NOS3 nitric oxide synthase 3 (endothelial cell) [Homo sapiens (human)] - Gene

Summary

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Official Symbol: NOS3provided by HGNC
Official Full Name: nitric oxide synthase 3 (endothelial cell)provided by HGNC
Primary source: HGNC:7876
See related: Ensembl:ENSG00000164867; HPRD:01224; MIM:163729; Vega:OTTHUMG00000158343
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: eNOS; ECNOS
Summary: Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

Genomic context

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Location :: 7q36

Sequence :: Chromosome: 7; NC_000007.13 (150688144..150711687)

See NOS3 in Epigenomics, MapViewer

Chromosome 7 - NC_000007.13 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

a new mechanism by which eNOS translocation to mitochondria is regulated by the phosphorylation of eNOS at Ser(617) and Ser(1179) by Akt1 and that this is enhanced when Akt1 becomes nitrated at Tyr(350).
Title: Asymmetric dimethylarginine induces endothelial nitric-oxide synthase mitochondrial redistribution through the nitration-mediated activation of Akt1.
Tanshinone IIA restored eNOS uncoupling induced by high glucose.
Title: Mechanism of reversal of high glucose-induced endothelial nitric oxide synthase uncoupling by tanshinone IIA in human endothelial cell line EA.hy926.
Oral hydrogen sulfide therapy prevents the transition from compensated to decompensated heart failure, in part via upregulation of eNOS and increased nitric oxide bioavailability.
Title: H₂S protects against pressure overload-induced heart failure via upregulation of endothelial nitric oxide synthase.
The NOS3 T allele strongly interacts with CETP B1 allele to augment the risk of coronary artery disease and type 2 diabetes mellitus in the population of Western Iran.
Title: Strong interaction between T allele of endothelial nitric oxide synthase with B1 allele of cholesteryl ester transfer protein TaqIB highly elevates the risk of coronary artery disease and type 2 diabetes mellitus.
beta-carotene reverses the IL-1beta-mediated reduction in paraoxonase-1 expression via induction of the CaMKKII pathway in human endothelial cells
Title: β-carotene reverses the IL-1β-mediated reduction in paraoxonase-1 expression via induction of the CaMKKII pathway in human endothelial cells.
Endothelial nitric-oxide synthase activation generates an inducible nitric-oxide synthase-like output of nitric oxide in inflamed endothelium.
Title: Endothelial nitric-oxide synthase activation generates an inducible nitric-oxide synthase-like output of nitric oxide in inflamed endothelium.
Data suggest estradiol alone has no effect on DDAH/ADMA/NO (dimethylargininase/asymmetric dimethylarginine/nitric oxide) pathway in arterial endothelium, but rather counters oxidized LDL; estradiol restores DDAH activity and prevents loss of eNOS.
Title: Estradiol, acting through estrogen receptor alpha, restores dimethylarginine dimethylaminohydrolase activity and nitric oxide production in oxLDL-treated human arterial endothelial cells.
NOS3 was transiently induced in NT2/D1 cells by retinoic acid treatment coinciding with the cell cycle exit of NT2-derived neuronal precursors. Epigenetic modifications upstream of the proximal promoter occurred.
Title: Involvement of NOS3 in RA-Induced neural differentiation of human NT2/D1 cells.
eNOS genes T786C and G894T may be associated with the pathogenesis of orthostatic intolerance.
Title: [A family-based transmission disequilibrium test of polymorphisms of endothelial nitric oxide synthase gene in children with orthostatic intolerance].
Patients who have the "a" type allele of the eNOS gene may have an increased risk for coronary artery ectasia
Title: The relationship between coronary artery ectasia and eNOS intron 4a/b gene polymorphisms.

Submit: New GeneRIF Correction See all (917)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Alzheimer disease (AD) is characterized by dementia that typically begins with subtle and poorly recognized failure of memory and slowly becomes more severe and, eventually, incapacitating. Other common findings include confusion, poor judgment, language disturbance, agitation, withdrawal, and hallucinations. Occasionally, seizures, Parkinsonian features, increased muscle tone, myoclonus, incontinence, and mutism occur. Death usually results from general inanition, malnutrition, and pneumonia. The typical clinical duration of the disease is eight to ten years, with a range from one to 25 years. Approximately 25% of all AD is familial (i.e., >/=2 persons in a family have AD) of which approximately 95% is late onset (age >60-65 years) and 5% is early onset (age <65 years).

