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Information on EC 1.6.3.1 - NAD(P)H oxidase (H2O2-forming) and Organism(s) Homo sapiens
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1.6.3.1 NAD(P)H oxidase (H2O2-forming)IUBMB Comments
Requires FAD, heme and calcium. When calcium is present, this transmembrane glycoprotein generates H2O2 by transfering electrons from intracellular NAD(P)H to extracellular molecular oxygen. The electron bridge within the enzyme contains one molecule of FAD and probably two heme groups. This flavoprotein is expressed at the apical membrane of thyrocytes, and provides H2O2 for the thyroid peroxidase-catalysed biosynthesis of thyroid hormones.
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Word Map
- 1.6.3.1
- endothelial
- neutrophil
- artery
- p22phox
- dismutase
- angiotensin
- cardiovascular
- apocynin
- hypertension
- oxidases
- nicotinamide
- granulomatous
- cardiac
- fibrosis
- aortic
- atherosclerosis
- catalase
- sod
- leukocyte
- monocyte
-
chemiluminescence
- tnf
- pkc
-
phorbol
- diphenyleneiodonium
-
ii-induced
- iodonium
-
diphenylene
- myeloperoxidase
-
endothelium-dependent
- hypothyroidism
-
oxidase-derived
-
renin-angiotensin
- fmlp
- dihydroethidium
- losartan
-
tempol
- lucigenin
-
nitrotyrosine
- peroxynitrite
-
microbicidal
-
oxidase-dependent
-
vsmcs
-
flavocytochrome
- rac2
- medicine
-
ros-generating
- tiron
-
oxidase-mediated
- synthesis
- agriculture
-
fmlp-induced
- thyroperoxidase
- industry
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
nad(p)h oxidase, p47phox, gp91phox, nadph-oxidase, p67phox, duox2, duox1, nadph oxidase 4, phagocyte nadph oxidase, nadph oxidase 2, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
dual oxidase
-
-
-
-
Duox
-
-
-
-
Duox1
Duox2
gp91phox
large NOX
-
-
-
-
LNOX
-
-
-
-
NADPH oxidase
NADPH oxidase 4
NOX1
Nox2
NOX3
Nox4
NOX5
p138 thyroid-oxidase
-
-
-
-
p138tox
-
-
-
-
ThOX
-
-
-
-
ThOX2
-
-
-
-
thyroid NADPH oxidase
-
-
-
-
thyroid oxidase
-
-
-
-
thyroid oxidase 2
-
-
-
-
NADPH oxidase
-
-
-
-
NADPH oxidase
-
the phagocyte NADPH oxidase is a multicomponent enzyme complex comprising six proteins, namely p22phox (phox: phagocyte oxidase), gp91phox, p47phox, p67phox, p40phox and the small G-protein Rac1 or Rac2
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
NAD(P)H + H+ + O2 = NAD(P)+ + H2O2
model of electron transport from NADPH to the terminal electron acceptor O2
-
NAD(P)H + H+ + O2 = NAD(P)+ + H2O2
a cytosolic C-terminal dehydrogenase domain includes an FAD cofactor and an NADPH substrate binding site. On activation, electrons are transferred from NADPH to FAD and across the membrane, via heme irons, to molecular oxygen, thus producing superoxide anion, which can be dismutated into hydrogen peroxide
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
NAD(P)H:oxygen oxidoreductase (H2O2-forming)
Requires FAD, heme and calcium. When calcium is present, this transmembrane glycoprotein generates H2O2 by transfering electrons from intracellular NAD(P)H to extracellular molecular oxygen. The electron bridge within the enzyme contains one molecule of FAD and probably two heme groups. This flavoprotein is expressed at the apical membrane of thyrocytes, and provides H2O2 for the thyroid peroxidase-catalysed biosynthesis of thyroid hormones.
CAS REGISTRY NUMBER
COMMENTARY
9032-22-8
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
NADPH + H+ + O2
NADP+ + H2O2
-
-
687742, 710782, 711166, 711688, 711763, 712075, 712673, 712711, 712713, 713338, 724704, 724778, 741619, 742310, 742556, 742557, 743686
-
-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
enzyme deficiency causes serious hypothyroidism
-
-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
-
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
-
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
-
NAD(P)H oxidase transfers electrons across membranes to oxygen and generate superoxide anions which rapidly dismutate to hydrogen peroxide
-
-
?
NADH + H+ + O2
NAD+ + H2O2
-
-
-
-
?
NADH + H+ + O2
NAD+ + H2O2
-
2 electrons are transferred from cytosolic NADPH to FAD and in succession across the membrane, via redox changes in heme irons. Finally, each electron reduces a molecule of oxygen to a superoxide radical, which is subsequently released outside the cell or in a topologically equivalent compartment, such as a vesicle lumen
-
-
?
NADPH + O2
NADP+ + O2-
-
enzyme is stimulated by phagocytizable particles
-
?
NADPH + O2
NADP+ + O2-
-
part of defense mechanism against a wide variety of bacteria
-
?
additional information
?
-
-
direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappaB
-
-
?
additional information
?
-
-
the production of reactive oxygen species is initiated by the phygocyte NADPH oxidase
-
-
?
additional information
?
-
-
enzyme isoform Nox3 plays an integral role in insulin-induced p42/44 MAPK signal transmission and VEGF-A production
-
-
?
additional information
?
-
-
essential role of enzyme-generated reactive oxigen species in insulin-stimulated activation of hypoxia-inducible factor 1
-
-
?
additional information
?
-
-
formation of a complex consisting of enzyme, guanine exchange factor for Rac, betaPix, and enzyme organizer NoxO1 is a critical step in EGF-induced generation of reactive oxygen species
-
-
?
additional information
?
-
-
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
?
-
-
NAD(P)H oxidase plays an essential role in maintaining basal levels of reactive oxygen species in NB-4 cells
-
-
?
additional information
?
-
-
subunit p40phox functions primarily to regulate Fcgamma receptor-induced NADPH oxidase activity rather than assembly of the enzyme, and stimulates superoxide production via a phosphoinositol 3-phosphate signal that increases after phagosome internalization
-
-
?
additional information
?
-
-
chronic granulomatous disease is a rare inherited immunodeficiency syndrome caused by mutations in four genes encoding essential nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex components
-
-
?
additional information
?
-
Duox NADPH oxidases generate hydrogen peroxide at the air-liquid interface of the respiratory tract and at apical membranes of thyroid follicular cells
-
-
?
additional information
?
-
Duox NADPH oxidases generate hydrogen peroxide at the air-liquid interface of the respiratory tract and at apical membranes of thyroid follicular cells
-
-
?
additional information
?
-
-
NADPH oxidase mediates angiotensin II-stimulated protein synthesis downstream of the type 1 receptor AT1 in myometrium smooth muscle cells
-
-
?
additional information
?
-
-
the membrane-bound NADPH oxidase in phagocytes, gp91phox/Nox2, produces superoxide, a precursor of microbicidal oxidants, thereby playing a crucial role in host defense. Activation of gp91phox/Nox2 requires assembly with the cytosolic proteins p67phox and p47phox, each containing two SH3 domains. p67phox-SH3(N) specifically functions in gp91phox/Nox2 activation probably via facilitating oxidase assembly
-
-
?
additional information
?
-
-
the potent anti-inflammatory, cytokine interleukin-10, acts as a down-regulator of the Nox1-based oxidase in the colon, and suggests an important role of ROS derived from Nox1-based oxidase in the initiation of inflammatory responses of the colon
-
-
?
additional information
?
-
-
Nox4 can produce a higher hydrogen peroxide to superoxide ratio than Nox1 and Nox2. NOX2-produced superoxide can be released outside the cell when Nox2 is located at the plasma membrane, thus allowing it to intercept, e.g., with endothelial-derived nitric oxide before it reaches the adjacent smooth muscle cell layer in vessels
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
NADPH + H+ + O2
NADP+ + H2O2
-
-
-
-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
enzyme deficiency causes serious hypothyroidism
-
-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
-
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
-
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
?
NAD(P)H + H+ + O2
NAD(P)+ + H2O2
production of hydrogen peroxide in thyroid gland that is required for thyroid hormone synthesis
-
-
?
NADH + H+ + O2
NAD+ + H2O2
-
2 electrons are transferred from cytosolic NADPH to FAD and in succession across the membrane, via redox changes in heme irons. Finally, each electron reduces a molecule of oxygen to a superoxide radical, which is subsequently released outside the cell or in a topologically equivalent compartment, such as a vesicle lumen
-
-
?
NADPH + O2
NADP+ + O2-
-
enzyme is stimulated by phagocytizable particles
-
?
NADPH + O2
NADP+ + O2-
-
part of defense mechanism against a wide variety of bacteria
-
?
additional information
?
-
-
direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappaB
-
-
?
additional information
?
-
-
the production of reactive oxygen species is initiated by the phygocyte NADPH oxidase
-
-
?
additional information
?
-
-
enzyme isoform Nox3 plays an integral role in insulin-induced p42/44 MAPK signal transmission and VEGF-A production
-
-
?
additional information
?
-
-
essential role of enzyme-generated reactive oxigen species in insulin-stimulated activation of hypoxia-inducible factor 1
-
-
?
additional information
?
-
-
formation of a complex consisting of enzyme, guanine exchange factor for Rac, betaPix, and enzyme organizer NoxO1 is a critical step in EGF-induced generation of reactive oxygen species
-
-
?
additional information
?
-
-
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
?
-
-
NAD(P)H oxidase plays an essential role in maintaining basal levels of reactive oxygen species in NB-4 cells
-
-
?
additional information
?
-
-
subunit p40phox functions primarily to regulate Fcgamma receptor-induced NADPH oxidase activity rather than assembly of the enzyme, and stimulates superoxide production via a phosphoinositol 3-phosphate signal that increases after phagosome internalization
-
-
?
additional information
?
-
-
chronic granulomatous disease is a rare inherited immunodeficiency syndrome caused by mutations in four genes encoding essential nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex components
-
-
?
additional information
?
-
Duox NADPH oxidases generate hydrogen peroxide at the air-liquid interface of the respiratory tract and at apical membranes of thyroid follicular cells
-
-
?
additional information
?
-
Duox NADPH oxidases generate hydrogen peroxide at the air-liquid interface of the respiratory tract and at apical membranes of thyroid follicular cells
-
-
?
additional information
?
-
-
NADPH oxidase mediates angiotensin II-stimulated protein synthesis downstream of the type 1 receptor AT1 in myometrium smooth muscle cells
-
-
?
additional information
?
-
-
the membrane-bound NADPH oxidase in phagocytes, gp91phox/Nox2, produces superoxide, a precursor of microbicidal oxidants, thereby playing a crucial role in host defense. Activation of gp91phox/Nox2 requires assembly with the cytosolic proteins p67phox and p47phox, each containing two SH3 domains. p67phox-SH3(N) specifically functions in gp91phox/Nox2 activation probably via facilitating oxidase assembly
-
-
?
additional information
?
-
-
the potent anti-inflammatory, cytokine interleukin-10, acts as a down-regulator of the Nox1-based oxidase in the colon, and suggests an important role of ROS derived from Nox1-based oxidase in the initiation of inflammatory responses of the colon
-
-
?
additional information
?
