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Gene Review

NOX1  -  NADPH oxidase 1

Homo sapiens

Synonyms: GP91-2, MOX-1, MOX1, Mitogenic oxidase 1, NADH/NADPH mitogenic oxidase subunit P65-MOX, ...
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Disease relevance of NOX1


Psychiatry related information on NOX1


High impact information on NOX1


Chemical compound and disease context of NOX1


Biological context of NOX1


Anatomical context of NOX1

  • Cultured rat astrocytes express mRNAs encoding for the regulatory subunit p47(phox), NOX1, 2, and 4, and the dual oxidases (DUOX)1 and 2, but not NOX3 [22].
  • In this context, our data demonstrate that the NOX1 cytoplasmic domains interact efficiently with the cytoplasmic subunits of the phagocyte NADPH oxidase and identify the second cytoplasmic loop of NOX electron transporters as a crucial domain for enzyme function [23].
  • These data show that endothelial cells simultaneously express NOX2, NOX4, and NOX1 [24].
  • In smooth-muscle cells, platelet-derived growth factor induces mox1 mRNA production, while antisense mox1 mRNA decreases superoxide generation and serum-stimulated growth [19].
  • Identification of a thermolabile component of the human neutrophil NADPH oxidase. A model for chronic granulomatous disease caused by deficiency of the p67-phox cytosolic component [25].

Associations of NOX1 with chemical compounds

  • In SEG1 cells, acid treatment increased mRNA expression of NOX5-S, but not NOX1, and knockdown of NOX5 by NOX5 small interfering RNA abolished acid-induced H(2)O(2) production [26].
  • We found that human umbilical vein endothelial cells treated with Ang1 produce ROS transiently, which was suppressed by NADPH oxidase inhibitor, diphenylene-iodonium chloride, and rotenone [27].
  • The human neutrophil NADPH oxidase-associated H+ channel acts as a charge compensator for the electrogenic generation of superoxide (O2-.). The expression of the channel activity was found to increase in parallel with that of the stimulatable generation of O2-. in differentiated HL60 cells [28].
  • We therefore conclude that the large subunit of the NADPH oxidase cytochrome b (gp91-phox) is the arachidonate activable H+ channel of human neutrophils [28].
  • A potent inhibitor for NF-kappaB (pyrrolidine dithiocarbamate) significantly blocked the rFliC-primed increase in O(2)(-) production and induction of Nox1 protein [2].

Physical interactions of NOX1

  • TPR domain mutants of NOXA1 that interfere with Rac1 binding were ineffective in supporting Nox1-dependent ROS generation [29].
  • Attenuation of NADPH oxidase derived ROS coupled with GSH/GSSG reduction and suppression of NF-kappaB activation are highlighted as the molecular mechanisms responsible for Cox-2 inhibition [30].
  • Here we show that Rac directly participates in Nox1 activation via interacting with Noxa1 [31].
  • Assembly of the human neutrophil NADPH oxidase involves binding of p67phox and flavocytochrome b to a common functional domain in p47phox [32].
  • The Rac target NADPH oxidase p67phox interacts preferentially with Rac2 rather than Rac1 [33].

Enzymatic interactions of NOX1


Regulatory relationships of NOX1

  • To demonstrate that the additional regions identified were biologically significant, peptides mimicking the gp91-phox sequences F77LRGSSACCSTRVRRQL93 and E451WFADLLQLLESQ463 were synthesized and assayed for their ability to inhibit NADPH oxidase activity [38].
  • Rac1(G12V) interaction with NOXA1 was enhanced by Nox1 and NOXO1, suggesting cooperative binding [29].
  • When Nox1 is co-expressed along with its regulatory subunits NOXO1 and NOXA1, significant ROS generation is seen [29].
  • The endothelial NADPH oxidase is activated by angiogenic factors including VEGF and angiopoietin-1 [39].
  • Rac is a GTPase that in the GTP-bound state binds p67phox to activate NADPH oxidase [40].
  • We showed that phosphorylation and 14-3-3 binding induce the dissociation of NoxA1 from the Nox1 complex at the plasma membrane, suggesting a mechanism for the inhibitory effect on Nox1 activity [41].

