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

    Gene ID: 4846, updated on 11-Jun-2017
    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; Vega:OTTHUMG00000158343
    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]
    Orthologs
    Location:
    7q36.1
    Exon count:
    30
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 7 NC_000007.14 (150991056..151014599)
    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 potassium voltage-gated channel subfamily H member 2 Neighboring gene uncharacterized LOC107986861 Neighboring gene uncharacterized LOC105375568 Neighboring gene autophagy related 9B Neighboring gene ATP binding cassette subfamily B member 8

    • 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 Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    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

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    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    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
     
    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 NAS
    Non-traceable Author Statement
    more info
    PubMed 
    heme binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    iron ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    nitric-oxide synthase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nitric-oxide synthase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    nitric-oxide synthase activity TAS
    Traceable Author Statement
    more info
     
    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
     
    arginine catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    blood vessel remodeling ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    cell redox homeostasis TAS
    Traceable Author Statement
    more info
     
    endothelial cell migration IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    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 blood pressure IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    negative regulation of calcium ion transport IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of cell 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
     
    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
     
    ovulation from ovarian follicle IEA
    Inferred from Electronic Annotation
    more info
     
    oxidation-reduction process IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of angiogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of blood vessel diameter IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    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
     
    regulation of blood pressure NAS
    Non-traceable Author Statement
    more info
    PubMed 
    regulation of blood vessel size 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 
    smooth muscle hyperplasia ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    vasodilation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    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 
    cytoskeleton IEA
    Inferred from Electronic Annotation
    more info
     
    cytosol TAS
    Traceable Author Statement
    more info
     
    endocytic vesicle membrane TAS
    Traceable Author Statement
    more info
     
    nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    plasma membrane TAS
    Traceable Author Statement
    more info
     
    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
    XP_006716065.1
    XP_016867721.1
    XP_016867722.1
    XP_016867723.1

    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
      4998..28541
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000603.4NP_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)
      AI082109, BC063294, DA859819
      Consensus CDS
      CCDS5912.1
      UniProtKB/Swiss-Prot
      P29474
      Related
      ENSP00000297494.3, OTTHUMP00000212826, ENST00000297494.7, OTTHUMT00000350750
      Conserved Domains (4) summary
      COG0369
      Location:5121159
      CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]
      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_001160109.1NP_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)
      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, OTTHUMP00000213185, ENST00000467517.1, OTTHUMT00000351551
      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, OTTHUMP00000213184, ENST00000484524.5, OTTHUMT00000351550
      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 108 details...Open this link in a new tab

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p7 Primary Assembly

      Range
      150991056..151014599
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017012232.1XP_016867721.1  nitric oxide synthase, endothelial isoform X1

      UniProtKB/Swiss-Prot
      P29474
      Conserved Domains (4) summary
      COG0369
      Location:5121159
      CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]
      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. XM_017012234.1XP_016867723.1  nitric oxide synthase, endothelial isoform X3

    3. XM_006716002.3XP_006716065.1  nitric oxide synthase, endothelial isoform X4

      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:522698
      Flavodoxin_1; Flavodoxin
    4. XM_017012233.1XP_016867722.1  nitric oxide synthase, endothelial isoform X2

      UniProtKB/TrEMBL
      E7ESA7
      Related
      ENSP00000417143.1, OTTHUMP00000213183, ENST00000461406.5, OTTHUMT00000351548

    Alternate CHM1_1.1

    Genomic

    1. NC_018918.2 Alternate CHM1_1.1

      Range
      150696541..150720093
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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