-
-
Nox4 can produce a higher hydrogen peroxide to superoxide ratio than Nox1 and Nox2. NOX2-produced superoxide can be released outside the cell when Nox2 is located at the plasma membrane, thus allowing it to intercept, e.g., with endothelial-derived nitric oxide before it reaches the adjacent smooth muscle cell layer in vessels
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
a dehydrogenase domain is binding FAD and NADPH, Nox1, Nox2, and Nox4 requires FAD and NADPH. Nox5 is similar to other Nox enzymes, with 6 transmembrane helices expected to bind 2 hemes and a cytosolic dehydrogenase domain including FAD and NADPH binding sites
heme
-
4 conserved histidine residues in transmembrane helices III and V, thought to coordinate 2 heme molecules, mutation of these histidines abolishes binding to p22phox
NADPH
-
-
NADPH
-
a dehydrogenase domain is binding FAD and NADPH, Nox1, Nox2, and Nox4 requires FAD and NADPH. Nox5 is similar to other Nox enzymes, with 6 transmembrane helices expected to bind 2 hemes and a cytosolic dehydrogenase domain including FAD and NADPH binding sites
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
additional information
-
Mg2+ cannot substitute for Ca2+, metal binding/dissociation kinetics, overview
Ca2+
-
Ca2+-induced conformation change of NADPH oxidase 5 N-terminus leads to enzyme activation through an intramolecular interaction
Ca2+
-
store-operated Ca2+ entry is required at the beginning of NADPH oxidase activation in response to N-formyl-L-methionyl-L-leucyl-Lphenylalanine in neutrophil-like HL-60 cells. When extracellular Ca2+ is initially removed, early addition of Ca2+ after stimulation causes a complete restoration of Ca2+ entry and H2O2production. Both Ca2+ entry and H2O2 production are decreased by purported SOCE blockers, 2-aminoethoxydiphenyl borane (2-APB) and SK&F 96365. Ca2+ influx in HL-60 cells relies on different membrane transient receptor potential canonical channels and Orai1 for allowing NADPH oxidase activation
Ca2+
-
an increase in cytosolic calcium concentration triggers high superoxide production by Nox5. Calcium induces binding of the N-terminal domain of Nox5 to the dehydrogenase domain, thus relieving autoinhibition. Two mechanisms may increase Nox5 sensitivity, allowing activation by resting calcium concentrations: (1) calcium-dependent binding of calmodulin to another site in the dehydrogenase domain157 and (2) phosphorylation of serine and threonine residues by protein kinase C and calcium/calmodulin-dependent kinase II
Ca2+
-
the activity of NOX5 appears to be regulated by a self-contained Ca2+ binding domain, residues 1-169, the conformational change of the domain upon Ca2+ binding is essential for domain-domain interaction and superoxide production. Ca2+ binding to Ca2+ binding domain induces a conformational change that exposes hydrophobic patches and increases the quenching accessibilities of its Trp residues and 5-((((2-iodoacetyl)amino)ethyl)amino)naphthalene-1-sulfonic acid at Cys107, no significant changes in the secondary structures of Ca2+ binding domain upon metal binding. The C-terminal half of the domain has a higher Ca2+ binding affinity, a higher chemical stability, and a slow Ca2+ dissociation. the N- and C-terminal halves of the domain are not completely structurally independent
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(-)-epicatechin
-
serves as prodrug for conversion into apocynin-like NAD(P)H oxidase inhibitors
(-)-epicatechin glucuronide
-
acts both as a superoxide anion scavenger,and inhibitory to NAD(P)H oxidase, with apocynin-like mode of NADPH oxidase inhibition
(-)-epigallocatechin gallate
-
inhibition of intracellular reactive oxygen species generation
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
-
complete inhibition at 0.01 mM
(3Z)-3-(3,4-dihydroxybenzylidene)-5-nitro-1,3-dihydro-2H-indol-2-one
-
complete inhibition at 0.01 mM
(3Z)-3-[4-hydroxy-3,5-di(propan-2-yl)benzylidene]-1,3-dihydro-2H-indol-2-one
-
complete inhibition at 0.01 mM
1-(2-chlorobenzyl)-4-methyl-5-[3-(2-oxopyrrolidin-1-yl)propyl]-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
1-(4-fluorobenzyl)-5-[2-(1H-indol-3-yl)ethyl]-4-methyl-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
1-acetyl-2-(2-chlorophenyl)-4-methyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
1-acetyl-4-methyl-2-(2-methylphenyl)-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
1-acetyl-4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
1-[(3-methoxyphenyl)acetyl]-4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
15-cis-(4-propyl-cyclohexyl)-16,17,18,19,20-pentanor-9-deoxy-9alpha,6-nitrilo-prostaglandin F1 methyl ester
-
0.021 mM, 50% inhibition of the enzyme in neutrophils possible due to scavenging of O2-, inhibition of SDS-induced activation in cell free extracts, 0.22 mM, 50% inhibition
2,3,8,9-tetrahydroxy-5-(2-hydroxy-5-nitrobenzyl)phenanthridin-6(5H)-one
-
complete inhibition at 0.01 mM
2,3,8,9-tetrahydroxy-5-(3-nitrobenzyl)phenanthridin-6(5H)-one
-
complete inhibition at 0.01 mM
2,3,8,9-tetrahydroxy-5-(4-nitrobenzyl)phenanthridin-6(5H)-one
-
93% inhibition at 0.01 mM
2,3,8,9-tetrahydroxy-5-[2-(phenylsulfonyl)benzyl]phenanthridin-6(5H)-one
-
95% inhibition at 0.01 mM
2,4-dimethyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-(1,3-benzothiazol-2-yl)-1-(2-chlorobenzyl)-4-methyl-5-(morpholin-4-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(1,3-benzothiazol-2-yl)-4-ethyl-5-(2-methoxyethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(1,3-benzothiazol-2-yl)-4-methyl-1-(pyridin-2-ylmethyl)-5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(1,3-benzothiazol-2-yl)-4-methyl-5-(morpholin-4-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(1,3-benzothiazol-2-yl)-5-[2-(1H-imidazol-4-yl)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(1,3-benzothiazol-2-yl)-5-[2-(1H-indol-3-yl)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2,5-dichlorobenzyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-(2-chloro-4-fluorobenzyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-(2-chloro-4-fluorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
-
-
2-(2-chloro-4-fluorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chloro-4-fluorophenyl)-5-(2-pyridin-2-ylethyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-(2-fluorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-([methyl(phenyl)amino]methyl)-5-[2-(pyridin-2-yl)ethyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-methyl-5-(3-phenylprop-2-yn-1-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-methyl-5-(4-[(4-methylpiperazin-1-yl)methyl]benzyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo-[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-methyl-5-[(6-morpholin-4-ylpyridin-2-yl)-methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-methyl-5-[4-(4-methylpiperazin-1-yl)-4-oxobutyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-[[4-(3-methoxyphenyl)piperazin-1-yl]-methyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-4-[[methyl(phenyl)amino]methyl]-5-(pyridin-4-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-5-(3-ethoxypropyl)-4-methyl-1-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-5-(3-hydroxypropyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-5-(cyclohexylmethyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-5-[(1-methyl-1H-pyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
-
-
2-(2-chlorophenyl)-5-[2-(dimethylamino)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(2-methoxyethyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-6-methoxy-4H-chromen-4-one
-
complete inhibition at 0.01 mM
2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one
-
complete inhibition at 0.01 mM
2-(3,4-dihydroxyphenyl)-5-hydroxy-3,7-dimethoxy-4H-chromen-4-one
-
88% inhibition at 0.01 mM
2-(4-chlorobenzyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-(4H-3,1-benzothiazin-2-yl)-1-benzyl-4-methyl-5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
2-(7-chloroquinolin-4-yl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-benzyl-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-[(2,3,8,9-tetrahydroxy-6-oxophenanthridin-5(6H)-yl)methyl]benzonitrile
-
97% inhibition at 0.01 mM
2-[(2E)-2-(3,4-dihydroxybenzylidene)hydrazinyl]-N-(3-nitrophenyl)-2-oxoacetamide
-
96% inhibition at 0.01 mM
2-[2-(4-chlorophenoxy)ethyl]-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
2-[4-(benzyloxy)phenyl]-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
3,5,7-trihydroxy-2-(4-hydroxy-3-methylphenyl)-4H-chromen-4-one
-
94% inhibition at 0.01 mM
3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
-
complete inhibition at 0.01 mM
3-(3,4-dihydroxycyclohexa-2,4-dien-1-yl)-2,7-dihydroxy-4H-chromen-4-one
-
86% inhibition at 0.01 mM
3-(3-chlorophenyl)-N-[2-(piperazin-1-yl)phenyl]-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxamide
-
Shionigi compound
3-(3-chlorophenyl)-N-[4-(piperidin-4-yl)phenyl]pyrazolo[1,5-a]pyrimidine-5-carboxamide
-
-
3-(4,5-dimethyl-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)benzonitrile
-
-
4,5-dimethyl-2-(4-phenyl-1,3-thiazol-2-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4,5-dimethyl-2-(5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-methyl-2-(2-methylphenyl)-5-(pyridine-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-methyl-2-phenyl-5-(2-phenylethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
-
-
4-methyl-3-methylidene-2-(2-phenylethyl)-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
4-methyl-3-methylidene-2-[2-(morpholin-4-yl)ethyl]-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
-
4-methyl-5-(3-phenoxybenzyl)-2-([1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-[(4-fluorophenoxy)methyl]-5-(2-methoxyethyl)-2-(2-morpholin-4-ylethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(pyrazin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-[[(2-chlorobenzyl)oxy]methyl]-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
4-[[2-(1,3-benzothiazol-2-yl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]methyl]benzoic acid
-
-
4-[[2-(2-chlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]methyl]benzenesulfonamide
-
-
4-[[benzyl(methyl)amino]methyl]-2-(2-chloro-4-fluorophenyl)-5-(3-methoxypropyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
-
complete inhibition at 0.01 mM
5-(1,3-benzodioxol-5-ylmethyl)-4-methyl-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
5-(E)-6,9-deoxa-6,9alpha-methylene-15-cyclopentyl-16,17,18,19,20-pentanor-prostaglandin I2
-
inhibition of sodiumdodecylsulfate-induced activation in cell free extracts, 0.17 mM, 50% inhibition
5-(furan-2-ylmethyl)-4-methyl-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
5-benzyl-2-(4-fluorophenyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
-
5-[(2,5-dihydroxybenzyl)amino]-2-hydroxybenzoic acid
-
82% inhibition at 0.01 mM
betaPix
-
guanine nucleotide exchange factor, overexpression of the central PH domain of betaPix results in inhibition of superoxide anion generation in response to EGF
-
betulinic acid
-
attenuates the expression of NAD(P)H oxidase subunits Nox4 and p22phox, thereby reducing oxidative stress and improving endothelial nitric oxide synthase function. Treated cells show in increased production of bioactive nitric oxide
bilirubin
-
bilirubin concentration-dependently reduces NADPH oxidase-dependent superoxide production stimulated by phorbol 12-myristate 13-acetate
Cdc42
-
a small monomeric GTPase, competitive inhibitor of Nox2, might also be a competitive inhibitor of Nox1
-
diphenylene iodinium
-
treatment of NB-4 cells blocks basal generation of reactive oxygen species and arsenic trioxide-induced apoptosis
diphenylene iodinium chloride
-
enzyme inhibitor, pretreatment of cells completely blocks insulin-stimulated activation of hypoxia-inducible factor 1
endothelin-1
-
inhibits NADPH oxidase activity, superoxide generation, and cell proliferation in human abdominal aortic endothelial cells via the ETB1-Pyk2-Rac1-Nox1 pathway. Endothelin-1 significantly attenuates NADPH oxidase activity and cell proliferation, which can be abolished by silencing of the Nox1 gene. RNA interference silencing of ETB1 receptors significantly increases NADPH oxidase activity, and blocks the inhibitory effect of endothelin-1 on NADPH oxidase activity. Endothelin-1 also attenuates angiotensin II-induced activation of NADPH oxidase and cell proliferation
N'1,N'2-bis[(E)-(2,3-dihydroxyphenyl)methylidene]ethanedihydrazide
-
complete inhibition at 0.01 mM
N'1,N'2-bis[(E)-(3,4-dihydroxyphenyl)methylidene]ethanedihydrazide
-
complete inhibition at 0.01 mM
N-(3-aminophenyl)-N'-[1-(4-hydroxy-3-methoxyphenyl)ethyl]ethanediamide
-
complete inhibition at 0.01 mM
N-[(3Z)-3-(4-hydroxy-3-methoxybenzylidene)-2-oxo-2,3-dihydro-1H-indol-5-yl]acetamide
-
complete inhibition at 0.01 mM
N-[1-(3,4-dihydroxyphenyl)ethyl]-N'-(3-nitrophenyl)ethanediamide
-
complete inhibition at 0.01 mM
N-[2-(2-chlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-2-(4-fluorophenoxy)acetamide
-
-
N-[3-(4,5-dimethyl-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)phenyl]acetamide
-
-
N4-(3-aminophenyl)[1]benzothieno[3,2-d]pyrimidine-4,8-diamine
-
98% inhibition at 0.01 mM
N4-(4-aminophenyl)[1]benzothieno[3,2-d]pyrimidine-4,8-diamine
-
complete inhibition at 0.01 mM
O-methyl-epicatechin
-
inhibits endothelial NAD(P)H oxidase activity and prevents superoxide anion formation
phallacidin
-
pretreatment of human pulmonary artery endothelial cells before induction of hyperoxia attenuates hyperoxia-induced cortical actin thickening and reactive oxygen species production
procyanidin B2
-
acts both as a superoxide anion scavenger, and inhibitory to NAD(P)H oxidase, with apocynin-like mode of NADPH oxidase inhibition
prostaglandin E1
-
inhibition of sodiumdodecylsulfate-induced activation in cell free extracts, 0.044 mM, 50% inhibition
rosiglitazone
-
activates 5'-AMP-activated protein kinase which, in turn, prevents hyperactivity of NAD(P)H oxidase induced by high glucose, possibly through protein kinase C inhibition. Rosiglitazone protects endothelial cells against glucose-induced oxidative stress with an 5'-AMP-activated protein kinase-dependent and a PPARgamma-independent mechanism
VAS3947
-
i.e. 3-benzyl-7-(2-oxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine, specific low micromolar NADPH oxidase inhibitor
apocynin
-
enzyme inhibitor, pretreatment of cells completely blocks insulin-stimulated activation of hypoxia-inducible factor 1
apocynin
-
significantly blunts both the generation of reactive oxygen species and induction of apoptosis induced by apigenin
apocynin
-
4-hydroxy-3-methoxyacetophenonesubstituted, a natural molecule structurally related to vanillin, acts on p47phox, requires a peroxidase such as MPO
diphenylene iodonium
-
significantly blunts both the generation of reactive oxygen species and induction of apoptosis induced by apigenin
diphenylene iodonium
-
inhibition of NADPH oxidase. In cells deficient for von Hippel-Lindau tumor suppressor gene, presence of diphenyleneiodonium decreases the expression of hypoxia-inducible factor 2alpha
diphenylene iodonium
-
directly inhibits the activity of enzyme component gp91phox/NOX2, the inhibitor targets the FAD binding sequence found in other flavoproteins and is therefore not specific for NOX2
