Nitric oxide synthase, endothelial

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityⁱ

• H⁺

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  + 2 L-arginine

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  + 3 NADPH

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  + 4 O₂

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  = 4 H₂O

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  + 2 L-citrulline

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  + 3 NADP⁺

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  + 2 nitric oxide

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  EC:1.14.13.39
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  Source: Rhea

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  H⁺

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  +

  2

  L-arginine

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  +

  3

  NADPH

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  +

  4

  O₂

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  =

  4

  H₂O

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  +

  2

  L-citrulline

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  +

  3

  NADP⁺

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  +

  2

  nitric oxide

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<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactorⁱ

• heme
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• FAD
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  Note: Binds 1 FAD.
• FMN
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  Note: Binds 1 FMN.
• (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin
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  Note: Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationⁱ

Sites

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• actin binding Source: RGD <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "Regulation of Sertoli-germ cell adherens junction dynamics in the testis via the nitric oxide synthase (NOS)/cGMP/protein kinase G (PRKG)/beta-catenin (CATNB) signaling pathway: an in vitro and in vivo study."
    Lee N.P., Mruk D.D., Wong C.H., Cheng C.Y.
    Biol Reprod 73:458-471(2005) [PubMed] [Europe PMC] [Abstract]
• actin monomer binding Source: RGD
• arginine binding Source: RGD
• beta-catenin binding Source: RGD <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Regulation of Sertoli-germ cell adherens junction dynamics in the testis via the nitric oxide synthase (NOS)/cGMP/protein kinase G (PRKG)/beta-catenin (CATNB) signaling pathway: an in vitro and in vivo study."
    Lee N.P., Mruk D.D., Wong C.H., Cheng C.Y.
    Biol Reprod 73:458-471(2005) [PubMed] [Europe PMC] [Abstract]
• cadherin binding Source: RGDInferred from physical interactionⁱ
  • "Regulation of Sertoli-germ cell adherens junction dynamics in the testis via the nitric oxide synthase (NOS)/cGMP/protein kinase G (PRKG)/beta-catenin (CATNB) signaling pathway: an in vitro and in vivo study."
    Lee N.P., Mruk D.D., Wong C.H., Cheng C.Y.
    Biol Reprod 73:458-471(2005) [PubMed] [Europe PMC] [Abstract]
• calmodulin binding Source: RGDInferred from direct assayⁱ
  • "Interaction of calmodulin with its binding domain of rat cerebellar nitric oxide synthase. A multinuclear NMR study."
    Zhang M., Yuan T., Aramini J.M., Vogel H.J.
    J Biol Chem 270:20901-20907(1995) [PubMed] [Europe PMC] [Abstract]
• flavin adenine dinucleotide binding Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• FMN binding Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• heme binding Source: RGD
• Hsp90 protein binding Source: RGDInferred from direct assayⁱ
  • "Heat shock regulates the respiration of cardiac H9c2 cells through upregulation of nitric oxide synthase."
    Ilangovan G., Osinbowale S., Bratasz A., Bonar M., Cardounel A.J., Zweier J.L., Kuppusamy P.
    Am J Physiol Cell Physiol 287:C1472-81(2004) [PubMed] [Europe PMC] [Abstract]
• metal ion binding Source: UniProtKB-KW
• NADP binding Source: InterPro
• nitric-oxide synthase activity Source: RGDInferred from direct assayⁱ
  • "Mechanism of eNOS gene transfer inhibition of vascular smooth muscle cell proliferation."
    D'Souza F.M., Sparks R.L., Chen H., Kadowitz P.J., Jeter J.R. Jr.
    Am J Physiol Cell Physiol 284:C191-9(2003) [PubMed] [Europe PMC] [Abstract]
• nitric-oxide synthase binding Source: RGDInferred from physical interactionⁱ
  • "Regulation of Sertoli-germ cell adherens junction dynamics in the testis via the nitric oxide synthase (NOS)/cGMP/protein kinase G (PRKG)/beta-catenin (CATNB) signaling pathway: an in vitro and in vivo study."
    Lee N.P., Mruk D.D., Wong C.H., Cheng C.Y.
    Biol Reprod 73:458-471(2005) [PubMed] [Europe PMC] [Abstract]
• oxidoreductase activity Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• scaffold protein binding Source: RGDInferred from physical interactionⁱ
  • "Caveolin-1 and -3 dissociations from caveolae to cytosol in the heart during aging and after myocardial infarction in rat."
    Ratajczak P., Damy T., Heymes C., Oliviero P., Marotte F., Robidel E., Sercombe R., Boczkowski J., Rappaport L., Samuel J.L.
    Cardiovasc Res 57:358-369(2003) [PubMed] [Europe PMC] [Abstract]
  • "Nitric oxide inhibition of adenylyl cyclase type 6 activity is dependent upon lipid rafts and caveolin signaling complexes."
    Ostrom R.S., Bundey R.A., Insel P.A.
    J Biol Chem 279:19846-19853(2004) [PubMed] [Europe PMC] [Abstract]
• tetrahydrobiopterin binding Source: RGD

