Figure 1. NADPH oxidase (NOX) family members.

NOXs comprise a family of transmembrane proteins with 6 or 7 transmembrane (TM) domains. NOX1–3 require assembly of cytosolic regulatory subunits (NOXA1, NOXO1, p47phox, p67phox and Rac1/2) for activation. NOX4 is constitutively active though its catalytic activity is increased by Poldip2 and tyrosine kinase substrates with 4 or 5 Src (SH3) homology domains (Tks 4/5). Tks 4/5 can also activate NOX1. NOXs 1–4 catalytic subunits are associated with p22phox which stabilizes the complex. NOX5 and DUOX1 & 2 do not bind to p22phox but have 4 or 2 Ca2+ binding sites, EF-hands, respectively. NOX5 possesses a calmodulin binding-domain, and its stability is regulated by heat shock protein 90 (HSP90). DUOX1 & 2 have an extra TM from which a peroxidase-like domain extends extracellularly at the N-terminus of the isoform.