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 (By similarity). H(+) + 2 L-arginine + 3 NADPH + 4 O2 = 4 H2O + 2 L-citrulline + 3 NADP(+) + 2 nitric oxide Binds 1 FAD. Binds 1 FMN. Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme. Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN (By similarity). Homodimer. Interacts with NOSIP and NOSTRIN (By similarity). Interacts with HSP90AB1 (By similarity). 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). 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. Repressed by pro-inflammatory cytokines. Phosphorylation by AMPK at Ser-1179 in the presence of Ca(2+)-calmodulin (CaM) activates activity. In absence of Ca(2+)-calmodulin, AMPK also phosphorylates Thr-497, resulting in inhibition of activity. Phosphorylation of Ser-116 by CDK5 reduces activity (By similarity). Belongs to the NOS family.