1.6.3.1: NAD(P)H oxidase (H2O2-forming)
This is an abbreviated version!
For detailed information about NAD(P)H oxidase (H2O2-forming), go to the full flat file.
Word Map on EC 1.6.3.1
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1.6.3.1
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endothelial
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neutrophil
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artery
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p22phox
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dismutase
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angiotensin
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cardiovascular
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apocynin
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hypertension
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oxidases
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nicotinamide
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granulomatous
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cardiac
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fibrosis
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aortic
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atherosclerosis
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catalase
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sod
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leukocyte
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monocyte
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chemiluminescence
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tnf
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pkc
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phorbol
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diphenyleneiodonium
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ii-induced
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iodonium
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diphenylene
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myeloperoxidase
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endothelium-dependent
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hypothyroidism
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oxidase-derived
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renin-angiotensin
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fmlp
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dihydroethidium
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losartan
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tempol
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lucigenin
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nitrotyrosine
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peroxynitrite
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microbicidal
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oxidase-dependent
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vsmcs
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flavocytochrome
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rac2
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medicine
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ros-generating
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tiron
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oxidase-mediated
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synthesis
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agriculture
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fmlp-induced
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thyroperoxidase
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industry
- 1.6.3.1
- endothelial
- neutrophil
- artery
- p22phox
- dismutase
- angiotensin
- cardiovascular
- apocynin
- hypertension
- oxidases
- nicotinamide
- granulomatous
- cardiac
- fibrosis
- aortic
- atherosclerosis
- catalase
- sod
- leukocyte
- monocyte
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chemiluminescence
- tnf
- pkc
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phorbol
- diphenyleneiodonium
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ii-induced
- iodonium
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diphenylene
- myeloperoxidase
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endothelium-dependent
- hypothyroidism
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oxidase-derived
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renin-angiotensin
- fmlp
- dihydroethidium
- losartan
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tempol
- lucigenin
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nitrotyrosine
- peroxynitrite
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microbicidal
-
oxidase-dependent
-
vsmcs
-
flavocytochrome
- rac2
- medicine
-
ros-generating
- tiron
-
oxidase-mediated
- synthesis
- agriculture
-
fmlp-induced
- thyroperoxidase
- industry
Reaction
Synonyms
100787949, 100812342, 100820185, Atrbohc, AtrbohD NADPH oxidase, AtrbohF NADPH oxidase, BLI-3, cytochrome b-245 heavy chain, dual oxidase, Duox, Duox-DuoxA NADPH oxidase, Duox1, Duox2, Glyma.03G236300, Glyma.19G233900, Glyma.20G236200, GLYMA_10G152200, gp91phox, gp91phox/Nox2, KOD1, large NOX, LNOX, NAD(P)H oxidase, NAD(P)H oxidase 4, NADH oxidase, NADPH oxidase, NADPH oxidase 1, NADPH oxidase 2, NADPH oxidase 4, NADPH oxidase 5, NADPH oxidase type 4, NADPH-oxidase, NADPHox, NAPDH oxidase, NM_001184780, NOX, NOX1, Nox2, NOX3, Nox4, NOX4-art, NOX5, p138 thyroid-oxidase, p138tox, p47phox, p67phox, phagocyte NADPH oxidase, phox, RBOH, RBOHB, RbohF, RDH2, RdxA, renal oxidase, renox, Respiratory Burst Oxidase Homolog, respiratory burst oxidase homologue, rth5, SsNOX38, superoxide-generating NADPH oxidase, ThOX, ThOX2, thyroid NADPH oxidase, thyroid oxidase, thyroid oxidase 2, TK0304, TK0828, TK1186, TK1299, TK1481