diphenyleneiodonium
-
inhibition of NAD(P)H oxidase abolishes depolarisation of the neutrophil plasma membrane by electron current
honokiol
-
submicromolar concentrations of honokiol suppress the increases of NADPH oxidase activity, Rac-1 phosphorylation, p22phox protein expression, and reactive oxygen species production in high glucose-stimulated HUVEC cells. Honokiol also suppresses high glucose-induced cyclooxygenase-2 upregulation and prostaglandin E2 production. Honokiol can reduce increased caspase-3 activity and the subsequent apoptosis and cell death triggered by high glucose medium
neopterin
-
significantly blunts both the generation of reactive oxygen species and induction of apoptosis induced by apigenin
additional information
-
unidentified inhibitor found in 3000 g particulate fraction from patients with Grave's disease
-
additional information
-
epicatechin is a superoxide anion scavenger, but not inhibitory to NAD(P)H oxidase. HUVEC cells are able to convert (-)-epicatechin to its inhibitory O-methyl esters. IC50-values of (-)epicatechin and (+)catechin are above 0.1 mM in cell lysates
-
additional information
-
presence of Candida albicans inhibits by contrasting the assembly of the enzyme on dedritic cell's plasma membrane
-
additional information
-
trimer hydroxylated quinone is the major active compound in AOP-1, with strong inhibitory activity against vascular endothelial cell NADPH oxidase with an IC50 of 0.000031 mM at 22°C, pH not specified in the publication
-
additional information
-
Francisella tularensis inhibits NADPH oxidase activity in a cell-free assay; the regulatory factor fevR is essential for NADPH oxidase inhibition, whereas iglI and iglJ, candidate secretion system effectors, and the acid phosphatase acpA are not
-
additional information
-
V204A mutant is a competitive inhibitor of wild-type p67phox
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(+)-(S)-2-(6-methoxynaphthalen-2-yl)propanoic acid
-
i.e. naproxen, nonsteroidal anti-inflammatory drug. Treatment increases isoform Nox2 expression in endothelial cells and diminishes production of bioactive nitric oxide. In healthy volunteers, treatment reduces nitroglycerin-induced, nitric oxide-mediated vasodilatation of the brachial artery
2-(2-(2,6-dichlorophenylamino)-phenyl)acetic acid
-
i.e. diclofenac, nonsteroidal anti-inflammatory drug. Treatment increases isoform Nox2 expression in endothelial cells and diminishes production of bioactive nitric oxide. In healthy volunteers, treatment reduces nitroglycerin-induced, nitric oxide-mediated vasodilatation of the brachial artery
4-(4-methylsulfonylphenyl)-3-phenyl-5H-furan-2-one
-
i.e. rofecoxib, nonsteroidal anti-inflammatory drug. Treatment increases isoform Nox2 expression in endothelial cells and diminishes production of bioactive nitric oxide. In healthy volunteers, treatment reduces nitroglycerin-induced, nitric oxide-mediated vasodilatation of the brachial artery
4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
-
i.e. celecoxib, nonsteroidal anti-inflammatory drug. Treatment increases isoform Nox2 expression in endothelial cells and diminishes production of bioactive nitric oxide. In healthy volunteers, treatment reduces nitroglycerin-induced, nitric oxide-mediated vasodilatation of the brachial artery
5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b] pyridin-3-yl]-pyrimidin-4-ylamine
-
i.e. BAY 41-2272. THP-1 cells treated with BAY 41-2272 for 48 h significantly increase the superoxide anion release. BAY 41-2272 increases subunit gp91phox gene expression and causes a significant increase in cGMP and cAMP levels
A23187
-
calcium ionophore. HaCaT keratinocytes overexpressing calcium- and arachidonic acid binding proteins S100A8/S100A9 showed enhanced, transient reactive oxygen species generation in response to A23187, as well as nuclear factor kappaB activation and increase in interleukin-8 mRNA levels
apigenin
-
apigenin reduces cell viability, and induces apoptotic cell death in a dose-dependent manner. In addition, it evokes a dose-related elevation of intracellular reactive oxygen species level. Treatment with various inhibitors of the NADPH oxidase significantly blunts both the generation of reactive oxygen species and induction of apoptosis induced by apigenin
betaPix
-
a Rac1 guanine nucleotide exchange factor, appears to be constitutively bound to Nox1 and essential for its activity
-
cytochalasin D
-
enhancement of basal and hyperoxia-induced reactive oxygen species formation
H2O2
-
Nox5 can be upregulated and activated by minute concentrations of hydrogen peroxide
heat shock protein 90
-
binding of heat shock protein 90 to the C-terminus of Nox5 appears to stabilize the protein and enhance expression and activity
-
isoobtusilactone A
-
isoobtusilactone A elicits a concentration-dependent growth impediment with IC50 value of 37.5 microM. Treated cells also display transient increase of reactive oxygen species during the earlier stage of the experiment, followed by the disruption of mitochondrial transmembrane potential. The presence of a reactive oxygen species scavenger N-acetyl-L-cysteine and the inhibitor of NADPH oxidase diphenyleneiodonium chloride block reactive oxygen species production and the subsequent apoptotic cell death
latrunculin A
-
enhancement of basal and hyperoxia-induced reactive oxygen species formation
N-formyl-L-methionyl-L-leucyl-L-phenylalanine
-
store-operated Ca2+ entry is required at the beginning of NADPH oxidase activation in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine in neutrophil-like HL-60 cells. When extracellular Ca2+ is initially removed, early addition of Ca2+ after stimulation causes a complete restoration of Ca2+ entry and H2O2production. Both Ca2+ entry and H2O2 production are decreased by purported SOCE blockers, 2-aminoethoxydiphenyl borane (2-APB) and SK&F 96365. Ca2+ influx in HL-60 cells relies on different membrane transient receptor potential canonical channels and Orai1 for allowing NADPH oxidase activation
NOXA1
-
in contrast to its Noxo1 partner, Noxa1 activity appears to be tightly regulated. Noxa1 contains four Rac-binding TPR motifs, a Nox activation domain and an SH3 domain that interacts with the prolinerich region of an organizer subunit, But the p40phox-binding PB1 domain is not well conserved and the SH3 domain in the middle of the molecule is missing. Phosphorylation of Noxa1 by protein kinase A favors binding to 14-3-3 and dissociation from Nox1, whereas other kinases appear to decrease Noxa1 affinity for Rac1 and Nox1. In contrast, phosphorylation of Noxa1 by Src on tyrosine 110 increases Nox1 activity
-
NOXO1
-
In contrast to its Noxo1 partner, Noxa1 activity appears to be tightly regulated. Unlike p47phox, because Noxo1 lacks an autoinhibitory domain, it is thought to constitutively bind the cytochrome, but similar to p47phox, Noxo1 facilitates oxidase assembly by binding both an activator subunit and p22phox. The proline-rich region of Noxo1 binds to an SH3 domain of the activator, whereas the tandem SH3 domains of Noxo1 bind to the proline-rich region of p22phox. Noxo1 also binds to the dehydrogenase domain of Nox1. The PX domain of Noxo1 provides an essential affinity for membrane phosphoinositides
-
p67phox
-
activation domain of p67phox triggers FAD reduction by Nox2. P40phox appears to increase oxidase activity in cooperation with p47phox not by inducing translocation to the membrane, but by retaining the oxidase at the phagosome
-
phosphatidylinositol 3-phosphate
-
subunit p40phox phosphatidylinositol 3-phosphate binding PX domain has phosphatidylinositol 3-phosphate-dependent and -independent functions. Translocation of subunit p67phox requires the PX domain but not 3-phosphoinositide binding. Activation of the oxidase by p40phox, however, requires both phosphatidylinositol 3-phosphate binding and an Src homology 3 domain competent to bind to poly-Pro ligands
Poldip2
-
reactive oxygen species production is enhanced by the multifunctional Poldip2, which also interacts with p22phox, presumably at the beginning of the cytosolic C-terminus, upstream of the region dispensable for Nox4 activity
-
Rac
-
small GTPase Rac plays a positive role in isoform Nox3 activation in the presence of subunit p47phox and either subunits p67phox or Noxa1, whereas Rac fails to upregulate Nox3 activity when p47phox is replaced with Noxo1. Expression of constitutively active Rac1 mutant Q61L enhances not only superoxide production but also membrane translocation of p67phox
-
Rac1
-
in addition to cytosolic organizers and activators, Nox1 also requires Rac1 for activity. Rac1 interacts directly with the C-terminus of Nox1, even in the absence of Noxa1. Nox1 is stimulated by constitutively active Rac1 and inhibited by Rac1 knockdown. Rac1 provides a crucial mechanism for activation by agonists, particularly in cells that exclusively express Nox1/Noxo1/Noxal. Rac1 does not activate Nox4 in transfected cells. Rac1 may participate in Nox5 activation
-
salbutamol
-
salbutamol treatment enhances superoxide anion production in asthma patients through nitric oxide-mediated mechanisms. It exerts beneficial antioxidant effects through activation of catalase and attenuation of lipid peroxidation
tumor necrosis factor-alpha
-
treatment of monocytic cells and isolated monocytes results in up-regulation of the NAD(P)H oxidase gene, neutrophil cytosolic factor 2. Treated cells have increased levels of mRNA and up-regulated expression of NADPH oxidase subunits p47phox, p67phox, and gp91phox, as well as increased oxidase activity. Pharmacological inhibitors of NF-kappaB activation block tumor necrosis factor-induced up-regulation, which correlates with a reduction in expression of the corresponding oxidase proteins and decreased superoxide anion production
-
angiotensin II
-
potent stimulator of NAD(P)H oxidase O2- production in the vasculature
formyl-Met-Leu-Phe
-
stimulation. In addition, heterologous expression of subunit p40phox markedly enhances superoxide production in stimulated cells. Upon stimulation with phorbol 12-myristate 13-acetate or formyl-Met-Leu-Phe, p40phox translocates to plasma membrane in a p67phox- and p47phox-dependent manner
phorbol 12-myristate 13-acetate
-
after transfection with calcium- and arachidonic acid binding proteins S100A8/S100A9 genes, HeLa cells show dramatically increased activation of NAD(P)H oxidase in presence of phorbol 12-myristate 13-acetate
phorbol 12-myristate 13-acetate
-
stimualtion. Treated dendritic cells are are more competent in killing Candida albicans
phorbol 12-myristate 13-acetate
-
stimulation. In addition, heterologous expression of subunit p40phox markedly enhances superoxide production in stimulated cells. Upon stimulation with phorbol 12-myristate 13-acetate or formyl-Met-Leu-Phe, p40phox translocates to plasma membrane in a p67phox- and p47phox-dependent manner
phorbol 12-myristate 13-acetate
-
upon treatment, plasma membranes from stimulated cells show an increased amount of regulatory protein Rac1, but other components of the NAD(P)H oxidase complex do not change before and after the stimulation. When the constitutively active form of Rac, Q61L or GTP-bound Rac1 is added exogenously to the membrane, superoxied anion producing activity is enhanced up to 1.5-fold above the basal level,but GDP-loaded Rac1 does not affect superoxide generating kinetics
thrombin
-
administration of thrombin to endothelial cells leads to upregulation of enzyme subunit p22phox accompanied by a delayed increase in generation of reactive oxygen species and enhanced proliferation. Existence of a positive feedback mechanism, whereby reactive oxygen species lead to elevated levels of p22phox and thus, sustained generation of reactive oxygen species as is observed in endothelial dysfunction
-
additional information
-
presence of Candida albicans does not activate NADPH oxidase in dendritic cells
-
additional information
-
NADPH oxidase can be activated in a cell-free system by mixing cytosol and plasma membranes isolated from resting neutrophils or macrophages in the presence of Mg2+, GTP and an anionic amphiphile such as arachidonic acid or sodium dodecyl sulfate
-
additional information
-
activation of NADPH oxidase in phagocytes can be induced by a large number of inflammatory stimuli such as opsonized bacteria, opsonized zymosan, bacterial formylated peptides such as formyl-Met-Leu-Phe, C5a and platelet-activating factor, and also by pharmacological agents such as calcium ionophores A23127, ionomycin and PKC activators such as phorbol myristate acetate. In intact cells, NADPH oxidase activation is accompanied by phosphorylation of enzyme components p47phox, p67phox, p40phox, p22phox and gp91phox, along with several protein-protein interactions. In human neutrophils, various protein kinases have been implicated in the activation of NADPH oxidase, among which the PKC and MAP kinase families appear to play a major role
-
additional information
-
agonists appear to stimulate Nox1 in specific locations, thus determining where superoxide is produced: extracellularly by muscarinic agonists and thrombin, in endosomes by IL-1beta and TNF-alpha, both inside and outside cells by angiotensin II. Nox activators comprise p67phox and the structurally similar Noxa1. In colon the cytosolic subunits p47phox and p67phox are not expressed and are replaced by Noxo1 and Noxa1. Besides p47phox, other possible organizers include Tks4 and Tks5, two Src substrates with a PX domain and multiple SH3 domains capable of binding p22phox and Noxa1, but not p67phox. Cdc42 cannot activate Nox1
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.015
NADPH
-
subunit p40phox-depleted cytosol in the absencee of recombinant wild-type p40phox, pH 7.3, 37°C
0.024
NADPH
-
subunit p40phox-depleted cytosol in the presence of recombinant wild-type p40phox, pH 7.3, 37°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.03
1-(2-chlorobenzyl)-4-methyl-5-[3-(2-oxopyrrolidin-1-yl)propyl]-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.03
1-(4-fluorobenzyl)-5-[2-(1H-indol-3-yl)ethyl]-4-methyl-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.00024
1-acetyl-2-(2-chlorophenyl)-4-methyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000398
1-acetyl-4-methyl-2-(2-methylphenyl)-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000409
1-acetyl-4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000285
1-[(3-methoxyphenyl)acetyl]-4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.002175
2,4,5-trimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000387
2,4-dimethyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.03
2-(1,3-benzothiazol-2-yl)-1-(2-chlorobenzyl)-4-methyl-5-(morpholin-4-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.03
2-(1,3-benzothiazol-2-yl)-4-methyl-1-(pyridin-2-ylmethyl)-5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.001208
2-(1,3-benzothiazol-2-yl)-4-methyl-5-(morpholin-4-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.004729
2-(1,3-benzothiazol-2-yl)-5-[2-(1H-imidazol-4-yl)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.001845
2-(1,3-benzothiazol-2-yl)-5-[2-(1H-indol-3-yl)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000218
2-(2,5-dichlorobenzyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000342