GO - Biological processⁱ

• aging Source: RGD <p>Inferred from Expression Pattern</p> <p>Covers cases where the annotation is inferred from the timing or location of expression of a gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "Age-related alterations in reactivity of cerebral arterioles: role of oxidative stress."
    Mayhan W.G., Arrick D.M., Sharpe G.M., Sun H.
    Microcirculation 15:225-236(2008) [PubMed] [Europe PMC] [Abstract]
• angiogenesis Source: RGD
• aortic valve morphogenesis Source: RGD
• arginine catabolic process Source: RGD
• blood vessel diameter maintenance Source: RGD
• blood vessel remodeling Source: RGD
• bone development Source: RGDInferred from expression patternⁱ
  • "Developmental regulation of nitric oxide synthase expression in rat skeletal bone."
    Hukkanen M.V., Platts L.A., Fernandez De Marticorena I., O'Shaughnessy M., MacIntyre I., Polak J.M.
    J Bone Miner Res 14:868-877(1999) [PubMed] [Europe PMC] [Abstract]
• cellular response to cAMP Source: RGDInferred from expression patternⁱ
  • "Nitric oxide synthase (NOS3) and contractile responsiveness to adrenergic and cholinergic agonists in the heart. Regulation of NOS3 transcription in vitro and in vivo by cyclic adenosine monophosphate in rat cardiac myocytes."
    Belhassen L., Kelly R.A., Smith T.W., Balligand J.L.
    J Clin Invest 97:1908-1915(1996) [PubMed] [Europe PMC] [Abstract]
• cellular response to growth factor stimulus Source: RGDInferred from expression patternⁱ
  • "Nitric oxide mediates the survival action of IGF-1 and insulin in pancreatic beta cells."
    Cahuana G.M., Tejedo J.R., Hmadcha A., Ramirez R., Cuesta A.L., Soria B., Martin F., Bedoya F.J.
    Cell Signal 20:301-310(2008) [PubMed] [Europe PMC] [Abstract]
• cellular response to heat Source: RGDInferred from expression patternⁱ
  • "Heat shock regulates the respiration of cardiac H9c2 cells through upregulation of nitric oxide synthase."
    Ilangovan G., Osinbowale S., Bratasz A., Bonar M., Cardounel A.J., Zweier J.L., Kuppusamy P.
    Am J Physiol Cell Physiol 287:C1472-81(2004) [PubMed] [Europe PMC] [Abstract]
• cellular response to high density lipoprotein particle stimulus Source: RGDInferred from expression patternⁱ
  • "High-density lipoprotein administration attenuates liver proinflammatory response, restores liver endothelial nitric oxide synthase activity, and lowers portal pressure in cirrhotic rats."
    Thabut D., Tazi K.A., Bonnefont-Rousselot D., Aller M., Farges O., Guimont M.C., Tellier Z., Guichard C., Ogier-Denis E., Poynard T., Moreau R., Lebrec D.
    Hepatology 46:1893-1906(2007) [PubMed] [Europe PMC] [Abstract]
• cellular response to insulin stimulus Source: RGDInferred from expression patternⁱ
  • "Study of insulin vascular sensitivity in aortic rings and endothelial cells from aged rats subjected to caloric restriction: Role of perivascular adipose tissue."
    Amor S., Martin-Carro B., Rubio C., Carrascosa J.M., Hu W., Huang Y., Garcia-Villalon A.L., Granado M.
    Exp Gerontol 109:126-136(2018) [PubMed] [Europe PMC] [Abstract]
• cellular response to low-density lipoprotein particle stimulus Source: RGDInferred from expression patternⁱ
  • "Catechins Blunt the Effects of oxLDL and its Primary Metabolite Phosphatidylcholine Hydroperoxide on Endothelial Dysfunction Through Inhibition of Oxidative Stress and Restoration of eNOS in Rats."
    Chang H.H., Chien C.Y., Chen K.H., Huang S.C., Chien C.T.
    Kidney Blood Press Res 42:919-932(2017) [PubMed] [Europe PMC] [Abstract]
• cellular response to magnesium ion Source: RGDInferred from expression patternⁱ
  • "Magnesium supplementation prevents chronic cyclosporine nephrotoxicity via adjusting nitric oxide synthase activity."
    Yuan J., Zhou J., Chen B.C., Zhang X., Zhou H.M., Du D.F., Chang S., Chen Z.K.
    Transplant Proc 37:1892-1895(2005) [PubMed] [Europe PMC] [Abstract]
• cellular response to mechanical stimulus Source: RGD <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Mechanical stretch induces endothelial nitric oxide synthase gene expression in neonatal rat cardiomyocytes."
    Cheng T.H., Chen J.J., Shih N.L., Lin J.W., Liu J.C., Chen Y.L., Chen C.H., Chen J.J.
    Clin Exp Pharmacol Physiol 36:559-566(2009) [PubMed] [Europe PMC] [Abstract]