ECTree
1.6.3.1 NAD(P)H oxidase (H2O2-forming)Advanced search results
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results (Engineering
Engineering on EC 1.6.3.1 - NAD(P)H oxidase (H2O2-forming)
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
S174A
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substitution of Ser174 to Ala results in about 40% reduction in the phosphorylation of AtrbohF by SnRK2 protein kinase open stomata 1 (OST1)
D484T
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mutant of the alpha-helical loop of isoform Nox2, neither NADPH oxidase nor iodonitrotetrazolium reductase activity
D500A
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mutant of the alpha-helical loop of isoform Nox2, neither NADPH oxidase nor iodonitrotetrazolium reductase activity
D500G
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mutant of the alpha-helical loop of isoform Nox2, neither NADPH oxidase nor iodonitrotetrazolium reductase activity
D500R
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mutant of the alpha-helical loop of isoform Nox2, neither NADPH oxidase nor iodonitrotetrazolium reductase activity
D506N
E99Q/E143Q
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site-directed mutagenesis, mutation in the Ca2+ binding domain of NOX5
K195A
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mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
K195E
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mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
medicine
epigenetic silencing of Duox is frequently observed in lung cancer
P437H
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the mutation in the canonical NADPH binding motif of Nox4, analogous to the Nox2 mutation of a CGD patient, abolishes activity
Q36H
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naturally occuring missense mutation. Mutation completely prevents routing of the protein to the cell surface. Protein is predominantly present as core N-glycosylated, thiol-reduced folding intermediate and retained within the endoplasmic reticulum
R198A/R198A
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mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
R198Q/R199Q
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mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
R199E
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mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
R199Q
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mutation in D-loop of isoform Nox2. Formylmethionine-activated mutant shows 4- to 8fold higher activity than wild-type
R376W
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naturally occuring missense mutation. Mutation completely prevents routing of the protein to the cell surface. Protein is predominantly present as core N-glycosylated, thiol-reduced folding intermediate and retained within the endoplasmic reticulum
R57Q
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mutation in the phophatidylinositol 3-phosphate binding region of subunit p47phox. Mutation abrogates phophatidylinositol 3-phosphate binding and produces a dominant inhibitory effect on agonist-induced superoxide production and membrane translocation of subunits p47phox and p67phox. Mutant p40phox displayes increased association with actin and moesin and is found enriched in the Triton X-100-insoluble fraction along with p67phox and p47phox
R57Q/D289A
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double mutant of subunit p40phox. Mutant fails to associate with subunits p67phox or p47phox in co-immunoprecipitation and Western blotting assays and abolishes the dominant inhibitory effect of mutant R57Q in phorbol 12-myristate 13-acetate- or formyl-Met-Leu-Phe-induced superoxide production
R96E
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Nox4 is inhibited by an R96E mutation in the cytosolic B loop, a region of the amino-terminal domain that interacts with the NADPH binding site
S303D/S304D/S320D
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mutant in subunit p47phox,which mimics phosphorylation by p21-activated kinase-1 PAK1. Expression of mutant induces basal superoxide generation in vivo
V674G
medicine
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mRNA for the NAD(P)H oxidase subunits NOX1, NOX2, NOX4, p47phox, and p22phox is present in both celiac ganglion and dorsal root ganglion, mRNA for NOX4 is significantly higher in celiac ganglion than in dorsal root ganglion. Catalytic subunit p22phox mRNA and protein expression is greater in celiac ganglion of hypertensive rats but not in dorsal root ganglion. Subunit p47phox mRNA and protein, as well as Rac-1protein, are significantly decreased in hypertensive dorsal root ganglion but not in celiac ganglion. Subunit p47phox is translocated from cytoplasm to membrane in hypertensive celiac ganglion but not in hypertensive dorsal root ganglion
S82A/S97A
additional information
D506N