Diagnosis Testing

Establishing the diagnosis of Alzheimer disease relies on clinical-neuropathologic assessment. Neuropathologic findings of beta-amyloid plaques and intraneuronal neurofibrillary tangles remain the gold standard for diagnosis. The clinical diagnosis of AD, based on signs of slowly progressive dementia and findings of gross cerebral cortical atrophy on neuroimaging, is correct approximately 80%-90% of the time. The association of the APOE e4 allele with AD is significant; however, APOE genotyping is neither fully specific nor sensitive. While APOE genotyping may have an adjunct role in the diagnosis of AD in symptomatic individuals, it appears to have little role at this time in predictive testing of asymptomatic individuals. Three forms of early-onset familial AD (EOFAD) caused by mutations in one of three genes (APP, PSEN1, PSEN2) are recognized. Molecular genetic testing of the three genes is available in clinical laboratories.

Genetic Counseling

Because AD is genetically heterogeneous, genetic counseling of persons with AD and their family members must be tailored to the information available for that family. It should be pointed out that AD is common and that the overall lifetime risk for any individual of developing dementia is approximately 10%-12%. Genetic counseling for people with non-familial AD and their family members must be empiric and relatively nonspecific. First-degree relatives of a simplex case of AD (i.e., single occurrence in a family) have a cumulative lifetime risk of developing AD of approximately 15%-30%, which is typically reported as a 20%-25% risk. This risk is approximately 2.5 times that of the background risk (~27% vs 10.4%). In contrast, early-onset familial Alzheimer disease (EOFAD) is inherited in an autosomal dominant manner.

