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

Summary

Official Symbol: NOS3provided by HGNC
Official Full Name: nitric oxide synthase 3provided by HGNC
Primary source: HGNC:HGNC:7876
See related: Ensembl:ENSG00000164867 MIM:163729; AllianceGenome:HGNC:7876
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. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]
Expression: Biased expression in spleen (RPKM 28.4), placenta (RPKM 4.0) and 11 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q36.1

Exon count:: 28

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (150991017..151014588)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (152163824..152187711)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (150688105..150711676)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Low HDL cholesterol and the eNOS Glu298Asp polymorphism are associated with inducible myocardial ischemia in patients with suspected stable coronary artery disease.
Title: Low HDL cholesterol and the eNOS Glu298Asp polymorphism are associated with inducible myocardial ischemia in patients with suspected stable coronary artery disease.
Endothelial nitric oxide synthase (eNOS) gene polymorphism (Glu298asp) and nitric oxide (NO) levels in patients with ST-segment elevation myocardial infarction (STEMI).
Title: Endothelial nitric oxide synthase (eNOS) gene polymorphism (Glu298asp) and nitric oxide (NO) levels in patients with ST-segment elevation myocardial infarction (STEMI).
Lymphocyte-Specific Protein 1 Regulates Expression and Stability of Endothelial Nitric Oxide Synthase.
Title: Lymphocyte-Specific Protein 1 Regulates Expression and Stability of Endothelial Nitric Oxide Synthase.
GPR56 Promotes Diabetic Kidney Disease Through eNOS Regulation in Glomerular Endothelial Cells.
Title: GPR56 Promotes Diabetic Kidney Disease Through eNOS Regulation in Glomerular Endothelial Cells.
SUMOylation and coupling of eNOS mediated by PIAS1 contribute to maintenance of vascular homeostasis.
Title: SUMOylation and coupling of eNOS mediated by PIAS1 contribute to maintenance of vascular homeostasis.
A Comprehensive Investigation of Risk Association Between the -786 T > C, + 884 G > A, VNTR, rs743506, rs3918226 of eNOS and Susceptibility of Migraine: A Updated Meta-Analysis Utilizing Trial Sequential Analysis.
Title: A Comprehensive Investigation of Risk Association Between the -786 T > C, + 884 G > A, VNTR, rs743506, rs3918226 of eNOS and Susceptibility of Migraine: A Updated Meta-Analysis Utilizing Trial Sequential Analysis.
Association between NOS3 gene polymorphisms and genetic susceptibility to congenital heart Disease: A systematic review and meta-analysis.
Title: Association between NOS3 gene polymorphisms and genetic susceptibility to congenital heart Disease: A systematic review and meta-analysis.
TRPC6 Deletion Enhances eNOS Expression and Reduces LPS-Induced Acute Lung Injury.
Title: TRPC6 Deletion Enhances eNOS Expression and Reduces LPS-Induced Acute Lung Injury.
Association of endothelial nitric oxide synthase gene variants in pre-eclampsia: an updated systematic review and meta-analysis.
Title: Association of endothelial nitric oxide synthase gene variants in pre-eclampsia: an updated systematic review and meta-analysis.
Differential roles of eNOS in late effects of VEGF-A on hyperpermeability in different types of endothelial cells.
Title: Differential roles of eNOS in late effects of VEGF-A on hyperpermeability in different types of endothelial cells.

Submit: New GeneRIF Correction See all GeneRIFs (1658)

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

Associated conditions

Description	Tests
Alzheimer disease type 1 MedGen: C1863052 OMIM: 104300 GeneReviews: Alzheimer Disease Overview	Compare labs
Essential hypertension, genetic MedGen: CN305331 OMIM: 145500 GeneReviews: Not available	Compare labs
Ischemic stroke MedGen: C0948008 OMIM: 601367 GeneReviews: Not available	Compare labs
Preeclampsia/eclampsia 1 MedGen: C5574918 OMIM: 189800 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

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	nef	HIV Nef significantly decreases endothelial NOS3 expression in the vessels and human pulmonary artery endothelial cells	PubMed
Tat	tat	HIV-1 Tat potentiates NMDA-evoked (Ca2+)I responses involve LRP and a Src family kinase via the NOS/sGC/PKG pathway	PubMed
	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 Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

