, can support the Msr reaction in the absence of either Trx or DTT [1].
  • The results indicate that thionein (T), which is formed when the zinc is removed from Zn-MT, can function as a reducing system for the Msr proteins because of its high content of cysteine residues and that Trx can reduce oxidized T [1].
  • The significantly decreased activity of the Cys-218 and Cys-227 variants in the presence of thioredoxin suggested that these residues shuttle reducing equivalents from thioredoxin to the active site [3].
  • Mammalian thioredoxin reductases (TrxR) are homodimers, homologous to glutathione reductase (GR), with an essential selenocysteine (SeCys) residue in an extension containing the conserved C-terminal sequence -Gly-Cys-SeCys-Gly [4].
  • We have now used the thioredoxin system to probe Ca(2+)-induced conformational changes and interaction between modules in the light chain of factor X. Thioredoxin, in conjunction with thioredoxin reductase and NADPH, allows direct measurements of the rate and extent of disulfide bond reduction [5].

Biological context of TXN


Anatomical context of TXN

  • Bovine thioredoxin system. Purification of thioredoxin reductase from calf liver and thymus and studies of its function in disulfide reduction [10].
  • Protein disulfide isomerase (PDI), a very abundant protein in the endoplasmic reticulum, facilitates the formation and rearrangement of disulfide bonds using two nonequivalent redox active-sites, located in two different thioredoxin homology domains [Lyles, M. M., & Gilbert, H. F. (1994) J. Biol. Chem. 269, 30946-30952] [9].
  • Essentially all of the thioredoxin in endothelial cells at control state was in the reduced form and 70-85% remained in the reduced form even after the H2O2 treatment [11].
  • As ROS are involved in mast cell activation and facilitate mediator release, TRX may be a key signaling molecule regulating the early events in the IgE signaling in mast cells and the allergic inflammation.Cell Research (2006) 16: 230-239. doi:10.1038/; published online 16 February 2006 [12].
  • Thioredoxin appears to be only weakly antigenic for bovine T cells and is, therefore, an unpromising candidate for inducing resistance to F. hepatica [13].

Associations of TXN with chemical compounds

  • At variance with these enzymes, bovine liver fructose-1,6-bisphosphatase, yeast glyceraldehyde-3-P dehydrogenase, and chloroplast ribulose 1,5-bisphosphate carboxylase, whose activities are not modulated by reduced thioredoxin, were inactivated by high pressure [14].
  • Catalase, peroxidase, superoxide dismutase, glutathione, and thioredoxin are widely distributed in many taxa and constitute elements of a nearly ubiquitous antioxidant metabolic strategy [15].
  • The work reported here used an NADPH-coupled assay with thioredoxin reductase to show that reduced thioredoxin at micromolar concentrations is also an effective sulfur-acceptor substrate for rhodanese under conditions where millimolar concentrations of lipoate or dithiothreitol would be required [16].
  • In order to identify a likely physiological cofactor, reduced lipoic acid and reduced thioredoxin were tested as cofactors in beef and rat liver microsomal systems [17].
  • The concentration of DTT required to obtain maximal enzyme activity may be as much as 485 times greater than the corresponding concentration of reduced thioredoxin that gives the same enzyme activity [17].

Regulatory relationships of TXN

  • There were some exceptions: e.g., follicular cells in the ovary did not contain immunohistochemically demonstrable glutaredoxin but expressed thioredoxin [18].

Other interactions of TXN

  • Finally, restoring intracellular levels of the reduced substrate Trx (thioredoxin) in Sedeficient BAECs was sufficient to increase HO-1 activation following 15-HPETE stimulation [19].
  • As the concentration of the oxidant system was decreased stepwise from 1 mM to 1 microM to mimic conditions that may be associated with oxidative tissue injury in situ, deactivation of thioredoxin was decreased proportionately, whereas thioltransferase remained much more susceptible [8].
  • Reduced thioredoxin as a sulfur-acceptor substrate for rhodanese [16].
  • Owing to the structure-based sequence alignment revealing homology between the "nonessential" disulfide of bpDNase and the active-site motif of thioredoxin, we measured 39% of the thioredoxin-like activity for bpDNase based on the rate of insulin precipitation (DeltaA650nm/min) [20].
  • The inactivated glyceraldehyde-3-phosphate dehydrogenase in a cell lysate prepared from the H2O2-treated endothelial cells was regenerated by incubating the lysate with 3 mM NADPH at 37 degrees C and the antiserum raised against bovine liver thioredoxin inhibited the regeneration [11].

Analytical, diagnostic and therapeutic context of TXN

  • We determined the full-length cDNA sequence of bovine thioredoxin by RT-PCR, 5'-RACE and 3'-RACE methods [6].
  • Tissue distrubution and subcellular localization of bovine thioredoxin determined by radioimmunoassay [21].
  • 8. Structural changes undergone by the thioredoxin molecule upon oxido-reduction were detected by isoelectric focusing, with a shift of 0.1 pH unit of its pI, and by analytical anion exchange chromatography, with a conspicuous shift of its retention time [22].