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV gp120 and TNF-alpha synergistically reduce endothelial nitric oxide synthase (eNOS) expression and cause endothelial dysfunction via ICAM-1	PubMed
Envelope transmembrane glycoprotein gp41	env	The amino terminus of HIV-1 gp41 induces nitric oxide synthase in human glial and astrocyte cultures and that causes the dysregulation of nitric oxide production	PubMed
Nef, p27	nef	HIV Nef significantly decreases endothelial NOS3 expression in the vessels and human pulmonary artery endothelial cells	PubMed
Tat, p14	tat	HIV-1 Tat induces the expression of NOS-2 and NOS-3 which appears to be a mechanism for regulating Tat-mediated degradation of IkappaBalpha and activation of NFkappaB	PubMed
	tat	HIV-1 Tat protein significantly decreased endothelium-dependent vasorelaxation and eNOS mRNA and protein expression in endothelial cells of porcine coronary arteries, suggesting a role for Tat in coronary heart disease in HIV-infected patients	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P29474	P30556	AGTR1	HPRD	PubMed
P29474	P31749	AKT1	HPRD	PubMed
P29474	P30411	BDKRB2	HPRD	PubMed
P29474	P23560	BDNF	HPRD	PubMed
P29474	Q03135	CAV1	HPRD	PubMed
P29474	P24530	EDNRB	HPRD	PubMed
P29474	P07900	HSP90AA1	HPRD	PubMed
P29474	P30419	NMT1	HPRD	PubMed
P29474	P29474	NOS3	HPRD	PubMed
P29474	Q9Y314	NOSIP	HPRD	PubMed
P29474	Nitric oxide synthase trafficking	NOSTRIN	HPRD	PubMed
P29474	Q15172	PPP2R5A	HPRD	PubMed
P29474	P08047	SP1	HPRD	PubMed
BioGRID:110909	BioGRID:106524	A2M	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:106603	ACTN2	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:106596	ACTN4	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:106710	AKT1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110909	BioGRID:106845	APOE	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:110909	BioGRID:106848	APP	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:110909	BioGRID:107252	CALM1	BioGRID	PubMed	Affinity Capture-Western; Far Western; Protein-peptide
BioGRID:110909	BioGRID:107265	CAMK2A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110909	BioGRID:107305	CAV1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110909	BioGRID:116312	CDC37	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:110909	BioGRID:120465	CEP55	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:108496	EFEMP1	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:119026	EFEMP2	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:108309	ELAVL1	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:108310	ELAVL3	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:120023	EXOC6	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:119220	EXOSC1	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:119230	FIS1	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:108909	GCDH	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:110909	BioGRID:109238	GUCY1B3	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110909	BioGRID:109272	H3F3A	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:114368	HDAC3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110909	BioGRID:109552	HSP90AA1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:110909	BioGRID:111635	HTRA1	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:116185	IMMT	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:117449	KANK2	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:116632	MAST1	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:116776	MPRIP	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:110909	NOS3	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:119261	NOSIP	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:110909	BioGRID:125446	NOSTRIN	BioGRID	PubMed	Affinity Capture-Western; Co-localization; Reconstituted Complex; Two-hybrid
BioGRID:110909	BioGRID:116625	PAXIP1	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:120639	PI4K2A	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:111642	PSEN1	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:111643	PSEN2	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:120389	RNF31	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:126622	RNF32	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:112644	ST13	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:110909	BioGRID:114900	TECR	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:119253	TXNDC11	BioGRID	PubMed	Two-hybrid
BioGRID:110909	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110909	BioGRID:113218	UMPS	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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ACE Inhibitor Pathway, organism-specific biosystem (from WikiPathways)
ACE Inhibitor Pathway, organism-specific biosystemThe core of this pathway was elucidated over a century ago and involves the conversion of angiotensinogen to angiotensin I (Ang I) by renin, its subsequent conversion to angiotensin II (Ang II) by an...
