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Aliases for NOS3 Gene

Aliases for NOS3 Gene

  • Nitric Oxide Synthase 3 (Endothelial Cell) 2 3
  • Constitutive NOS 3 4
  • Endothelial NOS 3 4
  • EC 4 63
  • NOS Type III 3 4
  • EC-NOS 3 4
  • NOSIII 3 4
  • CNOS 3 4
  • ENOS 3 4
  • Nitric Oxide Synthase 3 Transcript Variant ENOS-Delta20-21 3
  • Nitric Oxide Synthase 3 Transcript Variant ENOS-Delta20 3
  • Nitric Oxide Synthase 3 Transcript Variant ENOS-Delta21 3
  • Nitric Oxide Synthase, Endothelial 3
  • Endothelial Nitric Oxide Synthase 2
  • ECNOS 3

External Ids for NOS3 Gene

Previous GeneCards Identifiers for NOS3 Gene

  • GC07P148937
  • GC07P150005
  • GC07P150082
  • GC07P150079
  • GC07P150125
  • GC07P150319
  • GC07P150688
  • GC07P144500

Summaries for NOS3 Gene

Entrez Gene Summary for NOS3 Gene

  • 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]

GeneCards Summary for NOS3 Gene

NOS3 (Nitric Oxide Synthase 3 (Endothelial Cell)) is a Protein Coding gene. Diseases associated with NOS3 include stroke, ischemic and preeclampsia/eclampsia 1. Among its related pathways are PI3K-Akt signaling pathway and GPCR Pathway. GO annotations related to this gene include calmodulin binding and heme binding. An important paralog of this gene is NOS1.

UniProtKB/Swiss-Prot for NOS3 Gene

  • 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

Tocris Summary for NOS3 Gene

  • Endothelial nitric oxide synthase (eNOS), along with inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS), catalyze the generation of nitric oxide and L-citrulline from L-arginine and molecular oxygen. It is activated at concentrations of calcium greater than 100 nM and requires tetrahydrobiopterin, flavin adenine dinucleotide, flavin mononucleotide and NADPH for catalytic activity. eNOS is tightly regulated by co- and post-translational lipid modifications, phosphorylation by Akt/PKB, PKA and AMPK and protein-protein interactions. Negative protein-protein interactions are mediated by Hsp90 and Cav-1 in the Golgi and by NOSIP and NOSTRIN at the plasma membrane, whilst dynamin, porin and soluble guanylyl cyclase are positive regulators of eNOS activity. eNOS is a critical mediator of cardiovascular homeostasis through regulation of the diameter of blood vessels and maintenance of an antiproliferative and antiapoptotic environment in the vasculature. The human gene encoding eNOS is localized to chromosome 7q36.

Gene Wiki entry for NOS3 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NOS3 Gene

Genomics for NOS3 Gene

Regulatory Elements for NOS3 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for NOS3 Gene

150,990,995 bp from pter
151,014,944 bp from pter
23,950 bases
Plus strand

Genomic View for NOS3 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for NOS3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NOS3 Gene

Proteins for NOS3 Gene

  • Protein details for NOS3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Nitric oxide synthase, endothelial
    Protein Accession:
    Secondary Accessions:
    • A0S0A7
    • A0S0A8
    • A8KA63
    • B2RCQ1
    • E9PFR2
    • Q13662
    • Q14251
    • Q14434
    • Q548C1
    • Q6GSL5
    • Q9UDC6

    Protein attributes for NOS3 Gene

    1203 amino acids
    Molecular mass:
    133289 Da
    Name=5,6,7,8-tetrahydrobiopterin; Xref=ChEBI:CHEBI:15372; Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.;
    Name=FAD; Xref=ChEBI:CHEBI:57692; Note=Binds 1 FAD.;
    Name=FMN; Xref=ChEBI:CHEBI:58210; Note=Binds 1 FMN.;
    Name=heme; Xref=ChEBI:CHEBI:30413;
    Quaternary structure:
    • Homodimer. Interacts with NOSIP and NOSTRIN.

