Nitric oxide synthase, inducible

<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

Caution

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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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  zoom

  +

  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_section">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-go-evidence-codes#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]
• 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-go-evidence-codes#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: UniProtKB-KW
• cAMP-dependent protein kinase regulator activity Source: RGDInferred from direct assayⁱ
  • "Attenuation of cAMP accumulation in adult rat cardiac fibroblasts by IL-1beta and NO: role of cGMP-stimulated PDE2."
    Gustafsson A.B., Brunton L.L.
    Am J Physiol Cell Physiol 283:C463-71(2002) [PubMed] [Europe PMC] [Abstract]
• flavin adenine dinucleotide binding Source: RGD
• FMN binding Source: RGD
• 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]
• identical protein binding Source: RGDInferred from physical interactionⁱ
  • "Monomeric inducible nitric oxide synthase localizes to peroxisomes in hepatocytes."
    Loughran P.A., Stolz D.B., Vodovotz Y., Watkins S.C., Simmons R.L., Billiar T.R.
    Proc Natl Acad Sci U S A 102:13837-13842(2005) [PubMed] [Europe PMC] [Abstract]
• metal ion binding Source: UniProtKB-KW
• NADP binding Source: InterPro
• nitric-oxide synthase activity Source: RGDInferred from direct assayⁱ
  • "Inducible nitric oxide synthase plays a role in LPS-induced hyperglycemia and insulin resistance."
    Sugita H., Kaneki M., Tokunaga E., Sugita M., Koike C., Yasuhara S., Tompkins R.G., Martyn J.A.
    Am J Physiol Endocrinol Metab 282:E386-94(2002) [PubMed] [Europe PMC] [Abstract]
  • "Monomeric inducible nitric oxide synthase localizes to peroxisomes in hepatocytes."
    Loughran P.A., Stolz D.B., Vodovotz Y., Watkins S.C., Simmons R.L., Billiar T.R.
    Proc Natl Acad Sci U S A 102:13837-13842(2005) [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_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-go-evidence-codes#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]
• 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]
• protein homodimerization activity Source: RGD
• protein kinase binding Source: RGDInferred from physical interactionⁱ
  • "iNOS regulation by calcium/calmodulin-dependent protein kinase II in vascular smooth muscle."
    Jones R.J., Jourd'heuil D., Salerno J.C., Smith S.M., Singer H.A.
    Am J Physiol Heart Circ Physiol 292:H2634-42(2007) [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-go-evidence-codes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "Endothelial dysfunction in the early- and late-stage type-2 diabetic Goto-Kakizaki rat aorta."
    Kazuyama E., Saito M., Kinoshita Y., Satoh I., Dimitriadis F., Satoh K.
    Mol Cell Biochem 332:95-102(2009) [PubMed] [Europe PMC] [Abstract]
• arginine catabolic process Source: RGD
• blood vessel remodeling 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-go-evidence-codes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Relationship between iNOS expression and aortic cell proliferation and apoptosis in an elastase-induced model of aorta aneurysm and the effect of 1400 W administration."
    Sigala F., Papalambros E., Kotsinas A., Andreadou I., Sigalas P., Kremastinos D., Bastounis E., Gorgoulis V.G.
    Surgery 137:447-456(2005) [PubMed] [Europe PMC] [Abstract]
• cellular response to cytokine stimulus Source: MGIInferred from direct assayⁱ
  • "JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-kappaB activation and the JAK/STAT pathway."
