// Workers AI · dad joke modeWhat did NOX4 say to its friend? Ox-pect me to help.

NOX4
Identifiers
Aliases	NOX4, KOX, KOX-1, RENOX, NADPH oxidase 4
External IDs	OMIM: 605261; MGI: 1354184; HomoloGene: 41065; GeneCards: NOX4; OMA:NOX4 - orthologs
Enzyme activity EC # BRENDA ExPASy KEGG MetaCyc 1.6.3.1 ↗ ↗ ↗ ↗
Gene location (Human) Chr. Chromosome 11 (human) Band 11q14.3 Start 89,324,353 bp End 89,498,187 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7|7 D3 Start 86,895,304 bp End 87,047,918 bp
RNA expression pattern 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 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 PubMed search
Wikidata
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NADPH oxidase 4 is an enzyme that in humans is encoded by the NOX4 gene, and is a member of the NOX family of NADPH oxidases.

Function

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

Nox4 protects the vasculature against 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 beneficial adaptive responses to exercise mediated by ROS. Moreover, reductions in skeletal muscle NOX4 in aging and obesity was shown to contribute to the development of insulin resistance and may promote oxidative stress.

Further reading

• Lachgar A, Sojic N, Arbault S, Bruce D, Sarasin A, Amatore C, et al. (February 1999). "Amplification of the inflammatory cellular redox state by human immunodeficiency virus type 1-immunosuppressive tat and gp160 proteins". Journal of Virology. 73 (2): 1447–1452. doi:10.1128/JVI.73.2.1447-1452.1999. PMC 103969. PMID 9882350.
• Geiszt M, Kopp JB, Várnai P, Leto TL (2000). "Identification of renox, an NAD(P)H oxidase in kidney". Proceedings of the National Academy of Sciences of the United States of America. 97 (14): 8010–8014. Bibcode:2000PNAS...97.8010G. doi:10.1073/pnas.130135897. PMC 16661. PMID 10869423.
• Shiose A, Kuroda J, Tsuruya K, Hirai M, Hirakata H, Naito S, et al. (January 2001). "A novel superoxide-producing NAD(P)H oxidase in kidney". The Journal of Biological Chemistry. 276 (2): 1417–1423. doi:10.1074/jbc.M007597200. PMID 11032835.
• Cheng G, Cao Z, Xu X, van Meir EG, Lambeth JD (May 2001). "Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5". Gene. 269 (1–2): 131–140. doi:10.1016/S0378-1119(01)00449-8. PMID 11376945.
• Brar SS, Kennedy TP, Sturrock AB, Huecksteadt TP, Quinn MT, Whorton AR, et al. (June 2002). "An NAD(P)H oxidase regulates growth and transcription in melanoma cells". American Journal of Physiology. Cell Physiology. 282 (6): C1212–24. doi:10.1152/ajpcell.00496.2001. PMID 11997235. S2CID 25900754.
• Kalinina N, Agrotis A, Tararak E, Antropova Y, Kanellakis P, Ilyinskaya O, et al. (December 2002). "Cytochrome b558-dependent NAD(P)H oxidase-phox units in smooth muscle and macrophages of atherosclerotic lesions". Arteriosclerosis, Thrombosis, and Vascular Biology. 22 (12): 2037–2043. doi:10.1161/01.ATV.0000040222.02255.0F. PMID 12482831.
• Hilenski LL, Clempus RE, Quinn MT, Lambeth JD, Griendling KK (April 2004). "Distinct subcellular localizations of Nox1 and Nox4 in vascular smooth muscle cells". Arteriosclerosis, Thrombosis, and Vascular Biology. 24 (4): 677–683. doi:10.1161/01.ATV.0000112024.13727.2c. PMID 14670934.
• Mahadev K, Motoshima H, Wu X, Ruddy JM, Arnold RS, Cheng G, et al. (March 2004). "The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction". Molecular and Cellular Biology. 24 (5): 1844–1854. doi:10.1128/MCB.24.5.1844-1854.2004. PMC 350558. PMID 14966267.
• Chamulitrat W, Stremmel W, Kawahara T, Rokutan K, Fujii H, Wingler K, et al. (April 2004). "A constitutive NADPH oxidase-like system containing gp91phox homologs in human keratinocytes". The Journal of Investigative Dermatology. 122 (4): 1000–1009. doi:10.1111/j.0022-202X.2004.22410.x. PMID 15102091.
• Vaquero EC, Edderkaoui M, Pandol SJ, Gukovsky I, Gukovskaya AS (August 2004). "Reactive oxygen species produced by NAD(P)H oxidase inhibit apoptosis in pancreatic cancer cells". The Journal of Biological Chemistry. 279 (33): 34643–34654. doi:10.1074/jbc.M400078200. PMID 15155719.
• Schwarzer C, Machen TE, Illek B, Fischer H (2004). "NADPH oxidase-dependent acid production in airway epithelial cells". The Journal of Biological Chemistry. 279 (35): 36454–36461. doi:10.1074/jbc.M404983200. PMID 15210697.
• Guzik TJ, Sadowski J, Kapelak B, Jopek A, Rudzinski P, Pillai R, et al. (September 2004). "Systemic regulation of vascular NAD(P)H oxidase activity and nox isoform expression in human arteries and veins". Arteriosclerosis, Thrombosis, and Vascular Biology. 24 (9): 1614–1620. doi:10.1161/01.ATV.0000139011.94634.9d. PMID 15256399.
• Ambasta RK, Kumar P, Griendling KK, Schmidt HH, Busse R, Brandes RP (October 2004). "Direct interaction of the novel Nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase". The Journal of Biological Chemistry. 279 (44): 45935–45941. doi:10.1074/jbc.M406486200. PMID 15322091.
• Park HS, Jung HY, Park EY, Kim J, Lee WJ, Bae YS (September 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". Journal of Immunology. 173 (6). Baltimore: 3589–3593. doi:10.4049/jimmunol.173.6.3589. PMID 15356101.
• Jana A, Pahan K (2005). "Human immunodeficiency virus type 1 gp120 induces apoptosis in human primary neurons through redox-regulated activation of neutral sphingomyelinase". The Journal of Neuroscience. 24 (43): 9531–9540. doi:10.1523/JNEUROSCI.3085-04.2004. PMC 1955476. PMID 15509740.
• Pedruzzi E, Guichard C, Ollivier V, Driss F, Fay M, Prunet C, et al. (December 2004). "NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells". Molecular and Cellular Biology. 24 (24): 10703–10717. doi:10.1128/MCB.24.24.10703-10717.2004. PMC 533993. PMID 15572675.
• Djordjevic T, BelAiba RS, Bonello S, Pfeilschifter J, Hess J, Görlach A (March 2005). "Human urotensin II is a novel activator of NADPH oxidase in human pulmonary artery smooth muscle cells". Arteriosclerosis, Thrombosis, and Vascular Biology. 25 (3): 519–525. doi:10.1161/01.ATV.0000154279.98244.eb. PMID 15618545.