Other interactions of NOX1


Analytical, diagnostic and therapeutic context of NOX1


  1. Involvement of p40phox in activation of phagocyte NADPH oxidase through association of its carboxyl-terminal, but not its amino-terminal, with p67phox. Tsunawaki, S., Kagara, S., Yoshikawa, K., Yoshida, L.S., Kuratsuji, T., Namiki, H. J. Exp. Med. (1996) [Pubmed]
  2. Role of nicotinamide adenine dinucleotide phosphate oxidase 1 in oxidative burst response to Toll-like receptor 5 signaling in large intestinal epithelial cells. Kawahara, T., Kuwano, Y., Teshima-Kondo, S., Takeya, R., Sumimoto, H., Kishi, K., Tsunawaki, S., Hirayama, T., Rokutan, K. J. Immunol. (2004) [Pubmed]
  3. Inhibition of NADPH oxidase 4 activates apoptosis via the AKT/apoptosis signal-regulating kinase 1 pathway in pancreatic cancer PANC-1 cells. Mochizuki, T., Furuta, S., Mitsushita, J., Shang, W.H., Ito, M., Yokoo, Y., Yamaura, M., Ishizone, S., Nakayama, J., Konagai, A., Hirose, K., Kiyosawa, K., Kamata, T. Oncogene (2006) [Pubmed]
  4. Type I Helicobacter pylori lipopolysaccharide stimulates toll-like receptor 4 and activates mitogen oxidase 1 in gastric pit cells. Kawahara, T., Teshima, S., Oka, A., Sugiyama, T., Kishi, K., Rokutan, K. Infect. Immun. (2001) [Pubmed]
  5. Nox1 expression determines cellular reactive oxygen and modulates c-fos-induced growth factor, interleukin-8, and Cav-1. Arnold, R.S., He, J., Remo, A., Ritsick, D., Yin-Goen, Q., Lambeth, J.D., Datta, M.W., Young, A.N., Petros, J.A. Am. J. Pathol. (2007) [Pubmed]
  6. Fibrillar amyloid-beta peptides kill human primary neurons via NADPH oxidase-mediated activation of neutral sphingomyelinase. Implications for Alzheimer's disease. Jana, A., Pahan, K. J. Biol. Chem. (2004) [Pubmed]
  7. Novel isoforms of NADPH-oxidase in cerebral vascular control. Miller, A.A., Drummond, G.R., Sobey, C.G. Pharmacol. Ther. (2006) [Pubmed]
  8. Changing the conformation state of cytochrome b558 initiates NADPH oxidase activation: MRP8/MRP14 regulation. Berthier, S., Paclet, M.H., Lerouge, S., Roux, F., Vergnaud, S., Coleman, A.W., Morel, F. J. Biol. Chem. (2003) [Pubmed]
  9. Smoking and erectile dysfunction: the role of NADPH oxidase. Koupparis, A., Jeremy, J.Y., Persad, R., Angelini, G.D., Shukla, N. BJU international. (2004) [Pubmed]
  10. How neutrophils kill microbes. Segal, A.W. Annu. Rev. Immunol. (2005) [Pubmed]
  11. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Bedard, K., Krause, K.H. Physiol. Rev. (2007) [Pubmed]
  12. Phagosome neutrality in host defense. Watts, C. Cell (2006) [Pubmed]
  13. Vascular NAD(P)H oxidases: specific features, expression, and regulation. Lassègue, B., Clempus, R.E. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2003) [Pubmed]
  14. Rac1-NADPH oxidase-regulated generation of reactive oxygen species mediates glutamate-induced apoptosis in SH-SY5Y human neuroblastoma cells. Nikolova, S., Lee, Y.S., Lee, Y.S., Kim, J.A. Free Radic. Res. (2005) [Pubmed]
  15. Suppression of oxidative stress in the endothelium and vascular wall. Jiang, F., Drummond, G.R., Dusting, G.J. Endothelium (2004) [Pubmed]
  16. Upregulation of NAD(P)H oxidase 1 in hypoxia activates hypoxia-inducible factor 1 via increase in reactive oxygen species. Goyal, P., Weissmann, N., Grimminger, F., Hegel, C., Bader, L., Rose, F., Fink, L., Ghofrani, H.A., Schermuly, R.T., Schmidt, H.H., Seeger, W., Hänze, J. Free Radic. Biol. Med. (2004) [Pubmed]