• cellular response to organic cyclic compound Source: RGDInferred from expression patternⁱ
  • "FXR-mediated regulation of eNOS expression in vascular endothelial cells."
    Li J., Wilson A., Kuruba R., Zhang Q., Gao X., He F., Zhang L.M., Pitt B.R., Xie W., Li S.
    Cardiovasc Res 77:169-177(2008) [PubMed] [Europe PMC] [Abstract]
• cellular response to rotenone Source: RGDInferred from expression patternⁱ
  • "Safranal prevents rotenone-induced oxidative stress and apoptosis in an in vitro model of Parkinson's disease through regulating Keap1/Nrf2 signaling pathway."
    Pan P.K., Qiao L.Y., Wen X.N.
    Cell Mol Biol (Noisy-le-grand) 62:11-17(2016) [PubMed] [Europe PMC] [Abstract]
• cellular response to transforming growth factor beta stimulus Source: RGDInferred from mutant phenotypeⁱ
  • "TGFbeta receptor activation enhances cardiac apoptosis via SMAD activation and concomitant NO release."
    Heger J., Warga B., Meyering B., Abdallah Y., Schluter K.D., Piper H.M., Euler G.
    J Cell Physiol 226:2683-2690(2011) [PubMed] [Europe PMC] [Abstract]
• cellular response to tumor necrosis factor Source: RGDInferred from expression patternⁱ
  • "Tumor necrosis factor alpha decreases nitric oxide synthase type 3 expression primarily via Rho/Rho kinase in the thick ascending limb."
    Ramseyer V.D., Hong N.J., Garvin J.L.
    Hypertension 59:1145-1150(2012) [PubMed] [Europe PMC] [Abstract]
• endocardial cushion morphogenesis Source: RGD
• endothelial cell migration Source: RGD
• female pregnancy Source: RGDInferred from expression patternⁱ
  • "Pregnancy alters nitric oxide synthase and natriuretic peptide systems in the rat left ventricle."
    Jankowski M., Wang D., Mukaddam-Daher S., Gutkowska J.
    J Endocrinol 184:209-217(2005) [PubMed] [Europe PMC] [Abstract]
  • "Renal nitric oxide production in rat pregnancy: role of constitutive nitric oxide synthases."
    Smith C.A., Santymire B., Erdely A., Venkat V., Losonczy G., Baylis C.
    Am J Physiol Renal Physiol 299:F830-6(2010) [PubMed] [Europe PMC] [Abstract]
• homeostasis of number of cells within a tissue Source: RGD
• in utero embryonic development Source: RGD
• lipopolysaccharide-mediated signaling pathway Source: RGD
• lung development Source: RGD
• negative regulation of biomineral tissue development Source: RGD
• negative regulation of blood pressure Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• negative regulation of calcium ion transport Source: RGD
• negative regulation of cell population proliferation Source: RGD
• negative regulation of hydrolase activity Source: RGD
• negative regulation of muscle hyperplasia Source: RGD
• negative regulation of potassium ion transport Source: RGD
• negative regulation of smooth muscle cell proliferation Source: RGDInferred from mutant phenotypeⁱ
  • "Mechanism of eNOS gene transfer inhibition of vascular smooth muscle cell proliferation."
    D'Souza F.M., Sparks R.L., Chen H., Kadowitz P.J., Jeter J.R. Jr.
    Am J Physiol Cell Physiol 284:C191-9(2003) [PubMed] [Europe PMC] [Abstract]
  • "Nitric oxide synthase and NAD(P)H oxidase modulate coronary endothelial cell growth."
    Bayraktutan U.
    J Mol Cell Cardiol 36:277-286(2004) [PubMed] [Europe PMC] [Abstract]
• nitric oxide biosynthetic process Source: RGDInferred from mutant phenotypeⁱ
  • "Mechanism of eNOS gene transfer inhibition of vascular smooth muscle cell proliferation."
    D'Souza F.M., Sparks R.L., Chen H., Kadowitz P.J., Jeter J.R. Jr.
    Am J Physiol Cell Physiol 284:C191-9(2003) [PubMed] [Europe PMC] [Abstract]
• nitric oxide mediated signal transduction Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• ovulation from ovarian follicle Source: RGD
• positive regulation of angiogenesis Source: RGD
• positive regulation of apoptotic process Source: RGDInferred from mutant phenotypeⁱ
  • "TGFbeta receptor activation enhances cardiac apoptosis via SMAD activation and concomitant NO release."
    Heger J., Warga B., Meyering B., Abdallah Y., Schluter K.D., Piper H.M., Euler G.
    J Cell Physiol 226:2683-2690(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of blood vessel endothelial cell migration Source: RGD
• positive regulation of gene expression Source: RGD