  1. Thionein can serve as a reducing agent for the methionine sulfoxide reductases. Sagher, D., Brunell, D., Hejtmancik, J.F., Kantorow, M., Brot, N., Weissbach, H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. Disulfide formation in reduced tetanus toxin by thioredoxin: the pharmacological role of interchain covalent and noncovalent bonds. Kistner, A., Sanders, D., Habermann, E. Toxicon (1993) [Pubmed]
  3. Thiol-disulfide exchange is involved in the catalytic mechanism of peptide methionine sulfoxide reductase. Lowther, W.T., Brot, N., Weissbach, H., Honek, J.F., Matthews, B.W. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  4. Structure and mechanism of mammalian thioredoxin reductase: the active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine-selenocysteine sequence. Zhong, L., Arnér, E.S., Holmgren, A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  5. Calcium-dependent interaction between gamma-carboxyglutamic acid-containing and N-terminal epidermal growth factor-like modules in factor X. Valcarce, C., Holmgren, A., Stenflo, J. J. Biol. Chem. (1994) [Pubmed]
  6. cDNA sequence of bovine thioredoxin. Terashima, H., Gotoh, S., Yagi, K., Mizoguchi, T. DNA Seq. (1999) [Pubmed]
  7. Calcium binding of bovine protein S. Effect of thrombin cleavage and removal of the gamma-carboxyglutamic acid-containing region. Sugo, T., Dahlbäck, B., Holmgren, A., Stenflo, J. J. Biol. Chem. (1986) [Pubmed]
  8. Sensitivity of protein sulfhydryl repair enzymes to oxidative stress. Starke, D.W., Chen, Y., Bapna, C.P., Lesnefsky, E.J., Mieyal, J.J. Free Radic. Biol. Med. (1997) [Pubmed]
  9. Catalysis of oxidative protein folding by mutants of protein disulfide isomerase with a single active-site cysteine. Walker, K.W., Lyles, M.M., Gilbert, H.F. Biochemistry (1996) [Pubmed]
  10. Bovine thioredoxin system. Purification of thioredoxin reductase from calf liver and thymus and studies of its function in disulfide reduction. Holmgren, A. J. Biol. Chem. (1977) [Pubmed]
  11. Thioredoxin regenerates proteins inactivated by oxidative stress in endothelial cells. Fernando, M.R., Nanri, H., Yoshitake, S., Nagata-Kuno, K., Minakami, S. Eur. J. Biochem. (1992) [Pubmed]
  12. Redox regulation of mast cell histamine release in thioredoxin-1 (TRX) transgenic mice. Son, A., Nakamura, H., Kondo, N., Matsuo, Y., Liu, W., Oka, S., Ishii, Y., Yodoi, J. Cell Res. (2006) [Pubmed]
  13. Bovine T cell responses to recombinant thioredoxin of Fasciola hepatica. Shoda, L.K., Rice-Ficht, A.C., Zhu, D., McKown, R.D., Brown, W.C. Vet. Parasitol. (1999) [Pubmed]
  14. The effect of high hydrostatic pressure on the modulation of regulatory enzymes from spinach chloroplasts. Prat-Gay, G., Paladini, A., Stein, M., Wolosiuk, R.A. J. Biol. Chem. (1991) [Pubmed]
  15. Regulation of Brucella abortus catalase. Kim, J.A., Sha, Z., Mayfield, J.E. Infect. Immun. (2000) [Pubmed]
  16. Reduced thioredoxin as a sulfur-acceptor substrate for rhodanese. Nandi, D.L., Westley, J. Int. J. Biochem. Cell Biol. (1998) [Pubmed]
  17. Reduced thioredoxin: a possible physiological cofactor for vitamin K epoxide reductase. Further support for an active site disulfide. Silverman, R.B., Nandi, D.L. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
  18. Immunochemical characterization and tissue distribution of glutaredoxin (thioltransferase) from calf. Rozell, B., Bárcena, J.A., Martínez-Galisteo, E., Padilla, C.A., Holmgren, A. Eur. J. Cell Biol. (1993) [Pubmed]
  19. Thioredoxin reductase regulates the induction of haem oxygenase-1 expression in aortic endothelial cells. Trigona, W.L., Mullarky, I.K., Cao, Y., Sordillo, L.M. Biochem. J. (2006) [Pubmed]
  20. Biological functions of the disulfides in bovine pancreatic deoxyribonuclease. Chen, W.J., Lee, I.S., Chen, C.Y., Liao, T.H. Protein Sci. (2004) [Pubmed]
  21. Tissue distrubution and subcellular localization of bovine thioredoxin determined by radioimmunoassay. Holmgren, A., Luthman, M. Biochemistry (1978) [Pubmed]
  22. Purification and properties of bovine thioredoxin system. Martínez-Galisteo, E., Padilla, C.A., García-Alfonso, C., López-Barea, J., Bárcena, J.A. Biochimie (1993) [Pubmed]
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