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

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
involved_in angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in aortic valve morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in aortic valve morphogenesis	TAS Traceable Author Statement more info	PubMed
involved_in arginine catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in arginine catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in blood vessel diameter maintenance	ISS Inferred from Sequence or Structural Similarity more info
involved_in blood vessel remodeling	ISS Inferred from Sequence or Structural Similarity more info
involved_in calcium ion transport	IEA Inferred from Electronic Annotation more info
involved_in cell redox homeostasis	TAS Traceable Author Statement more info
involved_in endocardial cushion morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in establishment of localization in cell	IEA Inferred from Electronic Annotation more info
involved_in homeostasis of number of cells within a tissue	ISS Inferred from Sequence or Structural Similarity more info
involved_in in utero embryonic development	IEA Inferred from Electronic Annotation more info
involved_in lipopolysaccharide-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in lung development	IEA Inferred from Electronic Annotation more info
involved_in mitochondrion organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of biomineral tissue development	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of blood pressure	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of calcium ion transport	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of muscle hyperplasia	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of platelet activation	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of potassium ion transport	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of smooth muscle cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in nitric oxide biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in nitric oxide biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in nitric oxide mediated signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in ovulation from ovarian follicle	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of Notch signaling pathway	IC Inferred by Curator more info	PubMed
involved_in positive regulation of angiogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of blood vessel endothelial cell migration	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_positive_effect positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of guanylate cyclase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of guanylate cyclase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of guanylate cyclase activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in potassium ion transport	IEA Inferred from Electronic Annotation more info
involved_in pulmonary valve morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of blood pressure	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of nervous system process	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of sodium ion transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of systemic arterial blood pressure by endothelin	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of the force of heart contraction by chemical signal	IEA Inferred from Electronic Annotation more info
involved_in removal of superoxide radicals	IDA Inferred from Direct Assay more info	PubMed
involved_in response to fluid shear stress	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to heat	NAS Non-traceable Author Statement more info	PubMed
involved_in response to hormone	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to lipopolysaccharide	IBA Inferred from Biological aspect of Ancestor more info
involved_in smooth muscle hyperplasia	ISS Inferred from Sequence or Structural Similarity more info
involved_in vasodilation	NAS Non-traceable Author Statement more info	PubMed
involved_in ventricular septum morphogenesis	IEA Inferred from Electronic Annotation more info

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

General protein information

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Preferred Names: nitric oxide synthase 3

Names: EC-NOS; NOS type III; NOSIII; cNOS; constitutive NOS; endothelial NOS; nitric oxide synthase 3 (endothelial cell)

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

4959..28530

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000603.5 → NP_000594.2 nitric oxide synthase 3 isoform 1

See identical proteins and their annotated locations for NP_000594.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1). The 5' end of this transcript contains long terminal repeat (LTR) sequence, initiates from an LTR promoter and results in placenta-specific expression. (PMID: 18474398)

Source sequence(s)

AC010973, AI082109, BC063294, DA859819

Consensus CDS

CCDS5912.1

UniProtKB/Swiss-Prot

A0S0A7, A0S0A8, A8KA63, B2RCQ1, E9PFR2, P29474, Q13662, Q14251, Q14434, Q548C1, Q6GSL5, Q9UDC6

UniProtKB/TrEMBL

A0A090N8H8

Related

ENSP00000297494.3, ENST00000297494.8

Conserved Domains (3) summary

cd00795
Location:68 → 480

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 → 698

Flavodoxin_1; Flavodoxin

cl06868
Location:762 → 1164

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_001160109.2 → NP_001153581.1 nitric oxide synthase 3 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)

AC010973, BC063294, DQ256129

UniProtKB/TrEMBL

A0S0A6

Conserved Domains (2) summary

cd00795
Location:68 → 480

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

Flavodoxin_1; Flavodoxin
NM_001160110.1 → NP_001153582.1 nitric oxide synthase 3 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/TrEMBL

A0S0A6

Related

ENSP00000420551.1, ENST00000467517.1

Conserved Domains (2) summary

cd00795
Location:68 → 480

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 → 594

Flavodoxin_1; Flavodoxin
NM_001160111.1 → NP_001153583.1 nitric oxide synthase 3 isoform 4

See identical proteins and their annotated locations for NP_001153583.1

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/TrEMBL

A0S0A6

Related

ENSP00000420215.1, ENST00000484524.5

Conserved Domains (2) summary

cd00795
Location:68 → 480

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 → 586

Flavodoxin_1; Flavodoxin