    Lv N., Kim E.K., Song M.Y., Choi H.N., Moon W.S., Park S.J., Park J.W., Kwon K.B., Park B.H.
    Exp Cell Res 315:2064-2071(2009) [PubMed] [Europe PMC] [Abstract]
• cellular response to drug Source: RGD
• cellular response to interferon-gamma Source: RGD
• cellular response to interleukin-1 Source: RGDInferred from expression patternⁱ
  • "Tetrandrine down-regulates ERK/NF-kappaB signaling and inhibits activation of mesangial cells."
    Wu C.J., Wang Y.H., Lin C.J., Chen H.H., Chen Y.J.
    Toxicol In Vitro 25:1834-1840(2011) [PubMed] [Europe PMC] [Abstract]
• cellular response to lipopolysaccharide Source: RGDInferred from expression patternⁱ
  • "Antioxidative and anti-inflammatory effects of phenolic compounds from the roots of Ulmus macrocarpa."
    Kwon J.H., Kim S.B., Park K.H., Lee M.W.
    Arch Pharm Res 34:1459-1466(2011) [PubMed] [Europe PMC] [Abstract]
• cellular response to lithium ion Source: RGDInferred from expression patternⁱ
  • "Effects of lithium on lipopolysaccharide-induced inflammation in rat primary glia cells."
    Nahman S., Belmaker R.H., Azab A.N.
    Innate Immun 18:447-458(2012) [PubMed] [Europe PMC] [Abstract]
• cellular response to organic cyclic compound Source: MGIInferred from direct assayⁱ
  • "JANEX-1, a JAK3 inhibitor, protects pancreatic islets from cytokine toxicity through downregulation of NF-kappaB activation and the JAK/STAT pathway."
    Lv N., Kim E.K., Song M.Y., Choi H.N., Moon W.S., Park S.J., Park J.W., Kwon K.B., Park B.H.
    Exp Cell Res 315:2064-2071(2009) [PubMed] [Europe PMC] [Abstract]
• cellular response to redox state Source: RGDInferred from expression patternⁱ
  • "Extracellular cysteine (Cys)/cystine (CySS) redox regulates metabotropic glutamate receptor 5 activity."
    Zhu J.W., Yuan J.F., Yang H.M., Wang S.T., Zhang C.G., Sun L.L., Yang H., Zhang H.
    Biochimie 94:617-627(2012) [PubMed] [Europe PMC] [Abstract]
• cellular response to tumor necrosis factor Source: RGDInferred from expression patternⁱ
  • "Reciprocal regulation between proinflammatory cytokine-induced inducible NO synthase (iNOS) and connexin43 in bladder smooth muscle cells."
    Li K., Yao J., Shi L., Sawada N., Chi Y., Yan Q., Matsue H., Kitamura M., Takeda M.
    J Biol Chem 286:41552-41562(2011) [PubMed] [Europe PMC] [Abstract]
• cellular response to vitamin D Source: RGDInferred from expression patternⁱ
  • "1,25-Dihydroxyvitamin D3 prevented allergic asthma in a rat model by suppressing the expression of inducible nitric oxide synthase."
    Zhou Y., Zhou X., Wang X.
    Allergy Asthma Proc 29:258-267(2008) [PubMed] [Europe PMC] [Abstract]
• cGMP-mediated signaling Source: RGDInferred from direct assayⁱ
  • "Attenuation of cAMP accumulation in adult rat cardiac fibroblasts by IL-1beta and NO: role of cGMP-stimulated PDE2."
    Gustafsson A.B., Brunton L.L.
    Am J Physiol Cell Physiol 283:C463-71(2002) [PubMed] [Europe PMC] [Abstract]
• circadian rhythm Source: RGD
• defense response to bacterium Source: UniProtKB
• defense response to Gram-negative bacterium Source: RGDInferred from expression patternⁱ
  • "Role of neuronal nitric oxide synthase and inducible nitric oxide synthase in intestinal injury in neonatal rats."
    Lu H., Zhu B., Xue X.D.
    World J Gastroenterol 12:4364-4368(2006) [PubMed] [Europe PMC] [Abstract]
• endothelial cell proliferation Source: RGDInferred from expression patternⁱ
  • "Relationship between iNOS expression and aortic cell proliferation and apoptosis in an elastase-induced model of aorta aneurysm and the effect of 1400 W administration."
    Sigala F., Papalambros E., Kotsinas A., Andreadou I., Sigalas P., Kremastinos D., Bastounis E., Gorgoulis V.G.