• positive regulation of guanylate cyclase activity Source: RGD
• pulmonary valve morphogenesis Source: RGD
• regulation of nervous system process Source: RGD
• regulation of sodium ion transport Source: RGD
• regulation of systemic arterial blood pressure by endothelin Source: RGD
• regulation of the force of heart contraction by chemical signal Source: RGD
• removal of superoxide radicals Source: RGD
• response to activity Source: RGDInferred from expression patternⁱ
  • "The effect of regular exercise on penile nitric oxide synthase expression in rats."
    Ozbek E., Tasci A.I., Ilbey Y.O., Simsek A., Somay A., Metin G.
    Int J Androl 33:623-628(2010) [PubMed] [Europe PMC] [Abstract]
• response to amino acid Source: RGDInferred from expression patternⁱ
  • "Receptor-mediated activation of nitric oxide synthesis by arginine in endothelial cells."
    Joshi M.S., Ferguson T.B. Jr., Johnson F.K., Johnson R.A., Parthasarathy S., Lancaster J.R. Jr.
    Proc Natl Acad Sci U S A 104:9982-9987(2007) [PubMed] [Europe PMC] [Abstract]
• response to axon injury Source: RGDInferred from expression patternⁱ
  • "Nitric oxide synthase and arginase expression changes in the rat perirhinal and entorhinal cortices following unilateral vestibular damage: a link to deficits in object recognition?"
    Liu P., Gliddon C.M., Lindsay L., Darlington C.L., Smith P.F.
    J Vestib Res 14:411-417(2004) [PubMed] [Europe PMC] [Abstract]
• response to candesartan Source: RGDInferred from expression patternⁱ
  • "Involvement of angiotensin II in the remodeling induced by a chronic decrease in blood flow in rat mesenteric resistance arteries."
    Baron-Menguy C., Toutain B., Cousin M., Dumont O., Guihot A.L., Vessieres E., Subra J.F., Custaud M.A., Loufrani L., Henrion D.
    Hypertens Res 33:857-866(2010) [PubMed] [Europe PMC] [Abstract]
• response to carbohydrate Source: RGDInferred from expression patternⁱ
  • "Structural-Activity Relationship of Ginsenosides from Steamed Ginseng in the Treatment of Erectile Dysfunction."
    Ying A., Yu Q.T., Guo L., Zhang W.S., Liu J.F., Li Y., Song H., Li P., Qi L.W., Ge Y.Z., Liu E.H., Liu Q.
    Am J Chin Med 46:137-155(2018) [PubMed] [Europe PMC] [Abstract]
• response to corticosterone Source: RGDInferred from expression patternⁱ
  • "Decreased renal expression of nitric oxide synthase isoforms in adrenocorticotropin-induced and corticosterone-induced hypertension."
    Lou Y.K., Wen C., Li M., Adams D.J., Wang M.X., Yang F., Morris B.J., Whitworth J.A.
    Hypertension 37:1164-1170(2001) [PubMed] [Europe PMC] [Abstract]
• response to cytokine Source: RGDInferred from expression patternⁱ
  • "Interleukin-6 sustains hepatic regeneration in cirrhotic rat."
    Tiberio G.A., Tiberio L., Benetti A., Cervi E., Pandolfo G., Dreano M., Garotta G., Comini L., Martini M., Giulini S.M., Schiaffonati L.
    Hepatogastroenterology 54:878-883(2007) [PubMed] [Europe PMC] [Abstract]
• response to drug Source: RGDInferred from expression patternⁱ
  • "Angiotensin II type 1 receptor blocker preserves tolerance to ischemia-reperfusion injury in Dahl salt-sensitive rat heart."
    Matsuhisa S., Otani H., Okazaki T., Yamashita K., Akita Y., Sato D., Moriguchi A., Imamura H., Iwasaka T.
    Am J Physiol Heart Circ Physiol 294:H2473-9(2008) [PubMed] [Europe PMC] [Abstract]
  • "Treatment with low-dose atorvastatin, losartan, and their combination increases expression of vasoactive-related genes in rat aortas."
    Lunder M., Drevensek G., Cerne D., Marc J., Janic M., Sabovic M.
    J Cardiovasc Pharmacol Ther 18:177-183(2013) [PubMed] [Europe PMC] [Abstract]
• response to erythropoietin Source: RGDInferred from expression patternⁱ
  • "Nephroprotection through the Akt/eNOS pathway by centrally administered erythropoietin in a rat model of fixed-volume hemorrhage."
    Seifi B., Kadkhodaee M., Ranjbaran M., Bakhshi E.
    Life Sci 193:180-185(2018) [PubMed] [Europe PMC] [Abstract]
• response to estradiol Source: RGDInferred from direct assayⁱ
  • "Post-translational regulation of endothelial nitric oxide synthase (eNOS) by estrogens in the rat vagina."
    Musicki B., Liu T., Strong T.D., Lagoda G.A., Bivalacqua T.J., Burnett A.L.
