Format

Send to:

Choose Destination

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

Gene ID: 4846, updated on 24-Nov-2020

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
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

Genomic context

See NOS3 in Genome Data Viewer
Location:
7q36.1
Exon count:
28
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 7 NC_000007.14 (150991017..151014588)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (150688144..150711687)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105375567 Neighboring gene amine oxidase copper containing 1 Neighboring gene VISTA enhancer hs2192 Neighboring gene potassium voltage-gated channel subfamily H member 2 Neighboring gene NOS3 5' regulatory region Neighboring gene autophagy related 9B Neighboring gene ATP binding cassette subfamily B member 8 Neighboring gene acid sensing ion channel subunit 3

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
FMN binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
flavin adenine dinucleotide binding NAS
Non-traceable Author Statement
more info
PubMed 
heme binding IDA
Inferred from Direct Assay
more info
PubMed 
nitric-oxide synthase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nitric-oxide synthase activity IDA
Inferred from Direct Assay
more info
PubMed 
nitric-oxide synthase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
oxidoreductase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
scaffold protein binding IEA
Inferred from Electronic Annotation
more info
 
tetrahydrobiopterin binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
angiogenesis IEA
Inferred from Electronic Annotation
more info
 
aortic valve morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
arginine catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
arginine catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
blood vessel diameter maintenance ISS
Inferred from Sequence or Structural Similarity
more info
 
blood vessel remodeling ISS
Inferred from Sequence or Structural Similarity
more info
 
cell redox homeostasis TAS
Traceable Author Statement
more info
 
endocardial cushion morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
endothelial cell migration IMP
Inferred from Mutant Phenotype
more info
PubMed 
homeostasis of number of cells within a tissue ISS
Inferred from Sequence or Structural Similarity
more info
 
in utero embryonic development IEA
Inferred from Electronic Annotation
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 biomineral tissue development ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of blood pressure IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of calcium ion transport IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cell population proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors 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
 
negative regulation of smooth muscle cell proliferation IEA
Inferred from Electronic Annotation
more info
 
nitric oxide biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
PubMed 
ovulation from ovarian follicle IEA
Inferred from Electronic Annotation
more info
 
oxidation-reduction process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of Notch signaling pathway IC
Inferred by Curator
more info
PubMed 
positive regulation of angiogenesis IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of angiogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of blood vessel endothelial cell migration IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of gene expression ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
positive regulation of guanylate cyclase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
 
pulmonary valve morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of blood pressure NAS
Non-traceable Author Statement
more info
PubMed 
regulation of nervous system process ISS
Inferred from Sequence or Structural Similarity
more info
 
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
 
removal of superoxide radicals IDA
Inferred from Direct Assay
more info
PubMed 
response to fluid shear stress IEP
Inferred from Expression Pattern
more info
PubMed 
response to heat NAS
Non-traceable Author Statement
more info
PubMed 
response to hormone IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
response to lipopolysaccharide IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
smooth muscle hyperplasia ISS
Inferred from Sequence or Structural Similarity
more info
 
vasodilation NAS
Non-traceable Author Statement
more info
PubMed 
ventricular septum morphogenesis IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
Golgi apparatus IDA
Inferred from Direct Assay
more info
PubMed 
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 
cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
 
cytoskeleton IEA
Inferred from Electronic Annotation
more info
 
cytosol IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
endocytic vesicle membrane TAS
Traceable Author Statement
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus ISS
Inferred from Sequence or Structural Similarity
more info
 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
vesicle membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 

General protein information

Preferred Names
nitric oxide synthase, endothelial
Names
EC-NOS
NOS type III
NOSIII
cNOS
constitutive NOS
endothelial NOS
nitric oxide synthase 3 (endothelial cell)
nitric oxide synthase 3 transcript variant eNOS-delta20
nitric oxide synthase 3 transcript variant eNOS-delta20-21
nitric oxide synthase 3 transcript variant eNOS-delta21
NP_000594.2
NP_001153581.1
NP_001153582.1
NP_001153583.1

NCBI Reference Sequences (RefSeq)

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

  1. NG_011992.1 RefSeqGene

    Range
    4959..28530
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000603.5NP_000594.2  nitric oxide synthase, endothelial 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
    P29474
    Related
    ENSP00000297494.3, ENST00000297494.8
    Conserved Domains (3) summary
    cd00795
    Location:68480
    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:522698
    Flavodoxin_1; Flavodoxin
    cl06868
    Location:7621164
    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 ...
  2. NM_001160109.2NP_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)
    AC010973, BC063294, DQ256129
    UniProtKB/Swiss-Prot
    P29474
    UniProtKB/TrEMBL
    A0S0A6
    Conserved Domains (2) summary
    cd00795
    Location:68480
    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:522584
    Flavodoxin_1; Flavodoxin
  3. NM_001160110.1NP_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
    UniProtKB/TrEMBL
    A0A0A0MTA6
    Related
    ENSP00000420551.1, ENST00000467517.1
    Conserved Domains (2) summary
    cd00795
    Location:68480
    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:522594
    Flavodoxin_1; Flavodoxin
  4. NM_001160111.1NP_001153583.1  nitric oxide synthase, endothelial 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/Swiss-Prot
    P29474
    Related
    ENSP00000420215.1, ENST00000484524.5
    Conserved Domains (2) summary
    cd00795
    Location:68480
    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:522586
    Flavodoxin_1; Flavodoxin

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p13 Primary Assembly

    Range
    150991017..151014588
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Support Center