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heterozygous mutation isolating in clinically unaffected mother and in a brother, while the patient suffering congenital hypothyroidism additionally carries heterozygous mutation ins602g to fsX300
D506N
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naturally occuring missense mutation. Mutant display a partial deficiency phenotype with reduced surface expression of protein with normal intrinsic activity in generating H2O2. N-glycan moieties of the mutant protein are not subject to normal modification in the Golgi apparatus
V674G
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spontaneous mutation in exon 16 of the Duox2 gene. Thyroid glands of mutant mice are goitrous and contain few normal follicles, anterior pituitaries are dysplastic. Serum thyroxine in homozygotes is about one-tenth the level of controls. The weight of adult mutant mice is approximately half that of littermate controls, and serum IGF-I is reduced. The cochleae of mutant mice exhibit abnormalities characteristic of hypothyroidism, including a delayed formation of the inner sulcus and tunnel of Corti and an abnormally thickened tectorial membrane. Hearing thresholds of adult mutant mice are on average 50-60 decibels above those of controls
V674G
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the mutation is associated with severe congenital hypothyroidism. The mutant enzyme fails to release extracellular H2O2
S82A/S97A
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loss of catalytic activity, with concomitant loss of the potential phosphorylation sites
S82A/S97A
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site-directed mutagenesis, the mutant enzyme is not phosphorylated by StCDPK4 and StCDPK5
additional information
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mutants lacking the activity of isoform rdh2/Atrbohc exhibit an impaired root epidermal cell wall, and mutant root hair bulges burst more than wild-type when challegned in situ with hypo-osmotic low ionic strength medium
additional information
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identification of heterozygous mutation in enzyme gene leading to premature stop at codon 300 and resulting in primary hypothyroidism
additional information
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replacement of D-loop of isoform Nox2 with the homolog of Nox1, Nox3, or Nox4 is fully functional. Formylmethionine-activated mutant D-loopNox4 in Nox2 shows 4- to 8fold higher activity than wild-type
additional information
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a fusion protein NOXA1N-RacQ61L between truncated subunit NOXA1 residues1-211 and constitutively active Rac1 mutant Q61L exhibits 6-fold increase of the basal Nox1 activity, but C-terminal truncated NOXO1 residues 1-292 show little effect on the activity
additional information
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depletion of endogenous subunit p40phoxusing lentiviral short hairpin RNA reduces reactive oxygen species production and impairs bacterial killing by phagolysosomes under conditions where subunit p67phox levels remain constant. Depletion of p40phox reduces both the maximal rate and total amount of ROS produced without altering theKM value of the oxidase forNADPH
additional information
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in cells deficient for von Hippel-Lindau tumor suppressor gene, protein levels of subunit p22phox, of isoform Nox4 and NADPH-dependent superoxide levels are increased. Down-regulation of isoforms Nox1, Nox4, and p22phox expression by small interfering RNA decreases hypoxia-inducible factor 2alpha# protein expression and inhibits Akt and 4E-BP1 phosphorylation
additional information
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in cells with knock-out of beta sub-unit of cytochrome b558 of subunit NOX2, a nitric oxide synthase is able to provide NAD(P)H oxidase activity. Mutants produce roughly the same amount of superoxide anion as wild-type cells, but only half the amount of nitric oxide. In presence of nitric oxides synthase inhibitor L-NAME, production of H2O2 and ONOO- by mutant cells is almost abolished
additional information
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inhibition of subunit Nox4 expression by small interfering RNA reduces angiogenic responses, in both human microvascular and umbilical vein endothelial cells. Overexpression of wild-type Nox4 enhances, whereas expression of a dominant negative form of Nox4 suppresses the angiogenic responses in endothelial cells. These effects are mimicked by exogenous H2O2 and the antioxidant compound ebselen, respectively. Overexpression of Nox4 enhances receptor tyrosine kinase phosphorylation and the activation of extracellular signal-regulated kinase. Nox4 expression also promotes proliferation and migration of endothelial cells, and reduces serum deprivation-induced apoptosis
additional information
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knock-down of isoform Nox4 expression by RNAi results in cell-growth inhibition and enhances induction of apoptosis by chemotherapeutic agents in cultured glioma cell lines
additional information
