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.FUNCTION 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 O2 + H(+) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H2OCOFACTOR Binds 1 FAD.COFACTOR Binds 1 FMN.COFACTOR Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.ACTIVITY REGULATION Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN.SUBUNIT Homodimer. Interacts with NOSIP and NOSTRIN (PubMed:11149895, PubMed:12446846). Interacts with HSP90AB1 (By similarity) (PubMed:11149895, PubMed:12446846, PubMed:23585225). Forms a complex with ASL, ASS1 and SLC7A1; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway (By similarity).INTERACTION 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.ALTERNATIVE PRODUCTS 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.DISEASE Variation Asp-298 in NOS3 may be associated with susceptibility to coronary spasm.MISCELLANEOUS Lacks eNOS activity.SIMILARITY Belongs to the NOS family.ONLINE INFORMATION Nitric oxide synthase entry