NOS3

Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Alternative splicing and the use of alternative promoters results in multiple transcript variants.

Full Name

Nitric Oxide Synthase 3

Alternative Names

Nitric Oxide Synthase 3; Nitric Oxide Synthase 3 (Endothelial Cell); Constitutive NOS; Endothelial NOS; EC 1.14.13.39; NOS Type III; EC-NOS; NOSIII; CNOS;

Function

Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832).
NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.
Isoform eNOS13C
Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.

Biological Process

AngiogenesisIEA:Ensembl
Aortic valve morphogenesisISS:BHF-UCL
Arginine catabolic processManual Assertion Based On ExperimentIDA:BHF-UCL
Blood vessel diameter maintenanceISS:BHF-UCL
Blood vessel remodelingISS:BHF-UCL
Cell redox homeostasisTAS:Reactome
Endocardial cushion morphogenesisISS:BHF-UCL
Endothelial cell migrationManual Assertion Based On ExperimentIMP:BHF-UCL
Homeostasis of number of cells within a tissueISS:BHF-UCL
In utero embryonic developmentIEA:Ensembl
Lipopolysaccharide-mediated signaling pathwayIEA:Ensembl
Lung developmentIEA:Ensembl
Mitochondrion organizationISS:BHF-UCL
Negative regulation of biomineral tissue developmentISS:BHF-UCL
Negative regulation of blood pressureManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of calcium ion transportIEA:Ensembl
Negative regulation of cell population proliferationISS:BHF-UCL
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptorsISS:BHF-UCL
Negative regulation of hydrolase activityIEA:Ensembl
Negative regulation of muscle hyperplasiaISS:BHF-UCL
Negative regulation of platelet activation1 PublicationNAS:BHF-UCL
Negative regulation of potassium ion transportIEA:Ensembl
Negative regulation of smooth muscle cell proliferationIEA:Ensembl
Nitric oxide biosynthetic processManual Assertion Based On ExperimentIDA:BHF-UCL
Nitric oxide mediated signal transductionManual Assertion Based On ExperimentIBA:GO_Central
Ovulation from ovarian follicleIEA:Ensembl
Positive regulation of angiogenesisManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of blood vessel endothelial cell migrationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of gene expressionBy SimilarityISS:BHF-UCL
Positive regulation of guanylate cyclase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of Notch signaling pathway1 PublicationIC:BHF-UCL
Pulmonary valve morphogenesisISS:BHF-UCL
Regulation of blood pressure1 PublicationNAS:BHF-UCL
Regulation of nervous system processISS:ARUK-UCL
Regulation of sodium ion transportIEA:Ensembl
Regulation of systemic arterial blood pressure by endothelinManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of the force of heart contraction by chemical signalIEA:Ensembl
Removal of superoxide radicalsManual Assertion Based On ExperimentIDA:BHF-UCL
Response to fluid shear stressManual Assertion Based On ExperimentIEP:BHF-UCL
Response to heat1 PublicationNAS:BHF-UCL
Response to hormoneManual Assertion Based On ExperimentIBA:GO_Central
Response to lipopolysaccharideManual Assertion Based On ExperimentIBA:GO_Central
Smooth muscle hyperplasiaISS:BHF-UCL
Vasodilation2 PublicationsNAS:BHF-UCL
Ventricular septum morphogenesisIEA:Ensembl

Cellular Location

Cell membrane
Membrane, caveola
Cytoplasm, cytoskeleton
Golgi apparatus
Specifically associates with actin cytoskeleton in the G2 phase of the cell cycle; which is favored by interaction with NOSIP and results in a reduced enzymatic activity.

Involvement in disease

Variation Asp-298 in NOS3 may be associated with susceptibility to coronary spasm.

PTM

Phosphorylation by AMPK at Ser-1177 in the presence of Ca2+-calmodulin (CaM) activates activity. In absence of Ca2+-calmodulin, AMPK also phosphorylates Thr-495, resulting in inhibition of activity (By similarity).
Phosphorylation of Ser-114 by CDK5 reduces activity.

Anti-NOS3 antibodies

Fig.3 Signaling pathways in cancers. (Creative Biolabs Authorized)