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Gene Review

PRDX6  -  peroxiredoxin 6

Homo sapiens

Synonyms: 1-Cys, 1-Cys PRX, 1-Cys peroxiredoxin, 24 kDa protein, AOP2, ...
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Disease relevance of PRDX6


Psychiatry related information on PRDX6


High impact information on PRDX6

  • The glycoprotein and viral protein of 24 kDa genes showed no nucleotide differences between symptomatic and asymptomatic individuals [7].
  • Reduction of 1-Cys peroxiredoxins by ascorbate changes the thiol-specific antioxidant paradigm, revealing another function of vitamin C [8].
  • Peroxiredoxins (Prx) are widely distributed peroxidases that can be divided into 1-Cys and 2-Cys Prx groups based on the number of conserved cysteine residues that participate in their catalytical cycle [8].
  • Prx have been described to be strictly dependent on thiols, but here, we show that ascorbate (vitamin C) also reduces 1-Cys Prx, but not 2-Cys Prx, from several taxonomic groups [8].
  • Reduction by ascorbate is partly related to the fact that the oxidized form of 1-Cys Prx is a stable sulfenic acid (Cys-SOH) instead of a disulfide [8].

Chemical compound and disease context of PRDX6

  • A new construct which contains the His-tag plus two extra amino acids at the COOH terminus when expressed in Escherichia coli generated a protein that hydrolyzed the sn-2 acyl chain of phospholipids at pH 4, and exhibited NSGPx activity with H(2)O(2) at pH 8 [9].
  • Three lines are producing IgG antibody to the 41-kDa HIV transmembrane glycoprotein gp41 and 4 produce IgG antibodies to the 24-kDa HIV core protein p24, its precursors and a breakdown product [10].
  • Intriguingly, the phosphorylation of ataxia telangectasia-mutated kinases at S1981 was suppressed in p29-depleted HeLa cells with UV irradiation, but not in hydroxyurea- and ionizing radiation-treated cells [11].
  • The 24-kDa MOMP from L. pneumophila was purified, and antibody produced to this protein cross-reacted with all species of Legionella as determined from an immunoblot of a sodium dodecyl sulfate gel [12].
  • Type C1 and D toxins produced by Clostridium botulinum caused ADP-ribosylation of a protein of 24 kDa in membrane preparations of rat clonal pheochromocytoma cells (PC12) and of proteins of 25 and 26 kDa in neuron-rich culture of fetal rat brain cells [13].

Biological context of PRDX6


Anatomical context of PRDX6


Associations of PRDX6 with chemical compounds

  • Antioxidant protein 2 (AOP2), a member of the newly defined family of thiol-specific antioxidant proteins, has been shown to remove H(2)O(2) and protect proteins and DNA from oxidative stress [14].
  • We now demonstrate that a heterodimer complex is formed between 1-Cys Prx with a C-terminal His6 tag and GST pi upon incubation of the two proteins at pH 8.0 in buffer containing 20% 1,6-hexanediol to dissociate the homodimers, followed by dialysis against buffer containing 2.5 mM glutathione (GSH) but lacking 1,6-hexanediol [15].
  • The heterodimer is also formed in the presence of S-methylglutathione, but no 1-Cys Prx activity is found under these conditions [15].
  • Although AOP2 possesses TSA activity, it has several unique characteristics, including the absence of a second cysteine residue that is conserved in all other TSA proteins, the presence of a unique carboxy-terminal domain, and a demonstrated phospholipase activity [18].
  • In addition, rh-p29 exhibited PLA(2) activity, which was Ca(2+) independent, optimal at low pH, and preferential for phosphatidylcholine substrates [2].

Physical interactions of PRDX6


Regulatory relationships of PRDX6

  • RhoB controls the 24 kDa FGF-2-induced radioresistance in HeLa cells by preventing post-mitotic cell death [23].
  • We have cloned the gene encoding the 24-kDa protein and show that it is expressed as a 22-kDa alpha-zein with an uncleaved signal peptide [24].
  • However, the IL-18 protein was expressed intracellularly and predominantly released as an unprocessed inactive 24-kDa form [25].
  • Together, our results demonstrate that H2O2-mediated hyperoxidation of Prdx6 induces cell cycle arrest at the G2/M transition through up-regulation of iPLA2 activity [26].