    J Sex Med 7:1768-1777(2010) [PubMed] [Europe PMC] [Abstract]
• response to ethanol Source: RGDInferred from expression patternⁱ
  • "Ethanol consumption increases blood pressure and alters the responsiveness of the mesenteric vasculature in rats."
    Tirapelli C.R., Leone A.F., Yogi A., Tostes R.C., Lanchote V.L., Uyemura S.A., Resstel L.B., Correa F.M., Padovan C.M., de Oliveira A.M., Coelho E.B.
    J Pharm Pharmacol 60:331-341(2008) [PubMed] [Europe PMC] [Abstract]
• response to fluid shear stress Source: RGD
• response to fructose Source: RGDInferred from expression patternⁱ
  • "Decrease in renal medullary endothelial nitric oxide synthase of fructose-fed, salt-sensitive hypertensive rats."
    Nishimoto Y., Tomida T., Matsui H., Ito T., Okumura K.
    Hypertension 40:190-194(2002) [PubMed] [Europe PMC] [Abstract]
• response to hormone Source: GO_CentralInferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• response to hyperoxia Source: RGDInferred from expression patternⁱ
  • "[Dynamic changes in vascular endothelial growth factor and endothelial nitric oxide synthase in lungs of premature rats after hyperoxia exposure]."
    Wei W., Wang W., Ning Q., Luo X.P.
    Zhongguo Dang Dai Er Ke Za Zhi 9:473-478(2007) [PubMed] [Europe PMC] [Abstract]
• response to hypoxia Source: RGDInferred from expression patternⁱ
  • "Differential effects of chronic hypoxia and intermittent hypocapnic and eucapnic hypoxia on pulmonary vasoreactivity."
    Snow J.B., Kitzis V., Norton C.E., Torres S.N., Johnson K.D., Kanagy N.L., Walker B.R., Resta T.C.
    J Appl Physiol (1985) 104:110-118(2008) [PubMed] [Europe PMC] [Abstract]
• response to ketone Source: RGDInferred from expression patternⁱ
  • "Role of tetrahydrobiopterin in resistance to myocardial ischemia in Brown Norway and Dahl S rats."
    An J., Du J., Wei N., Xu H., Pritchard K.A. Jr., Shi Y.
    Am J Physiol Heart Circ Physiol 297:H1783-91(2009) [PubMed] [Europe PMC] [Abstract]
• response to L-arginine Source: RGDInferred from expression patternⁱ
  • "Effect of cardamonin on hepatic ischemia reperfusion induced in rats: Role of nitric oxide."
    Atef Y., El-Fayoumi H.M., Abdel-Mottaleb Y., Mahmoud M.F.
    Eur J Pharmacol 815:446-453(2017) [PubMed] [Europe PMC] [Abstract]
• response to lead ion Source: RGDInferred from expression patternⁱ
  • "Direct effects of lead (Pb2+) on the relaxation of in vitro cultured rat aorta to acetylcholine."
    Zhang L.F., Peng S.Q., Wang S., Li B.L., Han G., Dong Y.S.
    Toxicol Lett 170:104-110(2007) [PubMed] [Europe PMC] [Abstract]
  • "Nitric oxide synthase immunolocalization and expression in the rat hippocampus after sub-acute lead acetate exposure in rats."
    Nava-Ruiz C., Alcaraz-Zubeldia M., Mendez-Armenta M., Vergara P., Diaz-Ruiz A., Rios C.
    Exp Toxicol Pathol 62:311-316(2010) [PubMed] [Europe PMC] [Abstract]
• response to lipopolysaccharide Source: RGDInferred from expression patternⁱ
  • "Discrepant effects of inducible nitric oxide synthase modulation on systemic and splanchnic endothelial nitric oxide synthase activity and expression in cirrhotic rats."
    Malyshev E., Tazi K.A., Moreau R., Lebrec D.
    J Gastroenterol Hepatol 22:2195-2201(2007) [PubMed] [Europe PMC] [Abstract]
• response to magnetism Source: RGDInferred from expression patternⁱ
  • "Therapeutic ultrasound plus pulsed electromagnetic field improves recovery from peripheral arterial disease in hypertension."
    Lu Z.Y., Zhou H.S., Su Z.X., Qi J., Zhang J., Xue G.H., Li Y., Hao C.N., Shi Y.Q., Duan J.L.
    Am J Transl Res 9:4184-4194(2017) [PubMed] [Europe PMC] [Abstract]
• response to mechanical stimulus Source: RGDInferred from expression patternⁱ
  • "Orthodontic force stimulates eNOS and iNOS in rat osteocytes."
    Tan S.D., Xie R., Klein-Nulend J., van Rheden R.E., Bronckers A.L., Kuijpers-Jagtman A.M., Von den Hoff J.W., Maltha J.C.
    J Dent Res 88:255-260(2009) [PubMed] [Europe PMC] [Abstract]
• response to mercury ion Source: RGDInferred from expression patternⁱ
  • "Xanthine Oxidase Activation Modulates the Endothelial (Vascular) Dysfunction Related to HgCl₂ Exposure Plus Myocardial Infarction in Rats."
    Faria T.O., Simoes M.R., Vassallo D.V., Forechi L., Almenara C.C.P., Marchezini B.A., Stefanon I., Vassallo P.F.
