Neutrophil cytosolic factor 4

Neutrophil cytosol factor 4 is a protein that in humans is encoded by the NCF4 gene.^[5][6]

NCF4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1H6H, 1OEY, 1W6X, 1W70, 1Z9Q, 2DYB
Identifiers
Aliases	NCF4, NCF, P40PHOX, SH3PXD4, Neutrophil cytosolic factor 4, CGD3
External IDs	OMIM: 601488; MGI: 109186; HomoloGene: 525; GeneCards: NCF4; OMA:NCF4 - orthologs
Gene location (Human) Chr. Chromosome 22 (human)[1] Band 22q12.3 Start 36,860,988 bp[1] End 36,878,017 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15 E1|15 37.1 cM Start 78,129,001 bp[2] End 78,146,780 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in blood spleen granulocyte bone marrow monocyte bone marrow cells appendix lymph node synovial membrane placenta Top expressed in granulocyte blood tibiofemoral joint spleen mesenteric lymph nodes bone marrow fetal liver hematopoietic progenitor cell stroma of bone marrow embryo internal carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein dimerization activity phosphatidylinositol-3-phosphate binding protein binding phosphatidylinositol binding lipid binding superoxide-generating NADPH oxidase activator activity Cellular component cytoplasm cytosol endosome membrane phagolysosome endosome membrane trans-Golgi network NADPH oxidase complex Biological process vascular endothelial growth factor receptor signaling pathway immune response positive regulation of catalytic activity vesicle-mediated transport phagocytosis respiratory burst superoxide metabolic process antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent cellular response to oxidative stress cell redox homeostasis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4689 17972 Ensembl ENSG00000275990 ENSG00000100365 ENSMUSG00000071715 UniProt Q15080 P97369 RefSeq (mRNA) NM_000631 NM_013416 NM_008677 RefSeq (protein) NP_000622 NP_038202 NP_032703 Location (UCSC) Chr 22: 36.86 – 36.88 Mb Chr 15: 78.13 – 78.15 Mb PubMed search [3] [4]
Wikidata
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Function

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

GWAS studies showed that Crohn's disease patient with certain SNPs in NCF4 are more susceptible to get Crohn's disease.^[7] Crohn's patient with rs4821544 variants showed a decreased reactive oxygen species after stimulation with GM-CSF which is a proinflammtory cytokine.^[8]

Interactions

Neutrophil cytosolic factor 4 has been shown to interact with Ku70,^[9] Neutrophil cytosolic factor 1^[10][11][12] and Moesin.^[13]