2-(2-chloro-4-fluorobenzyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000213
2-(2-chloro-4-fluorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000235
2-(2-chloro-4-fluorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000114
2-(2-chloro-4-fluorophenyl)-5-(2-pyridin-2-ylethyl)-4-(pyrrolidin-1-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000215
2-(2-chlorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000128
2-(2-chlorophenyl)-4-(2-fluorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000172
2-(2-chlorophenyl)-4-([methyl(phenyl)amino]methyl)-5-[2-(pyridin-2-yl)ethyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000158
2-(2-chlorophenyl)-4-methyl-5-(3-phenylprop-2-yn-1-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000515
2-(2-chlorophenyl)-4-methyl-5-(4-[(4-methylpiperazin-1-yl)methyl]benzyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000165
2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo-[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000236
2-(2-chlorophenyl)-4-methyl-5-[(6-morpholin-4-ylpyridin-2-yl)-methyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000428
2-(2-chlorophenyl)-4-methyl-5-[4-(4-methylpiperazin-1-yl)-4-oxobutyl]-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000114
2-(2-chlorophenyl)-4-[(4-fluorophenoxy)methyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000065
2-(2-chlorophenyl)-4-[[4-(3-methoxyphenyl)piperazin-1-yl]-methyl]-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000151
2-(2-chlorophenyl)-4-[[methyl(phenyl)amino]methyl]-5-(pyridin-4-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.03
2-(2-chlorophenyl)-5-(3-ethoxypropyl)-4-methyl-1-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.000565
2-(2-chlorophenyl)-5-(3-hydroxypropyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.00052
2-(2-chlorophenyl)-5-(cyclohexylmethyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000047
2-(2-chlorophenyl)-5-[(1-methyl-1H-pyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000235
2-(2-chlorophenyl)-5-[2-(dimethylamino)ethyl]-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000308
2-(2-fluorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000313
2-(2-methoxyethyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.00034
2-(3-chlorophenyl)-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000259
2-(4-chlorobenzyl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.03
2-(4H-3,1-benzothiazin-2-yl)-1-benzyl-4-methyl-5-(tetrahydrofuran-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.000458
2-(7-chloroquinolin-4-yl)-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000463
2-benzyl-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000326
2-[2-(4-chlorophenoxy)ethyl]-4-methyl-3-methylidene-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.00306
2-[4-(benzyloxy)phenyl]-4,5-dimethyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000293
3-(4,5-dimethyl-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)benzonitrile
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.001947
4,5-dimethyl-2-(4-phenyl-1,3-thiazol-2-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.001418
4,5-dimethyl-2-(5-[(4-methylpiperazin-1-yl)sulfonyl]pyridin-2-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000173
4-methyl-2-(2-methylphenyl)-5-(pyridine-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.005232
4-methyl-2-phenyl-5-(2-phenylethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000373
4-methyl-2-phenyl-5-(pyridin-3-ylmethyl)-1H-pyrazolo[4,3-c]-pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000334
4-methyl-3-methylidene-2-(2-phenylethyl)-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000445
4-methyl-3-methylidene-2-[2-(morpholin-4-yl)ethyl]-5-(pyridin-2-ylmethyl)-1,2,3,5-tetrahydro-6H-pyrazolo[4,3-c]pyridin-6-one
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.03
4-methyl-5-(3-phenoxybenzyl)-2-([1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
Ki above 0.03 mM, 0.1 M phosphate buffer, pH 7.4, 37°C
0.000153
4-[(4-fluorophenoxy)methyl]-5-(2-methoxyethyl)-2-(2-morpholin-4-ylethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000095
4-[(benzyloxy)methyl]-2-(2-chlorophenyl)-5-(pyrazin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000082
4-[[(2-chlorobenzyl)oxy]methyl]-2-(2-chlorophenyl)-5-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.004222
4-[[2-(1,3-benzothiazol-2-yl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]methyl]benzoic acid
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000259
4-[[2-(2-chlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]methyl]benzenesulfonamide
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000165
4-[[benzyl(methyl)amino]methyl]-2-(2-chloro-4-fluorophenyl)-5-(3-methoxypropyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.00544
5-(1,3-benzodioxol-5-ylmethyl)-4-methyl-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.00949
5-(furan-2-ylmethyl)-4-methyl-2-phenyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000878
5-benzyl-2-(4-fluorophenyl)-4-methyl-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000218
N-[2-(2-chlorophenyl)-4-methyl-3,6-dioxo-1,2,3,6-tetrahydro-5H-pyrazolo[4,3-c]pyridin-5-yl]-2-(4-fluorophenoxy)acetamide
-
0.1 M phosphate buffer, pH 7.4, 37°C
0.000328
N-[3-(4,5-dimethyl-3,6-dioxo-1,3,5,6-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)phenyl]acetamide
-
0.1 M phosphate buffer, pH 7.4, 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.001
(2Z)-2-(5-hydroxy-4,6-dimethyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene)-N,N-di(prop-2-en-1-yl)hydrazinecarbothioamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00113
(3Z)-3-(3,4-dihydroxybenzylidene)-5-nitro-1,3-dihydro-2H-indol-2-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00063
(3Z)-3-[4-hydroxy-3,5-di(propan-2-yl)benzylidene]-1,3-dihydro-2H-indol-2-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00017
2,3,8,9-tetrahydroxy-5-(2-hydroxy-5-nitrobenzyl)phenanthridin-6(5H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00026
2,3,8,9-tetrahydroxy-5-(3-nitrobenzyl)phenanthridin-6(5H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00158
2,3,8,9-tetrahydroxy-5-(4-nitrobenzyl)phenanthridin-6(5H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00158
2,3,8,9-tetrahydroxy-5-[2-(phenylsulfonyl)benzyl]phenanthridin-6(5H)-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00074
2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-6-methoxy-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00085
2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00102
2-(3,4-dihydroxyphenyl)-5-hydroxy-3,7-dimethoxy-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00096
2-hydroxy-5-[(2-hydroxybenzyl)amino]benzoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.00059
2-[(2,3,8,9-tetrahydroxy-6-oxophenanthridin-5(6H)-yl)methyl]benzonitrile
Homo sapiens
-
pH and temperature not specified in the publication
0.00102
2-[(2E)-2-(3,4-dihydroxybenzylidene)hydrazinyl]-N-(3-nitrophenyl)-2-oxoacetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00068
3,5,7-trihydroxy-2-(4-hydroxy-3-methylphenyl)-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.0012
3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00079
3-(3,4-dihydroxycyclohexa-2,4-dien-1-yl)-2,7-dihydroxy-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00113
5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one
Homo sapiens
-
pH and temperature not specified in the publication
0.00134
5-[(2,5-dihydroxybenzyl)amino]-2-hydroxybenzoic acid
Homo sapiens
-
pH and temperature not specified in the publication
0.004
ISNSESGPRGVHFIFNKENF
Homo sapiens
-
pH and temperature not specified in the publication
0.00127
methyl 2-hydroxy-5-[(2-hydroxybenzyl)amino]benzoate
Homo sapiens
-
pH and temperature not specified in the publication
0.00091
N'1,N'2-bis[(E)-(2,3-dihydroxyphenyl)methylidene]ethanedihydrazide
Homo sapiens
-
pH and temperature not specified in the publication
0.00116
N'1,N'2-bis[(E)-(3,4-dihydroxyphenyl)methylidene]ethanedihydrazide
Homo sapiens
-
pH and temperature not specified in the publication
0.0013
N-(3-aminophenyl)-N'-[1-(4-hydroxy-3-methoxyphenyl)ethyl]ethanediamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0014
N-[(3Z)-3-(4-hydroxy-3-methoxybenzylidene)-2-oxo-2,3-dihydro-1H-indol-5-yl]acetamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00164
N-[1-(3,4-dihydroxyphenyl)ethyl]-N'-(3-nitrophenyl)ethanediamide
Homo sapiens
-
pH and temperature not specified in the publication
0.00024
N4-(3-aminophenyl)[1]benzothieno[3,2-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00107
N4-(4-aminophenyl)[1]benzothieno[3,2-d]pyrimidine-4,8-diamine
Homo sapiens
-
pH and temperature not specified in the publication
0.00083
quercetin 3-O-alpha-D-glucopyranoside
Homo sapiens
-
pH and temperature not specified in the publication
0.034
VWYYRVYDIPPKFFYTRKLL
Homo sapiens
-
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
voltage-clamp experiments, enzyme activity depends on both membrane potential and concentration of NADPH, the shape of the Ie-V curve is influenced by the concentration of NADPH in the submillimolar range
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
636501, 658889, 659332, 659626, 659956, 671246, 671829, 673788, 684695, 684771, 684779, 684781, 684859, 684866, 684872, 684904, 684970, 685016, 685277, 685410, 685793, 685998, 686126, 686418, 686520, 686556, 686848, 686879, 686880, 687050, 687587, 687620, 687649, 687674, 687742, 688206, 688216, 688583, 688599, 688605, 688753, 689213, 696030, 696573
-
-
-
699176, 699287, 700052, 710782, 710897, 711166, 711688, 711763, 712075, 712673, 712711, 712713, 713338, 713360, 724704, 724778, 726081, 741619, 742310, 742556, 742557, 743686
-
-
dual NADPH oxidases/peroxidases, Duox1 and Duox2. Regulation of expression by immunomodulatory Th1 and Th2 cytokines
-
-
isoforms Duox1, Duox2, stable transfection in HEK293 and Chinese hamster ovary cells. Enzymes demonstrate a functional NADPH/Ca2+-dependent H2O2-generating activity. Human Duox2 is more active than human Duox1, but only half as active as its porcine counterpart
-
-
multicomponent NADPH-oxidase consisting of a heterodimeric flavocytochrome b558, localized in the membrane and at least two cytosolic components p47-phox and p67-phox, enzyme plays a role in chronic granulomatous diseases, enzyme system is activated upon exposure to the appropriate stimuli leading to assembly in the plasma membrane of membrane-bound and cytosolic components
-
-
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
expression of isoform Nox4 mRNA in glioblastomas of WHO grade IV is significantly higher than other astrocytomas of WHO grades II and III
-
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. Nox5S may be constitutively active or be a competitive inhibitor of calcium-dependent activation when present in the same tetrameric complex as Nox5L
-
in ischemic cardiomyocytes, Nox2 is upregulated in the cytosol and targeted to the nuclear pore complex
-
expression of isoform Nox4 mRNA in glioblastomas of WHO grade IV is significantly higher than other astrocytomas of WHO grades II and III
-
-
-
NADPH oxidase mediates angiotensin II-stimulated protein synthesis downstream of the type 1 receptor AT1 in myometrium smooth muscle cells
-
neuroblastoma cell, cells differentiated by retinoic acid die after exposure to glycated albumin, a model of advanced glycation end product-modified protein. Undifferentiated cells are resistant to glycated albumin. Differentiated cells pre-treated with NAD(P)K oxidase inhibitor diphenyleneiodinium or with rottlerin, an inhibitor of protein kinase C delta, are able to prevent neuronal death induced by glycated albumin
-
primary tracheobronchial epithelial cell. Study on enzyme isoforms Duox1 and Duox2 mRNA expression after treatment with multiple cytokines. Duox1 expression is increased severalfold by treatment with Th2 cytokines IL-4 and IL-13, and by polyinosine-polycytydilic acid and rhinovirus infection. Duox2 expression is highly induced following treatment with Th1-cytokine IFN-gamma
additional information
-
human pulmonary artery endothelial cell, induction of NAD(P)H oxidase by exposure to hyperoxia for 3 h. Pretreatment of cells with the actin-stabilizing agent phallacidin attenuates hyperoxia-induced cortical actin thickening and reactive oxygen species production, whereas cytochalasin D and latrunculin A enhance basal and hyperoxia-induced reactive oxygen species formation. A 3-h hyperoxic exposure enhances the tyrosine phosphorylation of cortactin and interaction between cortactin and subunit p47phox. Transfection of cells with cortactin small interfering RNA or myristoylated cortactin Src homology domain 3 blocking peptide attenuated reactive oxygen species production and the hyperoxia-induced translocation of p47phox to the cell periphery
-
the potent anti-inflammatory, cytokine interleukin-10, acts as a down-regulator of the Nox1-based oxidase in the colon, and suggests an important role of ROS derived from Nox1-based oxidase in the initiation of inflammatory responses of the colon
-
Nox1 is most highly expressed in colon epithelium. In colon the cytosolic subunits p47phox and p67phox are not expressed and are replaced by Noxo1 and Noxa1
-
keratinocyte cell line. Long-term survival mechanisms in niacin deficient cells involve accumulation of reactive oxygen species and increased DNA damage with concomitant increase in expression and activity of NAD(P)H oxidase
-
transfection of isoform Nox3-specific siRNA abrogates H2O2 production and inhibitis exclusively the second phase of p42/44 MAPK phosphorylation and Sp1 DNA binding thus preventing upregulation of VEGF-A mRNA expression
-
bilirubin concentration-dependently reduces NADPH oxidase-dependent superoxide production stimulated by phorbol 12-myristate 13-acetate
-
five splice variants of Nox4, named Nox4A through E, are found in lung epithelial cells
Duox1 and Duox2 localize distinctly in lung epithelial cells as well as in ex-vivo differentiated lung epithelia. The localization of functional Duox-DuoxA heterodimers seems to be controlled by the associated DuoxA subunit
Duox1 and Duox2 localize distinctly in lung epithelial cells as well as in ex-vivo differentiated lung epithelia. The localization of functional Duox-DuoxA heterodimers seems to be controlled by the associated DuoxA subunit, including Duox2 expression in ciliated cells in an ex vivo differentiated lung epithelium
-
Burkholderia cenocepacia resides in macrophage vacuoles displaying an altered recruitment of the NADPH oxidase complex at the phagosomal membrane
-
subunit gp91phox gene expression is significantly higher in monocytes from sickle cell disease patients compared with normal controls. Monocytes from patients show higher levels of p47phox phosphorylation compared with normal controls
additional information
different tissues screened for ThOX2, except for a weak signal in trachea ThOX2 in exclusively found in thyroid cells
additional information
-
expression of isoform Duox2 in all tissues of the digestive tract examined. Enzyme is located at the apical membrane of the enterocytes in the brush border
additional information
-
