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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
Related
nitric oxide (NO, endothelium derived relaxation factor {EDRF})
General
nitric oxide [NO] synthase
phosphoprotein
Properties
CONFIGURATION: dimer
SIZE: entity length = 1203 aa
MW = 133 kD
COMPARTMENT: cytoplasm
golgi
MOTIF: myristoylation site
SITE: G2
EFFECTOR-BOUND: myristate
cysteine residue {C15}
MODIFICATION: palmitate
COMPARTMENT: membrane
cysteine residue {C26}
MODIFICATION: palmitate
COMPARTMENT: membrane
Zn+2-binding site
SITE: 94-94
NOSIP interaction {98-486}
MOTIF: Zn+2-binding site
SITE: 99-99
Iron [Fe]-binding site
SITE: 184-184
binding site
SITE: 491-510
FOR-BINDING-OF: calmodulin
MOTIF: Thr phosphorylation site {T495}
Flavodoxin-like {520-703}
MOTIF: Ser phosphorylation site {S633}
cofactor-binding site [793-804]
COFACTOR-BOUND: flavin adenine dinucleotide
cofactor-binding site [935-945]
COFACTOR-BOUND: flavin adenine dinucleotide
cofactor-binding site [1010-1028]
COFACTOR-BOUND: NADP
cofactor-binding site [1108-1123]
COFACTOR-BOUND: NADP
Thr phosphorylation site {T1175}
Ser phosphorylation site {S1177}
Database Correlations
OMIM 163729
MORBIDMAP 163729
UniProt P29474
PFAM correlations
Kegg hsa/hsaKEGG
ENZYME 1.14.13.39
References
- UniProt :accession P29474
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=NOS3
- Wikipedia, Nitric oxide synthase entry
http://en.wikipedia.org/wiki/Nitric_oxide_synthase