    Three dimensional structures from OCA and Proteopedia for NOS3 Gene

    Alternative splice isoforms for NOS3 Gene


neXtProt entry for NOS3 Gene

Proteomics data for NOS3 Gene at MOPED

Post-translational modifications for NOS3 Gene

  • Phosphorylation by AMPK at Ser-1177 in the presence of Ca(2+)-calmodulin (CaM) activates activity. In absence of Ca(2+)-calmodulin, AMPK also phosphorylates Thr-495, resulting in inhibition of activity (By similarity). Phosphorylation of Ser-114 by CDK5 reduces activity.
  • Ubiquitination at Lys1035
  • Modification sites at PhosphoSitePlus

Other Protein References for NOS3 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for NOS3 (eNOS)

Domains for NOS3 Gene

Gene Families for NOS3 Gene


Suggested Antigen Peptide Sequences for NOS3 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Contains 1 FAD-binding FR-type domain.
  • Belongs to the NOS family.
  • Contains 1 FAD-binding FR-type domain.
  • Contains 1 flavodoxin-like domain.
  • Belongs to the NOS family.
genes like me logo Genes that share domains with NOS3: view

Function for NOS3 Gene

Molecular function for NOS3 Gene

GENATLAS Biochemistry:
nitric oxide synthase 3,constitutively expressed,endothelial,also expressed in cardiac myocytes,regulating vascular tone,overexpressed in squamous hyperplasia,dysplasia and squamous cell carcinoma of the head and neck,putative susceptibility factor for late onset Alzheimer disease
UniProtKB/Swiss-Prot CatalyticActivity:
2 L-arginine + 3 NADPH + 4 O(2) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H(2)O
UniProtKB/Swiss-Prot EnzymeRegulation:
Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN.
UniProtKB/Swiss-Prot 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
UniProtKB/Swiss-Prot Function:
Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1

Enzyme Numbers (IUBMB) for NOS3 Gene

Gene Ontology (GO) - Molecular Function for NOS3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003785 actin monomer binding IPI 17502619
GO:0003958 NADPH-hemoprotein reductase activity IBA --
GO:0004517 nitric-oxide synthase activity IDA 1378832
GO:0005506 iron ion binding IEA --
GO:0005515 protein binding IPI 11149895
genes like me logo Genes that share ontologies with NOS3: view
genes like me logo Genes that share phenotypes with NOS3: view

Animal Models for NOS3 Gene

MGI Knock Outs for NOS3:

Animal Model Products

miRNA for NOS3 Gene

miRTarBase miRNAs that target NOS3

No data available for Transcription Factor Targets and HOMER Transcription for NOS3 Gene

Localization for NOS3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NOS3 Gene

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.

Subcellular locations from

Jensen Localization Image for NOS3 Gene COMPARTMENTS Subcellular localization image for NOS3 gene
Compartment Confidence
cytoskeleton 5
golgi apparatus 5
plasma membrane 5
cytosol 4
extracellular 3
nucleus 3
endoplasmic reticulum 2
mitochondrion 2
peroxisome 2

Gene Ontology (GO) - Cellular Components for NOS3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0005634 nucleus ISS --
GO:0005737 cytoplasm IDA 9794441
GO:0005829 cytosol TAS --
GO:0005856 cytoskeleton IEA --
genes like me logo Genes that share ontologies with NOS3: view

Pathways for NOS3 Gene

genes like me logo Genes that share pathways with NOS3: view

PCR Array Products

Gene Ontology (GO) - Biological Process for NOS3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IEA --
GO:0001542 ovulation from ovarian follicle IEA --
GO:0001701 in utero embryonic development IEA --
GO:0001974 blood vessel remodeling ISS --
GO:0002028 regulation of sodium ion transport IEA --
genes like me logo Genes that share ontologies with NOS3: view

Drugs for NOS3 Gene

(41) Drugbank Compounds for NOS3 Gene

Compound Status Synonyms Cas Number PubChem ID Type Actions PubMed IDs
  • (1S,3S)-3-Glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranoside
23214-92-8 31703 Enzyme substrate approved, investigational
  • 1-(2,4-Dichloro-beta-((2,4-dichlorobenzyl)oxy)phenethyl)imidazole
22916-47-8 4189 Target inhibitor approved, investigational
  • (6R)-2-Amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydropteridin-4(1H)-one
17528-72-2 1125 Target cofactor approved, investigational
  • (2S)-2-amino-5-(Carbamimidamido)pentanoic acid
74-79-3 Target approved, nutraceutical
  • (S)-2-Amino-5-ureidopentanoic acid
372-75-8 9750 Target approved, nutraceutical

