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    NOS1 nitric oxide synthase 1 [ Homo sapiens (human) ]

    Gene ID: 4842, updated on 7-Feb-2016
    Official Symbol
    NOS1provided by HGNC
    Official Full Name
    nitric oxide synthase 1provided by HGNC
    Primary source
    HGNC:HGNC:7872
    See related
    Ensembl:ENSG00000089250; HPRD:01226; MIM:163731; Vega:OTTHUMG00000137376
    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
    NOS; bNOS; nNOS; IHPS1; N-NOS; NC-NOS
    Summary
    The protein encoded by this gene belongs to the family of nitric oxide synthases, which synthesize nitric oxide from L-arginine. Nitric oxide is a reactive free radical, which acts as a biologic mediator in several processes, including neurotransmission, and antimicrobial and antitumoral activities. In the brain and peripheral nervous system, nitric oxide displays many properties of a neurotransmitter, and has been implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis, and penile erection. This protein is ubiquitously expressed, with high level of expression in skeletal muscle. Multiple transcript variants that differ in the 5' UTR have been described for this gene but the full-length nature of these transcripts is not known. Additionally, alternatively spliced transcript variants encoding different isoforms (some testis-specific) have been found for this gene.[provided by RefSeq, Feb 2011]
    Orthologs
    See NOS1 in Epigenomics, MapViewer
    Location:
    12q24.22
    Exon count:
    35
    Annotation release Status Assembly Chr Location
    107 current GRCh38.p2 (GCF_000001405.28) 12 NC_000012.12 (117208142..117361802, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (117645921..117799607, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370010 Neighboring gene TESC antisense RNA 1 (head to head) Neighboring gene F-box protein 21 Neighboring gene uncharacterized LOC105370012 Neighboring gene kinase suppressor of ras 2 Neighboring gene uncharacterized LOC105370011

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    NHGRI GWAS Catalog

    Description
    Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations.
    NHGRI GWA Catalog

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Preincubation of human astrocytoma cells with HIV-1 gp120 produces a significant increase of nitrite and PGE2 in cell supernatants; the effect of gp120 on both nitrite and PGE2 production is inhibited by antagonists of NO synthase or cyclooxygenase 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
    Tat tat The gene expression of NOS1 is significantly upregulated in both clade B and clade C Tat treated SK-N-MC neuroblastoma cells PubMed
    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 Tat treatment causes activation of neuronal nitric oxide synthase (nNOS) through association with NMDA receptors 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 ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    NADP binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    arginine binding TAS
    Traceable Author Statement
    more info
    PubMed 
    cadmium ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    calmodulin binding IEA
    Inferred from Electronic Annotation
    more info
     
    enzyme binding IEA
    Inferred from Electronic Annotation
    more info
     
    flavin adenine dinucleotide binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    heme binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    ion channel binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    ion channel binding TAS
    Traceable Author Statement
    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein homodimerization activity IEA
    Inferred from Electronic Annotation
    more info
     
    scaffold protein binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    sodium channel regulator activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    tetrahydrobiopterin binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    Process Evidence Code Pubs
    aging IEA
    Inferred from Electronic Annotation
    more info
     
    arginine catabolic process IC
    Inferred by Curator
    more info
    PubMed 
    behavioral response to cocaine IEA
    Inferred from Electronic Annotation
    more info
     
    blood coagulation TAS
    Traceable Author Statement
    more info
     
    cardiac conduction TAS
    Traceable Author Statement
    more info
     
    cell redox homeostasis TAS
    Traceable Author Statement
    more info
     
    cellular response to growth factor stimulus ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    cellular response to mechanical stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    exogenous drug catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    female pregnancy IEA
    Inferred from Electronic Annotation
    more info
     
    multicellular organismal response to stress IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    myoblast fusion TAS
    Traceable Author Statement
    more info
    PubMed 
    negative regulation of adrenergic receptor signaling pathway involved in heart process TAS
    Traceable Author Statement
    more info
    PubMed 
    negative regulation of apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of blood pressure IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    negative regulation of calcium ion transport ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of calcium ion transport into cytosol TAS
    Traceable Author Statement
    more info
    PubMed 
    negative regulation of cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of cytosolic calcium ion concentration IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of heart contraction IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of hydrolase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of insulin secretion IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of potassium ion transport ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of serotonin uptake ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of vasoconstriction IEA
    Inferred from Electronic Annotation
    more info
     
    neurotransmitter biosynthetic process TAS
    Traceable Author Statement
    more info
    PubMed 
    nitric oxide biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    nitric oxide mediated signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    oxidation-reduction process IEA
    Inferred from Electronic Annotation
    more info
     
