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Gene Review

Ncf1  -  neutrophil cytosolic factor 1

Mus musculus

Synonyms: 47 kDa neutrophil oxidase factor, NADPH oxidase subunit (47kDa), NCF-1, NCF-47K, NOXO2, ...
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Disease relevance of Ncf1


High impact information on Ncf1

  • Mice genetically deficient ((-/-)) in either iNOS or the p47phox subunit of NADPH oxidase, transgenic (Tg) mice that overexpress SOD, and their respective wild-type (WT) littermates were fed dextran sulfate sodium (DSS) in drinking water for 7 days to induce colitis [5].
  • The p47phox mouse knock-out model of chronic granulomatous disease [6].
  • Identical to the case in human CGD, leukocytes from p47phox-/- mice produced no superoxide and killed staphylococci ineffectively. p47phox-/- mice developed lethal infections and granulomatous inflammation similar to those encountered in human CGD patients [6].
  • Ang II phosphorylated p47phox, a regulatory subunit of NADPH oxidase, and induced reactive oxygen species formation via NADPH oxidase activity [7].
  • After bile duct ligation, p47phox-/- mice showed attenuated liver injury and fibrosis compared with WT counterparts [7].

Chemical compound and disease context of Ncf1


Biological context of Ncf1


Anatomical context of Ncf1


Associations of Ncf1 with chemical compounds

  • Next, we used ECs obtained from p47phox-/- mice (MAE-p47-/-), which do not produce ROS in response to OS, to determine the role of NADPH oxidases [16].
  • VSMC from p47phox-/- mice showed markedly reduced ROS generation and NF-kappaB activation in response to Ang II and AT1-AA [17].
  • CD95L induced within 1 min ceramide formation and serine phosphorylation of p47phox, which was sensitive to inhibitors of sphingomyelinase and protein kinase Czeta (PKCzeta) [18].
  • Like p47phox, p41 contains an amino-terminal Phox homology domain, two SH3 domains, and a conserved carboxyl-terminal, proline-rich motif [12].
  • Voglibose treatment decreased the myocardial expression of an NADPH oxidase subunit (p47phox) [13].

Physical interactions of Ncf1

  • LPS-induced NF-kappaB binding activity and accumulation of RelA in nuclear protein extracts of lung tissue were markedly increased in WT compared to p47phox-/- mice 90 min after treatment with 20 but not 5 microg of i.p. LPS per g [9].

Enzymatic interactions of Ncf1


Other interactions of Ncf1

  • Furthermore, Lyme arthritis severity was not altered in mice lacking either the Ncf1 or Gp91phox subunits of the NADPH oxidase complex [2].
  • Both iNOS-/- and p47phox-/- mice were attenuated in the ability to control C. burnetii infection compared to wild-type mice [20].
  • Here we describe two proteins, p41 and p51, with significant homology to two cytosolic components of the phagocytic oxidase, p47phox and p67phox [12].
  • p47phox deficiency impairs NF-kappa B activation and host defense in Pseudomonas pneumonia [21].
  • In both control and gp91phox(-/-) animals, reactive oxygen species (ROS) production and MMP induction was enhanced by AVF, whereas in p47phox(-/-) and eNOS(-/-) mice such response was negligible [22].