    Cardiovasc Toxicol 18:161-174(2018) [PubMed] [Europe PMC] [Abstract]
• response to metal ion Source: RGDInferred from expression patternⁱ
  • "Titanium implants alter endothelial function and vasoconstriction via a protein kinase C-regulated pathway."
    Yang R.S., Tzeng H.P., Ho F.M., Chuang C.C., Chen B.L., Huang C.F., Chen Y.W., Chen R.M., Liu S.H.
    Acta Biomater 5:3258-3264(2009) [PubMed] [Europe PMC] [Abstract]
• response to metformin Source: RGDInferred from expression patternⁱ
  • "Hypothermic machine perfusion with metformin-University of Wisconsin solution for ex vivo preservation of standard and marginal liver grafts in a rat model."
    Chai Y.C., Dang G.X., He H.Q., Shi J.H., Zhang H.K., Zhang R.T., Wang B., Hu L.S., Lv Y.
    World J Gastroenterol 23:7221-7231(2017) [PubMed] [Europe PMC] [Abstract]
• response to nicotine Source: RGDInferred from expression patternⁱ
  • "Oral nicotine aggravates endothelial dysfunction and vascular inflammation in diet-induced obese rats: Role of macrophage TNFalpha."
    Liu C., Zhou M.S., Li Y., Wang A., Chadipiralla K., Tian R., Raij L.
    PLoS One 12:e0188439-e0188439(2017) [PubMed] [Europe PMC] [Abstract]
• response to nutrient levels Source: RGDInferred from expression patternⁱ
  • "Study of insulin vascular sensitivity in aortic rings and endothelial cells from aged rats subjected to caloric restriction: Role of perivascular adipose tissue."
    Amor S., Martin-Carro B., Rubio C., Carrascosa J.M., Hu W., Huang Y., Garcia-Villalon A.L., Granado M.
    Exp Gerontol 109:126-136(2018) [PubMed] [Europe PMC] [Abstract]
• response to organic cyclic compound Source: RGDInferred from expression patternⁱ
  • "Time-related changes in constitutive and inducible nitric oxide synthases in the rat striatum in a model of Huntington's disease."
    Aguilera P., Chanez-Cardenas M.E., Floriano-Sanchez E., Barrera D., Santamaria A., Sanchez-Gonzalez D.J., Perez-Severiano F., Pedraza-Chaverri J., Jimenez P.D.
    Neurotoxicology 28:1200-1207(2007) [PubMed] [Europe PMC] [Abstract]
• response to peptide Source: RGDInferred from expression patternⁱ
  • "Effects of rat urotensin II on coronary flow and myocardial eNOS protein expression in isolated rat heart."
    Li L., Yuan W.J., Su D.F.
    Acta Pharmacol Sin 25:1444-1449(2004) [PubMed] [Europe PMC] [Abstract]
• response to peptide hormone Source: RGDInferred from expression patternⁱ
  • "Adiponectin improves endothelial function in hyperlipidemic rats by reducing oxidative/nitrative stress and differential regulation of eNOS/iNOS activity."
    Li R., Wang W.Q., Zhang H., Yang X., Fan Q., Christopher T.A., Lopez B.L., Tao L., Goldstein B.J., Gao F., Ma X.L.
    Am J Physiol Endocrinol Metab 293:E1703-8(2007) [PubMed] [Europe PMC] [Abstract]
• response to salt Source: RGDInferred from expression patternⁱ
  • "Dietary sodium intake regulates angiotensin II type 1, mineralocorticoid receptor, and associated signaling proteins in heart."
    Ricchiuti V., Lapointe N., Pojoga L., Yao T., Tran L., Williams G.H., Adler G.K.
    J Endocrinol 211:47-54(2011) [PubMed] [Europe PMC] [Abstract]
• response to ultrasound Source: RGDInferred from expression patternⁱ
  • "Therapeutic ultrasound plus pulsed electromagnetic field improves recovery from peripheral arterial disease in hypertension."
    Lu Z.Y., Zhou H.S., Su Z.X., Qi J., Zhang J., Xue G.H., Li Y., Hao C.N., Shi Y.Q., Duan J.L.
    Am J Transl Res 9:4184-4194(2017) [PubMed] [Europe PMC] [Abstract]
• retina development in camera-type eye Source: RGDInferred from expression patternⁱ
  • "Endothelial nitric oxide synthase is expressed in amacrine cells of developing human retinas."
    Li S., Tay D., Shu S., Bao X., Wu Y., Wang X., Yip H.K.
    Invest Ophthalmol Vis Sci 47:2141-2149(2006) [PubMed] [Europe PMC] [Abstract]
• signal transduction Source: RGDInferred from mutant phenotypeⁱ
  • "Mechanism of eNOS gene transfer inhibition of vascular smooth muscle cell proliferation."
    D'Souza F.M., Sparks R.L., Chen H., Kadowitz P.J., Jeter J.R. Jr.
    Am J Physiol Cell Physiol 284:C191-9(2003) [PubMed] [Europe PMC] [Abstract]
• smooth muscle hyperplasia Source: RGD
• ventricular septum morphogenesis Source: RGD

