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Gene Review

NOXO1  -  NADPH oxidase organizer 1

Homo sapiens

Synonyms: NADPH oxidase regulatory protein, Nox organizer 1, Nox-organizing protein 1, P41NOX, P41NOXA, ...
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High impact information on NOXO1

  • Plasma membrane targeting of Noxa1 depends on Noxo1, through tail-to-tail interactions between these proteins [1].
  • When Nox1 is co-expressed along with its regulatory subunits NOXO1 and NOXA1, significant ROS generation is seen [2].
  • We previously showed that the initial suppression of the oxidase response of chemoattractant-stimulated adherent neutrophils is mediated via inhibition of Vav1-induced activation of the NADPH oxidase regulatory GTPase Rac2 by adhesion signals [3].
  • Unexpectedly, Nox3 was strongly activated by NOXO1 in the absence of NOXA1 or p67(phox) [4].
  • A point mutation in the PX domain of holo-NOXO1 decreases lipid binding resulting in cytosolic localization and also inhibits NOXO1-activation of Nox1 [5].

Biological context of NOXO1

  • Splice forms were generated by alternative splicing of the two ends of exon 3 of the NOXO1 gene, and resulted in differences in the PX domain [6].

Anatomical context of NOXO1

  • This localization of NOXO1 is dictated by its PX domain, since this domain but not the remainder of the molecule localizes to membranes [5].
  • Here we describe an alternative splicing form of Noxo1, Noxo1gamma, which is expressed in the testis and fetal brain [7].
  • Electropermeabilized HeLa cells, ectopically expressing Nox1, Noxo1, and Noxa1, produce superoxide in a GTP-dependent manner, which is abrogated by expression of a mutant Noxa1(R103E), defective in Rac binding [8].
  • Here, we show that Noxo1 supports superoxide production in a cell-free system for gp91(phox)/Nox2 activation by arachidonic acid [9].

Associations of NOXO1 with chemical compounds


Other interactions of NOXO1

  • These results suggest that the formation of the complex consisting of Nox1, betaPix, and NoxO1 is likely to be a critical step in EGF-induced ROS generation [10].

Analytical, diagnostic and therapeutic context of NOXO1


  1. Involvement of Rac1 in activation of multicomponent Nox1- and Nox3-based NADPH oxidases. Ueyama, T., Geiszt, M., Leto, T.L. Mol. Cell. Biol. (2006) [Pubmed]
  2. Nox1-dependent reactive oxygen generation is regulated by Rac1. Cheng, G., Diebold, B.A., Hughes, Y., Lambeth, J.D. J. Biol. Chem. (2006) [Pubmed]
  3. Critical role of proline-rich tyrosine kinase 2 in reversion of the adhesion-mediated suppression of reactive oxygen species generation by human neutrophils. Zhao, T., Bokoch, G.M. J. Immunol. (2005) [Pubmed]
  4. Nox3 regulation by NOXO1, p47phox, and p67phox. Cheng, G., Ritsick, D., Lambeth, J.D. J. Biol. Chem. (2004) [Pubmed]
  5. NOXO1, regulation of lipid binding, localization, and activation of Nox1 by the Phox homology (PX) domain. Cheng, G., Lambeth, J.D. J. Biol. Chem. (2004) [Pubmed]
  6. Alternative mRNA splice forms of NOXO1: differential tissue expression and regulation of Nox1 and Nox3. Cheng, G., Lambeth, J.D. Gene (2005) [Pubmed]
  7. Expression and function of Noxo1gamma, an alternative splicing form of the NADPH oxidase organizer 1. Takeya, R., Taura, M., Yamasaki, T., Naito, S., Sumimoto, H. FEBS J. (2006) [Pubmed]
  8. 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]
  9. Interaction between the SH3 domains and C-terminal proline-rich region in NADPH oxidase organizer 1 (Noxo1). Yamamoto, A., Kami, K., Takeya, R., Sumimoto, H. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  10. Molecular interaction of NADPH oxidase 1 with betaPix and Nox Organizer 1. Park, H.S., Park, D., Bae, Y.S. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
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