Family

Neutrophil cytosol factor 2 (IPR034889)

Short name: P67-PHOX

Overlapping homologous superfamilies

None.

Family relationships

None.

Description

NADPH oxidase is a multisubunit complex that assembles during phagocytosis to generate reactive oxygen species. Neutrophil cytosol factor 2 (NCF2/p67-phox) and 1 (NCF1/p47-phox) are required for activation of the phagocyte NADPH oxidase. The activators p67phox and p47phox form a ternary complex together with adaptor protein p40phox. P40phox is involved in activation of the phagocyte oxidase by regulating membrane recruitment of p67phox and p47phox [PMID: 12207919, PMID: 27487400]. p40phox associates with p67phox via binding of the p40phox PC motif to the p67phox PB1 domain [PMID: 27487400].

Phagocytes form the first line of defence against invasion by microorganisms. Engulfing of bacteria by neutrophils is accompanied by the consumption of large amounts of oxygen - a so-called respiratory burst. Defects in phagocytosis involving the lack of a respiratory burst give rise to chronic granulomatous disease (CGD), in which patients are pre- disposed to infection, often from otherwise non-pathogenic bacteria [PMID: 8796870].

Regulation of the respiratory burst takes place at the phagocytic vacuole. The process is mediated by NADPH oxidase, which transports electrons across the plasma membrane to form superoxide (an oxygen molecule with an extra electron that is toxic to normal cells) in the vacuole interior. The electrons are carried across the membrane by a short electron transport chain in the form of an unusual flavocytochrome b [PMID: 8796870]. To conserve NADPH and avoid the toxic effects of superoxide, the oxidase remains inactive until it receives an appropriate stimulus. Activation involves the participation of a number of cytosolic proteins, some of which attach to the flavocytochrome. Upon activation, p47phox and p67phox are phosphorylated and, with p40phox, translocate to the region of the plasma membrane forming the phagocytic vacuole, where they associates with hydrophilic regions of the flavocytochrome [PMID: 8796870].

GO terms

Biological Process

GO:0006909 phagocytosis
GO:0045730 respiratory burst

Molecular Function

GO:0016176 superoxide-generating NADPH oxidase activator activity

Cellular Component

GO:0043020 NADPH oxidase complex

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PANTHER