Nos3 nitric oxide synthase 3, endothelial cell [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Nos3provided by MGI
Official Full Name: nitric oxide synthase 3, endothelial cellprovided by MGI
Primary source: MGI:MGI:97362
See related: Ensembl:ENSMUSG00000028978 AllianceGenome:MGI:97362
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: eNOS; Nos-3; ecNOS; 2310065A03Rik
Summary: Enables nitric-oxide synthase activity and scaffold protein binding activity. Involved in several processes, including heart development; negative regulation of muscle hyperplasia; and smooth muscle hyperplasia. Acts upstream of or within several processes, including lipopolysaccharide-mediated signaling pathway; nitric oxide biosynthetic process; and regulation of metal ion transport. Located in cytoplasm and nucleus. Is expressed in several structures, including alimentary system; cardiovascular system; genitourinary system; hemolymphoid system gland; and nervous system. Used to study aortic valve disease; essential hypertension; and persistent fetal circulation syndrome. Human ortholog(s) of this gene implicated in several diseases, including Alzheimer's disease (multiple); artery disease (multiple); eye disease (multiple); reproductive organ cancer (multiple); and vasculitis (multiple). Orthologous to human NOS3 (nitric oxide synthase 3). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in subcutaneous fat pad adult (RPKM 22.0), mammary gland adult (RPKM 20.1) and 26 other tissues See more
Orthologs: human all
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Genomic context

Location:: 5 A3; 5 11.32 cM

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	5	NC_000071.7 (24569772..24589472)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	5	NC_000071.6 (24364816..24384474)

Chromosome 5 - NC_000071.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

C1q/Tumor Necrosis Factor-Related Protein-9 Is a Novel Vasculoprotective Cytokine That Restores High Glucose-Suppressed Endothelial Progenitor Cell Functions by Activating the Endothelial Nitric Oxide Synthase.
Title: C1q/Tumor Necrosis Factor-Related Protein-9 Is a Novel Vasculoprotective Cytokine That Restores High Glucose-Suppressed Endothelial Progenitor Cell Functions by Activating the Endothelial Nitric Oxide Synthase.
Lymphocyte-Specific Protein 1 Regulates Expression and Stability of Endothelial Nitric Oxide Synthase.
Title: Lymphocyte-Specific Protein 1 Regulates Expression and Stability of Endothelial Nitric Oxide Synthase.
GPR56 Promotes Diabetic Kidney Disease Through eNOS Regulation in Glomerular Endothelial Cells.
Title: GPR56 Promotes Diabetic Kidney Disease Through eNOS Regulation in Glomerular Endothelial Cells.
SUMOylation and coupling of eNOS mediated by PIAS1 contribute to maintenance of vascular homeostasis.
Title: SUMOylation and coupling of eNOS mediated by PIAS1 contribute to maintenance of vascular homeostasis.
eNOS plays essential roles in the developing heart and aorta linked to disruption of Notch signalling.
Title: eNOS plays essential roles in the developing heart and aorta linked to disruption of Notch signalling.
Deletion of adipocyte NOS3 potentiates high-fat diet-induced hypertension and vascular remodelling via chemerin.
Title: Deletion of adipocyte NOS3 potentiates high-fat diet-induced hypertension and vascular remodelling via chemerin.
Effects of endothelial nitric oxide synthase on mouse arteriovenous fistula hemodynamics.
Title: Effects of endothelial nitric oxide synthase on mouse arteriovenous fistula hemodynamics.
Endothelial lipid droplets suppress eNOS to link high fat consumption to blood pressure elevation.
Title: Endothelial lipid droplets suppress eNOS to link high fat consumption to blood pressure elevation.
TRPC6 Deletion Enhances eNOS Expression and Reduces LPS-Induced Acute Lung Injury.
Title: TRPC6 Deletion Enhances eNOS Expression and Reduces LPS-Induced Acute Lung Injury.
Endothelial VEGFR2-PLCgamma signaling regulates vascular permeability and antitumor immunity through eNOS/Src.
Title: Endothelial VEGFR2-PLCγ signaling regulates vascular permeability and antitumor immunity through eNOS/Src.

Submit: New GeneRIF Correction See all GeneRIFs (564)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (2)
Endonuclease-mediated (6)
Gene trapped (1)
Targeted (9) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:548386