AGE/RAGE pathway, organism-specific biosystem (from WikiPathways)
AGE/RAGE pathway, organism-specific biosystemAdvanced glycation end products (AGEs) are heterogeneous group of non-enzymatic malliard reaction products of aldose sugar with proteins and lipids. Formation of AGEs is an indicator of one of the ma...
Angiogenesis, organism-specific biosystem (from WikiPathways)
Angiogenesis, organism-specific biosystemThis pathway is a concise and simplified version of the basic proteins involved in angiogenesis. The proces is regulated by hyopoxia, which results in the transcription of eg. VEGF1, FGF2, PDGFbeta, ...
Angiopoietin receptor Tie2-mediated signaling, organism-specific biosystem (from Pathway Interaction Database)
Angiopoietin receptor Tie2-mediated signaling, organism-specific biosystem
Angiopoietin receptor Tie2-mediated signaling
Arginine and proline metabolism, organism-specific biosystem (from KEGG)
Arginine and proline metabolism, organism-specific biosystem
Arginine and proline metabolism
Arginine and proline metabolism, conserved biosystem (from KEGG)
Arginine and proline metabolism, conserved biosystem
Arginine and proline metabolism
Calcium signaling pathway, organism-specific biosystem (from KEGG)
Calcium signaling pathway, organism-specific biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
Calcium signaling pathway, conserved biosystem (from KEGG)
Calcium signaling pathway, conserved biosystemCa2+ that enters the cell from the outside is a principal source of signal Ca2+. Entry of Ca2+ is driven by the presence of a large electrochemical gradient across the plasma membrane. Cells use this...
Disease, organism-specific biosystem (from REACTOME)
Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
Endothelin, organism-specific biosystem (from WikiPathways)
Endothelin, organism-specific biosystemEndothelin-1 is a bicyclic 21 amino acid peptide, produced primarily in the endothelium. It is a potent stimulus of long-lasting and persistent vasoconstriction. It also has a role as a stimulus of i...
Estrogen signaling pathway, organism-specific biosystem (from KEGG)
Estrogen signaling pathway, organism-specific biosystemEstrogens are steroid hormones that regulate a plethora of physiological processes in mammals, including reproduction, cardiovascular protection, bone integrity, cellular homeostasis, and behavior. E...
Estrogen signaling pathway, conserved biosystem (from KEGG)
Estrogen signaling pathway, conserved biosystemEstrogens are steroid hormones that regulate a plethora of physiological processes in mammals, including reproduction, cardiovascular protection, bone integrity, cellular homeostasis, and behavior. E...
HIF-1 signaling pathway, organism-specific biosystem (from KEGG)
HIF-1 signaling pathway, organism-specific biosystemHypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. It consists of two subunits: an inducibly-expressed HIF-1alpha subunit and a c...
Hemostasis, organism-specific biosystem (from REACTOME)
Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
Latent infection of Homo sapiens with Mycobacterium tuberculosis, organism-specific biosystem (from REACTOME)
Latent infection of Homo sapiens with Mycobacterium tuberculosis, organism-specific biosystemInfection by Mycobacterium tuberculosis (Mtb) is soon countered by the host's immune system, the organism is however almost never eradicated; ten per cent of infections will develop into "open tuberc...
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of nitric oxide, organism-specific biosystem (from REACTOME)
Metabolism of nitric oxide, organism-specific biosystemNitric oxide (NO), a multifunctional second messenger, is implicated in physiological functions in mammals that range from immune response and potentiation of synaptic transmission to dilation of blo...
Myometrial Relaxation and Contraction Pathways, organism-specific biosystem (from WikiPathways)
Myometrial Relaxation and Contraction Pathways, organism-specific biosystemThis pathway illustrates signaling networks implicated in uterine muscle contraction at labor and quiescence throughout gestation (pregnancy). The muscle of the uterus, responsible for contractile ac...
NOSIP mediated eNOS trafficking, organism-specific biosystem (from REACTOME)
NOSIP mediated eNOS trafficking, organism-specific biosystemeNOS-interacting protein (NOSIP) is a 34-kDa nucleocytoplasmic shuttling protein that binds to the COOH-terminal region (amino acids 366-486) of the eNOS oxygenase domain. This protein association p...
NOSTRIN mediated eNOS trafficking, organism-specific biosystem (from REACTOME)
NOSTRIN mediated eNOS trafficking, organism-specific biosystemeNOS traffic inducer (NOSTRIN) is a novel 506-amino acid eNOS-interacting protein. Along with a decrease in eNOS activity, NOSTRIN causes translocation of eNOS from the plasma membrane to intracellu...
Nitric oxide stimulates guanylate cyclase, organism-specific biosystem (from REACTOME)
