Names & Taxonomy

Uniprot ID:
P29474
Entry Name:
NOS3_HUMAN
Status:
reviewed
Protein Names:
Nitric oxide synthase, endothelial (EC 1.14.13.39) (Constitutive NOS) (cNOS) (EC-NOS) (Endothelial NOS) (eNOS) (NOS type III) (NOSIII)
Gene Names:
NOS3
Gene Names Primary:
NOS3
Organism:
Homo sapiens (Human)

Structure

Length:
1203
Sequence:
MGNLKSVAQEPGPPCGLGLGLGLGLCGKQGPATPAPEPSRAPASLLPPAPEHSPPSSPLTQPPEGPKFPRVKNWEVGSITYDTLSAQAQQDGPCTPRRCLGSLVFPRKLQGRPSPGPPAPEQLLSQARDFINQYYSSIKRSGSQAHEQRLQEVEAEVAATGTYQLRESELVFGAKQAWRNAPRCVGRIQWGKLQVFDARDCRSAQEMFTYICNHIKYATNRGNLRSAITVFPQRCPGRGDFRIWNSQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDEPPELFLLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFPAAPFSGWYMSTEIGTRNLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINVAVLHSYQLAKVTIVDHHAATASFMKHLENEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYFLSPAFRYQPDPWKGSAAKGTGITRKKTFKEVANAVKISASLMGTVMAKRVKATILYGSETGRAQSYAQQLGRLFRKAFDPRVLCMDEYDVVSLEHETLVLVVTSTFGNGDPPENGESFAAALMEMSGPYNSSPRPEQHKSYKIRFNSISCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYPHFCAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAQAAFQAACETFCVGEDAKAAARDIFSPKRSWKRQRYRLSAQAEGLQLLPGLIHVHRRKMFQATIRSVENLQSSKSTRATILVRLDTGGQEGLQYQPGDHIGVCPPNRPGLVEALLSRVEDPPAPTEPVAVEQLEKGSPGGPPPGWVRDPRLPPCTLRQALTFFLDITSPPSPQLLRLLSTLAEEPREQQELEALSQDPRRYEEWKWFRCPTLLEVLEQFPSVALPAPLLLTQLPLLQPRYYSVSSAPSTHPGEIHLTVAVLAYRTQDGLGPLHYGVCSTWLSQLKPGDPVPCFIRGAPSFRLPPDPSLPCILVGPGTGIAPFRGFWQERLHDIESKGLQPTPMTLVFGCRCSQLDHLYRDEVQNAQQRGVFGRVLTAFSREPDNPKTYVQDILRTELAAEVHRVLCLERGHMFVCGDVTMATNVLQTVQRILATEGDMELDEAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERQLRGAVPWAFDPPGSDTNSP
Proteomes:
UP000005640

Subcellular location

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.

Function

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.; 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:
COFACTOR: Name=heme; Xref=ChEBI:CHEBI:30413; ; COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; ; Note=Binds 1 FAD.;; COFACTOR: Name=FMN; Xref=ChEBI:CHEBI:58210; ; Note=Binds 1 FMN.;; COFACTOR: Name=5,6,7,8-tetrahydrobiopterin; Xref=ChEBI:CHEBI:15372; ; Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.;
Enzyme Regulation:
ENZYME REGULATION: Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN.
Cross Reference Drug Bank:
DB05676 DB00997 DB00125 DB00155 DB01110 DB00360
Gene Ontology Go:
caveola
cytoplasm
cytoskeleton
cytosol
endocytic vesicle membrane
Golgi membrane
nucleus
plasma membrane
actin monomer binding
arginine binding
cadmium ion binding
flavin adenine dinucleotide binding
FMN binding
heme binding
iron ion binding
NADP binding
nitric-oxide synthase activity
tetrahydrobiopterin binding
angiogenesis
arginine catabolic process
blood coagulation
blood vessel remodeling
cell redox homeostasis
endothelial cell migration
in utero embryonic development
lipopolysaccharide-mediated signaling pathway
lung development
mitochondrion organization
negative regulation of blood pressure
negative regulation of calcium ion transport
negative regulation of cell proliferation
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
negative regulation of hydrolase activity
negative regulation of muscle hyperplasia
negative regulation of platelet activation
negative regulation of potassium ion transport
nitric oxide biosynthetic process
nitric oxide mediated signal transduction
nitric oxide metabolic process
ovulation from ovarian follicle
positive regulation of angiogenesis
positive regulation of guanylate cyclase activity
positive regulation of vasodilation
regulation of blood pressure
regulation of blood vessel size
regulation of nitric-oxide synthase activity
regulation of sodium ion transport
regulation of systemic arterial blood pressure by endothelin
regulation of the force of heart contraction by chemical signal
removal of superoxide radicals
response to fluid shear stress
response to heat
small molecule metabolic process
smooth muscle hyperplasia
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Biological Process:
angiogenesis
arginine catabolic process
blood coagulation
blood vessel remodeling
cell redox homeostasis
endothelial cell migration
in utero embryonic development
lipopolysaccharide-mediated signaling pathway
lung development
mitochondrion organization
negative regulation of blood pressure
negative regulation of calcium ion transport
negative regulation of cell proliferation
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
negative regulation of hydrolase activity
negative regulation of muscle hyperplasia
negative regulation of platelet activation
negative regulation of potassium ion transport
nitric oxide biosynthetic process
nitric oxide mediated signal transduction
nitric oxide metabolic process
ovulation from ovarian follicle
positive regulation of angiogenesis
positive regulation of guanylate cyclase activity
positive regulation of vasodilation
regulation of blood pressure
regulation of blood vessel size
regulation of nitric-oxide synthase activity
regulation of sodium ion transport
regulation of systemic arterial blood pressure by endothelin
regulation of the force of heart contraction by chemical signal
removal of superoxide radicals
response to fluid shear stress
response to heat
small molecule metabolic process
smooth muscle hyperplasia
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Molecular Function:
actin monomer binding
arginine binding
cadmium ion binding
flavin adenine dinucleotide binding
FMN binding
heme binding
iron ion binding
NADP binding
nitric-oxide synthase activity
tetrahydrobiopterin binding
Gene Ontology Cellular Component:
caveola
cytoplasm
cytoskeleton
cytosol
endocytic vesicle membrane
Golgi membrane
nucleus
plasma membrane
Keywords:
3D-structure
Alternative splicing
Calcium
Calmodulin-binding
Cell membrane
Complete proteome
Cytoplasm
Cytoskeleton
Direct protein sequencing
FAD
FMN
Flavoprotein
Golgi apparatus
Heme
Iron
Lipoprotein
Membrane
Metal-binding
Myristate
NADP
Oxidoreductase
Palmitate
Phosphoprotein
Polymorphism
Reference proteome
Zinc
Interacts With:
P31749; Q16543; P35222; Q08379; P43364-2; Q8IVI9; P50502; P14079

Publication

PubMed ID:
1378832 1379542 7688726 7509596 7519987 17264164 14702039 12853948 15489334 7514568 7475956 7515611 11149895 12446846 16126727 16234328 16135813 20213743 24275569 10074942 12437348 18849972 9737779 11740345 16959974