Table 1.

Nox Family of Proteins

Nox isozyme	Subunits/regulators	Tissue expression/ROS type	Main features
Nox1	p22phox, NOXO1, NOXA1, Rac1 (canonical), or p22phox, p47phox, NOXA1, Rac1 (hybrid)	Heart, lungs, blood vessels, brain.	Depending on the cell type can utilize varied cytosolic subunits (canonical or hybrid). The canonical system is constitutively active. Involved in necrosis, hypertrophy, migration, and tissue growth.
		Superoxide anion.
Nox2	p22phox, p47phox, p67phox, p40phox, Rac1, or Rac2	Innate immune cells, heart, lungs, blood vessels, brain.	Prototype Nox. Tightly regulated. Involved in immune defense, angiogenesis, neurodegenerative disorders, and necrosis.
		Superoxide anion.
Nox3	p22phox, NOXO1, NOXA1 (p47/p67), Rac1	Inner ear (cochlear and vestibular sensory epithelia).	Constitutively active. Involved in balance, otoconia biosynthesis, and potentially hearing loss.
		Superoxide anion.
Nox4	p22phox, Poldip2	Heart, lungs, blood vessels, kidney, prostate.	Involved in differentiation, migration, growth, and survival.
		Hydrogen peroxide (?).
Nox5	No subunit identified to date. Regulated by Ca2+	Cardiovascular system, spleen lymph nodes, testes.	EF hand domains. Involved in inflammatory gene expression, growth, and proliferation.
		Superoxide anion.
Duox1	DUOXA1 (for maturation)	Thyroid gland, airway epithelium, cerebellum, testis, prostate.	EF hand domains and N-terminal peroxidase-like domain. Involved in thyroid function.
		Hydrogen peroxide.
Duox2	DUOXA2 (for maturation)	Thyroid gland, airway epithelium, gastrointestinal epithelia, uterus, gallbladder.	EF hand domains and N-terminal peroxidase-like domain. Involved in thyroid hormone synthesis.
		Hydrogen peroxide.

(?)=noted controversy as to whether H₂O₂ or superoxide is the primary metabolite.

Nox, NADPH oxidase; ROS, reactive oxygen species.