Nitric oxide stimulates guanylate cyclase, organism-specific biosystemNitric Oxide (NO) inhibits smooth muscle cell proliferation and migration, oxidation of low-density lipoproteins, and platelet aggregation and adhesion. It can stimulate vasodilatation of the endothe...
PI3K-Akt signaling pathway, organism-specific biosystem (from KEGG)
PI3K-Akt signaling pathway, organism-specific biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
PI3K-Akt signaling pathway, conserved biosystem (from KEGG)
PI3K-Akt signaling pathway, conserved biosystemThe phosphatidylinositol 3' -kinase(PI3K)-Akt signaling pathway is activated by many types of cellular stimuli or toxic insults and regulates fundamental cellular functions such as transcription, tra...
Phagosomal maturation (early endosomal stage), organism-specific biosystem (from REACTOME)
Phagosomal maturation (early endosomal stage), organism-specific biosystemAlveolar macrophages normally develop their phagosome along the endolysosomal pathway. However, after having internalized Mtb, this development is arrested at an early stage and only includes acidifi...
Plasma membrane estrogen receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
Plasma membrane estrogen receptor signaling, organism-specific biosystem
Plasma membrane estrogen receptor signaling
Platelet homeostasis, organism-specific biosystem (from REACTOME)
Platelet homeostasis, organism-specific biosystemUnder normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhesion and activation, suppresses coagulation, enhances fibrin cleavage and is anti-inflammatory in charact...
Signaling events mediated by VEGFR1 and VEGFR2, organism-specific biosystem (from Pathway Interaction Database)
Signaling events mediated by VEGFR1 and VEGFR2, organism-specific biosystem
Signaling events mediated by VEGFR1 and VEGFR2
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation, organism-specific biosystem (from REACTOME)
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation, organism-specific biosystemTetrahydrobiopterin (BH4) is an essential co-factor for the aromatic amino acid hydroxylases and glycerol ether monooxygenase and it regulates nitric oxide synthase (NOS) activity. Inherited BH4 defi...
Thromboxane A2 receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
Thromboxane A2 receptor signaling, organism-specific biosystem
Thromboxane A2 receptor signaling
VEGF signaling pathway, organism-specific biosystem (from KEGG)
VEGF signaling pathway, organism-specific biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
VEGF signaling pathway, conserved biosystem (from KEGG)
VEGF signaling pathway, conserved biosystemThere is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic a...
VEGFR1 specific signals, organism-specific biosystem (from Pathway Interaction Database)
VEGFR1 specific signals, organism-specific biosystem
VEGFR1 specific signals
Validated transcriptional targets of AP1 family members Fra1 and Fra2, organism-specific biosystem (from Pathway Interaction Database)
Validated transcriptional targets of AP1 family members Fra1 and Fra2, organism-specific biosystem
Validated transcriptional targets of AP1 family members Fra1 and Fra2
citrulline-nitric oxide cycle, organism-specific biosystem (from BIOCYC)
citrulline-nitric oxide cycle, organism-specific biosystemNitric oxide (NO) plays an important role in cell signaling in the nervous system, and is implicated in synaptic plasticity. It also participates in the immunologic response to infection. In the vasc...
citrulline-nitric oxide cycle, conserved biosystem (from BIOCYC)
citrulline-nitric oxide cycle, conserved biosystem|FRAME: NITRIC-OXIDE Nitric oxide| (NO) plays an important role in cell signaling in the nervous system, and is implicated in synaptic plasticity. It also participates in the immunologic response to ...
eNOS activation, organism-specific biosystem (from REACTOME)
eNOS activation, organism-specific biosystemeNOS activity is regulated by numerous post-translational modifications including phosphorylation and acylation, which also modulate its interactions with other proteins and its subcellular localizat...
eNOS activation and regulation, organism-specific biosystem (from REACTOME)
eNOS activation and regulation, organism-specific biosystemOriginally identified as endothelium-derived relaxing factor, eNOS derived NO is a critical signaling molecule in vascular homeostasis. It regulates blood pressure and vascular tone, and is involved...
superpathway of citrulline metabolism, organism-specific biosystem (from BIOCYC)
superpathway of citrulline metabolism, organism-specific biosystem
superpathway of citrulline metabolism
superpathway of citrulline metabolism, conserved biosystem (from BIOCYC)
superpathway of citrulline metabolism, conserved biosystemGeneral Background |FRAME: L-CITRULLINE| is a non-standard amino acid that is not normally incorporated into proteins during protein synthesis. The name citrulline was coined in 1930 from Citrullus...