Nox5 expression is restricted to fewer tissues. Nox4 activity is constitutive, addition of cytosol to membrane fractions in transfected cells does not increase Nox4 activity, also transfection of organizer and activator subunits does not increase reactive oxygen species production
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
Burkholderia cenocepacia resides in macrophage vacuoles displaying an altered recruitment of the NADPH oxidase complex at the phagosomal membrane
-
after Fcgamma receptor-induced phagocytosis, yellow fluorescent protein-tagged subunits p67phox and p40phox translocate to granulocyte phagosomes before phagosome internalization and accumulation of a probe for phosphoinositol 3-phosphate. p67phox and p47phox accumulation on nascent and internalized phagosomes does not require p40phox or PI3 kinase activity. Translocation of p40phox to nascent phagosomes requires binding to p67phox but not phosphoinositol 3-phosphate
-
-
in resting cells, enzyme complex components p22phox and gp91phox are located in the plasma membrane and membranes of specific granules
-
critical role for granules as a site for assembly and activation of the oxidase enzyme system
additional information
-
minor part of protein is expressed at cell surface, not found at surface of transfected CHO and PLB-XCGD cells
-
full-length subunit p40phox exhibits a cytoplasmic localization pattern in resting cells. Upon stimulation with phorbol 12-myristate 13-acetate or formyl-Met-Leu-Phe, p40phox translocates to plasma membrane in a p67phox- and p47phox-dependent manner
-
NOX components are distributed between the cytosol (p47phox, p67phox, p40phox and Rac1/2) and the plasma membrane and membranes of specific granules
-
in resting cells, enzyme complex components p47phox, p67phox, p40phox and Rac1/2 are localized in the cytosol
-
NOX1, Nox1 stimulation in endosomes is dependent on ClC-3, where this ion exchanger is required to balance the electrogenic activity of the enzyme
-
-
-
subunit gp91-phox of cytochrome b558 of the multicomponent complex is an integral membrane protein with several membrane-spanning regions
-
active subunit Nox1 endogenously co-localizes with its regulatory components p22phox, NOXO1, NOXA1 and Rac1
-
small GTPase Rac is involved in membrane translocation of subunit p67phox
-
the electron current depolarises the neutrophil plasma membrane at a rate of 2.3 V per s and this depolarisation is opposed when voltage-gated proton channels are activated. 3 mM ZnCl2 depolarises the membrane potential to +97.8 mV , and this depolarisation is abolished after NADPH oxidase inhibition
-
NOX components are distributed between the cytosol (p47phox, p67phox, p40phox and Rac1/2) and the plasma membrane and membranes of specific granules
-
Nox1, like Nox2, associates with p22phox to form a membrane-bound cytochrome
-
full-length subunit p40phox exhibits a cytoplasmic localization pattern in resting cells. Upon stimulation with phorbol 12-myristate 13-acetate or formyl-Met-Leu-Phe, p40phox translocates to plasma membrane in a p67phox- and p47phox-dependent manner
-
in resting cells, enzyme complex components p22phox and gp91phox are located in the plasma membrane and membranes of specific granules
-
NOX1, NOX5, NOX2, and NOX4. The signal peptide at the N-terminus of Nox1 is important for localization at the plasma membrane, as it is prevented by replacement with the N-terminus of Nox4. A polybasic region in Nox5 with affinity for phosphoinositides may favor translocation to the plasma membrane and extracellular superoxide release
additional information
-
coexpression of enzyme and enzyme maturation factor DuoxA2 allows ER-to-Golgi transition, maturation, and translocation to the plasma membrane of functional isoform Duox2 in a heterologous system
-
additional information
-
in resting cells, enzyme complex components p47phox, p67phox, p40phox and Rac1/2 are localized in the cytosol, whereas p22phox and gp91phox are located in the plasma membrane and membranes of specific granules
-
additional information
-
Nox4 location varies according to cell type, different Nox4 isoforms may be present in specific subcellular locations
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
-
tight regulation, critical to avoid excessive production of deleterious superoxide, is evident from the large number of proteins involved in oxidase assembly. These include Nox2 itself, p22phox, p47phox, p67phox, and p40phox, all essential subunits whose mutations can cause CGD Also crucial is Rac GTPase, which binds p67phox and the dehydrogenase domain of Nox2. In the resting state, Nox2 and p22phox form an inactive membrane complex known as cytochrome b558. Product superoxide is the first reactive oxygen species in a cascade of metabolites including hydrogen peroxide and peroxynitrite
physiological function
additional information
malfunction
-
isozyme Nox4 is involved in a variety of diseases such as idiopathic pulmonary fibrosis, pulmonary arterial hypertension, diabetic nephropathy, and complications such as diabetic cardiomyopathy and neuropathy and retinopathy or cancers like metastatic renal cell carcinoma
malfunction
-
excessive NADPH oxidase activation and reactive oxygen species overproduction are believed to participate in disorders such as joint, lung, vascular and intestinal inflammation
malfunction
-
in pathological circumstances, excess Nox2 can lead to oxidative stress and disease development. NOX2 V204A mutant is a competitive inhibitor of wild-type p67phox. Binding of the PB1 domain of NOX2 to p40phox is abolished by a K355A mutation in NOX2. Depletion or mutation of p40phox impairs reactive oxygen species production in neutrophils and endothelial cells. Upregulation of Nox1 can lead to oxidative stress in the cardiovascular system
malfunction
-
phagocyte NADPH oxidase deficiency causes chronic granulomatous disease
physiological function
-
cardiovascular NAD(P)H oxidases play important roles in physiological processes such as blood pressure regulation as well as pathophysiological events including hypertension and atherosclerosis
physiological function
-
NAD(P)H oxidase is the major source of reactive oxygen species generation in the vasculature in response to high glucose and advanced glycation end-products. NAD(P)H oxidase in phagocytic cells releases reactive oxygen species as a defense against pathogens. Activation of NAD(P)H oxidase in diabetes leads to a cascade of reactive oxygen species production and impaired antioxidant defenses. In early stages of diabetes, NAD(P)H oxidase-derived reactive oxygen species may serve as intracellular mediators to regulate redox-sensitive transcription factors (e.g. Nrf2) involved in adaptive responses to oxidative stress
physiological function
-
NAD(P)H oxidase-derived reactive oxygen species play a role in the development and progression of atherosclerosis
physiological function
-
oxidative stress is dependent on the upregulation of NAD(P)H oxidase 4, a reactive oxygen species Nox homologue, triggering endoplasmic reticulum stress. The endoplasmic reticulum stress pathway through activation of Nox4 by integrins alpha1beta1 plays a key role in 3-deoxyglucosone-collagen-induced caspase-3 activation, which may play an important role in the pathogenesis of diabetic wounds
physiological function
-
NADPH oxidase enzymes are critical mediators of cardiovascular physiology and pathophysiology. They are expressed in virtually all cardiovascular cells, and regulate such diverse functions as differentiation, proliferation, apoptosis, senescence, inflammatory responses and oxygen sensing. They target a number of important signaling molecules, including kinases, phosphatases, transcription factors, ion channels, and proteins that regulate the cytoskeleton. On activation, Nox2 uses NADPH to reduce molecular oxygen to superoxide anion, which, in concert with its metabolites, is used by phagocytes to destroy invading microorganisms. Nox organizers include both p47phox and its homologue, Noxo1, whereas Nox activators comprise p67phox and the structurally similar Noxa1. Because Nox2 and Nox1 are closely related, both enzymes can be activated in transfected cells by various organizer and activator pairs. Nox1 plays a host defensive role in colon epithelium. primary biochemical function of vascular Nox1 is superoxide production, which is then rapidly converted to hydrogen peroxide. The moderate physiological activity of Nox1, compared with the phagocytic Nox2, can be attributed to its low expression as well as specific regulatory subunits and signaling cascades. Nox4 is a constitutively active enzyme mostly regulated by transcription. Role of enzyme complex component p22phox, detailed overview. Nox4 can produce a higher hydrogen peroxide to superoxide ratio than Nox1 and Nox2. Isozyme Nox5S may be constitutively active or be a competitive inhibitor of calcium-dependent activation when present in the same tetrameric complex as Nox5L
physiological function
-
reactive oxygen species production by the phagocyte NADPH oxidase is essential for host defenses against pathogens. Reactive oxygen species are very reactive with biological molecules such as lipids, proteins and DNA, potentially resulting in cell dysfunction and tissue insult. Enzyme component P47phox is phosphorylated on multiple sites located in its carboxy-terminal portion, including serines 303-379, which play a central role in NADPH oxidase activation and regulation. In human neutrophils, various protein kinases have been implicated in the activation of NADPH oxidase, among which the PKC and MAP kinase families appear to play a major role
physiological function
-
the activity of NOX5 appears to be regulated by a self-contained Ca2+ binding domain, the conformational change of the domain upon Ca2+ binding is essential for domain-domain interaction and superoxide production
physiological function
-
NADPH oxidase NOX4 is a critical mediator of BRAF(V600E)-induced downregulation of the sodium/iodide symporter in papillary thyroid carcinomas
physiological function
-
the enzyme promotes long-term persistence of oxidative stress after an exposure to irradiation. Enzyme-dependent H2O2 production, which induces DNA double-strand breaks, can cause genomic instability and promote the generation of neoplastic cells through its mutagenic effect
physiological function
NOX2 is ubiquitously expressed in acute myeloid leukemia blasts, and particularly in cells from the myelomonocytic (M4) and monocytic (M5) stages. It is less expressed in leukemic stem cells and in relapsed acute myeloid leukemia. No endogenous NOX activity is detected in the absence of phorbol 12-myristate 13-acetate stimulation. Cytochrome b-245 heavy chain knockdown hampers induced NOX2 activity, but does not affect the proliferation and differentiation of THP-1 and HL-60 cells
physiological function
NOX5 overexpression induces changes in the expression of the unfolded protein response components, which are associated with increased apoptosis. 298 genes are differentially expressed in the overexpression line. In endothelial-specific NOX5 knock-in mice, changes in the expression of the unfolded protein response components genes are observed. In these animals, significant associations between the unfolded protein response components gene expression and echocardiographic parameters are found
additional information
-
active phagocyte NADPH oxidase is a multicomponent enzyme complex composed of six proteins: p22phox (phox: phagocyte oxidase), gp91phox/NOX2, p47phox, p67phox, p40phox and the small G-protein Rac1 or Rac2
additional information
-
Nox5 is similar to other Nox enzymes, with 6 transmembrane helices expected to bind 2 hemes and a cytosolic dehydrogenase domain including FAD and NADPH binding sites, but neither Nox5 isoform appears to require cytosolic subunits or p22phox. Presence of an additional cytosolic N-terminal segment, containing 4 calcium binding EF-hands in Nox5. Nox4 activity is constitutive, isozyme Nox4D appears to be fully active, although it lacks most of the transmembrane domain, it might retain activity by coupling to electron acceptors, such as cytochrome c in mitochondria, which might also be an alternative route of hydrogen peroxide formation by full-length Nox4. Nox4, Nox1 and Nox2 bind to p22phox, the interaction is abolished by mutation of heme-binding histidine 115. Nox2 is composed of two main domains of equal sizes with very different properties. The amino-terminal moiety includes six transmembrane alpha-helices I-VI connected by 5 loops A-E. Because both N- and C-termini are cytosolic, 3 loops are extracellular and include consensus asparagine glycosylation sites, whereas the other 2 are intracellular and accessible to cytosolic regulators. The cytosolic carboxy-terminal moiety of Nox2 constitutes a dehydrogenase domain that includes consensus binding sites for its NADPH substrate and FAD cofactor, activation domain of p67phox triggers FAD reduction by Nox2. A charge compensation mechanism, required to balance electron transport by Nox2 and sustain its activity, is provided by a voltage-gated proton channel8 and the chloride/proton antiporter ClC-3. The first SH3 domain of NOX2 increases oxidase activity, the NOX2 PB1 domain allows binding to p40phox. The C-terminal SH3 domain of p67phox of NOX2 is responsible for binding the proline-rich region of p47phox and therefore allows p67phox translocation to the membrane after activation. The C-terminal PB1 domain of p40phox interacts with the PB1 domain of p67phox. Nox1, like Nox2, associates with p22phox to form a membrane-bound cytochrome
additional information
mechanistic computational model, which incorporates a generalized random rapid equilibrium binding mechanism for NOX2 assembly and activation as well as regulations by GTP (activation), GDP (inhibition), and individual subunits enhancing the binding of other subunits (mutual binding enhancement). The model replicates diverse published kinetic data. The model provides a mechanistic, quantitative, and integrated framework for investigating the critical roles of NOX2 subunits in NOX2 assembly and activation facilitating ROS production in a variety of physiological and pathophysiological conditions
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). DUOX1_HUMAN
1551
6
177235
Swiss-Prot
Secretory Pathway (Reliability: 1)
DUOX2_HUMAN
1548
6
175364
Swiss-Prot
Secretory Pathway (Reliability: 3)
MICA1_HUMAN
1067
0
117875
Swiss-Prot
other Location (Reliability: 3)
FMO5_HUMAN
533
1
60221
Swiss-Prot
other Location (Reliability: 2)
Q14C85_HUMAN
1551
6
177322
TrEMBL
Secretory Pathway (Reliability: 1)
A8K2V7_HUMAN
1551
6
177322
TrEMBL
Secretory Pathway (Reliability: 1)
Q59GU9_HUMAN
550
1
62055
TrEMBL
other Location (Reliability: 3)
A0A024R5R2_HUMAN
1318
6
150773
TrEMBL
Mitochondrion (Reliability: 5)
X6RAN8_HUMAN
1548
6
175337
TrEMBL
Secretory Pathway (Reliability: 3)
Q53H53_HUMAN
533
1
60249
TrEMBL
other Location (Reliability: 2)
NOX5_HUMAN
765
0
86439
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
180000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
1 * 22000-23000 + 1 * 76000-91000, subunits of the membrane component of the enzyme complex, cytochrome b558, SDS-PAGE
additional information
?
-
x * 47000-48000, p47-phox, cytosolic component of the multicomponent complex, SDS-PAGE
?
