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

Gene ID: 4846, updated on 27-Nov-2022

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
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Try the new Transcript table

Genomic context

See NOS3 in Genome Data Viewer
Location:
7q36.1
Exon count:
28
Annotation release Status Assembly Chr Location
110 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (150991017..151014588)
110 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_000007.14Genomic Context describing neighboring genes Neighboring gene potassium voltage-gated channel subfamily H member 2 Neighboring gene VISTA enhancer hs2192 Neighboring gene uncharacterized LOC124901776 Neighboring gene NOS3 5' regulatory region Neighboring gene autophagy related 9B Neighboring gene uncharacterized LOC124901777 Neighboring gene ATP binding cassette subfamily B member 8

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
enables FMN binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
PubMed 
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
PubMed 
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 oxidoreductase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
PubMed 
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
PubMed 
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 hydrolase activity IEA
Inferred from Electronic Annotation
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
PubMed 
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
PubMed 
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
PubMed 
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
PubMed 
involved_in response to lipopolysaccharide IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
PubMed 
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
PubMed 
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
PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
located_in plasma membrane TAS
Traceable Author Statement
more info
 
is_active_in 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)
NP_000594.2
NP_001153581.1
NP_001153582.1
NP_001153583.1

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

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, Q9UDC6
    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 Annotation Release 110 details...Open this link in a new tab

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

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

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    152163824..152187711
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)