ID:NOS3_HUMAN DESCRIPTION: RecName: Full=Nitric oxide synthase, endothelial; EC=1.14.13.39; AltName: Full=Constitutive NOS; Short=cNOS; AltName: Full=EC-NOS; AltName: Full=Endothelial NOS; Short=eNOS; AltName: Full=NOS type III; Short=NOSIII; FUNCTION: Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. FUNCTION: Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1. CATALYTIC ACTIVITY: 2 L-arginine + 3 NADPH + 4 O(2) = 2 L- citrulline + 2 nitric oxide + 3 NADP(+) + 4 H(2)O. COFACTOR: Heme group. COFACTOR: Binds 1 FAD. COFACTOR: Binds 1 FMN. COFACTOR: Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme. ENZYME REGULATION: Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN. SUBUNIT: Homodimer. Interacts with NOSIP and NOSTRIN. INTERACTION: Q16543:CDC37; NbExp=4; IntAct=EBI-1391623, EBI-295634; Q8IVI9:NOSTRIN; NbExp=7; IntAct=EBI-1391623, EBI-1391643; P50502:ST13; NbExp=3; IntAct=EBI-1391623, EBI-357285; SUBCELLULAR LOCATION: Cell membrane. Membrane, caveola. Cytoplasm, cytoskeleton. Golgi apparatus. Note=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. TISSUE SPECIFICITY: Platelets, placenta, liver and kidney. PTM: Phosphorylation by AMPK at Ser-1177 in the presence of Ca(2+)-calmodulin (CaM) activates activity. In absence of Ca(2+)- calmodulin, AMPK also phosphorylates Thr-495, resulting in inhibition of activity (By similarity). Phosphorylation of Ser-114 by CDK5 reduces activity. POLYMORPHISM: Variation in NOS3 seem to be associated with susceptibility to coronary spasm. SIMILARITY: Belongs to the NOS family. SIMILARITY: Contains 1 FAD-binding FR-type domain. SIMILARITY: Contains 1 flavodoxin-like domain. WEB RESOURCE: Name=Wikipedia; Note=Nitric oxide synthase entry; URL="http://en.wikipedia.org/wiki/Nitric_oxide_synthase"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NOS3"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/nos3/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P29474
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001525 angiogenesis GO:0001542 ovulation from ovarian follicle GO:0001701 in utero embryonic development GO:0001974 blood vessel remodeling GO:0002028 regulation of sodium ion transport GO:0003057 regulation of the force of heart contraction by chemical signal GO:0003100 regulation of systemic arterial blood pressure by endothelin GO:0006527 arginine catabolic process GO:0006809 nitric oxide biosynthetic process GO:0007005 mitochondrion organization GO:0007263 nitric oxide mediated signal transduction GO:0008217 regulation of blood pressure GO:0008285 negative regulation of cell proliferation GO:0009408 response to heat GO:0010544 negative regulation of platelet activation GO:0014740 negative regulation of muscle hyperplasia GO:0014806 smooth muscle hyperplasia GO:0019430 removal of superoxide radicals GO:0030324 lung development GO:0031284 positive regulation of guanylate cyclase activity GO:0031663 lipopolysaccharide-mediated signaling pathway GO:0034405 response to fluid shear stress GO:0042311 vasodilation GO:0043267 negative regulation of potassium ion transport GO:0043536 positive regulation of blood vessel endothelial cell migration GO:0043542 endothelial cell migration GO:0045454 cell redox homeostasis GO:0045766 positive regulation of angiogenesis GO:0045776 negative regulation of blood pressure GO:0050880 regulation of blood vessel size GO:0050999 regulation of nitric-oxide synthase activity GO:0051186 cofactor metabolic process GO:0051346 negative regulation of hydrolase activity GO:0051926 negative regulation of calcium ion transport GO:0055114 oxidation-reduction process GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