General gene information

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Markers

D7S636 (e-PCR)
- UniSTS:148993

GDB:374071 (e-PCR)
- UniSTS:156938

RH99113 (e-PCR)
- UniSTS:87829

GDB:4585682 (e-PCR)
- UniSTS:61751

NOS3 (e-PCR)
- UniSTS:37692

NOS3 (e-PCR)
- UniSTS:53319

Nos3 (e-PCR), detects polymorphism
- UniSTS:546896

D7S636 (e-PCR)
- UniSTS:44625

MARC_6739-6740:982537599:1 (e-PCR)
- UniSTS:231255

D7S1880 (e-PCR)
- UniSTS:45402

NOS3 (e-PCR)
- UniSTS:503696

D7S636 (e-PCR)
- UniSTS:52125

D7S759 (e-PCR)
- UniSTS:40896

STS-U24214 (e-PCR)
- UniSTS:15311

PMC155039P1 (e-PCR)
- UniSTS:271323

D7S2866 (e-PCR)
- UniSTS:64495

Genotypes

See NOS3 SNP Geneview Report
See NOS3 SNP Genotype Report
See NOS3 SNP Variation Viewer Report

Homology

Homologs of the NOS3 gene: The NOS3 gene is conserved in chimpanzee, dog, cow, mouse, and rat.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
FMN binding	NAS Non-traceable Author Statement more info	PubMed
NADP binding	NAS Non-traceable Author Statement more info	PubMed
NADPH-hemoprotein reductase activity	IBA Inferred from Biological aspect of Ancestor more info
actin monomer binding	IPI Inferred from Physical Interaction more info	PubMed
arginine binding	IDA Inferred from Direct Assay more info	PubMed
cadmium ion binding	NAS Non-traceable Author Statement more info	PubMed
calmodulin binding	IEA Inferred from Electronic Annotation more info
flavin adenine dinucleotide binding	NAS Non-traceable Author Statement more info	PubMed
heme binding	IDA Inferred from Direct Assay more info	PubMed
iron ion binding	IEA Inferred from Electronic Annotation more info
nitric-oxide synthase activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
tetrahydrobiopterin binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
angiogenesis	IEA Inferred from Electronic Annotation more info
arginine catabolic process	IDA Inferred from Direct Assay more info	PubMed
blood coagulation	TAS Traceable Author Statement more info
blood vessel remodeling	ISS Inferred from Sequence or Structural Similarity more info
endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
in utero embryonic development	IEA Inferred from Electronic Annotation more info
interaction with host	TAS Traceable Author Statement more info
lipopolysaccharide-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
lung development	IEA Inferred from Electronic Annotation more info
mitochondrion organization	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of blood pressure	IBA Inferred from Biological aspect of Ancestor more info
negative regulation of calcium ion transport	IEA Inferred from Electronic Annotation more info
negative regulation of cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of hydrolase activity	IEA Inferred from Electronic Annotation more info
negative regulation of muscle hyperplasia	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of platelet activation	NAS Non-traceable Author Statement more info	PubMed
negative regulation of potassium ion transport	IEA Inferred from Electronic Annotation more info
nitric oxide biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
nitric oxide mediated signal transduction	IBA Inferred from Biological aspect of Ancestor more info
nitric oxide metabolic process	TAS Traceable Author Statement more info
ovulation from ovarian follicle	IEA Inferred from Electronic Annotation more info
phagosome maturation	TAS Traceable Author Statement more info
positive regulation of angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of guanylate cyclase activity	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of guanylate cyclase activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of vasodilation	NAS Non-traceable Author Statement more info	PubMed
regulation of blood pressure	NAS Non-traceable Author Statement more info	PubMed
regulation of blood vessel size	ISS Inferred from Sequence or Structural Similarity more info
regulation of blood vessel size	NAS Non-traceable Author Statement more info	PubMed
regulation of nitric-oxide synthase activity	TAS Traceable Author Statement more info
regulation of sodium ion transport	IEA Inferred from Electronic Annotation more info
regulation of systemic arterial blood pressure by endothelin	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of the force of heart contraction by chemical signal	IEA Inferred from Electronic Annotation more info
response to fluid shear stress	IEP Inferred from Expression Pattern more info	PubMed
response to heat	NAS Non-traceable Author Statement more info	PubMed
small molecule metabolic process	TAS Traceable Author Statement more info
smooth muscle hyperplasia	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
Golgi membrane	TAS Traceable Author Statement more info
caveola	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytoskeleton	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info
endocytic vesicle membrane	TAS Traceable Author Statement more info
nucleus	ISS Inferred from Sequence or Structural Similarity more info
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: nitric oxide synthase, endothelial

Names: nitric oxide synthase, endothelial; cNOS; EC-NOS; NOSIII; NOS type III; endothelial NOS; constitutive NOS

NP_000594.2

EC 1.14.13.39

NP_001153581.1

EC 1.14.13.39

NP_001153582.1

EC 1.14.13.39

NP_001153583.1

EC 1.14.13.39

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011992.1 RefSeqGene

Range

4998..28541

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000603.4 → NP_000594.2 nitric oxide synthase, endothelial isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AI082109, BC063294, DA859819

Consensus CDS

CCDS5912.1

UniProtKB/Swiss-Prot

P29474

Related

ENSP00000297494, OTTHUMP00000212826, ENST00000297494, OTTHUMT00000350750

Conserved Domains (4) summary

cd00795
Location:68 – 480
Blast Score: 1806

NOS_oxygenase_euk; Nitric oxide synthase (NOS) eukaryotic oxygenase domain. NOS produces nitric oxide (NO) by catalyzing a five-electron heme-based oxidation of a guanidine nitrogen of L-arginine to L-citrulline via two successive monooxygenation reactions producing N ...

COG0369
Location:512 – 1160
Blast Score: 758

CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]

pfam00258
Location:522 – 698
Blast Score: 254

Flavodoxin_1; Flavodoxin

cl06868
Location:762 – 1164
Blast Score: 1413

FNR_like; Ferredoxin reductase (FNR), an FAD and NAD(P) binding protein, was intially identified as a chloroplast reductase activity, catalyzing the electron transfer from reduced iron-sulfur protein ferredoxin to NADP+ as the final step in the electron transport ...
NM_001160109.1 → NP_001153581.1 nitric oxide synthase, endothelial isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2), also known as eNOS13A, uses an alternate 3' exon and poly-adenylation site, compared to variant 1. The resulting isoform (2) has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

BC063294, DQ256129

UniProtKB/TrEMBL

A0S0A6

UniProtKB/Swiss-Prot

P29474

Conserved Domains (2) summary

cd00795
Location:68 – 480
Blast Score: 1805

NOS_oxygenase_euk; Nitric oxide synthase (NOS) eukaryotic oxygenase domain. NOS produces nitric oxide (NO) by catalyzing a five-electron heme-based oxidation of a guanidine nitrogen of L-arginine to L-citrulline via two successive monooxygenation reactions producing N ...