-
x * 65000-67000, p67-phox, cytosolic component of the multicomponent complex, SDS-PAGE
additional information
-
guanine nucleotide exchange factor betaPix interacts with enzyme with the PH domain of betaPix binding to the FAD-binding region of enzyme. Additionally, NADPH oxidase organizer 1, NoxO1, interacts with enzyme
additional information
-
the alpha-helical loop of isoform Nox2 is probably involved in the correct assembly of the NADPH oxidase complex, permitting cytosolic factor translocation and electron transfer from NADPH to FAD
additional information
-
subunit p22phox co-immunoprecipitates with Hippel-Lindau tumor suppressor in vivo and is target of ubiquitination
additional information
Duox proteins form functional heterodimers with their respective DuoxA subunits, in close analogy to the phagocyte NADPH oxidase. Characterization of novel DuoxA1 isoforms and mispaired Duox-DuoxA complexes reveals that heterodimerization is a prerequisite for reactive oxygen species production. Functional Duox1 and Duox2 localize to the leading edge of migrating cells, augmenting motility and wound healing. DuoxA subunits are responsible for targeting functional oxidases to distinct cellular compartments in lung epithelial cells
additional information
Duox proteins form functional heterodimers with their respective DuoxA subunits, in close analogy to the phagocyte NADPH oxidase. Characterization of novel DuoxA1 isoforms and mispaired Duox-DuoxA complexes reveals that heterodimerization is a prerequisite for reactive oxygen species production. Functional Duox1 and Duox2 localize to the leading edge of migrating cells, augmenting motility and wound healing. DuoxA subunits are responsible for targeting functional oxidases to distinct cellular compartments in lung epithelial cells
additional information
-
active phagocyte NADPH oxidase is a multicomponent enzyme complex composed of six proteins: p22phox (phox: phagocyte oxidase), gp91phox/NOX2, p47phox, p67phox, p40phox and the small G-protein Rac1 or Rac2, enzyme structure, overview
additional information
-
Nox2 structure homology modeling, and structure and activation mechanism of NOX proteins, overview. Nox2 is composed of two main domains of equal sizes with very different properties. The amino-terminal moiety includes six transmembrane alpha-helices I-VI connected by 5 loops A-E. The cytosolic carboxy-terminal moiety of Nox2 constitutes a dehydrogenase domain that includes consensus binding sites for its NADPH substrate and FAD cofactor. NOX2 p40phox is composed of an N-terminal PX domain, a central SH3 domain and a C-terminal PB1 domain. The C-terminal PB1 domain of p40phox interacts with the PB1 domain of p67phox
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
phosphoprotein
additional information
glycoprotein
-
cytochrome b558 subunit gp91-phox of the multicomponent complex is heavily glycosylated
glycoprotein
-
isoform Duox2, partial glycosylation. Post-translational modifications during the maturation process may be implicated in the mechanism of H2O2 formation by favoring intramolecular superoxide dismutation
glycoprotein
-
3 loops of Nox2 are extracellular and include consensus asparagine glycosylation sites. Phosphorylation of p67phox, mediated by PKCdelta, ERK2 and p38 MAPK, increases superoxide production by Nox2
phosphoprotein
-
subunit p47phox is a substrate for interleukin-1 receptor-associated kinase-4, which phosphorylates p47phox at residues T133, S288, and T356. p47phox is phosphorylated in granulocytes in response to lipopolysaccharide stimulation. Lipopolysaccharide-dependent phosphorylation of p47phox is enhanced by the inhibition of p38 MAP kinase
phosphoprotein
-
in intact cells, NADPH oxidase activation is accompanied by phosphorylation of enzyme components p47phox, p67phox, p40phox, p22phox and gp91phox, along with several protein-protein interactions. P47phox is phosphorylated on multiple sites located in its carboxy-terminal portion, including serines 303-379, which play a central role in NADPH oxidase activation and regulation
phosphoprotein
-
phosphorylation of serine 461 by protein kinase A, serine 282 by ERK1/2 or p38 MAPK, or serine 172 by PKA or PKC, decreases ROS production by Nox1. Phosphorylation of p40phox on serine and threonine by PKC is increased during stimulation, particularly at threonine 154
additional information
-
coexpression of enzyme and enzyme maturation factor DuoxA2 allows ER-to-Golgi transition, maturation, and translocation to the plasma membrane of functional isoform Duox2 in a heterologous system
additional information
-
oxidative folding of wild-type protein in the endoplasmic reticulum is the rate-limiting step in the maturation, which is not faciltated by the speific maturation factor DUOXA2. DUOXA2 may allow for rapid exit of folded protein from the endoplasmatic reticulum or enahnced degradation of mutant protein
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D484T
-
mutant of the alpha-helical loop of isoform Nox2, neither NADPH oxidase nor iodonitrotetrazolium reductase activity
D500A
-
mutant of the alpha-helical loop of isoform Nox2, neither NADPH oxidase nor iodonitrotetrazolium reductase activity
D500G
-
mutant of the alpha-helical loop of isoform Nox2, neither NADPH oxidase nor iodonitrotetrazolium reductase activity
D500R
-
mutant of the alpha-helical loop of isoform Nox2, neither NADPH oxidase nor iodonitrotetrazolium reductase activity
D506N
E99Q/E143Q
-
site-directed mutagenesis, mutation in the Ca2+ binding domain of NOX5
K195A
-
mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
K195E
-
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
-
the mutation in the canonical NADPH binding motif of Nox4, analogous to the Nox2 mutation of a CGD patient, abolishes activity
Q36H
-
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
-
mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
R198Q/R199Q
-
mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
R199E
-
mutation in D-loop of isoform Nox2, complete loss of enzymic activity, but normal p47phox translocation and normal iodonitrotetrazolium reductase activity
R199Q
-
mutation in D-loop of isoform Nox2. Formylmethionine-activated mutant shows 4- to 8fold higher activity than wild-type
R376W
-
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
-
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
-
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
-
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
additional information
D506N
-
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
-
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
additional information
-
identification of heterozygous mutation in enzyme gene leading to premature stop at codon 300 and resulting in primary hypothyroidism
additional information
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
association with p22phox is required for Nox4 activity, the 2 proteins stabilize each other
-
Nox1 activity is dependent on chaperones Hsp90 and PDI, which appear to be necessary not only for protein folding after synthesis, but also to maintain enzyme stability
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His6-tagged wild-type and E99Q/E143Q mutant Ca2+ binding domain of NOX5 from Escherichia coli strain BL21(DE3) by nickel affinity and hydrophobic interaction chromatography, followed by ultrafiltration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
Cos-7, CHO, Hek293, NIH3T3, HeLa and PLB-XCGD cells transfected with ThOX2 DNA, protein is expressed but is exclusively found in cytoplasm and shows no activity
-
expression of His6-tagged wild-type and E99Q/E143Q mutant Ca2+ binding domain, residues 1-169, of NOX5 in Escherichia coli strain BL21(DE3)
-
stable transfection of COS-7 cells of subunits gp91phox, p22phox, p67phox, p47phox, and also p40phox fused to the N-terminus of green fluorescent protein
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced suppression of NAD(P)H oxidase subunit expression is AMP-activated protein kinase alpha2-dependent
-
interleukin-3 incubation stimulates the synthesis of Nox2 cytosolic sub-unit p47phox
-
loss of AMP-activated protein kinase activity increases NAD(P)H oxidase subunit expression (gp91phox, p47phox, p67phox, NOX1 and -4) and NAD(P)H oxidase-mediated superoxide production
-
NOX1 is upregulated by angiotensin II, PDGF, PGF, LDL, TNF-alpha, oscillatory shear stress BMP4, aldosterone plus salt, IFN-gamma, ET-1, T3, urokinase8, oxidized LDL, and vascular injury. NOX2 is upregulated by angiotensin II, ET-1, TGF-beta, IFN-gamma, oxidized LDL oscillatory shear stress, aldosterone plus salt, Ischemia, and vascular injury.NOX4 is upregulated by TGF-beta, thromboxane, TNF-alpha. IFN-gamma, urotensin, urokinase, oscillatory shear stress, hypoxia, hyperoxia vascular injury. NOX5 iss upregulated by angiotensin II, ET-1, thromboxane A2, TNF-alpha, atherosclerosis. Nox5 can be upregulated and activated by minute concentrations of hydrogen peroxide. In ischemic cardiomyocytes, Nox2 is upregulated in the cytosol and targeted to the nuclear pore complex
-
NOX4 gene expression is stronger in brain samples from stroke patients compared to healthy controls
-
Nox4 mRNA expression increases to 88% in fibroblasts cultured on 3-deoxyglucosone-collagen for 24 h compared to fibroblasts cultured on native collagen
-
the BRAFV600E oncogene upregulates the enzyme NOX4 via TGF-beta1 signaling pathway in papillary thyroid cancer cell line
-
the enzyme is elevated in human radio-induced thyroid tumors and in sporadic thyroid tumors
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
administration of thrombin to endothelial cells leads to upregulation of enzyme subunit p22phox accompanied by a delayed increase in generation of reactive oxygen species and enhanced proliferation. Existence of a positive feedback mechanism, whereby reactive oxygen species lead to elevated levels of p22phox and thus, sustained generation of reactive oxygen species as is observed in endothelial dysfunction
medicine
-
mutations in enzyme gene should be considered as the molecular cause of congenital hypothyroidism in young patients with thyroid dyshormogenesis
medicine
-
analysis of pre-interventional intravascular ultrasound images and histological specimens obtained by directional coronary artherectomy of patients with atherosclerosis. Reactive oxygen positive area ratio in directional coronary artherectomy probes correlates positiviely with vessel cross-sectional area, and relative plaque area. The area immunopositive for subunit p22phox also correlates positively with vessel cross-sectional area, and relative plaque area
medicine
-
expression of isoform Nox4 mRNA in glioblastomas of WHO grade IV is significantly higher than other astrocytomas of WHO grades II and III. 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
medicine
-
in lungs from patients with idiopathic pulmonary arterial hypertension, expression levels of NOX4, which is localized in the vessel media, are 2.5-fold upregulated
medicine
-
in peripheral blood lymphocytes from children with acute asthma, activity of NAD(P)H oxidase is significantly increased. Plasma levels of malondialdehyde, and nitric oxide are also markedly elevated, while catalase activity is decreased. Treatment of lymphocytes with salbutamol at 10 microg per ml, prevents the attenuation of catalase activity but significantly increases the levels of nitroc oxide and NAD(P)H oxidase activity. Levels of isoform NOX-1 mRNA are significantly increased in peripheral blodd lymphocytes following treatment with NO donor, S-nitroso-N-acetyl penicillamine. Subunit gp91phox protein is also two- to threefold increased following treatment with S-nitroso-N-acetyl penicillamine and leads to increased NAD(P)H oxidase activity
medicine
-
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
medicine
-
isoobtusilactone A elicits a concentration-dependent growth impediment with IC50 value of 37.5 microM. Treated cells also display transient increase of reactive oxygen species during the earlier stage of the experiment, followed by the disruption of mitochondrial transmembrane potential. The presence of a reactive oxygen species scavenger N-acetyl-L-cysteine and the inhibitor of NADPH oxidase diphenyleneiodonium chloride block reactive oxygen species production and the subsequent apoptotic cell death
medicine
-
long-term survival mechanisms in niacin deficient HaCaT keratinocyte cells involve accumulation of reactive oxygen species and increased DNA damage with concomitant increase in expression and activity of NAD(P)H oxidase
medicine
-
monocytes from sickle cell disease patients show higher levels of NAD(P)H oxidase subunit gp91phox gene expression and p47phox phosphorylation, along with increased interferon-gamma release by lymphocytes
medicine
-
NADPH oxidase is involved in killing of Candida albicans by dendritic cells, which is increased by interferon-alpha or interferon-gamma. However, Candida escapes the oxidative damage by inhibiting NADPH oxidase and by entering dendritic cells through receptors not involved in NADPH oxidase activation
medicine
-
neuroblastoma cell, cells differentiated by retinoic acid die after exposure to glycated albumin, a model of advanced glycation end product-modified protein. Undifferentiated cells are resistant to glycated albumin. Differentiated cells pre-treated with NAD(P)K oxidase inhibitor diphenyleneiodinium or with rottlerin, an inhibitor of protein kinase C delta, are able to prevent neuronal death induced by glycated albumin
medicine
-
overweight and obese adults demonstrate increased vascular endothelial expression of NAD(P)H oxidase subunit p47phox and evidence of endothelial oxidative stress, with selective compensatory upregulation of antioxidant enzymes and Ser1177-phosphorylated endothelial nitric oxide synthase. Endothelin-1 and nuclear factor kappaB protein expression also appear to be elevated in obese compared with lean adults
medicine
-
pharmacological inhibition or deficiency of human NADPH oxidase abolishes dermal-epidermal separation caused by autoantibodies and granulocytes ex vivo. Granulocyte-derived NADPH oxidase is a key molecular effector engaged by pathogenic autoantibodies and provides relevant targets for prevention of tissue damage in granulocyte-mediated autoimmune diseases
medicine
-
pre-treatment of NB-4 cells with inhibitor diphenyleneiodinium blocks arsenic trioxide-induced apoptosis
medicine
-
rosiglitazone activates 5'-AMP-activated protein kinase which, in turn, prevents hyperactivity of NAD(P)H oxidase induced by high glucose, possibly through protein kinase C inhibition. Rosiglitazone protects endothelial cells against glucose-induced oxidative stress with an 5'-AMP-activated protein kinase-dependent and a PPARgamma-independent mechanism
medicine
-
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
medicine
-
study on the aggregation of platelets from high-risk cardiac patients with aspirin resistance in presence of adenosine diphosphate, collagen, and epinephrine. Inhibition of NAD(P)H oxidase effectively suppresses collagen and epinephrine-induced aggregation
medicine
-
Burkholderia cenocepacia resides in macrophage vacuoles displaying an altered recruitment of the NADPH oxidase complex at the phagosomal membrane. This phenomenon may contribute to preventing the efficient clearance of this opportunistic pathogen from the infected airways of susceptible patients
medicine
-
chronic granulomatous disease is a rare inherited immunodeficiency syndrome caused by mutations in four genes encoding essential nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex components. Clinical, functional, and molecular investigation of chronic granulomatous disease in nine Jordanian families
medicine
inactivating mutations of Duox2 are linked to congenital hypothyroidism, and epigenetic silencing of Duox is frequently observed in lung cancer
medicine
-
as NAD(P)H oxidase activation may have dual actions in diabetes, selective targeting of the deleterious effects of sustained NAD(P)H oxidase activation, such as eNOS uncoupling, mitochondrial dysfunction, and impaired antioxidant gene expression, may prove beneficial in the treatment of diabetes
medicine
-
NADPH oxidase type 4 is a major source of oxidative stress and an effective therapeutic target in acute stroke
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Umeki, S.
Prostaglandin E1 and analogs of prostacyclin influencing superoxide production by the human neutrophil NADPH oxidase system
Int. J. Biochem.
26
1003-1008
1994
Homo sapiens
Umeki, S.
Mechanisms for the activation/electron transfer of neutrophil NADPH-oxidase complex and molecular pathology of chronic granulomatous disease
Ann. Hematol.
68
267-277
1994
Bos taurus, Cavia porcellus, Homo sapiens, Sus scrofa
Moreno, J.C.; Bikker, H.; Kempers, M.J.; van Trotsenburg, A.S.; Baas, F.; de Vijlder, J.J.; Vulsma, T.; Ris-Stalpers, C.
Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism
N. Engl. J. Med.
347
95-102
2002
Homo sapiens (Q9NRD8), Homo sapiens
De Deken, X.; Wang, D.; Dumont, J.E.; Miot, F.
Characterization of ThOX proteins as components of the thyroid H2O2-generating system
Exp. Cell Res.
273
187-196
2002
Canis lupus familiaris, Homo sapiens, Rattus norvegicus
De Deken, X.; Wang, D.; Many, M.C.; Costagliola, S.; Libert, F.; Vassart, G.; Dumont, J.E.; Miot, F.
Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family
J. Biol. Chem.
275
23227-23233
2000
Canis lupus familiaris, Sus scrofa, Caenorhabditis elegans (O61213), Caenorhabditis elegans, Homo sapiens (Q9NRD8), Homo sapiens
Dupuy, C.; Ohayon, R.; Valent, A.; Noel-Hudson, M.S.; Deme, D.; Virion, A.
Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cDNAs
J. Biol. Chem.
274
37265-37269
1999
Caenorhabditis elegans (O61213), Sus scrofa (Q8HZK2), Sus scrofa, Homo sapiens (Q9NRD8), Homo sapiens
Leseney, A.M.; Deme, D.; Legue, O.; Ohayon, R.; Chanson, P.; Sales, J.P.; Pires de Carvalho, D.; Dupuy, C.; Virion, A.
Biochemical characterization of a Ca2+/NAD(P)H-dependent H2O2 generator in human thyroid tissue
Biochimie
81
373-380
1999
Homo sapiens, Sus scrofa
Caillou, B.; Dupuy, C.; Lacroix, L.; Nocera, M.; Talbot, M.; Ohayon, R.; Deme, D.; Bidart, J.M.; Schlumberger, M.; Virion, A.