Nos3 (e-PCR), detects polymorphism
- UniSTS:546896

Nos3 (e-PCR), detects polymorphism
- UniSTS:527453

NoName (e-PCR)
- UniSTS:235143

UniSTS:166287 (e-PCR)
- UniSTS:166287

Nos3 (e-PCR), detects polymorphism
- UniSTS:166287

Nos3 (e-PCR), detects polymorphism
- UniSTS:525460

Nos3 (e-PCR), detects polymorphism
- UniSTS:144043

D5Jcs56 (e-PCR), detects polymorphism
- UniSTS:478892

Nos3 (e-PCR), detects polymorphism
- UniSTS:499129

PMC155039P1 (e-PCR)
- UniSTS:271323

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables FMN binding	IBA Inferred from Biological aspect of Ancestor more info
enables Hsp90 protein binding	ISO Inferred from Sequence Orthology more info
enables NADP binding	IEA Inferred from Electronic Annotation more info
enables actin binding	ISO Inferred from Sequence Orthology more info
enables actin monomer binding	ISO Inferred from Sequence Orthology more info
enables arginine binding	ISO Inferred from Sequence Orthology more info
enables beta-catenin binding	ISO Inferred from Sequence Orthology more info
enables cadherin binding	ISO Inferred from Sequence Orthology more info
enables calmodulin binding	ISO Inferred from Sequence Orthology more info
enables flavin adenine dinucleotide binding	IBA Inferred from Biological aspect of Ancestor more info
enables heme binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nitric-oxide synthase activity	IBA Inferred from Biological aspect of Ancestor more info
enables nitric-oxide synthase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables nitric-oxide synthase activity	ISO Inferred from Sequence Orthology more info
enables nitric-oxide synthase binding	ISO Inferred from Sequence Orthology more info
enables oxidoreductase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables scaffold protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables scaffold protein binding	ISO Inferred from Sequence Orthology more info
enables tetrahydrobiopterin binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in aortic valve morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in aortic valve morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in arginine catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in arginine catabolic process	ISO Inferred from Sequence Orthology more info
involved_in blood vessel diameter maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in blood vessel remodeling	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of calcium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to mechanical stimulus	ISO Inferred from Sequence Orthology more info
involved_in cellular response to transforming growth factor beta stimulus	ISO Inferred from Sequence Orthology more info
involved_in endocardial cushion morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in endothelial cell migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of establishment of localization in cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in homeostasis of number of cells within a tissue	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within in utero embryonic development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lipopolysaccharide-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lung development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of biomineral tissue development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of blood pressure	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within negative regulation of calcium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of hydrolase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of muscle hyperplasia	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of potassium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of smooth muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of smooth muscle cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in nitric oxide biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within nitric oxide biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nitric oxide biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in nitric oxide mediated signal transduction	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within ovulation from ovarian follicle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of angiogenesis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of blood vessel endothelial cell migration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_positive_effect positive regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_positive_effect positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of guanylate cyclase activity	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of guanylate cyclase activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of potassium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in pulmonary valve morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of nervous system process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of sodium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of systemic arterial blood pressure by endothelin	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of the force of heart contraction by chemical signal	IGI Inferred from Genetic Interaction more info	PubMed
involved_in removal of superoxide radicals	ISO Inferred from Sequence Orthology more info
involved_in response to estradiol	ISO Inferred from Sequence Orthology more info
involved_in response to hormone	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to lipopolysaccharide	IBA Inferred from Biological aspect of Ancestor more info
involved_in smooth muscle hyperplasia	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ventricular septum morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in apical part of cell	ISO Inferred from Sequence Orthology more info
located_in caveola	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IC Inferred by Curator more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in sarcolemma	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: nitric oxide synthase 3

Names: EC-NOS; NOS type III; NOSIII; cNOS; constitutive NOS; endothelial NOS; endothelial nitric oxide synthase; nitric oxide synthase, endothelial

NP_032739.3

EC 1.14.13.39

XP_006535702.1

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.

mRNA and Protein(s)

NM_008713.4 → NP_032739.3 nitric oxide synthase 3

See identical proteins and their annotated locations for NP_032739.3

Status: VALIDATED

Source sequence(s)

AK077896, AW489695, U53142

Consensus CDS

CCDS19117.1

UniProtKB/Swiss-Prot

O55056, P70313, Q7TSV7

UniProtKB/TrEMBL

Q8C5P3

Related

ENSMUSP00000030834.5, ENSMUST00000030834.7

Conserved Domains (4) summary

COG0369
Location:511 → 1158

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

cd00795
Location:67 → 479

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:521 → 697

Flavodoxin_1; Flavodoxin

cl06868
Location:761 → 1163

FNR_like; Ferredoxin reductase (FNR), an FAD and NAD(P) binding protein, was intially identified as a chloroplast reductase activity, catalyzing the electron transfer from reduced iron-sulfur protein ferredoxin to NADP+ as the final step in the electron transport ...

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000071.7 Reference GRCm39 C57BL/6J

Range

24569772..24589472

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006535639.4 → XP_006535702.1 nitric oxide synthase 3 isoform X1

UniProtKB/TrEMBL

Q8C5P3

Conserved Domains (3) summary

cd00795
Location:15 → 427

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:469 → 645

Flavodoxin_1

cl06868
Location:709 → 1111

FNR_like; Ferredoxin reductase (FNR), an FAD and NAD(P) binding protein, was intially identified as a chloroplast reductase activity, catalyzing the electron transfer from reduced iron-sulfur protein ferredoxin to NADP+ as the final step in the electron transport ...