P70313 · NOS3_MOUSE

  • Protein
    Nitric oxide synthase 3
  • Gene
    Nos3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway. NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets. May play a significant role in normal and abnormal limb development.

Catalytic activity

Cofactor

Protein has several cofactor binding sites:
heme b (UniProtKB | Rhea| CHEBI:60344 )

FAD (UniProtKB | Rhea| CHEBI:57692 )

Note: Binds 1 FAD.
FMN (UniProtKB | Rhea| CHEBI:58210 )

Note: Binds 1 FMN.
(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | Rhea| CHEBI:59560 )

Note: Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.

Activity regulation

Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN (By similarity).

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site93Zn2+ (UniProtKB | ChEBI); ligand shared between homodimeric partners
Binding site98Zn2+ (UniProtKB | ChEBI); ligand shared between homodimeric partners
Binding site101(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI)
Binding site183Fe (UniProtKB | ChEBI) of heme b (UniProtKB | ChEBI); axial binding residue
Binding site246L-arginine (UniProtKB | ChEBI)
Binding site355L-arginine (UniProtKB | ChEBI)
Binding site356L-arginine (UniProtKB | ChEBI)
Binding site360L-arginine (UniProtKB | ChEBI)
Binding site445(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI)
Binding site446(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI)
Binding site459(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (UniProtKB | ChEBI)
Binding site474heme b (UniProtKB | ChEBI)
Binding site525FMN (UniProtKB | ChEBI)
Binding site526FMN (UniProtKB | ChEBI)
Binding site527FMN (UniProtKB | ChEBI)
Binding site529FMN (UniProtKB | ChEBI)
Binding site571FMN (UniProtKB | ChEBI)
Binding site572FMN (UniProtKB | ChEBI)
Binding site653FMN (UniProtKB | ChEBI)
Binding site660FMN (UniProtKB | ChEBI)
Binding site686FMN (UniProtKB | ChEBI)
Binding site690FMN (UniProtKB | ChEBI)
Binding site775NADP+ (UniProtKB | ChEBI)
Binding site797FAD (UniProtKB | ChEBI)
Binding site937FAD (UniProtKB | ChEBI)
Binding site939FAD (UniProtKB | ChEBI)
Binding site940FAD (UniProtKB | ChEBI)
Binding site955FAD (UniProtKB | ChEBI)
Binding site957FAD (UniProtKB | ChEBI)
Binding site961FAD (UniProtKB | ChEBI)
Binding site974FAD (UniProtKB | ChEBI)
Binding site975FAD (UniProtKB | ChEBI)
Binding site976FAD (UniProtKB | ChEBI)
Binding site1015NADP+ (UniProtKB | ChEBI)
Binding site1048NADP+ (UniProtKB | ChEBI)
Binding site1077NADP+ (UniProtKB | ChEBI)
Binding site1078NADP+ (UniProtKB | ChEBI)
Binding site1084NADP+ (UniProtKB | ChEBI)
Binding site1086NADP+ (UniProtKB | ChEBI)
Binding site1088NADP+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentapical part of cell
Cellular Componentcaveola
Cellular Componentcytoplasm
Cellular Componentcytoskeleton
Cellular Componentcytosol
Cellular ComponentGolgi apparatus
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular Componentsarcolemma
Molecular Functionactin binding
Molecular Functionactin monomer binding
Molecular Functionarginine binding
Molecular Functionbeta-catenin binding
Molecular Functioncadherin binding
Molecular Functioncalmodulin binding
Molecular Functionflavin adenine dinucleotide binding
Molecular FunctionFMN binding
Molecular Functionheme binding
Molecular FunctionHsp90 protein binding
Molecular Functionmetal ion binding
Molecular FunctionNADP binding
Molecular Functionnitric-oxide synthase activity
Molecular Functionnitric-oxide synthase binding
Molecular Functionscaffold protein binding
Molecular Functiontetrahydrobiopterin binding
Biological Processangiogenesis
Biological Processaortic valve morphogenesis
Biological Processarginine catabolic process
Biological Processblood vessel diameter maintenance
Biological Processblood vessel remodeling
Biological Processcalcium ion transport
Biological Processcellular response to mechanical stimulus
Biological Processcellular response to transforming growth factor beta stimulus
Biological Processendocardial cushion morphogenesis
Biological Processendothelial cell migration
Biological Processestablishment of localization in cell
Biological Processhomeostasis of number of cells within a tissue
Biological Processin utero embryonic development
Biological Processlipopolysaccharide-mediated signaling pathway
Biological Processlung development
Biological Processnegative regulation of biomineral tissue development
Biological Processnegative regulation of blood pressure
Biological Processnegative regulation of calcium ion transport
Biological Processnegative regulation of cell population proliferation
Biological Processnegative regulation of muscle hyperplasia
Biological Processnegative regulation of potassium ion transport
Biological Processnegative regulation of smooth muscle cell proliferation
Biological Processnitric oxide biosynthetic process
Biological Processnitric oxide mediated signal transduction
Biological Processovulation from ovarian follicle
Biological Processpositive regulation of angiogenesis
Biological Processpositive regulation of apoptotic process
Biological Processpositive regulation of blood vessel endothelial cell migration
Biological Processpositive regulation of gene expression
Biological Processpotassium ion transport
Biological Processpulmonary valve morphogenesis
Biological Processregulation of nervous system process
Biological Processregulation of sodium ion transport
Biological Processregulation of systemic arterial blood pressure by endothelin
Biological Processregulation of the force of heart contraction by chemical signal
Biological Processremoval of superoxide radicals
Biological Processresponse to estradiol
Biological Processresponse to fluid shear stress
Biological Processresponse to hormone
Biological Processresponse to lipopolysaccharide
Biological Processsmooth muscle hyperplasia
Biological Processventricular septum morphogenesis