  17. Point mutation in the cytoplasmic domain of the neutrophil p22-phox cytochrome b subunit is associated with a nonfunctional NADPH oxidase and chronic granulomatous disease. Dinauer, M.C., Pierce, E.A., Erickson, R.W., Muhlebach, T.J., Messner, H., Orkin, S.H., Seger, R.A., Curnutte, J.T. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  18. NOX1/NADPH oxidase negatively regulates nerve growth factor-induced neurite outgrowth. Ibi, M., Katsuyama, M., Fan, C., Iwata, K., Nishinaka, T., Yokoyama, T., Yabe-Nishimura, C. Free Radic. Biol. Med. (2006) [Pubmed]
  19. Cell transformation by the superoxide-generating oxidase Mox1. Suh, Y.A., Arnold, R.S., Lassegue, B., Shi, J., Xu, X., Sorescu, D., Chung, A.B., Griendling, K.K., Lambeth, J.D. Nature (1999) [Pubmed]
  20. Role of Src homology 3 domains in assembly and activation of the phagocyte NADPH oxidase. Sumimoto, H., Kage, Y., Nunoi, H., Sasaki, H., Nose, T., Fukumaki, Y., Ohno, M., Minakami, S., Takeshige, K. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  21. Nox3 regulation by NOXO1, p47phox, and p67phox. Cheng, G., Ritsick, D., Lambeth, J.D. J. Biol. Chem. (2004) [Pubmed]
  22. Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices. Reinehr, R., Görg, B., Becker, S., Qvartskhava, N., Bidmon, H.J., Selbach, O., Haas, H.L., Schliess, F., Häussinger, D. Glia (2007) [Pubmed]
  23. Mechanisms of activation of NADPH oxidases. Clark, R.A., Epperson, T.K., Valente, A.J. Jpn. J. Infect. Dis. (2004) [Pubmed]
  24. NOX2 and NOX4 Mediate Proliferative Response in Endothelial Cells. Petry, A., Djordjevic, T., Weitnauer, M., Kietzmann, T., Hess, J., Görlach, A. Antioxid. Redox Signal. (2006) [Pubmed]
  25. Identification of a thermolabile component of the human neutrophil NADPH oxidase. A model for chronic granulomatous disease caused by deficiency of the p67-phox cytosolic component. Erickson, R.W., Malawista, S.E., Garrett, M.C., Van Blaricom, G., Leto, T.L., Curnutte, J.T. J. Clin. Invest. (1992) [Pubmed]
  26. cAMP-response element-binding protein mediates acid-induced NADPH oxidase NOX5-S expression in Barrett esophageal adenocarcinoma cells. Fu, X., Beer, D.G., Behar, J., Wands, J., Lambeth, D., Cao, W. J. Biol. Chem. (2006) [Pubmed]
  27. Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis. Kim, Y.M., Kim, K.E., Koh, G.Y., Ho, Y.S., Lee, K.J. Cancer Res. (2006) [Pubmed]
  28. The arachidonate-activable, NADPH oxidase-associated H+ channel. Evidence that gp91-phox functions as an essential part of the channel. Henderson, L.M., Banting, G., Chappell, J.B. J. Biol. Chem. (1995) [Pubmed]
  29. Nox1-dependent reactive oxygen generation is regulated by Rac1. Cheng, G., Diebold, B.A., Hughes, Y., Lambeth, J.D. J. Biol. Chem. (2006) [Pubmed]
  30. Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH oxidase and glutathione redox-dependent mechanisms. Barbieri, S.S., Cavalca, V., Eligini, S., Brambilla, M., Caiani, A., Tremoli, E., Colli, S. Free Radic. Biol. Med. (2004) [Pubmed]
  31. Direct involvement of the small GTPase Rac in activation of the superoxide-producing NADPH oxidase Nox1. Miyano, K., Ueno, N., Takeya, R., Sumimoto, H. J. Biol. Chem. (2006) [Pubmed]
  32. Assembly of the human neutrophil NADPH oxidase involves binding of p67phox and flavocytochrome b to a common functional domain in p47phox. De Leo, F.R., Ulman, K.V., Davis, A.R., Jutila, K.L., Quinn, M.T. J. Biol. Chem. (1996) [Pubmed]
  33. The Rac target NADPH oxidase p67phox interacts preferentially with Rac2 rather than Rac1. Dorseuil, O., Reibel, L., Bokoch, G.M., Camonis, J., Gacon, G. J. Biol. Chem. (1996) [Pubmed]
