Neutrophil Cytosolic Factor 4 (NCF4)

NCF; P40PHOX; SH3PXD4; Neutrophil NADPH Oxidase Factor 4; SH3 and PX domain-containing protein 4

SPN	W452
HGNC	7662
MGI	109186
PubMed	23982929
RGD	1593157
UniProt	Q15080
Wiki	NCF4

Neutrophil cytosol factor 4 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.

Reference

"p40phox, a third cytosolic component of the activation complex of the NADPH oxidase to contain src homology 3 domains."
Biochem. J. 296:557-561(1993) [PubMed] [Europe PMC] [Abstract]

"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 88:2714-2721(1996) [PubMed] [Europe PMC] [Abstract]

"Identification of a splice variant mRNA of p40phox, an NADPH oxidase component of phagocytes."
FEBS Lett. 455:257-261(1999) [PubMed] [Europe PMC] [Abstract]

"A genome annotation-driven approach to cloning the human ORFeome."
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence of human chromosome 22."
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"p40(phox) is phosphorylated on threonine 154 and serine 315 during activation of the phagocyte NADPH oxidase. Implication of a protein kinase c-type kinase in the phosphorylation process."
J. Biol. Chem. 273:30097-30103(1998) [PubMed] [Europe PMC] [Abstract]

"The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate."
Mol. Cell 8:829-839(2001) [PubMed] [Europe PMC] [Abstract]

"PB1 domain-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62."
Mol. Cell 12:39-50(2003) [PubMed] [Europe PMC] [Abstract]

"Effects of p47phox C terminus phosphorylations on binding interactions with p40phox and p67phox. Structural and functional comparison of p40phox and p67phox SH3 domains."
J. Biol. Chem. 280:13752-13761(2005) [PubMed] [Europe PMC] [Abstract]

"Full-length p40phox structure suggests a basis for regulation mechanism of its membrane binding."
EMBO J. 26:1176-1186(2007) [PubMed] [Europe PMC] [Abstract]

"A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity."
Blood 114:3309-3315(2009) [PubMed] [Europe PMC] [Abstract]