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Nitric oxide synthase 3
  • EC number
  • Alternative names
    • Constitutive NOS (cNOS)
    • EC-NOS
    • NOS type III (NOSIII)
    • Nitric oxide synthase, endothelial
      (Endothelial NOS
      ; eNOS
      )

Gene names

    • Name
      Nos3
    • Synonyms
      Ecnos

Organism names

  • Taxonomic identifier
  • Strain
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P70313
  • Secondary accessions
    • O55056
    • Q7TSV7

Proteomes

Organism-specific databases

Subcellular Location

Membrane, caveola
Golgi apparatus
Cell membrane
Note: Specifically associates with actin cytoskeleton in the G2 phase of the cell cycle, which is favored by interaction with NOSIP and results in a reduced enzymatic activity.

Keywords

Phenotypes & Variants

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 53 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for initiator methionine, lipidation, chain, modified residue.

TypeIDPosition(s)Description
Initiator methionine1Removed
Lipidation2N-myristoyl glycine
ChainPRO_00001709442-1202Nitric oxide synthase 3
Lipidation15S-palmitoyl cysteine
Lipidation26S-palmitoyl cysteine
Modified residue494Phosphothreonine; by AMPK
Modified residue614Phosphoserine
Modified residue632Phosphoserine
Modified residue637Phosphoserine
Modified residue835Phosphoserine
Modified residue1174Phosphothreonine
Modified residue1176Phosphoserine; by AMPK
Modified residue1178Phosphoserine

Post-translational modification

Phosphorylation by AMPK at Ser-1176 in the presence of Ca2+-calmodulin (CaM) activates activity. In absence of Ca2+-calmodulin, AMPK also phosphorylates Thr-494, resulting in inhibition of activity (By similarity).

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Homodimer. Interacts with NOSIP and NOSTRIN (By similarity).
Interacts with HSP90AB1 (By similarity).
Forms a complex with ASL, ASS1 and SLC7A1; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region, compositional bias, domain.

TypeIDPosition(s)Description
Region1-70Disordered
Compositional bias35-64Pro residues
Region97-485Interaction with NOSIP
Region490-509Calmodulin-binding
Domain519-702Flavodoxin-like
Domain755-1001FAD-binding FR-type
Region817-843Disordered

Sequence similarities

Belongs to the NOS family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,202
  • Mass (Da)
    132,916
  • Last updated
    2011-07-27 v4
  • Checksum
    E1F65C43601F0937
MGNLKSVGQEPGPPCGLGLGLGLGLCGKQGPASPAPEPSQAPAPPSPTRPAPDHSPPLTRPPDGPRFPRVKNWEVGSITYDTLSAQAQQDGPCTSRRCLGSLVFPRKLQSRPTQGPSPTEQLLGQARDFINQYYNSIKRSGSQAHEQRLQEVEAEVAATGTYQLRESELVFGAKQAWRNAPRCVGRIQWGKLQVFDARDCRTAQEMFTYICNHIKYATNRGNLRSAITVFPQRCPGRGDFRIWNSQLIRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDEPPELFTLPPEMVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFPAAPFSGWYMSSEIGMRDLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINVAVLHSYQLAKVTIVDHHAATASFMKHLENEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYFLSPAFRYQPDPWKGSAAKGAGITRKKTFKEVANAVKISASLMGTVMAKRVKATILYGSETGRAQSYAQQLGRLFRKAFDPRVLCMDEYDVVSLEHEALVLVVTSTFGNGDPPENGESFAAALMEMSGPYNSSPRPEQHKSYKIRFNSVSCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYPHFCAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAQAAFQAACETFCVGEDAKAAARDIFSPKRSWKRQRYRLSTQAESLQLLPGLTHVHRRKMFQATILSVENLQSSKSTRATILVRLDTGGQEGLQYQPGDHIGVCPPNRPGLVEALLSRVEDPPPSTEPVAVEQLEKGSPGGPPPGWVRDPRLPPCTLRQALTYFLDITSPPSPRLLRLLSTLAEESSEQQELEALSQDPRRYEEWKWFSCPTLLEVLEQFPSVALPAPLILTQLPLLQPRYYSVSSAPSAHPGEIHLTIAVLAYRTQDGLGPLHYGVCSTWMSQLKAGDPVPCFIRGAPSFRLPPDPNLPCILVGPGTGIAPFRGFWQDRLHDIEIKGLQPAPMTLVFGCRCSQLDHLYRDEVLDAQQRGVFGQVLTAFSRDPGSPKTYVQDLLRTELAAEVHRVLCLEQGHMFVCGDVTMATSVLQTVQRILATEGGMELDEAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERQLRGAVPWSFDPPGPEIPGS

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
E9Q9X4E9Q9X4_MOUSENos31106

Features

Showing features for compositional bias, sequence conflict.

TypeIDPosition(s)Description
Compositional bias35-64Pro residues
Sequence conflict50in Ref. 1; AAC52766
Sequence conflict298in Ref. 1; AAC52766

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
U53142
EMBL· GenBank· DDBJ
AAC52766.1
EMBL· GenBank· DDBJ
mRNA
BC052636
EMBL· GenBank· DDBJ
AAH52636.1
EMBL· GenBank· DDBJ
mRNA
AF045940
EMBL· GenBank· DDBJ
AAC02553.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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