Expression of reduced nicotinamide adenine dinucleotide phosphate oxidase (ThoX, LNOX, Duox) genes and proteins in human thyroid tissues
J. Clin. Endocrinol. Metab.
86
3351-3358
2001
Homo sapiens (Q9NRD8)
Ferreira, A.C.F.; Cardoso, L.d.C.; Rosenthal, D.; Pires de Carvalho, D.
Thyroid Ca2+/NADPH-dependent H2O2 generation is partially inhibited by propylthiouracil and methimazole
Eur. J. Biochem.
270
2363-2368
2003
Homo sapiens
Fu, H.; Bylund, J.; Karlsson, A.; Pellme, S.; Dahlgren, C.
The mechanism for activation of the neutrophil NADPH-oxidase by the peptides formyl-Met-Leu-Phe and Trp-Lys-Tyr-Met-Val-Met differs from that for interleukin-8
Immunology
112
201-210
2004
Homo sapiens
Banfi, B.; Tirone, F.; Durussel, I.; Knisz, J.; Moskwa, P.; Molnar, G.Z.; Krause, K.H.; Cox, J.A.
Mechanism of Ca2+ activation of the NADPH oxidase 5 (NOX5)
J. Biol. Chem.
279
18583-18591
2004
Homo sapiens
Park, H.S.; Jung, H.Y.; Park, E.Y.; Kim, J.; Lee, W.J.; Bae, Y.S.
Direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kB
J. Immunol.
173
3589-3593
2004
Homo sapiens
Ambruso, D.R.; Cusack, N.; Thurman, G.
NADPH oxidase activity of neutrophil specific granules: requirements for cytosolic components and evidence of assembly during cell activation
Mol. Genet. Metab.
81
313-321
2004
Homo sapiens
El Hassani, R.A.; Benfares, N.; Caillou, B.; Talbot, M.; Sabourin, J.; Belotte, V.; Morand, S.; Gnidehou, S.; Agnandji, D.; Ohayon, R.; Kaniewski, J.; Noel-Hudson, M.; Bidart, J.; Schlumberger, M.; Virion, A.; Dupuy, C.
Dual oxidase2 is expressed all along the digestive tract
Am. J. Physiol.
288
G933-G942
2005
Homo sapiens, Sus scrofa
Biswas, S.; Gupta, M.K.; Chattopadhyay, D.; Mukhopadhyay, C.K.
Insulin-induced activation of hypoxia inducible factor-1 requires generation of reactive oxygen species by NADPH oxidase
Am. J. Physiol. Heart Circ. Physiol.
292
758-766
2006
Homo sapiens
Park, H.S.; Park, D.; Bae, Y.S.
Molecular interaction of NADPH oxidase 1 with betaPix and Nox Organizer 1
Biochem. Biophys. Res. Commun.
339
985-990
2006
Homo sapiens
Petheo, G.L.; Demaurex, N.
Voltage- and NADPH-dependence of electron currents generated by the phagocytic NADPH oxidase
Biochem. J.
388
485-491
2005
Homo sapiens
Pfarr, N.; Korsch, E.; Kaspers, S.; Herbst, A.; Stach, A.; Zimmer, C.; Pohlenz, J.
Congenital hypothyroidism caused by new mutations in the thyroid oxidase 2 (THOX2) gene
Clin. Endocrinol. (Oxf.)
65
810-815
2006
Homo sapiens
Carnesecchi, S.; Carpentier, J.L.; Foti, M.; Szanto, I.
Insulin-induced vascular endothelial growth factor expression is mediated by the NADPH oxidase NOX3
Exp. Cell Res.
312
3413-3424
2006
Homo sapiens
Harper, R.W.; Xu, C.; Eiserich, J.P.; Chen, Y.; Kao, C.Y.; Thai, P.; Setiadi, H.; Wu, R.
Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium
FEBS Lett.
579
4911-4917
2005
Homo sapiens
Djordjevic, T.; Pogrebniak, A.; BelAiba, R.S.; Bonello, S.; Wotzlaw, C.; Acker, H.; Hess, J.; Goerlach, A.
The expression of the NADPH oxidase subunit p22phox is regulated by a redox-sensitive pathway in endothelial cells
Free Radic. Biol. Med.
38
616-630
2005
Homo sapiens
Li, X.J.; Grunwald, D.; Mathieu, J.; Morel, F.; Stasia, M.J.
Crucial role of two potential cytosolic regions of Nox2, 191TSSTKTIRRS200 and 484DESQANHFAVHHDEEKD500, on NADPH oxidase activation
J. Biol. Chem.
280
14962-14973
2005
Homo sapiens
Ameziane-El-Hassani, R.; Morand, S.; Boucher, J.L.; Frapart, Y.M.; Apostolou, D.; Agnandji, D.; Gnidehou, S.; Ohayon, R.; Noel-Hudson, M.S.; Francon, J.; Lalaoui, K.; Virion, A.; Dupuy, C.
Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity
J. Biol. Chem.
280
30046-30054
2005
Homo sapiens, Sus scrofa
Grasberger, H.; Refetoff, S.
Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent
J. Biol. Chem.
281
18269-18272
2006
Homo sapiens
Marcal, L.E.; Dias-da-Motta, P.M.; Rehder, J.; Mamoni, R.L.; Blotta, M.H.; Whitney, C.B.; Newburger, P.E.; Costa, F.F.; Saad, S.T.; Condino-Neto, A.
Up-regulation of NADPH oxidase components and increased production of interferon-gamma by leukocytes from sickle cell disease patients
Am. J. Hematol.
83
41-45
2008
Homo sapiens
Steffen, Y.; Gruber, C.; Schewe, T.; Sies, H.
Mono-O-methylated flavanols and other flavonoids as inhibitors of endothelial NADPH oxidase
Arch. Biochem. Biophys.
469
209-219
2008
Homo sapiens
Choi, S.I.; Jeong, C.S.; Cho, S.Y.; Lee, Y.S.
Mechanism of apoptosis induced by apigenin in HepG2 human hepatoma cells: involvement of reactive oxygen species generated by NADPH oxidase
Arch. Pharm. Res.
30
1328-1335
2007
Homo sapiens
Datla, S.R.; Peshavariya, H.; Dusting, G.J.; Mahadev, K.; Goldstein, B.J.; Jiang, F.
Important role of Nox4 type NADPH oxidase in angiogenic responses in human microvascular endothelial cells in vitro
Arterioscler. Thromb. Vasc. Biol.
27
2319-2324
2007
Homo sapiens
Ceolotto, G.; Gallo, A.; Papparella, I.; Franco, L.; Murphy, E.; Iori, E.; Pagnin, E.; Fadini, G.P.; Albiero, M.; Semplicini, A.; Avogaro, A.
Rosiglitazone reduces glucose-induced oxidative stress mediated by NAD(P)H oxidase via AMPK-dependent mechanism
Arterioscler. Thromb. Vasc. Biol.
27
2627-2633
2007
Homo sapiens
Steffen, Y.; Schewe, T.; Sies, H.
(-)-Epicatechin elevates nitric oxide in endothelial cells via inhibition of NADPH oxidase
Biochem. Biophys. Res. Commun.
359
828-833
2007
Homo sapiens
Verchier, Y.; Lardy, B.; Nguyen, M.V.; Morel, F.; Arbault, S.; Amatore, C.
Concerted activities of nitric oxide synthases and NADPH oxidases in PLB-985 cells
Biochem. Biophys. Res. Commun.
361
493-498
2007
Homo sapiens
Nishikawa, H.; Wakano, K.; Kitani, S.
Inhibition of NADPH oxidase subunits translocation by tea catechin EGCG in mast cell
Biochem. Biophys. Res. Commun.
362
504-509
2007
Canis lupus familiaris, Homo sapiens
Ahluwalia, J.
Characterisation of electron currents generated by the human neutrophil NADPH oxidase
Biochem. Biophys. Res. Commun.
368
656-661
2008
Homo sapiens
Pacquelet, S.; Johnson, J.L.; Ellis, B.A.; Brzezinska, A.A.; Lane, W.S.; Munafo, D.B.; Catz, S.D.
Cross-talk between IRAK-4 and the NADPH oxidase
Biochem. J.
403
451-461
2007
Homo sapiens
Nisimoto, Y.; Tsubouchi, R.; Diebold, B.A.; Qiao, S.; Ogawa, H.; Ohara, T.; Tamura, M.
Activation of NADPH oxidase 1 in tumor colon epithelial cell
Biochem. J.
415
57-65
2008
Homo sapiens
Shen, K.; Sergeant, S.; Hantgan, R.R.; McPhail, L.C.; Horita, D.A.
Mutations in the PX-SH3A linker of p47phox decouple PI(3,4)P2 binding from NADPH oxidase activation
Biochemistry
47
8855-8865
2008
Homo sapiens
Miyano, K.; Sumimoto, H.
Role of the small GTPase Rac in p22phox-dependent NADPH oxidases
Biochimie
89
1133-1144
2007
Homo sapiens
Tian, W.; Li, X.J.; Stull, N.D.; Ming, W.; Suh, C.I.; Bissonnette, S.A.; Yaffe, M.B.; Grinstein, S.; Atkinson, S.J.; Dinauer, M.C.
Fc{gamma}R-stimulated activation of the NADPH oxidase: Phosphoinositide binding protein p40phox regulates NADPH oxidase activity after enzyme assembly on the phagosome
Blood
112
3867-3877
2008
Homo sapiens
Owayed, A.; Dhaunsi, G.S.; Al-Mukhaizeem, F.
Nitric oxide-mediated activation of NADPH oxidase by salbutamol during acute asthma in children
Cell Biochem. Funct.
26
603-608
2008
Homo sapiens
Brechard, S.; Melchior, C.; Plancon, S.; Schenten, V.; Tschirhart, E.J.
Store-operated Ca(2+) channels formed by TRPC1, TRPC6 and Orai1 and non-store-operated channels formed by TRPC3 are involved in the regulation of NADPH oxidase in HL-60 granulocytes
Cell Calcium
44
492-506
2008
Homo sapiens
Mittal, M.; Roth, M.; Koenig, P.; Hofmann, S.; Dony, E.; Goyal, P.; Selbitz, A.C.; Schermuly, R.T.; Ghofrani, H.A.; Kwapiszewska, G.; Kummer, W.; Klepetko, W.; Hoda, M.A.; Fink, L.; Haenze, J.; Seeger, W.; Grimminger, F.; Schmidt, H.H.; Weissmann, N.
Hypoxia-dependent regulation of nonphagocytic NADPH oxidase subunit NOX4 in the pulmonary vasculature
Circ. Res.
101
258-267
2007
Homo sapiens, Mus musculus
Silver, A.E.; Beske, S.D.; Christou, D.D.; Donato, A.J.; Moreau, K.L.; Eskurza, I.; Gates, P.E.; Seals, D.R.
Overweight and obese humans demonstrate increased vascular endothelial NAD(P)H oxidase-p47(phox) expression and evidence of endothelial oxidative stress
Circulation
115
627-637
2007
Homo sapiens
Dammanahalli, J.K.; Sun, Z.
Endothelin-1 inhibits NADPH oxidase activity in human abdominal aortic endothelial cells: A novel function of ETB1 receptors
Endocrinology
149
4979-4987
2008
Homo sapiens
Donini, M.; Zenaro, E.; Tamassia, N.; Dusi, S.
NADPH oxidase of human dendritic cells: role in Candida albicans killing and regulation by interferons, dectin-1 and CD206
Eur. J. Immunol.
37
1194-1203
2007
Homo sapiens
Borges de Oliveira-Junior, E.; Thomazzi, S.M.; Rehder, J.; Antunes, E.; Condino-Neto, A.
Effects of BAY 41-2272, an activator of nitric oxide-independent site of soluble guanylate cyclase, on human NADPH oxidase system from THP-1 cells
Eur. J. Pharmacol.
567
43-49
2007
Homo sapiens
Chen, C.Y.; Liu, T.Z.; Chen, C.H.; Wu, C.C.; Cheng, J.T.; Yiin, S.J.; Shih, M.K.; Wu, M.J.; Chern, C.L.
Isoobtusilactone A-induced apoptosis in human hepatoma Hep G2 cells is mediated via increased NADPH oxidase-derived reactive oxygen species (ROS) production and the mitochondria-associated apoptotic mechanisms
Food Chem. Toxicol.
45
1268-1276
2007
Homo sapiens, Rattus norvegicus
Sheu, M.L.; Chiang, C.K.; Tsai, K.S.; Ho, F.M.; Weng, T.I.; Wu, H.Y.; Liu, S.H.
Inhibition of NADPH oxidase-related oxidative stress-triggered signaling by honokiol suppresses high glucose-induced human endothelial cell apoptosis
Free Radic. Biol. Med.
44
2043-2050
2008
Homo sapiens
Benavente, C.A.; Jacobson, E.L.
Niacin restriction upregulates NADPH oxidase and reactive oxygen species (ROS) in human keratinocytes
Free Radic. Biol. Med.
44
527-537
2008
Homo sapiens
Datla, S.R.; Dusting, G.J.; Mori, T.A.; Taylor, C.J.; Croft, K.D.; Jiang, F.
Induction of heme oxygenase-1 in vivo suppresses NADPH oxidase derived oxidative stress
Hypertension
50
636-642
2007
Homo sapiens, Mus musculus, Rattus norvegicus
Izakovicova Holla, L.; Kankova, K.; Znojil, V.
Haplotype analysis of the NADPH oxidase p22 gene in patients with bronchial asthma
Int. Arch. Allergy Immunol.
148
73-80
2008
Homo sapiens
Shono, T.; Yokoyama, N.; Uesaka, T.; Kuroda, J.; Takeya, R.; Yamasaki, T.; Amano, T.; Mizoguchi, M.; Suzuki, S.O.; Niiro, H.; Miyamoto, K.; Akashi, K.; Iwaki, T.; Sumimoto, H.; Sasaki, T.
Enhanced expression of NADPH oxidase Nox4 in human gliomas and its roles in cell proliferation and survival
Int. J. Cancer
123
787-792
2008
Homo sapiens
Si, J.; Fu, X.; Behar, J.; Wands, J.; Beer, D.G.; Souza, R.F.; Spechler, S.J.; Lambeth, D.; Cao, W.
NADPH oxidase NOX5-S mediates acid-induced cyclooxygenase-2 expression via activation of NF-kappaB in Barretts esophageal adenocarcinoma cells
J. Biol. Chem.
282
16244-16255
2007
Homo sapiens
Usatyuk, P.V.; Romer, L.H.; He, D.; Parinandi, N.L.; Kleinberg, M.E.; Zhan, S.; Jacobson, J.R.; Dudek, S.M.; Pendyala, S.; Garcia, J.G.; Natarajan, V.
