Neutrophil cytosolic factor 1 explained

Neutrophil cytosol factor 1, also known as p47phox, is a protein that in humans is encoded by the NCF1 gene.^[1]

Function

The protein encoded by this gene is a 47 kDa cytosolic subunit of neutrophil NADPH oxidase. This oxidase is a multicomponent enzyme that is activated to produce superoxide anion. Mutations in this gene have been associated with chronic granulomatous disease.^[1]

Genetic variability in the NCF1 gene has been found to be related to a higher chance of getting autoimmune diseases such as Sjögren's syndrome, rheumatoid arthritis and lupus erythematosus.^[2]

p47 is vital to the activation of NADPH oxidase. P47 becomes heavily phosphorylated

Interactions

Neutrophil cytosolic factor 1 has been shown to interact with:

• Moesin,^[3]
• Neutrophil cytosolic factor 4,^{[4] [5] [6]} and
• RELA.^[7]

Further reading

• Dorseuil O, Gacon G . [Signal transduction by Rac small G proteins in phagocytes] . C. R. Séances Soc. Biol. Fil. . 191 . 2 . 237–46 . 1997 . 9255350 .
• Casimir CM, Bu-Ghanim HN, Rodaway AR, Bentley DL, Rowe P, Segal AW . Autosomal recessive chronic granulomatous disease caused by deletion at a dinucleotide repeat . Proc. Natl. Acad. Sci. U.S.A. . 88 . 7 . 2753–7 . 1991 . 2011585 . 51317 . 10.1073/pnas.88.7.2753 . 1991PNAS...88.2753C . free .
• Rodaway AR, Teahan CG, Casimir CM, Segal AW, Bentley DL . Characterization of the 47-kilodalton autosomal chronic granulomatous disease protein: tissue-specific expression and transcriptional control by retinoic acid . Mol. Cell. Biol. . 10 . 10 . 5388–96 . 1990 . 2398896 . 361238 . 10.1128/mcb.10.10.5388.
• Lomax KJ, Leto TL, Nunoi H, Gallin JI, Malech HL . Recombinant 47-kilodalton cytosol factor restores NADPH oxidase in chronic granulomatous disease . Science . 245 . 4916 . 409–12 . 1989 . 2547247 . 10.1126/science.2547247 . 1989Sci...245..409L .
• Volpp BD, Nauseef WM, Donelson JE, Moser DR, Clark RA . Cloning of the cDNA and functional expression of the 47-kilodalton cytosolic component of human neutrophil respiratory burst oxidase . Proc. Natl. Acad. Sci. U.S.A. . 86 . 18 . 7195–9 . 1989 . 2550933 . 298023 . 10.1073/pnas.86.18.7195 . 1989PNAS...86.7195V . free .
• Volpp BD, Nauseef WM, Clark RA . Two cytosolic neutrophil oxidase components absent in autosomal chronic granulomatous disease . Science . 242 . 4883 . 1295–7 . 1988 . 2848318 . 10.1126/science.2848318 . 1988Sci...242.1295V .
• Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W . A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1 . Science . 266 . 5182 . 66–71 . 1994 . 7545954 . 10.1126/science.7545954 . 1994Sci...266...66M . free .
• Leto TL, Adams AG, de Mendez I . Assembly of the phagocyte NADPH oxidase: binding of Src homology 3 domains to proline-rich targets . Proc. Natl. Acad. Sci. U.S.A. . 91 . 22 . 10650–4 . 1994 . 7938008 . 45079 . 10.1073/pnas.91.22.10650 . 1994PNAS...9110650L . free .
• el Benna J, Faust LP, Babior BM . The phosphorylation of the respiratory burst oxidase component p47phox during neutrophil activation. Phosphorylation of sites recognized by protein kinase C and by proline-directed kinases . J. Biol. Chem. . 269 . 38 . 23431–6 . 1994 . 10.1016/S0021-9258(17)31534-X . 8089108 . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Finan PM, Hall A, Kellie S . Sam68 from an immortalised B-cell line associates with a subset of SH3 domains . FEBS Lett. . 389 . 2 . 141–4 . 1996 . 8766817 . 10.1016/0014-5793(96)00552-2 . 19631155 . free . 1996FEBSL.389..141F .
• Sathyamoorthy M, de Mendez I, Adams AG, Leto TL . p40(phox) down-regulates NADPH oxidase activity through interactions with its SH3 domain . J. Biol. Chem. . 272 . 14 . 9141–6 . 1997 . 9083043 . 10.1074/jbc.272.14.9141 . free .
• Görlach A, Lee PL, Roesler J, Hopkins PJ, Christensen B, Green ED, Chanock SJ, Curnutte JT . A p47-phox pseudogene carries the most common mutation causing p47-phox- deficient chronic granulomatous disease . J. Clin. Invest. . 100 . 8 . 1907–18 . 1997 . 9329953 . 508379 . 10.1172/JCI119721 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Izuhara K, Arinobu Y, Sumimoto H, Nunoi H, Takeya R, Higuchi K, Takeshige K, Hamasaki N, Harada N . Association of the interleukin-4 receptor alpha chain with p47phox, an activator of the phagocyte NADPH oxidase in B cells . Mol. Immunol. . 36 . 1 . 45–52 . 1999 . 10369419 . 10.1016/S0161-5890(98)00111-4 .
• Nakamura F, Huang L, Pestonjamasp K, Luna EJ, Furthmayr H . Regulation of F-actin binding to platelet moesin in vitro by both phosphorylation of threonine 558 and polyphosphatidylinositides . Mol. Biol. Cell . 10 . 8 . 2669–85 . 1999 . 10436021 . 25498 . 10.1091/mbc.10.8.2669 .
• Rinckel LA, Faris SL, Hitt ND, Kleinberg ME . Rac1 disrupts p67phox/p40phox binding: a novel role for Rac in NADPH oxidase activation . Biochem. Biophys. Res. Commun. . 263 . 1 . 118–22 . 1999 . 10486263 . 10.1006/bbrc.1999.1334 .
• Chanock SJ, Roesler J, Zhan S, Hopkins P, Lee P, Barrett DT, Christensen BL, Curnutte JT, Görlach A . Genomic structure of the human p47-phox (NCF1) gene . Blood Cells Mol. Dis. . 26 . 1 . 37–46 . 2000 . 10772875 . 10.1006/bcmd.2000.0274 .
• Onofri F, Giovedi S, Kao HT, Valtorta F, Bongiorno Borbone L, De Camilli P, Greengard P, Benfenati F . Specificity of the binding of synapsin I to Src homology 3 domains . J. Biol. Chem. . 275 . 38 . 29857–67 . 2000 . 10899172 . 10.1074/jbc.M006018200 . free .