Analytical, diagnostic and therapeutic context of Ncf1


  1. Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene. Hultqvist, M., Olofsson, P., Holmberg, J., Bäckström, B.T., Tordsson, J., Holmdahl, R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  2. Bb2Bb3 regulation of murine Lyme arthritis is distinct from Ncf1 and independent of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase. Crandall, H., Ma, Y., Dunn, D.M., Sundsbak, R.S., Zachary, J.F., Olofsson, P., Holmdahl, R., Weis, J.H., Weiss, R.B., Teuscher, C., Weis, J.J. Am. J. Pathol. (2005) [Pubmed]
  3. Genomic organization of the genes Gtf2ird1, Gtf2i, and Ncf1 at the mouse chromosome 5 region syntenic to the human chromosome 7q11.23 Williams syndrome critical region. Bayarsaihan, D., Dunai, J., Greally, J.M., Kawasaki, K., Sumiyama, K., Enkhmandakh, B., Shimizu, N., Ruddle, F.H. Genomics (2002) [Pubmed]
  4. Deficiency of NADPH oxidase components p47phox and gp91phox caused granulomatous synovitis and increased connective tissue destruction in experimental arthritis models. van de Loo, F.A., Bennink, M.B., Arntz, O.J., Smeets, R.L., Lubberts, E., Joosten, L.A., van Lent, P.L., Coenen-de Roo, C.J., Cuzzocrea, S., Segal, B.H., Holland, S.M., van den Berg, W.B. Am. J. Pathol. (2003) [Pubmed]
  5. Regulation of murine intestinal inflammation by reactive metabolites of oxygen and nitrogen: divergent roles of superoxide and nitric oxide. Krieglstein, C.F., Cerwinka, W.H., Laroux, F.S., Salter, J.W., Russell, J.M., Schuermann, G., Grisham, M.B., Ross, C.R., Granger, D.N. J. Exp. Med. (2001) [Pubmed]
  6. The p47phox mouse knock-out model of chronic granulomatous disease. Jackson, S.H., Gallin, J.I., Holland, S.M. J. Exp. Med. (1995) [Pubmed]
  7. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. Bataller, R., Schwabe, R.F., Choi, Y.H., Yang, L., Paik, Y.H., Lindquist, J., Qian, T., Schoonhoven, R., Hagedorn, C.H., Lemasters, J.J., Brenner, D.A. J. Clin. Invest. (2003) [Pubmed]
  8. The PX domains of p47phox and p40phox bind to lipid products of PI(3)K. Kanai, F., Liu, H., Field, S.J., Akbary, H., Matsuo, T., Brown, G.E., Cantley, L.C., Yaffe, M.B. Nat. Cell Biol. (2001) [Pubmed]
  9. Impaired pulmonary NF-kappaB activation in response to lipopolysaccharide in NADPH oxidase-deficient mice. Koay, M.A., Christman, J.W., Segal, B.H., Venkatakrishnan, A., Blackwell, T.R., Holland, S.M., Blackwell, T.S. Infect. Immun. (2001) [Pubmed]
  10. Suppression of Plasmodium chabaudi parasitemia is independent of the action of reactive oxygen intermediates and/or nitric oxide. Gillman, B.M., Batchelder, J., Flaherty, P., Weidanz, W.P. Infect. Immun. (2004) [Pubmed]
  11. Effect of amphotericin B and micafungin combination on survival, histopathology, and fungal burden in experimental aspergillosis in the p47phox-/- mouse model of chronic granulomatous disease. Dennis, C.G., Greco, W.R., Brun, Y., Youn, R., Slocum, H.K., Bernacki, R.J., Lewis, R., Wiederhold, N., Holland, S.M., Petraitiene, R., Walsh, T.J., Segal, B.H. Antimicrob. Agents Chemother. (2006) [Pubmed]
  12. Proteins homologous to p47phox and p67phox support superoxide production by NAD(P)H oxidase 1 in colon epithelial cells. Geiszt, M., Lekstrom, K., Witta, J., Leto, T.L. J. Biol. Chem. (2003) [Pubmed]
  13. Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice. Liao, Y., Takashima, S., Zhao, H., Asano, Y., Shintani, Y., Minamino, T., Kim, J., Fujita, M., Hori, M., Kitakaze, M. Cardiovasc. Res. (2006) [Pubmed]
  14. Angiotensin II induces MMP-2 in a p47phox-dependent manner. Luchtefeld, M., Grote, K., Grothusen, C., Bley, S., Bandlow, N., Selle, T., Strüber, M., Haverich, A., Bavendiek, U., Drexler, H., Schieffer, B. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  15. Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development: a possible role for angiotensin-converting enzyme and the receptors for angiotensin II and aldosterone. Keidar, S., Kaplan, M., Pavlotzky, E., Coleman, R., Hayek, T., Hamoud, S., Aviram, M. Circulation (2004) [Pubmed]
  16. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress induces monocyte adhesion by stimulating reactive oxygen species production from a nox1-based NADPH oxidase. Sorescu, G.P., Song, H., Tressel, S.L., Hwang, J., Dikalov, S., Smith, D.A., Boyd, N.L., Platt, M.O., Lassègue, B., Griendling, K.K., Jo, H. Circ. Res. (2004) [Pubmed]
  17. AT1 receptor agonistic antibodies from preeclamptic patients stimulate NADPH oxidase. Dechend, R., Viedt, C., Müller, D.N., Ugele, B., Brandes, R.P., Wallukat, G., Park, J.K., Janke, J., Barta, P., Theuer, J., Fiebeler, A., Homuth, V., Dietz, R., Haller, H., Kreuzer, J., Luft, F.C. Circulation (2003) [Pubmed]
  18. Involvement of NADPH oxidase isoforms and Src family kinases in CD95-dependent hepatocyte apoptosis. Reinehr, R., Becker, S., Eberle, A., Grether-Beck, S., Häussinger, D. J. Biol. Chem. (2005) [Pubmed]
  19. Involvement of several protein kinases in the phosphorylation of p47-phox. Yamaguchi, M., Saeki, S., Yamane, H., Okamura, N., Ishibashi, S. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  20. Both inducible nitric oxide synthase and NADPH oxidase contribute to the control of virulent phase I Coxiella burnetii infections. Brennan, R.E., Russell, K., Zhang, G., Samuel, J.E. Infect. Immun. (2004) [Pubmed]
  21. p47phox deficiency impairs NF-kappa B activation and host defense in Pseudomonas pneumonia. Sadikot, R.T., Zeng, H., Yull, F.E., Li, B., Cheng, D.S., Kernodle, D.S., Jansen, E.D., Contag, C.H., Segal, B.H., Holland, S.M., Blackwell, T.S., Christman, J.W. J. Immunol. (2004) [Pubmed]
  22. p47phox-dependent NADPH oxidase regulates flow-induced vascular remodeling. Castier, Y., Brandes, R.P., Leseche, G., Tedgui, A., Lehoux, S. Circ. Res. (2005) [Pubmed]
  23. Genetics of autoimmune diseases: a multistep process. Johannesson, M., Hultqvist, M., Holmdahl, R. Curr. Top. Microbiol. Immunol. (2006) [Pubmed]
  24. Endothelial NADPH oxidase as the source of oxidants in lungs exposed to ischemia or high K+. Al-Mehdi, A.B., Zhao, G., Dodia, C., Tozawa, K., Costa, K., Muzykantov, V., Ross, C., Blecha, F., Dinauer, M., Fisher, A.B. Circ. Res. (1998) [Pubmed]
  25. Cdc42 regulates arsenic-induced NADPH oxidase activation and cell migration through actin filament reorganization. Qian, Y., Liu, K.J., Chen, Y., Flynn, D.C., Castranova, V., Shi, X. J. Biol. Chem. (2005) [Pubmed]
  26. Repressor activity of CCAAT displacement protein in HL-60 myeloid leukemia cells. Lievens, P.M., Donady, J.J., Tufarelli, C., Neufeld, E.J. J. Biol. Chem. (1995) [Pubmed]
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