Sequence in raw or FASTA format:
NCF4 neutrophil cytosolic factor 4, 40kDa [
Homo sapiens (human)]
Gene Symbol NCF4
Entrez Gene ID
Full Name neutrophil cytosolic factor 4, 40kDa
Synonyms NCF, P40PHOX, SH3PXD4
General protein information
neutrophil cytosol factor 4
neutrophil cytosol factor 4
neutrophil NADPH oxidase factor 4
SH3 and PX domain-containing protein 4
Gene Type protein-coding
Homo sapiens (human)
Chromosome:22 Map Location:22q13.1
Summary 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. [provided by RefSeq, Jul 2008].
ID Name Evidence
GO:0002474 antigen processing and presentation of peptide antigen via MHC class I TAS
GO:0002479 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent TAS
GO:0006955 immune response TAS
GO:0042590 antigen processing and presentation of exogenous peptide antigen via MHC class I TAS
GO:0043085 positive regulation of catalytic activity IMP
GO:0051701 interaction with host TAS
GO:0055114 oxidation-reduction process TAS
GO:0090382 phagosome maturation TAS
ID Name Evidence
GO:0005515 protein binding IPI
GO:0016176 superoxide-generating NADPH oxidase activator activity IMP
GO:0032266 phosphatidylinositol-3-phosphate binding IDA
GO:0046983 protein dimerization activity TAS
Related articles in PubMed Cutting edge: NADPH oxidase modulates MHC class II antigen presentation by B cells. Crotzer VL, et al. J Immunol, 2012 Oct 15. PMID 22984083. Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis. Paternoster L, et al. Nat Genet, 2011 Dec 25. PMID 22197932. Clinical and genetic risk factors for perianal Crohn's disease in a population-based cohort. Eglinton TW, et al. Am J Gastroenterol, 2012 Apr. PMID 22158027. Cooperation of p40(phox) with p47(phox) for Nox2-based NADPH oxidase activation during Fcγ receptor (FcγR)-mediated phagocytosis: mechanism for acquisition of p40(phox) phosphatidylinositol 3-phosphate (PI(3)P) binding. Ueyama T, et al. J Biol Chem, 2011 Nov 25. PMID 21956105. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Wagner SA, et al. Mol Cell Proteomics, 2011 Oct. PMID 21890473. See all (71) citations in PubMed See citations in PubMed for homologs of this gene provided by HomoloGene
GeneRIFs: Gene References Into Functions
What's a GeneRIF?
Constitutive and inducible intracellular production of reactive oxygen species (ROS) is higher in B cells expressing functional p40phox, supporting a direct role for p40phox in regulating B cell intracellular ROS generation.
Title: Cutting edge: NADPH oxidase modulates MHC class II antigen presentation by B cells.
Genome-wide association studies-reported associations between the NELL1, NCF4, and FAM92B genes and susceptibility to Crohn's disease could not be replicated in Canadian children and young adults.
Title: NELL1, NCF4, and FAM92B genes are not major susceptibility genes for Crohn's disease in Canadian children and young adults.
Younger age at diagnosis, complicated disease behavior, and ileal disease location are risk factors for perianal CD. First report of an association of the NCF4 gene with perianal disease.
Title: Clinical and genetic risk factors for perianal Crohn's disease in a population-based cohort.
cooperation of p40(phox) with p47(phox) for Nox2-based NADPH oxidase activation during Fcgamma receptor (FcgammaR)-mediated phagocytosis
Title: Cooperation of p40(phox) with p47(phox) for Nox2-based NADPH oxidase activation during Fcγ receptor (FcγR)-mediated phagocytosis: mechanism for acquisition of p40(phox) phosphatidylinositol 3-phosphate (PI(3)P) binding.
Results demonstrate that PBEF can prime for PMN respiratory burst activity by promoting p40 and p47 translocation to the membrane.
Title: Pre-B cell colony-enhancing factor (PBEF/Nampt/visfatin) primes neutrophils for augmented respiratory burst activity through partial assembly of the NADPH oxidase.
no association between SNP rs4821544 and the presence of granulomas in Crohn's disease
Title: Granulomas in Crohn's disease: are newly discovered genetic variants involved?
cytosolic localisation depends on direct interaction with F-actin
Title: Subcellular localisation of the p40phox component of NADPH oxidase involves direct interactions between the Phox homology domain and F-actin.
All mutations and some polymorphisms identified in the NCF4 gene in the autosomal forms of chronic granulomatous disease are listed. Review.
Title: Hematologically important mutations: the autosomal recessive forms of chronic granulomatous disease (second update).
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
p40(phox) functions primarily to regulate Fc gamma receptor-induced NADPH oxidase activity rather than assembly, and stimulates superoxide production via a phosphatidylinositol-3-phosphate signal that increases after phagosome internalization.
Title: Fc gamma R-stimulated activation of the NADPH oxidase: phosphoinositide-binding protein p40phox regulates NADPH oxidase activity after enzyme assembly on the phagosome.
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