Phospho-NOS3 (Ser1177)

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. [provided by RefSeq, Oct 2016]

Nitric Oxide Synthase 3

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.

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

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.

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

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.