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

• UniProt annotation
• GO - Cellular component

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

Chemistry databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

<p>This subsection of the 'Expression' section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified 'at the protein level'.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stageⁱ

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• actin binding Source: RGDInferred from direct assayⁱ
  • "Regulation of Sertoli-germ cell adherens junction dynamics in the testis via the nitric oxide synthase (NOS)/cGMP/protein kinase G (PRKG)/beta-catenin (CATNB) signaling pathway: an in vitro and in vivo study."
    Lee N.P., Mruk D.D., Wong C.H., Cheng C.Y.
    Biol Reprod 73:458-471(2005) [PubMed] [Europe PMC] [Abstract]
• actin monomer binding Source: RGD
• beta-catenin binding Source: RGDInferred from physical interactionⁱ
  • "Regulation of Sertoli-germ cell adherens junction dynamics in the testis via the nitric oxide synthase (NOS)/cGMP/protein kinase G (PRKG)/beta-catenin (CATNB) signaling pathway: an in vitro and in vivo study."
    Lee N.P., Mruk D.D., Wong C.H., Cheng C.Y.
    Biol Reprod 73:458-471(2005) [PubMed] [Europe PMC] [Abstract]
• cadherin binding Source: RGDInferred from physical interactionⁱ
  • "Regulation of Sertoli-germ cell adherens junction dynamics in the testis via the nitric oxide synthase (NOS)/cGMP/protein kinase G (PRKG)/beta-catenin (CATNB) signaling pathway: an in vitro and in vivo study."
    Lee N.P., Mruk D.D., Wong C.H., Cheng C.Y.
    Biol Reprod 73:458-471(2005) [PubMed] [Europe PMC] [Abstract]
• calmodulin binding Source: RGDInferred from direct assayⁱ
  • "Interaction of calmodulin with its binding domain of rat cerebellar nitric oxide synthase. A multinuclear NMR study."
    Zhang M., Yuan T., Aramini J.M., Vogel H.J.
    J Biol Chem 270:20901-20907(1995) [PubMed] [Europe PMC] [Abstract]
• Hsp90 protein binding Source: RGDInferred from direct assayⁱ
  • "Heat shock regulates the respiration of cardiac H9c2 cells through upregulation of nitric oxide synthase."
    Ilangovan G., Osinbowale S., Bratasz A., Bonar M., Cardounel A.J., Zweier J.L., Kuppusamy P.
    Am J Physiol Cell Physiol 287:C1472-81(2004) [PubMed] [Europe PMC] [Abstract]
• nitric-oxide synthase binding Source: RGDInferred from physical interactionⁱ
  • "Regulation of Sertoli-germ cell adherens junction dynamics in the testis via the nitric oxide synthase (NOS)/cGMP/protein kinase G (PRKG)/beta-catenin (CATNB) signaling pathway: an in vitro and in vivo study."
    Lee N.P., Mruk D.D., Wong C.H., Cheng C.Y.
    Biol Reprod 73:458-471(2005) [PubMed] [Europe PMC] [Abstract]
• scaffold protein binding Source: RGDInferred from physical interactionⁱ
  • "Caveolin-1 and -3 dissociations from caveolae to cytosol in the heart during aging and after myocardial infarction in rat."
    Ratajczak P., Damy T., Heymes C., Oliviero P., Marotte F., Robidel E., Sercombe R., Boczkowski J., Rappaport L., Samuel J.L.
    Cardiovasc Res 57:358-369(2003) [PubMed] [Europe PMC] [Abstract]
  • "Nitric oxide inhibition of adenylyl cyclase type 6 activity is dependent upon lipid rafts and caveolin signaling complexes."
    Ostrom R.S., Bundey R.A., Insel P.A.
    J Biol Chem 279:19846-19853(2004) [PubMed] [Europe PMC] [Abstract]

