NOX4

NOX4
Identifiers
Aliases	NOX4,KOX, KOX-1, RENOX, NADPH oxidase 4
External IDs	OMIM:605261;MGI:1354184;HomoloGene:41065;GeneCards:NOX4;OMA:NOX4 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) Band 11q14.3 Start 89,324,353bp End 89,498,187bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7|7 D3 Start 86,895,304bp End 87,047,918bp
RNA expressionpattern Bgee Human Mouse(ortholog) Top expressed in Achilles tendon kidney tubule glomerulus metanephric glomerulus ascending aorta human kidney Descending thoracic aorta pericardium popliteal artery tibial arteries Top expressed in human kidney tunica media of zone of aorta right kidney lumbar spinal ganglion epithelium of small intestine left lobe of liver ascending aorta carotid body aortic valve renal cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding NAD(P)H oxidase H2O2-forming activity flavin adenine dinucleotide binding oxidoreductase activity, acting on NAD(P)H, oxygen as acceptor modified amino acid binding protein binding heme binding electron transfer activity oxidoreductase activity oxygen gasoreceptor activity superoxide-generating NAD(P)H oxidase activity protein tyrosine kinase binding Cellular component integral component of membrane membrane focal adhesion plasma membrane stress fiber cell junction NADPH oxidase complex nucleolus apical plasma membrane mitochondrion endoplasmic reticulum perinuclear region of cytoplasm cell periphery endoplasmic reticulum membrane nucleus perinuclear endoplasmic reticulum Biological process cellular response to transforming growth factor beta stimulus positive regulation of protein kinase B signaling response to hypoxia gene expression positive regulation of MAP kinase activity cardiac muscle cell differentiation human ageing bone resorption reactive oxygen species metabolic process superoxide anion generation positive regulation of smooth muscle cell migration positive regulation of reactive oxygen species metabolic process cellular response to gamma radiation cell morphogenesis positive regulation of DNA biosynthetic process positive regulation of ERK1 and ERK2 cascade positive regulation of apoptotic process homocysteine metabolic process inflammatory response positive regulation of stress fiber assembly cellular response to cAMP cellular response to glucose stimulus superoxide metabolic process negative regulation of cell population proliferation cellular response to oxidative stress electron transport chain heart process positive regulation of protein tyrosine kinase activity reactive oxygen species biosynthetic process defense response Sources:Amigo/QuickGO
Orthologs Species Human Mouse Entrez 50507 50490 Ensembl ENSG00000086991 ENSMUSG00000030562 UniProt Q9NPH5 Q9JHI8 RefSeq (mRNA) NM_001143836 NM_001143837 NM_001291926 NM_001291927 NM_001291929 NM_001300995 NM_016931 NM_001285833 NM_001285835 NM_015760 RefSeq (protein) NP_001137308 NP_001137309 NP_001278855 NP_001278856 NP_001278858 NP_001287924 NP_058627 NP_001272762 NP_001272764 NP_056575 Location (UCSC) Chr 11: 89.32 – 89.5 Mb Chr 7: 86.9 – 87.05 Mb PubMedsearch
Wikidata
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NADPH oxidase 4is anenzymethat in humans is encoded by theNOX4gene,and is a member of the NOX family ofNADPH oxidases.

Function

Oxygen sensing is essential forhomeostasisin all aerobic organisms. A phagocyte-type oxidase, similar to that responsible for the production of large amounts ofreactive oxygen species(ROS) inneutrophil granulocytes,with resultant antimicrobial activity, has been postulated to function in the kidney as an oxygen sensor that regulates the synthesis oferythropoietinin therenal cortex.

Nox4 protects thevasculatureagainst inflammatory stress.Nox-dependent reactive oxygen species modulation by amino endoperoxides can induce apoptosis in high Nox4-expressing cancer cells.

A study found that NOX4 facilitates certain beneficialadaptive responsesto exercise mediated byROS.Moreover, reductions in skeletal muscle NOX4 in aging and obesity was shown to contribute to the development ofinsulin resistanceand may promote oxidative stress.