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knockdown of isoform NOX5-S or NF-kappaB1 p50 by their small interfering RNA significantly inhibits acid-induced cyclooxygenase COX2 expression and prostaglandin PGE2 production in SEG-1 cells. In a Barrett's cell line overexpressing isoform NOX5-S, inhibitor of kappaB is significantly reduced, and luciferase activity increased when these Barrett' s cells are transfected with a plasmid carrying NF-kappaB fused to luciferase. Overexpression of NOX5-S in Barretts cells significantly increases H2O2 production,cyclooxygenase COX2 expression, PGE2 production, and thymidine incorporation
additional information
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silencing of subunit p47phox with siRNA. Active NAD(P)H oxidase is required for vascular endothelial growth factor activation of phosphoinositide 3-kinase-Akt-forkhead, and p38 mitogen-activated kinase, but not extracellular signal-related kinase 1/2 or c-Jnu N-terminal kinase. The permissive role of NADPH oxidase on phosphoinositide 3-kinase-Akt-forkhead signaling is mediated at post-vascular endothelial growth factor receptor levels and involves the nonreceptor tyrosine kinase Src
additional information
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single nucleotide polymorphisms 242C/T and 640A/G in the gene encoding p22phox subunit of NAD(P)H oxidase are marginally significantly associated with asthma, but single nucleotide polymorphisms 640A/G shows a significant association with sensitization to two allergens tested. Haplotype 930G/242T/640A is associated with an increased risk of asthma
additional information
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the linker region between the phox homology domain and N-terminal SH3 domain plays a role in blocking the binding of the phosphoinositide 3,4-bisphosphate. Replacement of linker residues 151-158 with glycine alters NMR-measured spin lattice relaxation rates and sedimentation velocity, suggesting that the phox homology domain is released from its autoinhibited conformation. The mutant displays phosphoinositide 3,4-bisphosphate binding activity comparable to that of the isolated phox homology domain but has greatly reduced NAD(P)H oxidase activity upon activation
additional information
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Nox5 is unaffected by expression or knockdown p22phox intransfected cells. The cytosolic N-terminal segment, containing 4 calcium binding EF-hands is missing in Nox5S, a short calcium-insensitive variant, which is the dominant isoform in carcinoma cells, and expressed together with the long Nox5L in endothelial cells. Replacing the first transmembrane domain of Nox4 by that of Nox1, or altering the last extracellular loop of Nox4, makes it produce superoxide, rather than peroxide. Deletion of the NADPH binding domain produces a dominant-negative Nox4. Nox1-Nox4 and Nox2-Nox4 chimeras are active without transfection of cytosolic subunits, whereas the opposite Nox4-Nox2 chimera requires activation. Mutation of the proline-rich domain of p22phox required for docking organizers does not affect Nox4 activity
additional information
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aortic rings from mice deificient in subunit p47phox are more sensitive to apocynin-induced dilation than wild-type aortic rings
additional information
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compared to wild-type mice with myocardial infarction, subunit gp91phox knockout mice do not display significant difference in infarct size/thickness, cardiac hypertrophy, myocyte apoptosis, inflammatory/fibrogenic responses, as well as cardiac oxidative stress
additional information
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deletion of subunit gp91phox attenuates angiotensin II-induced responses
additional information
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genetic deletion of the NADPH oxidase subunit, p47phox, significantly suppresses increased vessel outgrowth induced by hypoxia/reoxygenation. Increases in myocardial serine-threonine kinase Akt and ERK1/2 activation and vascular endothelial growth factor expression are markedly blunted in the subunit p47phox-deficient mouse subjected to myocardial ischemia-reperfusion compared with the wild-type mouse
additional information
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high-cholesterol fed mice genetically deficient in NAD(P)H oxidase subunit Nox-2 show an attenuation in impaired endothelium-dependent vasodilation and enhanced superoxide generation compaired to wild-type
additional information
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in mice deficient in subunit gp91phox, middle cerebral artery occlusion-induced blood-brain barrier disruption and lesion volume in ischemia-induced animals are largely attenuated
additional information
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in mice lacking the subunit gp91phox, the effects of low K intake on superoxide production, c-Jun phosphorylation, c-Src expression, and tyrosine phosphorylation of ROMK channels are significantly attenuated
additional information
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in obese, diabetic, leptin-receptor deficient db-/db- mice, mRNA levels of enzyme subunits Nox-1, Nox-2, and Nox-4 as well as Nox-2 protein expression are elevated, whereas aortic Cu/Zn superoxide dismutase protein and PPARgamma mRNA levels are reduced
additional information
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macrophages derived from NADPH oxidase deficient mice display reduced superoxide production, released lower levels of cytokines/chemokines, and induce less neurotoxicity in response to HIV regulatory protein Tat compared to wild-type macrophages
