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Gene Review

NQO2  -  NAD(P)H dehydrogenase, quinone 2

Homo sapiens

Synonyms: DHQV, DIA6, NMOR2, NRH:quinone oxidoreductase 2, QR2, ...
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Disease relevance of NQO2


Psychiatry related information on NQO2


High impact information on NQO2

  • Now chloroquine-binding proteins in malaria-infected erythrocytes, surprisingly, have been identified as human aldehyde dehydrogenase 1 and quinone reductase 2, raising the interesting possibility that the target of the anti-malarial activity of chloroquine might be a host enzyme [7].
  • In the absence of this binding site in QR2, the enzyme retains the essential catalytic machinery, including affinity for FAD, but cannot bind phosphorylated hydride donors [8].
  • Recombinant human QR2: (i) reacts with N-ribosyl- and N-alkyldihydronicotinamides, but not with NADH, NADPH, or NMNH; (ii) is very weakly inhibited by dicumarol or Cibacron blue; (iii) is very potently inhibited by benzo[a]pyrene [8].
  • NQO2 activity appears to be related to expression of NQO1 (DT-diaphorase), an enzyme that is known to have a favorable distribution toward certain human cancers [9].
  • In particular, 1-carbamoylmethyl-3-carbamoyl-1,4dihydropyridine was shown to be a co-substrate for NQO2 with greater stability than NRH, with the ability to enter cells and potentiate the cytotoxicity of CB 1954 [9].

Chemical compound and disease context of NQO2


Biological context of NQO2


Anatomical context of NQO2

  • In addition, MMC caused an increase in DNA cross-links in a cell line transfected to overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1-expressing cell line [15].
  • Northern blot analysis indicates that NQO2 gene is expressed in human heart, brain, lung, liver, and skeletal muscle but does not express in placenta [16].
  • Here, we demonstrate that the NQO2 gene is differentially expressed by the polymorphic promoters in human fibroblasts and Hep-G2 cells transfected with NQO2 gene reporter constructs [17].
  • Our preliminary data, although sample size was not enough, demonstrated that the RNA concentration of NQO2 in white blood cells isolated from peripheral blood was higher in individuals homozygous (II) for the I allele than in those heterozygous (ID) or homozygous (DD) for the D allele [18].
  • Disruption of dihydronicotinamide riboside:quinone oxidoreductase 2 (NQO2) leads to myeloid hyperplasia of bone marrow and decreased sensitivity to menadione toxicity [10].