Further reading

• Lachgar A, Sojic N, Arbault S, et al. (1999)."Amplification of the inflammatory cellular redox state by human immunodeficiency virus type 1-immunosuppressive tat and gp160 proteins".J. Virol.73(2): 1447–52.doi:10.1128/JVI.73.2.1447-1452.1999.PMC103969.PMID9882350.
• Geiszt M, Kopp JB, Várnai P, Leto TL (2000)."Identification of renox, an NAD(P)H oxidase in kidney".Proc. Natl. Acad. Sci. U.S.A.97(14): 8010–4.Bibcode:2000PNAS...97.8010G.doi:10.1073/pnas.130135897.PMC16661.PMID10869423.
• Shiose A, Kuroda J, Tsuruya K, et al. (2001)."A novel superoxide-producing NAD(P)H oxidase in kidney".J. Biol. Chem.276(2): 1417–23.doi:10.1074/jbc.M007597200.PMID11032835.
• Cheng G, Cao Z, Xu X, et al. (2001). "Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5".Gene.269(1–2): 131–40.doi:10.1016/S0378-1119(01)00449-8.PMID11376945.
• Brar SS, Kennedy TP, Sturrock AB, et al. (2002). "An NAD(P)H oxidase regulates growth and transcription in melanoma cells".Am. J. Physiol., Cell Physiol.282(6): C1212–24.doi:10.1152/ajpcell.00496.2001.PMID11997235.S2CID25900754.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003)."Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences".Proc. Natl. Acad. Sci. U.S.A.99(26): 16899–903.Bibcode:2002PNAS...9916899M.doi:10.1073/pnas.242603899.PMC139241.PMID12477932.
• Kalinina N, Agrotis A, Tararak E, et al. (2002)."Cytochrome b558-dependent NAD(P)H oxidase-phox units in smooth muscle and macrophages of atherosclerotic lesions".Arterioscler. Thromb. Vasc. Biol.22(12): 2037–43.doi:10.1161/01.ATV.0000040222.02255.0F.PMID12482831.
• Hilenski LL, Clempus RE, Quinn MT, et al. (2004)."Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells".Arterioscler. Thromb. Vasc. Biol.24(4): 677–83.doi:10.1161/01.ATV.0000112024.13727.2c.PMID14670934.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004)."Complete sequencing and characterization of 21,243 full-length human cDNAs".Nat. Genet.36(1): 40–5.doi:10.1038/ng1285.PMID14702039.
• Mahadev K, Motoshima H, Wu X, et al. (2004)."The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction".Mol. Cell. Biol.24(5): 1844–54.doi:10.1128/MCB.24.5.1844-1854.2004.PMC350558.PMID14966267.
• Chamulitrat W, Stremmel W, Kawahara T, et al. (2004)."A constitutive NADPH oxidase-like system containing gp91phox homologs in human keratinocytes".J. Invest. Dermatol.122(4): 1000–9.doi:10.1111/j.0022-202X.2004.22410.x.PMID15102091.
• Vaquero EC, Edderkaoui M, Pandol SJ, et al. (2004)."Reactive oxygen species produced by NAD(P)H oxidase inhibit apoptosis in pancreatic cancer cells".J. Biol. Chem.279(33): 34643–54.doi:10.1074/jbc.M400078200.PMID15155719.
• Schwarzer C, Machen TE, Illek B, Fischer H (2004)."NADPH oxidase-dependent acid production in airway epithelial cells".J. Biol. Chem.279(35): 36454–61.doi:10.1074/jbc.M404983200.PMID15210697.
• Guzik TJ, Sadowski J, Kapelak B, et al. (2005)."Systemic regulation of vascular NAD(P)H oxidase activity and nox isoform expression in human arteries and veins".Arterioscler. Thromb. Vasc. Biol.24(9): 1614–20.doi:10.1161/01.ATV.0000139011.94634.9d.PMID15256399.
• Ambasta RK, Kumar P, Griendling KK, et al. (2004)."Direct interaction of the novel Nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase".J. Biol. Chem.279(44): 45935–41.doi:10.1074/jbc.M406486200.PMID15322091.
• Park HS, Jung HY, Park EY, et al. (2004)."Cutting edge: 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-kappa B".J. Immunol.173(6): 3589–93.doi:10.4049/jimmunol.173.6.3589.PMID15356101.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004)."The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)".Genome Res.14(10B): 2121–7.doi:10.1101/gr.2596504.PMC528928.PMID15489334.
• Jana A, Pahan K (2005)."Human immunodeficiency virus type 1 gp120 induces apoptosis in human primary neurons through redox-regulated activation of neutral sphingomyelinase".J. Neurosci.24(43): 9531–40.doi:10.1523/JNEUROSCI.3085-04.2004.PMC1955476.PMID15509740.
• Pedruzzi E, Guichard C, Ollivier V, et al. (2004)."NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells".Mol. Cell. Biol.24(24): 10703–17.doi:10.1128/MCB.24.24.10703-10717.2004.PMC533993.PMID15572675.
• Djordjevic T, BelAiba RS, Bonello S, et al. (2005)."Human urotensin II is a novel activator of NADPH oxidase in human pulmonary artery smooth muscle cells".Arterioscler. Thromb. Vasc. Biol.25(3): 519–25.doi:10.1161/01.ATV.0000154279.98244.eb.PMID15618545.