U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Links from GEO Profiles

    • Showing Current items.

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

    Gene ID: 4842, updated on 27-Dec-2024

    Summary

    Official Symbol
    NOS1provided by HGNC
    Official Full Name
    nitric oxide synthase 1provided by HGNC
    Primary source
    HGNC:HGNC:7872
    See related
    Ensembl:ENSG00000089250 MIM:163731; AllianceGenome:HGNC:7872
    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]
    Expression
    Biased expression in brain (RPKM 1.1), kidney (RPKM 1.0) and 11 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See NOS1 in Genome Data Viewer
    Location:
    12q24.22
    Exon count:
    33
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (117208142..117361626, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (117189186..117342679, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (117645947..117799431, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370010 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7102 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117556298-117556892 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:117580597-117581796 Neighboring gene TESC antisense RNA 1 (head to head) Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4913 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4914 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7104 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4915 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4916 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4917 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117645205-117645705 Neighboring gene F-box protein 21 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:117657550-117658106 Neighboring gene MPRA-validated peak1985 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr12:117670646-117670812 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117674186-117674690 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117674691-117675195 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:117718941-117719440 Neighboring gene elongin C pseudogene 32 Neighboring gene NOS1 1f and 1g alternate promoter region Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:117826376-117826876 Neighboring gene NOS1 1c alternate promoter Neighboring gene uncharacterized LOC105370012 Neighboring gene Sharpr-MPRA regulatory region 11046 Neighboring gene kinase suppressor of ras 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:118021615-118022115 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:118066292-118066792 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:118066793-118067293 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:118078225-118078724 Neighboring gene uncharacterized LOC105370011 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:118274024-118274569

    Genomic regions, transcripts, and products

    Expression

    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    EBI GWAS Catalog

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

    HIV-1 interactions

    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

    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables NADP binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables arginine binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables cadmium ion binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables calcium channel regulator activity TAS
    Traceable Author Statement
    more info
    PubMed 
    enables calcium-dependent protein binding ISS
    Inferred from Sequence or Structural Similarity
    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables heme binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    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 ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    enables nitric-oxide synthase activity TAS
    Traceable Author Statement
    more info
     
    enables peptidyl-cysteine S-nitrosylase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables scaffold protein binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables sodium channel regulator activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables tetrahydrobiopterin binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables transmembrane transporter binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables transmembrane transporter binding TAS
    Traceable Author Statement
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in arginine catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in arginine catabolic process TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in cell redox homeostasis TAS
    Traceable Author Statement
    more info
     
    involved_in cellular response to growth factor stimulus ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in multicellular organismal response to stress IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in myoblast fusion TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of blood pressure IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in negative regulation of calcium ion transport ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of calcium ion transport into cytosol TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of potassium ion transport ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of serotonin uptake ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in nitric oxide biosynthetic process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in nitric oxide biosynthetic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    involved_in nitric oxide mediated signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in positive regulation of DNA-templated transcription ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of membrane repolarization during ventricular cardiac muscle cell action potential TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of sodium ion transmembrane transport ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of the force of heart contraction ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of transcription by RNA polymerase II ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of calcium ion transmembrane transport via high voltage-gated calcium channel TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in regulation of cardiac muscle contraction TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in regulation of cardiac muscle contraction by calcium ion signaling TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in regulation of sodium ion transport ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in response to heat IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in response to hormone IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in response to hypoxia IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in response to lipopolysaccharide IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in striated muscle contraction ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in vasodilation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in vasodilation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in xenobiotic catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Component Evidence Code Pubs
    located_in cell periphery ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    located_in cytoplasm TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in cytoskeleton ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in dendritic spine IEA
    Inferred from Electronic Annotation
    more info
     
    located_in membrane raft ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in mitochondrion ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in perinuclear region of cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    located_in photoreceptor inner segment ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    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
     
    is_active_in postsynaptic density IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    part_of protein-containing complex ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in sarcolemma IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in sarcoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in synapse ISS
    Inferred from Sequence or Structural Similarity
    more info
     

    General protein information

    Preferred Names
    nitric oxide synthase 1
    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

    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_011991.2 RefSeqGene

      Range
      5152..158636
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000620.5NP_000611.1  nitric oxide synthase 1 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/Swiss-Prot
      E9PH30, O75713, P29475
      UniProtKB/TrEMBL
      B3VK56, B4DG68
      Related
      ENSP00000320758.6, ENST00000317775.11
      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_001204213.2NP_001191142.1  nitric oxide synthase 1 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/Swiss-Prot
      P29475
      UniProtKB/TrEMBL
      A0PJJ7, B4DG68
      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_001204214.2NP_001191143.1  nitric oxide synthase 1 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/Swiss-Prot
      P29475
      UniProtKB/TrEMBL
      A0PJJ7, B4DG68
      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_001204218.2NP_001191147.1  nitric oxide synthase 1 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
      B4DG68
      Related
      ENSP00000477999.1, ENST00000618760.4
      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: 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_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      117208142..117361626 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      117189186..117342679 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)