additional information
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mice deficient in NAD(P)H oxidase p47phox show an increase of 17% of the area occupied by airway smooth muscle cells in trachea, compared with wild-type. They exhibit a significantly reduced airway smooth muscle cell relaxation during electric field stimulation and after the end of stimulation
additional information
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mice deficient in NADPH oxidase subunit gp91phox, CYBB mice, are irradiated and receive wild-type hematopoietic cells to generate chimeric CYBB mice. In response to ovalbumin challenge, the chimeric CYBB mice have increased numbers of eosinophils bound to the endothelium as well as reduced eosinophilia in the lung tissue and bronchoalveolar lavage. Ovalbumin-challenged chimeric CYBB mice have reduced airway hyperresponsiveness that can be restored by bypassing the endothelium with intratracheal administration of eosinophils
additional information
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mice lacking the NAD(P)H oxidase gp91phox subunit respond to exposure to single-walled carbon nanotubes with a marked accumulation of polymorphnuclear neutrophils and elevated levels of apoptotic cells in the lungs, production of pro-inflammatory cytokines, decreased production of the anti-inflammatory and pro-fibrotic cytokine, TGF-beta, and significantly lower levels of collagen deposition
additional information
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neither mice lacking subunit gp91, lacking myeloperoxidase, nor lymphocyte-deficient recombinase activating gene-1 ko mice develop spontaneous infections when raised under specific pathogen-free conditions and all mice have life spans similar to wild-type animals. Subunit gp91/recombinase activating gene-1 double-deficient but not myeloperoxidase/recombinase activating gene-1 double-deficient mice develop spontaneous multi-organ bacterial and fungal infections early in life and live only a few months. Infections in the gp91/recombinase activating gene-1 double-deficient mice are characterized by granulomatous inflammation of the skin, liver, heart, brain, kidney, and lung. Oyster glycogen-elicited polymorphonuclear neutrophils and macrophages obtained from gp91 ko and gp91/recombinase activating gene-1 double-deficient mice have no detectable NADPH oxidase activity whereas wild-type, recombinase activating gene-1 ko, and myeloperoxidase/recombinase activating gene-1 polymorphonuclear neutrophils and macrophages produce large and similar amounts of superoxide in response to phorbol myristate acetate
additional information
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NOX2-deficient mice serve as chronic granulomatous disease mouse model
additional information
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a C242T mutation in the p22phox gene is associated with insulin resistance in non-diabetic subjects
additional information
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isoform NOX-1 elimination by gene replacement results in complete female sterility, decreased asexual development, and reduction of hyphal growth. The lack of isoform NOX-2 does not affect any of these processes but leads instead to the production of sexual spores that fail to germinate, even in the presence of exogenous oxidants. The elimination of NOR-1, an ortholog of the mammalian Nox2 regulatory subunit gp67phox, also causes female sterility, the production of unviable sexual spores, and a decrease in asexual development and hyphal growth
additional information
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transfection of tobacco pollen tubes with NAD(P)H oxidase-specific antisense oligodeoxynucleotides results in decreased amount of enzyme mRNA, lower enzyme activity, and tube growth inhibition
additional information
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transient co-expression of rice cytosolic regulator subunit Rac and the catalytic subunit Rboh enhances production of reactive oxygen species in Nicotiana benthamiana
additional information
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both genes coding for NAD(P)H oxidases, Nox1 and Nox2, are independently required for pathogenicity. Mutants lacking either nox1 or nox2 are incapable of causing plant disease because of unability to bring about appresorium-mediated cuticle penetration. A nox1nox2 double mutant shows significant increase in superoxide production at the hyphal tips
additional information
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silencing of genes Ssnox1 and Ssnox2 by siRNA using two silencing vectors (pSNOX1 and pSNOX2) carrying the hygromycin B resistance gene as the selectable marker, defect in sclerotial development of Nox silenced strains, phenotype overview
additional information
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silencing of genes Ssnox1 and Ssnox2 by siRNA using two silencing vectors (pSNOX1 and pSNOX2) carrying the hygromycin B resistance gene as the selectable marker, defect in sclerotial development of Nox silenced strains, phenotype overview
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additional information
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heterologous expression of protein kinase CDPK5 and the catalytic subunit RBOHB in Nicotiana benthamiana results in phosphorylated S82 of RBOHB
