NO synthase-3 (endothelial NO synthase, NOS3, ENOS)

Function

• produces nitric oxide (NO) 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 & promotes blood clotting through activation of platelets
• stimulated by Ca+2/calmodulin resulting in transient activation
• prolonged activation occurs in response to shear stress from turbulent blood flow
• occurs via activation of the phosphoinositide-3-kinase cascade & long-term activation of NO synthase-3 by Akt
• inhibited by NOSIP & NOSTRIN

L-arginine + n NADPH + m O2
       <-->
citrulline + nitric oxide + n NADP+

Cofactor:

• heme
• binds 1 FAD
• binds 1 FMN
• tetrahydrobiopterin (BH4)

Structure

• homodimer
• belongs to the NOS family
• contains 1 flavodoxin-like domain

Compartment

• cell membrane, caveola
• cytoplasm, cytoskeleton
• Golgi apparatus
• specifically associates with actin cytoskeleton in G2 phase of the cell cycle, favored by interaction with NOSIP & results in a diminished enzymatic activity

Expression

• constitutive enzyme, expressed in endothelial cells
• expressed in platelets, placenta, liver & kidney

Polymorphism

• variation in NOS3 seem to be associated with susceptibility to coronary spasm

More general terms

• nitric oxide [NO] synthase
• phosphoprotein

Additional terms

• nitric oxide (NO, endothelium derived relaxation factor {EDRF})

Database

• UniProt: http://www.uniprot.org/uniprot/P29474.html
• OMIM: https://mirror.omim.org/entry/163729