    peptidyl-cysteine S-nitrosylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of adrenergic receptor signaling pathway involved in heart process IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of guanylate cyclase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    positive regulation of histone acetylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of long-term synaptic potentiation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of neuron death IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of sodium ion transmembrane transport ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of the force of heart contraction ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of transcription from RNA polymerase II promoter ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of transcription, DNA-templated ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of vasodilation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of vasodilation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of cardiac conduction TAS
    Traceable Author Statement
    more info
     
    regulation of cardiac muscle contraction TAS
    Traceable Author Statement
    more info
    PubMed 
    regulation of generation of L-type calcium current TAS
    Traceable Author Statement
    more info
    PubMed 
    regulation of neurogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of ryanodine-sensitive calcium-release channel activity TAS
    Traceable Author Statement
    more info
    PubMed 
    regulation of sensory perception of pain IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of sodium ion transport ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    response to activity IEA
    Inferred from Electronic Annotation
    more info
     
    response to estrogen IEA
    Inferred from Electronic Annotation
    more info
     
    response to ethanol IEA
    Inferred from Electronic Annotation
    more info
     
    response to heat IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to hypoxia IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    response to lead ion IEA
    Inferred from Electronic Annotation
    more info
     
    response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
     
    response to nicotine IEA
    Inferred from Electronic Annotation
    more info
     
    response to nitric oxide IEA
    Inferred from Electronic Annotation
    more info
     
    response to peptide hormone IEA
    Inferred from Electronic Annotation
    more info
     
    response to vitamin E IEA
    Inferred from Electronic Annotation
    more info
     
    striated muscle contraction ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Component Evidence Code Pubs
    T-tubule IEA
    Inferred from Electronic Annotation
    more info
     
    Z disc IEA
    Inferred from Electronic Annotation
    more info
     
    azurophil granule IEA
    Inferred from Electronic Annotation
    more info
     
    caveola IEA
    Inferred from Electronic Annotation
    more info
     
    cytoplasm TAS
    Traceable Author Statement
    more info
    PubMed 
    cytoskeleton ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
     
    dendritic spine IEA
    Inferred from Electronic Annotation
    more info
     
    membrane raft ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    mitochondrial outer membrane IEA
    Inferred from Electronic Annotation
    more info
     
    mitochondrion ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    nuclear membrane IEA
    Inferred from Electronic Annotation
    more info
     
    perinuclear region of cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    photoreceptor inner segment ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    postsynaptic density IEA
    Inferred from Electronic Annotation
    more info
     
    protein complex ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    colocalizes_with ryanodine receptor complex TAS
    Traceable Author Statement
    more info
    PubMed 
    sarcolemma IDA
    Inferred from Direct Assay
    more info
    PubMed 
    sarcoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    PubMed 
    synapse ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    vesicle membrane IEA
    Inferred from Electronic Annotation
    more info
     
    Preferred Names
    nitric oxide synthase, brain
    Names
    NOS type I
    constitutive NOS
    neuronal NOS
    nitric oxide synthase 1 (neuronal)
    peptidyl-cysteine S-nitrosylase NOS1
    NP_000611.1
    NP_001191142.1
    NP_001191143.1
    NP_001191147.1

    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_011991.2 RefSeqGene

      Range
      4976..158636
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000620.4NP_000611.1  nitric oxide synthase, brain isoform 1

      See identical proteins and their annotated locations for NP_000611.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript, and encodes isoform 1 (also known as nNOS).
      Source sequence(s)
      AC026364, AK294435, AK307481, BC033208, BE207961, U17327
      Consensus CDS
      CCDS41842.1
      UniProtKB/TrEMBL
      A0PJJ7
      UniProtKB/TrEMBL
      B3VK56
      UniProtKB/TrEMBL
      B4DG68
      UniProtKB/Swiss-Prot
      P29475
      Related
      ENSP00000320758, OTTHUMP00000174427, ENST00000317775, OTTHUMT00000268052
      Conserved Domains (5) summary
      cd06202
      Location:10011404
      Nitric_oxide_synthase; The ferredoxin-reductase (FNR) like C-terminal domain of the nitric oxide synthase (NOS) fuses with a heme-containing N-terminal oxidase domain. The reductase portion is similar in structure to NADPH dependent cytochrome-450 reductase (CYPOR), having an ...
      COG0369
      Location:7591399
      CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]
      cd00795
      Location:305716
      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 ...
      cd00992
      Location:1598
      PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
      pfam00258
      Location:762935
      Flavodoxin_1; Flavodoxin
    2. NM_001204213.1NP_001191142.1  nitric oxide synthase, brain isoform 3