(1) Tocris Compounds for NOS3 Gene

Compound Action Cas Number
L-NIO dihydrochloride NOS inhibitor [159190-44-0]

(1) ApexBio Compounds for NOS3 Gene

Compound Action Cas Number
1400W dihydrochloride INOS inhibitor,potent and highly selective [214358-33-5]

(20) HMDB Compounds for NOS3 Gene

Compound Synonyms Cas Number PubMed IDs
Asymmetric dimethylarginine
  • 2-Amino-5-(amino-dimethylamino-methylidene)amino-pentanoate
  • Ca
  • Canavanin
  • (2S)-2-amino-5-(carbamoylamino)pentanoate
  • (6R)-6-(L-erythro-1,2-Dihydroxypropyl)-7,8-dihydro-6H-pterin

(126) Novoseek inferred chemical compound relationships for NOS3 Gene

Compound -log(P) Hits PubMed IDs
nitric oxide 96.3 450
tetrahydrobiopterin 85.2 90
citrulline 81.4 49
adma 79.7 81
arginine 78.9 147

(22) PharmGKB related drug/compound annotations for NOS3 Gene

Drug/compound Annotation
Ace Inhibitors, Plain Clinical Annotation
Angiotensin II Antagonists Clinical Annotation
anthracyclines and related substances Clinical Annotation
Antihypertensives Clinical Annotation
Antihypertensives And Diuretics In Combination Clinical Annotation
aspirin Clinical Annotation
Beta Blocking Agents Clinical Annotation
clopidogrel Clinical Annotation
cyclophosphamide Clinical Annotation
daunorubicin Clinical Annotation
digoxin Clinical Annotation
diuretics Clinical Annotation
doxorubicin Clinical Annotation
epirubicin Clinical Annotation
fluorouracil Clinical Annotation
hmg coa reductase inhibitors Clinical Annotation
methotrexate Clinical Annotation
oxaliplatin Clinical Annotation
Platinum compounds Clinical Annotation
salvianolic acid b Clinical Annotation
sildenafil Clinical Annotation
spironolactone Clinical Annotation
genes like me logo Genes that share compounds with NOS3: view

Compound Products

Transcripts for NOS3 Gene

Unigene Clusters for NOS3 Gene

Nitric oxide synthase 3 (endothelial cell):
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for NOS3

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for NOS3 Gene

No ASD Table

Relevant External Links for NOS3 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for NOS3 Gene

mRNA expression in normal human tissues for NOS3 Gene

mRNA differential expression in normal tissues according to GTEx for NOS3 Gene

This gene is overexpressed in Spleen (8.7).

Protein differential expression in normal tissues for NOS3 Gene

This gene is overexpressed in Placenta (22.1), Spleen (17.2), and Uterus (6.5).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for NOS3 Gene

SOURCE GeneReport for Unigene cluster for NOS3 Gene Hs.647092

mRNA Expression by UniProt/SwissProt for NOS3 Gene

Tissue specificity: Platelets, placenta, liver and kidney.
genes like me logo Genes that share expressions with NOS3: view