Other interactions of PRDX6

  • Among six antioxidant proteins, 1-Cys Prx showed significant increase (P > 0.05) in sCJD frontal cortex whereas Prx I was decreased (P > 0.01) [27].
  • Together, these data strongly suggest that AOP2 is a novel thiol-dependent antioxidant that functions to scavenge particular hydroperoxides in the cell and mediate specific signals [18].
  • In contrast, the 1-Cys Prx homodimer lacks peroxidase activity even in the presence of free GSH [15].
  • Mutations in the heat shock element and stress-related elements of the AOP2 promoter reduced LEDGF-dependent trans-activation [14].
  • Prxs I-IV form dimers held together by disulfide bonds, Prx V forms intramolecular bond, but the mechanism of Prx VI, so-called 1-Cys Prx, is still unclear [28].

Analytical, diagnostic and therapeutic context of PRDX6


  1. Characterization of a mammalian peroxiredoxin that contains one conserved cysteine. Kang, S.W., Baines, I.C., Rhee, S.G. J. Biol. Chem. (1998) [Pubmed]
  2. A 29-kDa protein associated with p67phox expresses both peroxiredoxin and phospholipase A2 activity and enhances superoxide anion production by a cell-free system of NADPH oxidase activity. Leavey, P.J., Gonzalez-Aller, C., Thurman, G., Kleinberg, M., Rinckel, L., Ambruso, D.W., Freeman, S., Kuypers, F.A., Ambruso, D.R. J. Biol. Chem. (2002) [Pubmed]
  3. Saitohin, which is nested in the tau locus and confers allele-specific susceptibility to several neurodegenerative diseases, interacts with peroxiredoxin 6. Gao, L., Tse, S.W., Conrad, C., Andreadis, A. J. Biol. Chem. (2005) [Pubmed]
  4. Reduced expression of 1-cys peroxiredoxin in oxidative stress-induced cataracts. Pak, J.H., Kim, T.I., Joon Kim, M., Yong Kim, J., Choi, H.J., Kim, S.A., Tchah, H. Exp. Eye Res. (2006) [Pubmed]
  5. Identification of breast cancer metastasis-associated proteins in an isogenic tumor metastasis model using two-dimensional gel electrophoresis and liquid chromatography-ion trap-mass spectrometry. Li, D.Q., Wang, L., Fei, F., Hou, Y.F., Luo, J.M., Zeng, R., Wu, J., Lu, J.S., Di, G.H., Ou, Z.L., Xia, Q.C., Shen, Z.Z., Shao, Z.M. Proteomics (2006) [Pubmed]
  6. Identification of a 24 kDa phosphoprotein associated with an intermediate stage of memory in Hermissenda. Crow, T., Xue-Bian, J.J. J. Neurosci. (2000) [Pubmed]
  7. Human asymptomatic Ebola infection and strong inflammatory response. Leroy, E.M., Baize, S., Volchkov, V.E., Fisher-Hoch, S.P., Georges-Courbot, M.C., Lansoud-Soukate, J., Capron, M., Debré, P., McCormick, J.B., Georges, A.J. Lancet (2000) [Pubmed]
  8. Reduction of 1-Cys peroxiredoxins by ascorbate changes the thiol-specific antioxidant paradigm, revealing another function of vitamin C. Monteiro, G., Horta, B.B., Pimenta, D.C., Augusto, O., Netto, L.E. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  9. 1-Cys peroxiredoxin, a bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities. Chen, J.W., Dodia, C., Feinstein, S.I., Jain, M.K., Fisher, A.B. J. Biol. Chem. (2000) [Pubmed]
  10. Generation of human monoclonal antibodies to human immunodeficiency virus. Gorny, M.K., Gianakakos, V., Sharpe, S., Zolla-Pazner, S. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  11. Silencing of p29 Affects DNA Damage Responses with UV Irradiation. Chu, P.C., Yang, Y.C., Lu, Y.T., Chen, H.T., Yu, L.C., Chang, M.S. Cancer Res. (2006) [Pubmed]
  12. Disulfide-bonded outer membrane proteins in the genus Legionella. Butler, C.A., Street, E.D., Hatch, T.P., Hoffman, P.S. Infect. Immun. (1985) [Pubmed]
  13. ADP-ribosylation of specific membrane proteins in pheochromocytoma and primary-cultured brain cells by botulinum neurotoxins type C and D. Matsuoka, I., Syoto, B., Kurihara, K., Kubo, S., Syuto, B. FEBS Lett. (1987) [Pubmed]