      See identical proteins and their annotated locations for NP_001191142.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3, also known as TnNOS) contains 2 unique alternate exons (Tex 1 and Tex 2) at the 5' end compared to variant 1, resulting in translation initiation from a downstream AUG, and an isoform (isoform 3, also known as nNOSgamma) with a shorter N-terminus compared to isoform 1. This variant is specifically expressed in the testis, and the encoded isoform has catalytic activity (PMID:9111048). Variants 3 and 4 encode the same isoform.
      Source sequence(s)
      AC026364, AC068799, AK294435, AK307481, BC033208, BE207961, U17327
      UniProtKB/TrEMBL
      A0PJJ7
      UniProtKB/TrEMBL
      B4DG68
      UniProtKB/Swiss-Prot
      P29475
      Conserved Domains (4) summary
      cd06202
      Location:6651068
      Nitric_oxide_synthase; The ferredoxin-reductase (FNR) like C-terminal domain of the nitric oxide synthase (NOS) fuses with a heme-containing N-terminal oxidase domain. The reductase portion is similar in structure to NADPH dependent cytochrome-450 reductase (CYPOR), having an ...
      COG0369
      Location:4231063
      CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]
      cd00795
      Location:1380
      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:426599
      Flavodoxin_1; Flavodoxin
    3. NM_001204214.1NP_001191143.1  nitric oxide synthase, brain isoform 3

      See identical proteins and their annotated locations for NP_001191143.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4, also known as TnNOSb) contains 2 unique alternate exons (Tex 1b and Tex 2) at the 5' end compared to variant 1, resulting in translation initiation from a downstream AUG, and an isoform (3, also known as nNOSgamma) with a shorter N-terminus compared to isoform 1. This variant is specifically expressed in the testis, and the encoded isoform has catalytic activity (PMID:9111048). Variants 3 and 4 encode the same isoform.
      Source sequence(s)
      AC026364, AC068799, AK294435, AK307481, BC033208, BE207961, U17327
      UniProtKB/TrEMBL
      A0PJJ7
      UniProtKB/TrEMBL
      B4DG68
      UniProtKB/Swiss-Prot
      P29475
      Conserved Domains (4) summary
      cd06202
      Location:6651068
      Nitric_oxide_synthase; The ferredoxin-reductase (FNR) like C-terminal domain of the nitric oxide synthase (NOS) fuses with a heme-containing N-terminal oxidase domain. The reductase portion is similar in structure to NADPH dependent cytochrome-450 reductase (CYPOR), having an ...
      COG0369
      Location:4231063
      CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]
      cd00795
      Location:1380
      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:426599
      Flavodoxin_1; Flavodoxin
    4. NM_001204218.1NP_001191147.1  nitric oxide synthase, brain isoform 2

      See identical proteins and their annotated locations for NP_001191147.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an additional in-frame coding exon compared to variant 1, resulting in a longer isoform (2, also known as nNOSmu) containing a 34 aa protein segment not found in isoform 1. A similar isoform has also been reported in rat and mouse, and the mouse isoform has been shown to have catalytic activity (PMID:9791007).
      Source sequence(s)
      AC026364, AJ004918, AK294435, AK307481, BC033208, BE207961, U17327
      Consensus CDS
      CCDS55890.1
      UniProtKB/TrEMBL
      A0PJJ7
      UniProtKB/TrEMBL
      B4DG68
      UniProtKB/Swiss-Prot
      P29475
      Related
      ENSP00000477999, ENST00000618760
      Conserved Domains (5) summary
      cd06202
      Location:10351438
      Nitric_oxide_synthase; The ferredoxin-reductase (FNR) like C-terminal domain of the nitric oxide synthase (NOS) fuses with a heme-containing N-terminal oxidase domain. The reductase portion is similar in structure to NADPH dependent cytochrome-450 reductase (CYPOR), having an ...
      COG0369
      Location:7591433
      CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]
      cd00795
      Location:305716
      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 ...
      cd00992
      Location:1598
      PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
      pfam00258
      Location:762969
      Flavodoxin_1; Flavodoxin

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107

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

    Reference GRCh38.p2 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p2 Primary Assembly

      Range
      117208142..117361802 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011538398.1XP_011536700.1  

      See identical proteins and their annotated locations for XP_011536700.1

      UniProtKB/Swiss-Prot
      P29475
      Conserved Domains (5) summary
      cd06202
      Location:10351438
      Nitric_oxide_synthase; The ferredoxin-reductase (FNR) like C-terminal domain of the nitric oxide synthase (NOS) fuses with a heme-containing N-terminal oxidase domain. The reductase portion is similar in structure to NADPH dependent cytochrome-450 reductase (CYPOR), having an ...
      COG0369
      Location:7591433
      CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]
      cd00795
      Location:305716
      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 ...
      cd00992
      Location:1598
      PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...
      pfam00258
      Location:762969
      Flavodoxin_1; Flavodoxin

    Alternate CHM1_1.1

    Genomic

    1. NC_018923.2 Alternate CHM1_1.1

      Range
      117611241..117767258 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)