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

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: mouse all
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Genomic context

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_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Caveolin and NOS in the Development of Muscular Dystrophy.
Title: Caveolin and NOS in the Development of Muscular Dystrophy.
The neuronal nitric oxide synthase expression increases during satellite cell-derived primary myoblasts differentiation.
Title: The neuronal nitric oxide synthase expression increases during satellite cell-derived primary myoblasts differentiation.
nNOS-induced tyrosine nitration of TRKB impairs BDNF signaling and restrains neuronal plasticity.
Title: nNOS-induced tyrosine nitration of TRKB impairs BDNF signaling and restrains neuronal plasticity.
The expanding roles of neuronal nitric oxide synthase (NOS1).
Title: The expanding roles of neuronal nitric oxide synthase (NOS1).
The Role of Macula Densa Nitric Oxide Synthase 1 Beta Splice Variant in Modulating Tubuloglomerular Feedback.
Title: The Role of Macula Densa Nitric Oxide Synthase 1 Beta Splice Variant in Modulating Tubuloglomerular Feedback.
NOS1 mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice.
Title: NOS1 mutations cause hypogonadotropic hypogonadism with sensory and cognitive deficits that can be reversed in infantile mice.
Functional Roles of Neuronal Nitric Oxide Synthase in Neurodegenerative Diseases and Mood Disorders.
Title: Functional Roles of Neuronal Nitric Oxide Synthase in Neurodegenerative Diseases and Mood Disorders.
Uncovering associations between mental illness diagnosis, nitric oxide synthase gene variation, and peripheral nitric oxide concentration.
Title: Uncovering associations between mental illness diagnosis, nitric oxide synthase gene variation, and peripheral nitric oxide concentration.
Differences of Transport Activity of Arginine and Regulation on Neuronal Nitric Oxide Synthase and Oxidative Stress in Amyotrophic Lateral Sclerosis Model Cell Lines.
Title: Differences of Transport Activity of Arginine and Regulation on Neuronal Nitric Oxide Synthase and Oxidative Stress in Amyotrophic Lateral Sclerosis Model Cell Lines.
The KiNG of reproduction: Kisspeptin/ nNOS interactions shaping hypothalamic GnRH release.
Title: The KiNG of reproduction: Kisspeptin/ nNOS interactions shaping hypothalamic GnRH release.

Submit: New GeneRIF Correction See all GeneRIFs (258)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

SHGC-145895 (e-PCR)
- UniSTS:174859

GDB:434012 (e-PCR)
- UniSTS:157204

SHGC-147540 (e-PCR)
- UniSTS:172827

SHGC-149522 (e-PCR)
- UniSTS:182577

D8S2279 (e-PCR)
- UniSTS:473907

GDB:437697 (e-PCR)
- UniSTS:157252

D12S1718 (e-PCR), detects polymorphism
- UniSTS:52553

L18426 (e-PCR)
- UniSTS:34648

SHGC-154191 (e-PCR)
- UniSTS:178008

RH103827 (e-PCR)
- UniSTS:98152

RK903_904 (e-PCR)
- UniSTS:11631

D1S1423 (e-PCR)
- UniSTS:149619

RH36905 (e-PCR)
- UniSTS:87932

D12S1144E (e-PCR)
- UniSTS:151428

SGC31491 (e-PCR)
- UniSTS:38552

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

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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

EC 1.14.13.39

NP_001191142.1

EC 1.14.13.39

NP_001191143.1

EC 1.14.13.39

NP_001191147.1

EC 1.14.13.39

NCBI Reference Sequences (RefSeq)

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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

NG_011991.2 RefSeqGene

Range

5152..158636

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000620.5 → NP_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:1001 → 1404

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:759 → 1399

CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]

cd00795
Location:305 → 716

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:15 → 98

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:762 → 935

Flavodoxin_1; Flavodoxin
NM_001204213.2 → NP_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:665 → 1068

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:423 → 1063

CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]

cd00795
Location:1 → 380

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:426 → 599

Flavodoxin_1; Flavodoxin
NM_001204214.2 → NP_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:665 → 1068

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:423 → 1063

CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]

cd00795
Location:1 → 380

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:426 → 599

Flavodoxin_1; Flavodoxin
NM_001204218.2 → NP_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:1035 → 1438

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:759 → 1433

CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]

cd00795
Location:305 → 716

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:15 → 98

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:762 → 969

Flavodoxin_1; Flavodoxin