    Surgery 137:447-456(2005) [PubMed] [Europe PMC] [Abstract]
• glycoside metabolic process Source: RGDInferred from expression patternⁱ
  • "Influence of N-methyl-D-aspartate receptors on ouabain activation of nuclear factor-kappaB in the rat hippocampus."
    Kawamoto E.M., Lima L.S., Munhoz C.D., Yshii L.M., Kinoshita P.F., Amara F.G., Pestana R.R., Orellana A.M., Cipolla-Neto J., Britto L.R., Avellar M.C., Rossoni L.V., Scavone C.
    J Neurosci Res 90:213-228(2012) [PubMed] [Europe PMC] [Abstract]
• G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Source: RGDInferred from direct assayⁱ
  • "Attenuation of cAMP accumulation in adult rat cardiac fibroblasts by IL-1beta and NO: role of cGMP-stimulated PDE2."
    Gustafsson A.B., Brunton L.L.
    Am J Physiol Cell Physiol 283:C463-71(2002) [PubMed] [Europe PMC] [Abstract]
• inflammatory response 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]
• intracellular signal transduction Source: RGDInferred from mutant phenotypeⁱ
  • "Angiotensin II differentially regulates interleukin-1-beta-inducible NO synthase (iNOS) and vascular cell adhesion molecule-1 (VCAM-1) expression: role of p38 MAPK."
    Jiang B., Xu S., Hou X., Pimentel D.R., Cohen R.A.
    J Biol Chem 279:20363-20368(2004) [PubMed] [Europe PMC] [Abstract]
• 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 gene expression Source: RGD
• negative regulation of protein catabolic process Source: RGD
• nitric oxide biosynthetic process Source: RGDInferred from direct assayⁱ
  • "Association between the expression of inducible nitric oxide synthase by chondrocytes and its nitric oxide-generating activity in adjuvant arthritis in rats."
    Yonekura Y., Koshiishi I., Yamada K., Mori A., Uchida S., Nakamura T., Utsumi H.
    Nitric Oxide 8:164-169(2003) [PubMed] [Europe PMC] [Abstract]
  • "Monomeric inducible nitric oxide synthase localizes to peroxisomes in hepatocytes."
    Loughran P.A., Stolz D.B., Vodovotz Y., Watkins S.C., Simmons R.L., Billiar T.R.
    Proc Natl Acad Sci U S A 102:13837-13842(2005) [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]
• peptidyl-cysteine S-nitrosylation Source: UniProtKB
• positive regulation of apoptotic process Source: RGDInferred from mutant phenotypeⁱ
  • "iNOS enhances rat intestinal apoptosis after ischemia-reperfusion."
    Wu B., Iwakiri R., Tsunada S., Utsumi H., Kojima M., Fujise T., Ootani A., Fujimoto K.
    Free Radic Biol Med 33:649-658(2002) [PubMed] [Europe PMC] [Abstract]
• positive regulation of guanylate cyclase 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]
• positive regulation of interleukin-6 production Source: UniProtKB
• positive regulation of interleukin-8 production Source: UniProtKB
• positive regulation of killing of cells of other organism Source: RGD
• prostaglandin secretion Source: UniProtKB
• regulation of blood pressure Source: RGDInferred from mutant phenotypeⁱ
  • "Accelerated ubiquitination and proteasome degradation of a genetic variant of inducible nitric oxide synthase."
    Ying W.Z., Sanders P.W.
    Biochem J 376:789-794(2003) [PubMed] [Europe PMC] [Abstract]
  • "Cardiovascular responses and neurotransmitter changes during static muscle contraction following blockade of inducible nitric oxide synthase (iNOS) within the ventrolateral medulla."
    Ally A., Phattanarudee S., Kabadi S., Patel M., Maher T.J.
    Brain Res 1090:123-133(2006) [PubMed] [Europe PMC] [Abstract]
• regulation of cell population proliferation Source: RGD
• regulation of cytokine production involved in inflammatory response Source: UniProtKB
• regulation of heart contraction Source: RGDInferred from mutant phenotypeⁱ