Regulation of hyperoxia-induced NADPH oxidase activation in human lung endothelial cells by the actin cytoskeleton and cortactin
J. Biol. Chem.
282
23284-23295
2007
Homo sapiens
Chen, J.; He, R.; Minshall, R.D.; Dinauer, M.C.; Ye, R.D.
Characterization of a mutation in the Phox homology domain of the NADPH oxidase component p40phox identifies a mechanism for negative regulation of superoxide production
J. Biol. Chem.
282
30273-30284
2007
Homo sapiens
Abid, M.R.; Spokes, K.C.; Shih, S.C.; Aird, W.C.
NADPH oxidase activity selectively modulates vascular endothelial growth factor signaling pathways
J. Biol. Chem.
282
35373-35385
2007
Homo sapiens
Block, K.; Gorin, Y.; Hoover, P.; Williams, P.; Chelmicki, T.; Clark, R.A.; Yoneda, T.; Abboud, H.E.
NAD(P)H oxidases regulate HIF-2alpha protein expression
J. Biol. Chem.
282
8019-8026
2007
Homo sapiens, Mus musculus
Bissonnette, S.A.; Glazier, C.M.; Stewart, M.Q.; Brown, G.E.; Ellson, C.D.; Yaffe, M.B.
Phosphatidylinositol 3-phosphate-dependent and -independent functions of p40phox in activation of the neutrophil NADPH oxidase
J. Biol. Chem.
283
2108-2119
2008
Homo sapiens
Benedyk, M.; Sopalla, C.; Nacken, W.; Bode, G.; Melkonyan, H.; Banfi, B.; Kerkhoff, C.
HaCaT keratinocytes overexpressing the S100 proteins S100A8 and S100A9 show increased NADPH oxidase and NF-kappaB activities
J. Invest. Dermatol.
127
2001-2011
2007
Homo sapiens
Gauss, K.A.; Nelson-Overton, L.K.; Siemsen, D.W.; Gao, Y.; DeLeo, F.R.; Quinn, M.T.
Role of NF-kappaB in transcriptional regulation of the phagocyte NADPH oxidase by tumor necrosis factor-alpha
J. Leukoc. Biol.
82
729-741
2007
Homo sapiens
Chiriac, M.T.; Roesler, J.; Sindrilaru, A.; Scharffetter-Kochanek, K.; Zillikens, D.; Sitaru, C.
NADPH oxidase is required for neutrophil-dependent autoantibody-induced tissue damage
J. Pathol.
212
56-65
2007
Homo sapiens, Mus musculus
Steinkamp-Fenske, K.; Bollinger, L.; Xu, H.; Yao, Y.; Horke, S.; Foerstermann, U.; Li, H.
Reciprocal regulation of endothelial nitric-oxide synthase and NADPH oxidase by betulinic acid in human endothelial cells
J. Pharmacol. Exp. Ther.
322
836-842
2007
Homo sapiens
Li, H.; Hortmann, M.; Daiber, A.; Oelze, M.; Ostad, M.A.; Schwarz, P.M.; Xu, H.; Xia, N.; Kleschyov, A.L.; Mang, C.; Warnholtz, A.; Muenzel, T.; Foerstermann, U.
Cyclooxygenase 2-selective and nonselective nonsteroidal anti-inflammatory drugs induce oxidative stress by up-regulating vascular NADPH oxidases
J. Pharmacol. Exp. Ther.
326
745-753
2008
Homo sapiens, Rattus norvegicus
Terashima, M.; Inoue, N.; Ohashi, Y.; Yokoyama, M.
Relationship between coronary plaque formation and NAD(P)H oxidase-derived reactive oxygen species - comparison of intravascular ultrasound finding of atherosclerotic lesions with histochemical characteristics-
Kobe J. Med. Sci.
53
107-117
2007
Homo sapiens
Wang, J.; Li, L.; Cang, H.; Shi, G.; Yi, J.
NADPH oxidase-derived reactive oxygen species are responsible for the high susceptibility to arsenic cytotoxicity in acute promyelocytic leukemia cells
Leuk. Res.
32
429-436
2008
Homo sapiens
Grasberger, H.; De Deken, X.; Miot, F.; Pohlenz, J.; Refetoff, S.
Missense mutations of dual oxidase 2 (DUOX2) implicated in congenital hypothyroidism have impaired trafficking in cells reconstituted with DUOX2 maturation factor
Mol. Endocrinol.
21
1408-1421
2007
Homo sapiens
Nitti, M.; Furfaro, A.L.; Traverso, N.; Odetti, P.; Storace, D.; Cottalasso, D.; Pronzato, M.A.; Marinari, U.M.; Domenicotti, C.
PKC delta and NADPH oxidase in AGE-induced neuronal death
Neurosci. Lett.
416
261-265
2007
Homo sapiens
Stef, G.; Csiszar, A.; Ziangmin, Z.; Ferdinandy, P.; Ungvari, Z.; Veress, G.
Inhibition of NAD(P)H oxidase attenuates aggregation of platelets from high-risk cardiac patients with aspirin resistance
Pharmacol. Rep.
59
428-436
2007
Homo sapiens
Maehara, Y.; Miyano, K.; Sumimoto, H.
Role for the first SH3 domain of p67phox in activation of superoxide-producing NADPH oxidases
Biochem. Biophys. Res. Commun.
379
589-593
2009
Homo sapiens
Cui, X.; Chang, B.; Myatt, L.
Expression and distribution of NADPH oxidase isoforms in human myometrium - role in angiotensin II-induced hypertrophy
Biol. Reprod.
82
305-312
2009
Homo sapiens
Luxen, S.; Noack, D.; Frausto, M.; Davanture, S.; Torbett, B.E.; Knaus, U.G.
Heterodimerization controls localization of Duox-DuoxA NADPH oxidases in airway cells
J. Cell Sci.
122
1238-1247
2009
Homo sapiens (Q9NRD8), Homo sapiens (Q9NRD9)
Bakri, F.G.; Martel, C.; Khuri-Bulos, N.; Mahafzah, A.; El-Khateeb, M.S.; Al-Wahadneh, A.M.; Hayajneh, W.A.; Hamamy, H.A.; Maquet, E.; Molin, M.; Stasia, M.J.
First report of clinical, functional, and molecular investigation of chronic granulomatous disease in nine Jordanian families
J. Clin. Immunol.
29
215-230
2009
Homo sapiens
Kamizato, M.; Nishida, K.; Masuda, K.; Takeo, K.; Yamamoto, Y.; Kawai, T.; Teshima-Kondo, S.; Tanahashi, T.; Rokutan, K.
Interleukin 10 inhibits interferon gamma- and tumor necrosis factor alpha-stimulated activation of NADPH oxidase 1 in human colonic epithelial cells and the mouse colon
J. Gastroenterol.
44
1172-1184
2009
Homo sapiens
Keith, K.E.; Hynes, D.W.; Sholdice, J.E.; Valvano, M.A.
Delayed association of the NADPH oxidase complex with macrophage vacuoles containing the opportunistic pathogen Burkholderia cenocepacia
Microbiology
155
1004-1015
2009
Homo sapiens
Arora, S.; Vaishya, R.; Dabla, P.K.; Singh, B.
NAD(P)H oxidases in coronary artery disease
Adv. Clin. Chem.
50
65-86
2010
Oryctolagus cuniculus, Homo sapiens, Mus musculus
Muller, G.; Morawietz, H.
Nitric oxide, NAD(P)H oxidase, and atherosclerosis
Antioxid. Redox Signal.
11
1711-1731
2009
Homo sapiens
El-Benna, J.; Dang, P.M.; Perianin, A.
Peptide-based inhibitors of the phagocyte NADPH oxidase
Biochem. Pharmacol.
80
778-785
2010
Homo sapiens, Rattus norvegicus
Gao, L.; Mann, G.E.
Vascular NAD(P)H oxidase activation in diabetes: a double-edged sword in redox signalling
Cardiovasc. Res.
82
9-20
2009
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus
Wang, S.; Zhang, M.; Liang, B.; Xu, J.; Xie, Z.; Liu, C.; Viollet, B.; Yan, D.; Zou, M.H.
AMPKalpha2 deletion causes aberrant expression and activation of NAD(P)H oxidase and consequent endothelial dysfunction in vivo: role of 26S proteasomes
Circ. Res.
106
1117-1128
2010
Homo sapiens, Mus musculus
Maraldi, T.; Prata, C.; Vieceli Dalla Sega, F.; Caliceti, C.; Zambonin, L.; Fiorentini, D.; Hakim, G.
NAD(P)H oxidase isoform Nox2 plays a prosurvival role in human leukaemia cells
Free Radic. Res.
43
1111-1121
2009
Homo sapiens
McCaffrey, R.L.; Schwartz, J.T.; Lindemann, S.R.; Moreland, J.G.; Buchan, B.W.; Jones, B.D.; Allen, L.A.
Multiple mechanisms of NADPH oxidase inhibition by type A and type B Francisella tularensis
J. Leukoc. Biol.
88
791-805
2010
Homo sapiens
Borbely, G.; Szabadkai, I.; Horvath, Z.; Marko, P.; Varga, Z.; Breza, N.; Baska, F.; Vantus, T.; Huszar, M.; Geiszt, M.; Hunyady, L.; Buday, L.; Orfi, L.; Keri, G.
Small-molecule inhibitors of NADPH oxidase 4
J. Med. Chem.
53
6758-6762
2010
Homo sapiens
Laleu, B.; Gaggini, F.; Orchard, M.; Fioraso-Cartier, L.; Cagnon, L.; Houngninou-Molango, S.; Gradia, A.; Duboux, G.; Merlot, C.; Heitz, F.; Szyndralewiez, C.; Page, P.
First in class, potent, and orally bioavailable NADPH oxidase isoform 4 (Nox4) inhibitors for the treatment of idiopathic pulmonary fibrosis
J. Med. Chem.
53
7715-7730
2010
Homo sapiens
Kleinschnitz, C.; Grund, H.; Wingler, K.; Armitage, M.E.; Jones, E.; Mittal, M.; Barit, D.; Schwarz, T.; Geis, C.; Kraft, P.; et al
Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration
PLoS Biol.
8
e1000479
2010
Homo sapiens, Mus musculus
Loughlin, D.T.; Artlett, C.M.
Precursor of advanced glycation end products mediates ER-stress-induced caspase-3 activation of human dermal fibroblasts through NAD(P)H oxidase 4
PLoS ONE
5
e11093
2010
Homo sapiens
El-Benna, J.; Dang, P.M.; Perianin, A.
Towards specific NADPH oxidase inhibition by small synthetic peptides
Cell. Mol. Life Sci.
69
2307-2314
2012
Homo sapiens
Lassegue, B.; San Martin, A.; Griendling, K.K.
Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system
Circ. Res.
110
1364-1390
2012
Homo sapiens
Wei, C.C.; Motl, N.; Levek, K.; Chen, L.Q.; Yang, Y.P.; Johnson, T.; Hamilton, L.; Stuehr, D.J.
Conformational States and kinetics of the calcium binding domain of NADPH oxidase 5
Open Biochem. J.
4
59-67
2010
Homo sapiens
Azouzi, N.; Cailloux, J.; Cazarin, J.M.; Knauf, J.A.; Cracchiolo, J.; Al Ghuzlan, A.; Hartl, D.; Polak, M.; Carre, A.; El Mzibri, M.; Filali-Maltouf, A.; Al Bouzidi, A.; Schlumberger, M.; Fagin, J.A.; Ameziane-El-Hassani, R.; Dupuy, C.
NADPH oxidase NOX4 is a critical mediator of BRAF(V600E)-induced downregulation of the sodium/iodide symporter in papillary thyroid carcinomas
Antioxid. Redox Signal.
26
864-877
2017
Homo sapiens
Cachat, J.; Deffert, C.; Hugues, S.; Krause, K.H.
Phagocyte NADPH oxidase and specific immunity
Clin. Sci.
128
635-648
2015
Homo sapiens
Antony, S.; Wu, Y.; Hewitt, S.M.; Anver, M.R.; Butcher, D.; Jiang, G.; Meitzler, J.L.; Liu, H.; Juhasz, A.; Lu, J.; Roy, K.K.; Doroshow, J.H.
Characterization of NADPH oxidase 5 expression in human tumors and tumor cell lines with a novel mouse monoclonal antibody
Free Radic. Biol. Med.
65
497-508
2013
Homo sapiens
Matsumoto, M.; Katsuyama, M.; Iwata, K.; Ibi, M.; Zhang, J.; Zhu, K.; Nauseef, W.M.; Yabe-Nishimura, C.
Characterization of N-glycosylation sites on the extracellular domain of NOX1/NADPH oxidase
Free Radic. Biol. Med.
68
196-204
2014
Homo sapiens, Mus musculus, Rattus norvegicus
Ameziane-El-Hassani, R.; Talbot, M.; de Souza Dos Santos, M.C.; Al Ghuzlan, A.; Hartl, D.; Bidart, J.M.; De Deken, X.; Miot, F.; Diallo, I.; de Vathaire, F.; Schlumberger, M.; Dupuy, C.
NADPH oxidase DUOX1 promotes long-term persistence of oxidative stress after an exposure to irradiation
Proc. Natl. Acad. Sci. USA
112
5051-5056
2015
Homo sapiens
Cortes, A.; Pejenaute, A.; Marques, J.; Izal, I.; Cenoz, S.; Ansorena, E.; Martinez-Irujo, J.J.; de Miguel, C.; Zalba, G.
NADPH oxidase 5 induces changes in the unfolded protein response in human aortic endothelial cells and in endothelial-specific knock-in mice
Antioxidants (Basel)
10
194
2021
Homo sapiens (Q96PH1), Homo sapiens
Dakik, H.; El Dor, M.; Leclerc, J.; Kouzi, F.; Nehme, A.; Deynoux, M.; Debeissat, C.; Khamis, G.; Ducrocq, E.; Ibrik, A.; Stasia, M.J.; Raad, H.; Rezvani, H.R.; Gouilleux, F.; Zibara, K.; Herault, O.; Mazurier, F.
Characterization of NADPH oxidase expression and activity in acute myeloid leukemia cell lines A correlation with the differentiation status
Antioxidants (Basel)
10
498
2021
Homo sapiens (P04839)
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