Notes and References

1. Web site: Entrez Gene: NCF1 neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1).
2. News: Study of complex genetic region finds hidden role of NCF1 in multiple autoimmune diseases. 2017-02-08. Medical Express. 2017-02-09.
3. Wientjes FB, Reeves EP, Soskic V, Furthmayr H, Segal AW . The NADPH oxidase components p47(phox) and p40(phox) bind to moesin through their PX domain . Biochem. Biophys. Res. Commun. . 289 . 2 . 382–8 . Nov 2001 . 11716484 . 10.1006/bbrc.2001.5982 .
4. Lapouge K, Smith SJ, Groemping Y, Rittinger K . Architecture of the p40-p47-p67phox complex in the resting state of the NADPH oxidase. A central role for p67phox . J. Biol. Chem. . 277 . 12 . 10121–8 . Mar 2002 . 11796733 . 10.1074/jbc.M112065200 . free .
5. Grizot S, Grandvaux N, Fieschi F, Fauré J, Massenet C, Andrieu JP, Fuchs A, Vignais PV, Timmins PA, Dagher MC, Pebay-Peyroula E . Small angle neutron scattering and gel filtration analyses of neutrophil NADPH oxidase cytosolic factors highlight the role of the C-terminal end of p47phox in the association with p40phox . Biochemistry . 40 . 10 . 3127–33 . Mar 2001 . 11258927 . 10.1021/bi0028439.
6. Sathyamoorthy M, de Mendez I, Adams AG, Leto TL . p40(phox) down-regulates NADPH oxidase activity through interactions with its SH3 domain . J. Biol. Chem. . 272 . 14 . 9141–6 . Apr 1997 . 9083043 . 10.1074/jbc.272.14.9141. free .
7. Gu Y, Xu YC, Wu RF, Nwariaku FE, Souza RF, Flores SC, Terada LS . p47phox participates in activation of RelA in endothelial cells . J. Biol. Chem. . 278 . 19 . 17210–7 . May 2003 . 12618429 . 10.1074/jbc.M210314200 . free .