Primer Products

In Situ Assay Products

No data available for Expression partners for NOS3 Gene

Orthologs for NOS3 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for NOS3 Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia NOS3 35
  • 90.67 (n)
  • 94.72 (a)
NOS3 36
  • 94 (a)
(Canis familiaris)
Mammalia NOS3 35
  • 90.41 (n)
  • 94.93 (a)
NOS3 36
  • 95 (a)
(Mus musculus)
Mammalia Nos3 35
  • 88.46 (n)
  • 94.73 (a)
Nos3 16
Nos3 36
  • 94 (a)
(Pan troglodytes)
Mammalia NOS3 35
  • 99.56 (n)
  • 99.83 (a)
NOS3 36
  • 100 (a)
(Rattus norvegicus)
Mammalia Nos3 35
  • 87.94 (n)
  • 94.65 (a)
(Monodelphis domestica)
Mammalia NOS3 36
  • 91 (a)
(Ornithorhynchus anatinus)
Mammalia NOS3 36
  • 82 (a)
(Gallus gallus)
Aves INOS 36
  • 49 (a)
(Anolis carolinensis)
Reptilia NOS3 36
  • 71 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia nos3 35
  • 66.96 (n)
  • 67.8 (a)
fruit fly
(Drosophila melanogaster)
Insecta Nos 37
  • 47 (a)
Nos 36
  • 41 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes NCP1 36
  • 25 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.5751 36
  • 49 (a)
Species with no ortholog for NOS3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for NOS3 Gene

Gene Tree for NOS3 (if available)
Gene Tree for NOS3 (if available)

Paralogs for NOS3 Gene

Paralogs for NOS3 Gene

(3) SIMAP similar genes for NOS3 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with NOS3: view

Variants for NOS3 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for NOS3 Gene

Variation in NOS3 seem to be associated with susceptibility to coronary spasm

Sequence variations from dbSNP and Humsavar for NOS3 Gene

SNP ID Clin Chr 07 pos Sequence Context AA Info Type MAF
rs189155703 -- 151,001,181(+) ATGGG(C/T)GAGGT intron-variant
rs189069620 -- 151,008,412(+) CCCTC(C/T)CAGGG intron-variant
rs188378451 -- 150,997,502(+) CACAG(A/C)CTCGG intron-variant, upstream-variant-2KB
rs188145570 -- 150,989,193(+) GCCCT(G/T)CAGAG upstream-variant-2KB
rs187993013 -- 150,990,512(+) GGACC(A/G)GGAGC upstream-variant-2KB

Structural Variations from Database of Genomic Variants (DGV) for NOS3 Gene

Variant ID Type Subtype PubMed ID
dgv7543n71 CNV Loss 21882294
dgv7544n71 CNV Loss 21882294
nsv889465 CNV Loss 21882294
nsv889469 CNV Gain 21882294
nsv889470 CNV Loss 21882294
esv2735394 CNV Deletion 23290073
nsv889471 CNV Loss 21882294
esv274999 CNV Loss 21479260
nsv889472 CNV Loss 21882294
nsv889473 CNV Loss 21882294
nsv889474 CNV Loss 21882294

Relevant External Links for NOS3 Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)
Locus Specific Mutation Databases (LSDB)

Disorders for NOS3 Gene

(4) OMIM Diseases for NOS3 Gene (163729)

(96) Novoseek inferred disease relationships for NOS3 Gene

Disease -log(P) Hits PubMed IDs
atherosclerosis 73.1 95
vascular diseases 70.5 36
cardiovascular diseases 70 92
coronary artery disease 62 98
hypertension pulmonary 58.5 44

Relevant External Links for NOS3

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with NOS3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for NOS3 Gene

Publications for NOS3 Gene

  1. A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese. (PMID: 9737779) Yoshimura M. … Nakao K. (Hum. Genet. 1998) 3 4 23
  2. Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation. (PMID: 10074942) Fischmann T.O. … Weber P.C. (Nat. Struct. Biol. 1999) 3 4 23
  3. Functional gene testing of the Glu298Asp polymorphism of the endothelial NO synthase. (PMID: 11132600) Schneider M.P. … Schmieder R.E. (J. Hypertens. 2000) 3 23 48
  4. A common variant of endothelial nitric oxide synthase (Glu298Asp) is an independent risk factor for carotid atherosclerosis. (PMID: 11239195) Lembo G. … Trimarco B. (Stroke 2001) 3 23 48
  5. Nitric oxide synthase gene polymorphisms in Alzheimer's disease and dementia with Lewy bodies. (PMID: 11297817) Singleton A.B. … Morris C.M. (Neurosci. Lett. 2001) 3 23 48

Products for NOS3 Gene

  • Addgene plasmids for NOS3

Sources for NOS3 Gene

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