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

    Gene ID: 4846, updated on 27-Nov-2024

    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
    NEW
    Try the new Gene table
    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
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (150991017..151014588)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (152163824..152187711)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (150688105..150711676)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105375567 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150549187-150549758 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150553923-150554766 Neighboring gene amine oxidase copper containing 1 Neighboring gene Sharpr-MPRA regulatory region 11983 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150607062-150607562 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:150642260-150643002 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150643003-150643744 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150645973-150646713 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150651428-150652026 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150654831-150655332 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150658991-150659600 Neighboring gene VISTA enhancer hs2192 Neighboring gene potassium voltage-gated channel subfamily H member 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150669129-150669642 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18785 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18786 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18787 Neighboring gene uncharacterized LOC124901776 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150672781-150673707 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18788 Neighboring gene NOS3 5' regulatory region Neighboring gene ReSE screen-validated silencer GRCh37_chr7:150697314-150697476 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr7:150698330-150699529 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150703744-150704324 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150704325-150704905 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26844 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:150710378-150711069 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18790 Neighboring gene uncharacterized LOC124901777 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:150722492-150723096 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr7:150723702-150724305 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr7:150724306-150724910 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:150725516-150726120 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:150726121-150726724 Neighboring gene autophagy related 9B Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:150736215-150736999 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150737000-150737783 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?

    Phenotypes

    Associated conditions

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

    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

    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 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

    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
    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 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: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 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: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 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: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 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: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: GCF_000001405.40-RS_2024_08

    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)