Neutrophil cytosolic factor 4

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Neutrophil cytosolic factor 4, 40kDa
Protein NCF4 PDB 1h6h.png
PDB rendering based on 1h6h.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols NCF4 ; NCF; P40PHOX; SH3PXD4
External IDs OMIM601488 MGI109186 HomoloGene525 GeneCards: NCF4 Gene
RNA expression pattern
PBB GE NCF4 207677 s at tn.png
PBB GE NCF4 205147 x at tn.png
More reference expression data
Species Human Mouse
Entrez 4689 17972
Ensembl ENSG00000100365 ENSMUSG00000071715
UniProt Q15080 P97369
RefSeq (mRNA) NM_000631 NM_008677
RefSeq (protein) NP_000622 NP_032703
Location (UCSC) Chr 22:
37.26 – 37.27 Mb
Chr 15:
78.24 – 78.26 Mb
PubMed search [1] [2]

Neutrophil cytosol factor 4 is a protein that in humans is encoded by the NCF4 gene.[1][2]


The protein encoded by this gene is a cytosolic regulatory component of the superoxide-producing phagocyte NADPH-oxidase, a multicomponent enzyme system important for host defense. This protein is preferentially expressed in cells of myeloid lineage. It interacts primarily with neutrophil cytosolic factor 2 (NCF2/p67-phox) to form a complex with neutrophil cytosolic factor 1 (NCF1/p47-phox), which further interacts with the small G protein RAC1 and translocates to the membrane upon cell stimulation. This complex then activates flavocytochrome b, the membrane-integrated catalytic core of the enzyme system. The PX domain of this protein can bind phospholipid products of the PI(3) kinase, which suggests its role in PI(3) kinase-mediated signaling events. The phosphorylation of this protein was found to negatively regulate the enzyme activity. Alternatively spliced transcript variants encoding distinct isoforms have been observed.

Clinical significance[edit]

GWAS studies showed that Crohn`s disease patient with certain SNPs in NCF4 are more susceptible to get Crohn`s disease.[3] Crohn`s patient with rs4821544 variants showed a decreased Reactive oxygen species after stimulation with GM-CSF which is a proinflammtory cytokine[4]


Neutrophil cytosolic factor 4 has been shown to interact with Ku70,[5] Neutrophil cytosolic factor 1[6][7][8] and Moesin.[9]


  1. ^ Zhan S, Vazquez N, Zhan S, Wientjes FB, Budarf ML, Schrock E et al. (Nov 1996). "Genomic structure, chromosomal localization, start of transcription, and tissue expression of the human p40-phox, a new component of the nicotinamide adenine dinucleotide phosphate-oxidase complex". Blood 88 (7): 2714–21. PMID 8839867. 
  2. ^ "Entrez Gene: NCF4 neutrophil cytosolic factor 4, 40kDa". 
  3. ^ Muise AM, Xu W, Guo CH, Walters TD, Wolters VM, Fattouh R et al. (2012). "NADPH oxidase complex and IBD candidate gene studies: identification of a rare variant in NCF2 that results in reduced binding to RAC2". Gut 61 (7): 1028–35. doi:10.1136/gutjnl-2011-300078. PMC 3806486. PMID 21900546. 
  4. ^ Somasundaram R, Deuring JJ, van der Woude CJ, Peppelenbosch MP, Fuhler GM (2012). "Linking risk conferring mutations in NCF4 to functional consequences in Crohn's disease". Gut 61 (7): 1097; author reply 1097–8. doi:10.1136/gutjnl-2011-301344. PMID 22027479. 
  5. ^ Grandvaux N, Grizot S, Vignais PV, Dagher MC (Feb 1999). "The Ku70 autoantigen interacts with p40phox in B lymphocytes". J. Cell. Sci. 112 ( Pt 4) (4): 503–13. PMID 9914162. 
  6. ^ Lapouge K, Smith SJ, Groemping Y, Rittinger K (Mar 2002). "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. doi:10.1074/jbc.M112065200. PMID 11796733. 
  7. ^ Grizot S, Grandvaux N, Fieschi F, Fauré J, Massenet C, Andrieu JP et al. (Mar 2001). "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. doi:10.1021/bi0028439. PMID 11258927. 
  8. ^ Sathyamoorthy M, de Mendez I, Adams AG, Leto TL (Apr 1997). "p40(phox) down-regulates NADPH oxidase activity through interactions with its SH3 domain". J. Biol. Chem. 272 (14): 9141–6. doi:10.1074/jbc.272.14.9141. PMID 9083043. 
  9. ^ Wientjes FB, Reeves EP, Soskic V, Furthmayr H, Segal AW (Nov 2001). "The NADPH oxidase components p47(phox) and p40(phox) bind to moesin through their PX domain". Biochem. Biophys. Res. Commun. 289 (2): 382–8. doi:10.1006/bbrc.2001.5982. PMID 11716484. 

Further reading[edit]