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Region

Compositional bias

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

        10         20         30         40         50
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSQ APVPPSPTRP 
        60         70         80         90        100
APDHSPPLTR PPDGPKFPRV KNWEVGSITY DTLSAQAQQD GPCTPRRCLG 
       110        120        130        140        150
SLVFPRKLQS RPTQGPSPTE QLLGQARDFI NQYYNSIKRS GSQAHEQRLQ 
       160        170        180        190        200
EVEAEVVATG TYQLRESELV FGAKQAWRNA PRCVGRIQWG KLQVFDARDC 
       210        220        230        240        250
RTAQEMFTYI CNHIKYATNR GNLRSAITVF PQRYAGRGDF RIWNSQLVRY 
       260        270        280        290        300
AGYRQQDGSV RGDPANVEIT ELCIQHGWTP GNGRFDVLPL LLQAPDEPPE 
       310        320        330        340        350
LFTLPPELVL EVPLEHPTLE WFAALGLRWY ALPAVSNMLL EIGGLEFPAA 
       360        370        380        390        400
PFSGWYMSSE IGMRDLCDPH RYNILEDVAV CMDLDTRTTS SLWKDKAAVE 
       410        420        430        440        450
INVAVLYSYQ LAKVTIVDHH AATASFMKHL ENEQKARGGC PADWAWIVPP 
       460        470        480        490        500
ISGSLTPVFH QEMVNYFLSP AFRYQPDPWK GSAAKGTGIT RKKTFKEVAN 
       510        520        530        540        550
AVKISASLMG TVMAKRVKAT ILYGSETGRA QSYAQQLGRL FRKAFDPRVL 
       560        570        580        590        600
CMDEYDVVSL EHEALVLVVT STFGNGDPPE NGESFAAALM EMSGPYNSSP 
       610        620        630        640        650
RPEQHKSYKI RFNSVSCSDP LVSSWRRKRK ESSNTDSAGA LGTLRFCVFG 
       660        670        680        690        700
LGSRAYPHFC AFARAVDTRL EELGGERLLQ LGQGDELCGQ EEAFRGWAQA 
       710        720        730        740        750
AFQAACETFC VGEDAKAAAR DIFSPKRSWK RQRYRLSTQA ESLQLLPRLT 
       760        770        780        790        800
HVHRRKMFQA TILSVENLQS SKSTRATILV RLDTGSQEGL QYQPGDHIGV 
       810        820        830        840        850
CPPNRPGLVE ALLSRVEDPP PSTEPVAVEQ LEKGSPGGPP PGWVRDPRLP 
       860        870        880        890        900
PCTLRQALTY FLDITSPPSP RLLRLLSTLA EESSEQQELE ALSQDPRRYE 
       910        920        930        940        950
EWKWFRCPTL LEVLEQFPSV ALPAPLILTQ LPLLQPRYYS VSSAPSAHPG 
       960        970        980        990       1000
EIHLTVAVLA YRTQDGLGPL HYGVCSTWMS QLKAGDPVPC FIRGAPSFRL 
      1010       1020       1030       1040       1050
PPDPNLPCIL VGPGTGIAPF RGFWQDRLHD IEIKGLQPAP MTLVFGCRCS 
      1060       1070       1080       1090       1100
QLDHLYRDEV LDAQQRGVFG QVLTAFSRDP GSPKTYVQDL LRTELAAEVH 
      1110       1120       1130       1140       1150
RVLCLEQGHM FVCGDVTMAT SVLQTVQRIL ATEGSMELDE AGDVIGVLRD 
      1160       1170       1180       1190       1200
QQRYHEDIFG LTLRTQEVTS RIRTQSFSLQ ERQLRGAVPW SFDPPTQETP 

GS                                                     

Experimental Info

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. SIMILARITY comments
   Index of protein domains and families