Associations of NQO2 with chemical compounds


Regulatory relationships of NQO2


Other interactions of NQO2


Analytical, diagnostic and therapeutic context of NQO2


  1. Differential gene expression of NAD(P)H:quinone oxidoreductase and NRH:quinone oxidoreductase in human hepatocellular and biliary tissue. Strassburg, A., Strassburg, C.P., Manns, M.P., Tukey, R.H. Mol. Pharmacol. (2002) [Pubmed]
  2. Nucleotide and deduced amino acid sequence of a human cDNA (NQO2) corresponding to a second member of the NAD(P)H:quinone oxidoreductase gene family. Extensive polymorphism at the NQO2 gene locus on chromosome 6. Jaiswal, A.K., Burnett, P., Adesnik, M., McBride, O.W. Biochemistry (1990) [Pubmed]
  3. An association between idiopathic Parkinson's disease and polymorphisms of phase II detoxification enzymes: glutathione S-transferase M1 and quinone oxidoreductase 1 and 2. Harada, S., Fujii, C., Hayashi, A., Ohkoshi, N. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  4. Inhibition of melanoma cell proliferation by resveratrol is correlated with upregulation of quinone reductase 2 and p53. Hsieh, T.C., Wang, Z., Hamby, C.V., Wu, J.M. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  5. Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase. Wu, K., Knox, R., Sun, X.Z., Joseph, P., Jaiswal, A.K., Zhang, D., Deng, P.S., Chen, S. Arch. Biochem. Biophys. (1997) [Pubmed]
  6. Association analyses between polymorphisms of the phase II detoxification enzymes (GSTM1, NQO1, NQO2) and alcohol withdrawal symptoms. Okubo, T., Harada, S., Higuchi, S., Matsushita, S. Alcohol. Clin. Exp. Res. (2003) [Pubmed]
  7. Can a proteomics strategy be used to identify the anti-malarial activity of chloroquine? Petri, W.A. Trends Pharmacol. Sci. (2003) [Pubmed]
  8. Unexpected genetic and structural relationships of a long-forgotten flavoenzyme to NAD(P)H:quinone reductase (DT-diaphorase). Zhao, Q., Yang, X.L., Holtzclaw, W.D., Talalay, P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. Bioactivation of 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB 1954) by human NAD(P)H quinone oxidoreductase 2: a novel co-substrate-mediated antitumor prodrug therapy. Knox, R.J., Jenkins, T.C., Hobbs, S.M., Chen, S., Melton, R.G., Burke, P.J. Cancer Res. (2000) [Pubmed]
  10. Disruption of dihydronicotinamide riboside:quinone oxidoreductase 2 (NQO2) leads to myeloid hyperplasia of bone marrow and decreased sensitivity to menadione toxicity. Long, D.J., Iskander, K., Gaikwad, A., Arin, M., Roop, D.R., Knox, R., Barrios, R., Jaiswal, A.K. J. Biol. Chem. (2002) [Pubmed]
  11. Identification and purification of resveratrol targeting proteins using immobilized resveratrol affinity chromatography. Wang, Z., Hsieh, T.C., Zhang, Z., Ma, Y., Wu, J.M. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  12. Crystal structure of quinone reductase 2 in complex with resveratrol. Buryanovskyy, L., Fu, Y., Boyd, M., Ma, Y., Hsieh, T.C., Wu, J.M., Zhang, Z. Biochemistry (2004) [Pubmed]
  13. Differential regulation of wheat quinone reductases in response to powdery mildew infection. Greenshields, D.L., Liu, G., Selvaraj, G., Wei, Y. Planta (2005) [Pubmed]
  14. NAD(P)H:quinone oxidoreductase 1 and nrh:quinone oxidoreductase 2 activity and expression in bladder and ovarian cancer and lower NRH:quinone oxidoreductase 2 activity associated with an NQO2 exon 3 single-nucleotide polymorphism. Jamieson, D., Wilson, K., Pridgeon, S., Margetts, J.P., Edmondson, R.J., Leung, H.Y., Knox, R., Boddy, A.V. Clin. Cancer Res. (2007) [Pubmed]
  15. Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor. Jamieson, D., Tung, A.T., Knox, R.J., Boddy, A.V. Br. J. Cancer (2006) [Pubmed]
  16. Human NAD(P)H:quinone oxidoreductase2. Gene structure, activity, and tissue-specific expression. Jaiswal, A.K. J. Biol. Chem. (1994) [Pubmed]
  17. Sp3 repression of polymorphic human NRH:quinone oxidoreductase 2 gene promoter. Wang, W., Jaiswal, A.K. Free Radic. Biol. Med. (2004) [Pubmed]
  18. A possible association between an insertion/deletion polymorphism of the NQO2 gene and schizophrenia. Harada, S., Tachikawa, H., Kawanishi, Y. Psychiatr. Genet. (2003) [Pubmed]
  19. Nuclear factor Nrf2 and antioxidant response element regulate NRH:quinone oxidoreductase 2 (NQO2) gene expression and antioxidant induction. Wang, W., Jaiswal, A.K. Free Radic. Biol. Med. (2006) [Pubmed]
  20. Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines. Fischer, T.W., Zmijewski, M.A., Zbytek, B., Sweatman, T.W., Slominski, R.M., Wortsman, J., Slominski, A. Int. J. Oncol. (2006) [Pubmed]
  21. No associations between Parkinson's disease and polymorphisms of the quinone oxidoreductase (NQO1, NQO2) genes. Okada, S., Farin, F.M., Stapleton, P., Viernes, H., Quigley, S.D., Powers, K.M., Smith-Weller, T., Franklin, G.M., Longstreth, W.T., Swanson, P.D., Checkoway, H. Neurosci. Lett. (2005) [Pubmed]
  22. CB 1954: from the Walker tumor to NQO2 and VDEPT. Knox, R.J., Burke, P.J., Chen, S., Kerr, D.J. Curr. Pharm. Des. (2003) [Pubmed]
  23. NQO1 and NQO2 Regulation of Humoral Immunity and Autoimmunity. Iskander, K., Li, J., Han, S., Zheng, B., Jaiswal, A.K. J. Biol. Chem. (2006) [Pubmed]
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