  • "Cardiovascular responses and neurotransmitter changes during static muscle contraction following blockade of inducible nitric oxide synthase (iNOS) within the ventrolateral medulla."
    Ally A., Phattanarudee S., Kabadi S., Patel M., Maher T.J.
    Brain Res 1090:123-133(2006) [PubMed] [Europe PMC] [Abstract]
• regulation of insulin secretion Source: RGD
• response to activity Source: RGDInferred from expression patternⁱ
  • "Oxidative injury due to chronic nitric oxide synthase inhibition in rat: effect of regular exercise on the heart."
    Husain K., Hazelrigg S.R.
    Biochim Biophys Acta 1587:75-82(2002) [PubMed] [Europe PMC] [Abstract]
• response to bacterium Source: RGD
• response to dexamethasone Source: RGDInferred from expression patternⁱ
  • "Biochemical and genetic alterations of oxidant/antioxidant status of the brain in rats treated with dexamethasone: protective roles of melatonin and acetyl-L-carnitine."
    Assaf N., Shalby A.B., Khalil W.K., Ahmed H.H.
    J Physiol Biochem 68:77-90(2012) [PubMed] [Europe PMC] [Abstract]
• response to estradiol Source: RGDInferred from expression patternⁱ
  • "[Effect of 17beta-estradiol on myocardial inducible NOS and endothelial NOS activities after ischemia-reperfusion in rat heart model]."
    Wang X.D., Wang Z.M., Jia D.L., Yu P.
    Zhonghua Yi Xue Za Zhi 87:1789-1791(2007) [PubMed] [Europe PMC] [Abstract]
• response to hormone Source: RGDInferred from expression patternⁱ
  • "Regulation of inducible nitric oxide synthase activity/expression in rat hearts from ghrelin-treated rats."
    Sudar E., Dobutovic B., Soskic S., Mandusic V., Zakula Z., Misirkic M., Vucicevic L., Janjetovic K., Trajkovic V., Mikhailidis D.P., Isenovic E.R.
    J Physiol Biochem 67:195-204(2011) [PubMed] [Europe PMC] [Abstract]
• response to hypoxia Source: RGD
• response to immobilization stress Source: RGDInferred from expression patternⁱ
  • "Mangiferin decreases inflammation and oxidative damage in rat brain after stress."
    Marquez L., Garcia-Bueno B., Madrigal J.L., Leza J.C.
    Eur J Nutr 51:729-739(2012) [PubMed] [Europe PMC] [Abstract]
• response to lipopolysaccharide Source: RGDInferred from expression patternⁱ
  • "Regulation of the urea cycle enzyme genes in nitric oxide synthesis."
    Mori M., Gotoh T., Nagasaki A., Takiguchi M., Sonoki T.
    J Inherit Metab Dis 21 Suppl 1:59-71(1998) [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 tumor necrosis factor Source: RGDInferred from mutant phenotypeⁱ
  • "TNF-alpha modulates iNOS expression in an experimental rat model of indomethacin-induced jejunoileitis."
    Nandi J., Saud B., Zinkievich J.M., Yang Z.J., Levine R.A.
    Mol Cell Biochem 336:17-24(2010) [PubMed] [Europe PMC] [Abstract]
• retinoic acid receptor signaling pathway Source: RGDInferred from expression patternⁱ
  • "Retinoic acid inhibits expression of TNF-alpha and iNOS in activated rat microglia."
    Dheen S.T., Jun Y., Yan Z., Tay S.S., Ling E.A.
    Glia 50:21-31(2005) [PubMed] [Europe PMC] [Abstract]
• signal transduction Source: RGDInferred from direct assayⁱ
  • "Attenuation of cAMP accumulation in adult rat cardiac fibroblasts by IL-1beta and NO: role of cGMP-stimulated PDE2."
    Gustafsson A.B., Brunton L.L.
    Am J Physiol Cell Physiol 283:C463-71(2002) [PubMed] [Europe PMC] [Abstract]
• superoxide metabolic process Source: UniProtKB
• wound healing Source: RGDInferred from expression patternⁱ
  • "Upregulation of the production of interferon-gamma and the gene expression of the inducible nitric oxide synthase after excimer laser ablation in rat corneas."
    Prada J., Ngo-Tu T.
    Clin Exp Ophthalmol 39:277-279(2011) [PubMed] [Europe PMC] [Abstract]

