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

Gene ID: 4842, updated on 4-Oct-2020

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
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

Genomic context

See NOS1 in Genome Data Viewer
Location:
12q24.22
Exon count:
33
Annotation release Status Assembly Chr Location
109.20200815 current GRCh38.p13 (GCF_000001405.39) 12 NC_000012.12 (117208142..117361626, 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 elongin C pseudogene 32 Neighboring gene NOS1 1f and 1g alternate promoter region Neighboring gene NOS1 1c alternate promoter Neighboring gene uncharacterized LOC105370012 Neighboring gene kinase suppressor of ras 2

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
Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations.
GeneReviews: Not available

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

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
FMN binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
FMN binding ISS
Inferred from Sequence or Structural Similarity
more info
 
NADP binding ISS
Inferred from Sequence or Structural Similarity
more info
 
NADPH-hemoprotein reductase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
arginine binding TAS
Traceable Author Statement
more info
PubMed 
cadmium ion binding ISS
Inferred from Sequence or Structural Similarity
more info
 
calcium-dependent protein binding ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
calmodulin binding IEA
Inferred from Electronic Annotation
more info
 
flavin adenine dinucleotide binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 
nitric-oxide synthase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 
oxidoreductase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
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
arginine catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
arginine catabolic process IC
Inferred by Curator
more info
PubMed 
cell redox homeostasis TAS
Traceable Author Statement
more info
 
cellular response to growth factor stimulus ISS
Inferred from Sequence or Structural Similarity
more info
 
exogenous drug catabolic process ISS
Inferred from Sequence or Structural Similarity
more info
 
multicellular organismal response to stress IMP
Inferred from Mutant Phenotype
more info
PubMed 
muscle contraction IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
myoblast fusion TAS
Traceable Author Statement
more info
PubMed 
negative regulation of blood pressure IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 hydrolase activity ISS
Inferred from Sequence or Structural Similarity
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
 
neurotransmitter biosynthetic process TAS
Traceable Author Statement
more info
PubMed 
nitric oxide biosynthetic process IBA
Inferred from Biological aspect of Ancestor
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
PubMed 
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 adenylate cyclase-activating 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
PubMed 
positive regulation of histone acetylation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of peptidyl-serine phosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
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 by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of transcription, DNA-templated ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of calcium ion transmembrane transport via high voltage-gated calcium channel TAS
Traceable Author Statement
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 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 sodium ion transport ISS
Inferred from Sequence or Structural Similarity
more info
 
response to heat IDA
Inferred from Direct Assay
more info
PubMed 
response to hormone IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
response to hypoxia IEP
Inferred from Expression Pattern
more info
PubMed 
response to lipopolysaccharide IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
retrograde trans-synaptic signaling by nitric oxide IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
striated muscle contraction ISS
Inferred from Sequence or Structural Similarity
more info
 
vasodilation IDA
Inferred from Direct Assay
more info
PubMed 
vasodilation IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
T-tubule IEA
Inferred from Electronic Annotation
more info
 
Z disc IEA
Inferred from Electronic Annotation
more info
 
calyx of Held IEA
Inferred from Electronic Annotation
more info
 
caveola IEA
Inferred from Electronic Annotation
more info
 
cell periphery ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
cytoplasm TAS
Traceable Author Statement
more info
PubMed 
cytoskeleton ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
cytosol IBA
Inferred from Biological aspect of Ancestor
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
 
mitochondrion ISS
Inferred from Sequence or Structural Similarity
more info
 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
 
postsynaptic density IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein-containing 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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 

General protein information

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

NCBI Reference Sequences (RefSeq)

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, 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/Swiss-Prot
    P29475
    UniProtKB/TrEMBL
    A0PJJ7, 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, 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/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, 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/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, 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/Swiss-Prot
    P29475
    UniProtKB/TrEMBL
    A0PJJ7, 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: Homo sapiens Updated Annotation Release 109.20200815

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p13 Primary Assembly

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