GeneID: 74


Common Name: NOS3 Type: Gene
Chromosome: 7 (NC_000007.14) Locus: NG_011992.1 (NOS3)
HUGO Symbol: NOS3 Full Name: nitric oxide synthase 3
Exons: 27 Introns: 26

NOS3 is one of the three isoforms that synthesize nitric oxide (NO), a reactive free radical, and is predominantly expressed in endothelial cells. Enzymatic acylation targets NOS3 to the caveolae in the plasma membrane. The enzyme functions as a dimer composed of a reductase and an oxygenase domain, and interacts with redox-active cofactors to catalyse the production of NO from L-arginine. This reaction involves a five-electron oxidation of a terminal guanidine nitrogen on L-arginine. NADPH acts as the source of electrons for oxygen activation and L-arginine oxidation to yield the stoichiometric production of NO and L-citrulline. NO functions as a signalling molecule in many biological processes, including blood flow regulation, platelet reactivity, neurotransmission, cytotoxicity and inflammation. Variations in this gene are associated with susceptibility to coronary spasm. Polymorphisms in this gene associated with acute chest syndrome and HbF levels in sickle cell patients. Also, individuals with sickle cell anaemia present endothelial dysfuntion, likely as a resut of impaired NO homeostasis due to scavenging of NO by cell-free plasma haemoglobin and ROS, as well as the consumption of L-arginine by cell-free arginase enzyme released from hemolyzed erythrocytes. Multiple transcript variants encoding different isoforms have been found for this gene.

Synonyms: eNOS , ECNOS


Publications / Origin

  1. Ricciardolo FL, Multiple roles of nitric oxide in the airways., Thorax , 58(2), 175-82, 2003
  2. Sharan K, Surrey S, Ballas S, Borowski M, Devoto M, Wang KF, Sandler E, Keller M, Association of T-786C eNOS gene polymorphism with increased susceptibility to acute chest syndrome in females with sickle cell disease., Br. J. Haematol. , 124(2), 240-3, 2004
  3. Duckworth L, Hsu L, Feng H, Wang J, Sylvester JE, Kissoon N, Sandler E, Lima JJ, Physician-diagnosed asthma and acute chest syndrome: associations with NOS polymorphisms., Pediatr. Pulmonol. , 42(4), 332-8, 2007
  4. Sebastiani P, Wang L, Nolan VG, Melista E, Ma Q, Baldwin CT, Steinberg MH, Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations., Am. J. Hematol. , 83(3), 189-95, 2008
  5. Wood KC, Hsu LL, Gladwin MT, Sickle cell disease vasculopathy: a state of nitric oxide resistance., Free Radic. Biol. Med. , 44(8), 1506-28, 2008
  6. Rafikov R, Fonseca FV, Kumar S, Pardo D, Darragh C, Elms S, Fulton D, Black SM, eNOS activation and NO function: structural motifs responsible for the posttranslational control of endothelial nitric oxide synthase activity., J. Endocrinol. , 210(3), 271-84, 2011
  7. Aguiar L, Matos A, Gil Â, Afonso C, Braga L, João L, Kjollerstrom P, Faustino P, Bicho M, Inácio Â, Sickle cell anemia - Nitric oxide related genetic modifiers of hematological and biochemical parameters., Clin. Hemorheol. Microcirc. , 2016
Created on 2016-04-26 15:03:03, Last reviewed on 2017-01-31 12:18:49 (Show full history)

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