  14. Transcriptional regulation of the antioxidant protein 2 gene, a thiol-specific antioxidant, by lens epithelium-derived growth factor to protect cells from oxidative stress. Fatma, N., Singh, D.P., Shinohara, T., Chylack, L.T. J. Biol. Chem. (2001) [Pubmed]
  15. Direct evidence for the formation of a complex between 1-cysteine peroxiredoxin and glutathione S-transferase pi with activity changes in both enzymes. Ralat, L.A., Manevich, Y., Fisher, A.B., Colman, R.F. Biochemistry (2006) [Pubmed]
  16. A novel stress-inducible antioxidant enzyme identified from the resurrection plant Xerophyta viscosa Baker. Mowla, S.B., Thomson, J.A., Farrant, J.M., Mundree, S.G. Planta (2002) [Pubmed]
  17. The human homologue of a bovine non-selenium glutathione peroxidase is a novel keratinocyte growth factor-regulated gene. Frank, S., Munz, B., Werner, S. Oncogene (1997) [Pubmed]
  18. AOP2 (antioxidant protein 2): structure and function of a unique thiol-specific antioxidant. Phelan, S.A. Antioxid. Redox Signal. (1999) [Pubmed]
  19. Tissue inhibitors of metalloproteinases 1 and 2 in human seminal plasma and their association with spermatozoa. Baumgart, E., Lenk, S.V., Loening, S.A., Jung, K. Int. J. Androl. (2002) [Pubmed]
  20. IGF-I treatment reduces hyperphagia, obesity, and hypertension in metabolic disorders induced by fetal programming. Vickers, M.H., Ikenasio, B.A., Breier, B.H. Endocrinology (2001) [Pubmed]
  21. The 24 kDa N-terminal sub-domain of the DNA gyrase B protein binds coumarin drugs. Gilbert, E.J., Maxwell, A. Mol. Microbiol. (1994) [Pubmed]
  22. The interaction of coumarin antibiotics with fragments of DNA gyrase B protein. Gormley, N.A., Orphanides, G., Meyer, A., Cullis, P.M., Maxwell, A. Biochemistry (1996) [Pubmed]
  23. RhoB controls the 24 kDa FGF-2-induced radioresistance in HeLa cells by preventing post-mitotic cell death. Ader, I., Toulas, C., Dalenc, F., Delmas, C., Bonnet, J., Cohen-Jonathan, E., Favre, G. Oncogene (2002) [Pubmed]
  24. A defective signal peptide in the maize high-lysine mutant floury 2. Coleman, C.E., Lopes, M.A., Gillikin, J.W., Boston, R.S., Larkins, B.A. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  25. Constitutive expression of interleukin-18 in head and neck squamous carcinoma cells. Martone, T., Bellone, G., Pagano, M., Beatrice, F., Palonta, F., Emanuelli, G., Cortesina, G. Head & neck. (2004) [Pubmed]
  26. H2O2-dependent hyperoxidation of peroxiredoxin 6 (Prdx6) plays a role in cellular toxicity via up-regulation of iPLA2 activity. Kim, S.Y., Jo, H.Y., Kim, M.H., Cha, Y.Y., Choi, S.W., Shim, J.H., Kim, T.J., Lee, K.Y. J. Biol. Chem. (2008) [Pubmed]
  27. Expression patterns of antioxidant proteins in brains of patients with sporadic Creutzfeldt-Jacob disease. Krapfenbauer, K., Yoo, B.C., Fountoulakis, M., Mitrova, E., Lubec, G. Electrophoresis (2002) [Pubmed]
  28. Variable overoxidation of peroxiredoxins in human lung cells in severe oxidative stress. Lehtonen, S.T., Markkanen, P.M., Peltoniemi, M., Kang, S.W., Kinnula, V.L. Am. J. Physiol. Lung Cell Mol. Physiol. (2005) [Pubmed]
  29. Targeted disruption of peroxiredoxin 6 gene renders the heart vulnerable to ischemia-reperfusion injury. Nagy, N., Malik, G., Fisher, A.B., Das, D.K. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  30. Autoantibodies against triosephosphate isomerase. A possible clue to pathogenesis of hemolytic anemia in infectious mononucleosis. Ritter, K., Brestrich, H., Nellen, B., Kratzin, H., Eiffert, H., Thomssen, R. J. Exp. Med. (1990) [Pubmed]
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