<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_processing_section">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 reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductionⁱ

<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_section">'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_section">'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_section">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]
• 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: UniProtKB-KW
• 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]
• identical protein binding Source: RGDInferred from physical interactionⁱ
  • "Monomeric inducible nitric oxide synthase localizes to peroxisomes in hepatocytes."
    Loughran P.A., Stolz D.B., Vodovotz Y., Watkins S.C., Simmons R.L., Billiar T.R.
    Proc Natl Acad Sci U S A 102:13837-13842(2005) [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]
• protein homodimerization activity Source: RGD
• protein kinase binding Source: RGDInferred from physical interactionⁱ
  • "iNOS regulation by calcium/calmodulin-dependent protein kinase II in vascular smooth muscle."
    Jones R.J., Jourd'heuil D., Salerno J.C., Smith S.M., Singer H.A.
    Am J Physiol Heart Circ Physiol 292:H2634-42(2007) [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

Motif

<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_length">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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

        10         20         30         40         50
MACPWKFLFR VKSYQGDLKE EKDINNNVEK TPGAIPSPTT QDDPKSHKHQ 
        60         70         80         90        100
NGFPQFLTGT AQNVPESLDK LHVTPSTRPQ HVRIKNWGNG EIFHDTLHHK 
       110        120        130        140        150
ATSDISCKSK LCMGSIMNSK SLTRGPRDKP TPVEELLPQA IEFINQYYGS 
       160        170        180        190        200
FKEAKIEEHL ARLEAVTKEI ETTGTYQLTL DELIFATKMA WRNAPRCIGR 
       210        220        230        240        250
IQWSNLQVFD ARSCSTASEM FQHICRHILY ATNSGNIRSA ITVFPQRSDG 
       260        270        280        290        300
KHDFRIWNSQ LIRYAGYQMP DGTIRGDPAT LEFTQLCIDL GWKPRYGRFD 
       310        320        330        340        350
VLPLVLQAHG QDPEVFEIPP DLVLEVTMEH PKYEWFQELG LKWYALPAVA 
       360        370        380        390        400
NMLLEVGGLE FPACPFNGWY MGTEIGVRDF CDTQRYNILE EVGRRMGLET 
       410        420        430        440        450
HTLASLWKDR AVTEINAAVL HSFQKQNVTI MDHHTASESF MKHMQNEYRA 
       460        470        480        490        500
RGGCPADWIW LVPPVSGSIT PVFHQEMLNY VLSPFYYYQI EPWKTHIWQD 
       510        520        530        540        550
EKLRPRRREI RFTVLVKAVF FASVLMRKVM ASRVRATVLF ATETGKSEAL 
       560        570        580        590        600
ARDLAALFSY AFNTKVVCME QYKANTLEEE QLLLVVTSTF GNGDCPSNGQ 
       610        620        630        640        650
TLKKSLFMMK ELGHTFRYAV FGLGSSMYPQ FCAFAHDIDQ KLSHLGASQL 
       660        670        680        690        700
APTGEGDELS GQEDAFRSWA VQTFRAACET FDVRSKHCIQ IPKRYTSNAT 
       710        720        730        740        750
WEPEQYKLTQ SPESLDLNKA LSSIHAKNVF TMRLKSLQNL QSEKSSRTTL 
       760        770        780        790        800
LVQLTFEGSR GPSYLPGEHL GIFPGNQTAL VQGILERVVD CSSPDQTVCL 
       810        820        830        840        850
EVLDESGSYW VKDKRLPPCS LRQALTYFLD ITTPPTQLQL HKLARFATEE 
       860        870        880        890        900
THRQRLEALC QPSEYNDWKF SNNPTFLEVL EEFPSLRVPA AFLLSQLPIL 
       910        920        930        940        950
KPRYYSISSS QDHTPSEVHL TVAVVTYRTR DGQGPLHHGV CSTWINNLKP 
       960        970        980        990       1000
EDPVPCFVRS VSGFQLPEDP SQPCILIGPG TGIAPFRSFW QQRLHDSQHR 
      1010       1020       1030       1040       1050
GLKGGRMTLV FGCRHPEEDH LYQEEMQEMV RKGVLFQVHT GYSRLPGKPK 
      1060       1070       1080       1090       1100
VYVQDILQKE LADEVFSVLH GEQGHLYVCG DVRMARDVAT TLKKLVAAKL 
      1110       1120       1130       1140 
NLSEEQVEDY FFQLKSQKRY HEDIFGAVFS YGAKKGNTLE EPKGTRL    

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