pfam00258
Location:522 – 584
Blast Score: 189

Flavodoxin_1; Flavodoxin
NM_001160110.1 → NP_001153582.1 nitric oxide synthase, endothelial isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3), also known as eNOS13B, uses an alternate 3' exon and poly-adenylation site, compared to variant 1. The resulting isoform (3) has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

BC063294, DQ256130

Consensus CDS

CCDS55183.1

UniProtKB/Swiss-Prot

P29474

Related

ENSP00000420551, OTTHUMP00000213185, ENST00000467517, OTTHUMT00000351551

Conserved Domains (2) summary

cd00795
Location:68 – 480
Blast Score: 1798

NOS_oxygenase_euk; Nitric oxide synthase (NOS) eukaryotic oxygenase domain. NOS produces nitric oxide (NO) by catalyzing a five-electron heme-based oxidation of a guanidine nitrogen of L-arginine to L-citrulline via two successive monooxygenation reactions producing N ...

pfam00258
Location:522 – 585
Blast Score: 190

Flavodoxin_1; Flavodoxin
NM_001160111.1 → NP_001153583.1 nitric oxide synthase, endothelial isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4), also known as eNOS13C, uses an alternate 3' exon and poly-adenylation site, compared to variant 1. The resulting isoform (4) has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

DQ256131

Consensus CDS

CCDS55182.1

UniProtKB/Swiss-Prot

P29474

Related

ENSP00000420215, OTTHUMP00000213184, ENST00000484524, OTTHUMT00000351550

Conserved Domains (2) summary

cd00795
Location:68 – 480
Blast Score: 1807

NOS_oxygenase_euk; Nitric oxide synthase (NOS) eukaryotic oxygenase domain. NOS produces nitric oxide (NO) by catalyzing a five-electron heme-based oxidation of a guanidine nitrogen of L-arginine to L-citrulline via two successive monooxygenation reactions producing N ...

pfam00258
Location:522 – 584
Blast Score: 190

Flavodoxin_1; Flavodoxin

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000007.13 Reference GRCh37.p10 Primary Assembly

Range

150688144..150711687

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000139.1 Alternate HuRef

Range

144500690..144524025

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CRA_TCAGchr7v2

Genomic

AC_000068.1 Alternate CRA_TCAGchr7v2

Range

150017398..150041276

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018918.1 Alternate CHM1_1.0

Range

154140330..154163822

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AACC02000108.1	EAL24494.1
genomic	ABBA01035167.1 (68523..71587)	None
genomic	ABBA01035168.1	None
genomic	AC010973.6 (191107..214636)	None
genomic	AF032908.1	AAB87083.1
genomic	AF387340.1	AAK71989.1
genomic	AF415200.1	AAL07497.1
genomic	AF519768.1	AAM74944.1
genomic	AMYH01018142.1 (34965..58457)	None
genomic	CH471173.2	EAW54069.1
genomic	D26607.1	BAA05652.1
genomic	EU332855.1	ABY87544.1
genomic	L10709.1	AAA36365.1
genomic	L23210.1	AAA36373.1
genomic	L26914.1	AAA36374.1
genomic	X76303.1	CAA53950.1
mRNA	AF400594.1	AAK83389.1
mRNA	AI082109.1	None
mRNA	AK223636.1	BAD97356.1
mRNA	AK225827.1	None
mRNA	AK292928.1	BAF85617.1
mRNA	AK300390.1	BAH13275.1
mRNA	AK302686.1	BAH13779.1
mRNA	AK315213.1	BAG37648.1
mRNA	BC063294.1	AAH63294.1
mRNA	BC069465.1	AAH69465.1
mRNA	BU731828.1	None
mRNA	CB987955.1	None
mRNA	DA859819.1	None
mRNA	DQ256129.1	ABB79838.1
mRNA	DQ256130.1	ABB79839.1
mRNA	DQ256131.1	ABB79840.1
mRNA	M93718.1	AAA36364.1
mRNA	M95296.1	AAA36372.1
mRNA	S80791.1	AAD14336.1
other-genetic	HQ257992.1	ADR82746.1