  34. Phosphorylation of p67phox in the neutrophil occurs in the cytosol and is independent of p47phox. Forbes, L.V., Moss, S.J., Segal, A.W. FEBS Lett. (1999) [Pubmed]
  35. Involvement of protein kinase D in Fc gamma-receptor activation of the NADPH oxidase in neutrophils. Davidson-Moncada, J.K., Lopez-Lluch, G., Segal, A.W., Dekker, L.V. Biochem. J. (2002) [Pubmed]
  36. NADPH oxidase. Babior, B.M. Curr. Opin. Immunol. (2004) [Pubmed]
  37. Purification of the solubilized NADPH:O2 oxidoreductase of human neutrophils. Isolation of its catalytically inactive cytochrome b and flavoprotein redox centers. Green, T.R., Pratt, K.L. J. Biol. Chem. (1988) [Pubmed]
  38. Mapping sites of interaction of p47-phox and flavocytochrome b with random-sequence peptide phage display libraries. DeLeo, F.R., Yu, L., Burritt, J.B., Loetterle, L.R., Bond, C.W., Jesaitis, A.J., Quinn, M.T. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  39. Redox signaling in angiogenesis: Role of NADPH oxidase. Ushio-Fukai, M. Cardiovasc. Res. (2006) [Pubmed]
  40. Rac1 disrupts p67phox/p40phox binding: a novel role for Rac in NADPH oxidase activation. Rinckel, L.A., Faris, S.L., Hitt, N.D., Kleinberg, M.E. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  41. Regulation of Nox1 activity via protein kinase A-mediated phosphorylation of NoxA1 and 14-3-3 binding. Kim, J.S., Diebold, B.A., Babior, B.M., Knaus, U.G., Bokoch, G.M. J. Biol. Chem. (2007) [Pubmed]
  42. Neutrophil nicotinamide adenine dinucleotide phosphate oxidase assembly. Translocation of p47-phox and p67-phox requires interaction between p47-phox and cytochrome b558. Heyworth, P.G., Curnutte, J.T., Nauseef, W.M., Volpp, B.D., Pearson, D.W., Rosen, H., Clark, R.A. J. Clin. Invest. (1991) [Pubmed]
  43. Four novel mutations in the gene encoding gp91-phox of human NADPH oxidase: consequences for oxidase assembly. Leusen, J.H., Meischl, C., Eppink, M.H., Hilarius, P.M., de Boer, M., Weening, R.S., Ahlin, A., Sanders, L., Goldblatt, D., Skopczynska, H., Bernatowska, E., Palmblad, J., Verhoeven, A.J., van Berkel, W.J., Roos, D. Blood (2000) [Pubmed]
  44. Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent. Grasberger, H., Refetoff, S. J. Biol. Chem. (2006) [Pubmed]
  45. NOX3, a superoxide-generating NADPH oxidase of the inner ear. Bánfi, B., Malgrange, B., Knisz, J., Steger, K., Dubois-Dauphin, M., Krause, K.H. J. Biol. Chem. (2004) [Pubmed]
  46. Direct interaction of the novel Nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase. Ambasta, R.K., Kumar, P., Griendling, K.K., Schmidt, H.H., Busse, R., Brandes, R.P. J. Biol. Chem. (2004) [Pubmed]
  47. Association of gp91phox homolog Nox1 with anchorage-independent growth and MAP kinase-activation of transformed human keratinocytes. Chamulitrat, W., Schmidt, R., Tomakidi, P., Stremmel, W., Chunglok, W., Kawahara, T., Rokutan, K. Oncogene (2003) [Pubmed]
  48. Differential NADPH- versus NADH-dependent superoxide production by phagocyte-type endothelial cell NADPH oxidase. Li, J.M., Shah, A.M. Cardiovasc. Res. (2001) [Pubmed]
  49. Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape. McCaffrey, R.L., Allen, L.A. J. Leukoc. Biol. (2006) [Pubmed]
  50. Immunoelectron microscopy shows a clustered distribution of NADPH oxidase components in the human neutrophil plasma membrane. Wientjes, F.B., Segal, A.W., Hartwig, J.H. J. Leukoc. Biol. (1997) [Pubmed]
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