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P70313 (NOS3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nitric oxide synthase, endothelial

EC=1.14.13.39
Alternative name(s):
Constitutive NOS
Short name=cNOS
EC-NOS
Endothelial NOS
Short name=eNOS
NOS type III
Short name=NOSIII
Gene names
Name:Nos3
Synonyms:Ecnos
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1202 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.3

Catalytic activity

2 L-arginine + 3 NADPH + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O.

Cofactor

Heme group.

Binds 1 FAD.

Binds 1 FMN.

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

Enzyme regulation

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

Subunit structure

Homodimer. Interacts with NOSIP and NOSTRIN By similarity.

Subcellular location

Membranecaveola By similarity. Cytoplasmcytoskeleton By similarity. Golgi apparatus By similarity. Cell membrane By similarity. 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 By similarity.

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.

Sequence similarities

Belongs to the NOS family.

Contains 1 FAD-binding FR-type domain.

Contains 1 flavodoxin-like domain.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Golgi apparatus
Membrane
   LigandCalcium
Calmodulin-binding
FAD
Flavoprotein
FMN
Heme
Iron
Metal-binding
NADP
Zinc
   Molecular functionOxidoreductase
   PTMLipoprotein
Myristate
Palmitate
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from mutant phenotype PubMed 15016731. Source: MGI

arginine catabolic process

Inferred from electronic annotation. Source: Ensembl

blood vessel remodeling

Inferred from mutant phenotype PubMed 9466966. Source: BHF-UCL

endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

in utero embryonic development

Inferred from mutant phenotype PubMed 11732991. Source: MGI

lipopolysaccharide-mediated signaling pathway

Inferred from mutant phenotype PubMed 15647265. Source: MGI

lung development

Inferred from mutant phenotype PubMed 15016731. Source: MGI

negative regulation of blood pressure

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of calcium ion transport

Inferred from mutant phenotype PubMed 12074580. Source: MGI

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 9466966. Source: BHF-UCL

negative regulation of hydrolase activity

Inferred from mutant phenotype PubMed 12074580. Source: MGI

negative regulation of muscle hyperplasia

Inferred from mutant phenotype PubMed 9466966. Source: BHF-UCL

negative regulation of potassium ion transport

Inferred from mutant phenotype PubMed 12074580. Source: MGI

nitric oxide biosynthetic process

Inferred from mutant phenotype PubMed 15647265. Source: MGI

nitric oxide mediated signal transduction

Inferred from Biological aspect of Ancestor. Source: RefGenome

ovulation from ovarian follicle

Inferred from mutant phenotype PubMed 11779605. Source: MGI

positive regulation of angiogenesis

Inferred from mutant phenotype PubMed 9616228. Source: BHF-UCL

positive regulation of guanylate cyclase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of vasodilation

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of blood vessel size

Inferred from mutant phenotype PubMed 9466966. Source: BHF-UCL

regulation of sodium ion transport

Inferred from mutant phenotype PubMed 12074580. Source: MGI

regulation of systemic arterial blood pressure by endothelin

Inferred from electronic annotation. Source: Ensembl

regulation of the force of heart contraction by chemical signal

Inferred from genetic interaction PubMed 18951881. Source: MGI

response to fluid shear stress

Inferred from electronic annotation. Source: Ensembl

smooth muscle hyperplasia

Inferred from mutant phenotype PubMed 9466966. Source: BHF-UCL

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

caveola

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay PubMed 11732991. Source: MGI

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from Biological aspect of Ancestor. Source: RefGenome

nucleus

Inferred from direct assay PubMed 11732991. Source: MGI

   Molecular_functionFMN binding

Inferred from electronic annotation. Source: InterPro

NADP binding

Inferred from electronic annotation. Source: InterPro

NADPH-hemoprotein reductase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

arginine binding

Inferred from electronic annotation. Source: Ensembl

flavin adenine dinucleotide binding

Inferred from electronic annotation. Source: InterPro

heme binding

Inferred from electronic annotation. Source: InterPro

iron ion binding

Inferred from electronic annotation. Source: InterPro

nitric-oxide synthase activity

Inferred from mutant phenotype PubMed 15647265. Source: MGI

tetrahydrobiopterin binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 12021201Nitric oxide synthase, endothelial
PRO_0000170944

Regions

Domain519 – 702184Flavodoxin-like
Domain755 – 1001247FAD-binding FR-type
Nucleotide binding648 – 67932FMN By similarity
Nucleotide binding792 – 80312FAD By similarity
Nucleotide binding934 – 94411FAD By similarity
Nucleotide binding1009 – 102719NADP By similarity
Nucleotide binding1107 – 112216NADP By similarity
Region97 – 485389Interaction with NOSIP By similarity
Region490 – 50920Calmodulin-binding Potential
Compositional bias31 – 6838Pro-rich

Sites

Metal binding931Zinc By similarity
Metal binding981Zinc By similarity
Metal binding1831Iron (heme axial ligand) By similarity

Amino acid modifications

Modified residue1401Phosphoserine By similarity
Modified residue4941Phosphothreonine; by AMPK By similarity
Modified residue6321Phosphoserine By similarity
Modified residue11741Phosphothreonine Ref.4
Modified residue11761Phosphoserine; by AMPK Probable
Lipidation21N-myristoyl glycine By similarity
Lipidation151S-palmitoyl cysteine By similarity
Lipidation261S-palmitoyl cysteine By similarity

Experimental info

Sequence conflict501P → A in AAC52766. Ref.1
Sequence conflict2981P → S in AAC52766. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P70313 [UniParc].

Last modified July 27, 2011. Version 4.
Checksum: E1F65C43601F0937

FASTA1,202132,916
        10         20         30         40         50         60 
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSQ APAPPSPTRP APDHSPPLTR 

        70         80         90        100        110        120 
PPDGPRFPRV KNWEVGSITY DTLSAQAQQD GPCTSRRCLG SLVFPRKLQS RPTQGPSPTE 

       130        140        150        160        170        180 
QLLGQARDFI NQYYNSIKRS GSQAHEQRLQ EVEAEVAATG TYQLRESELV FGAKQAWRNA 

       190        200        210        220        230        240 
PRCVGRIQWG KLQVFDARDC RTAQEMFTYI CNHIKYATNR GNLRSAITVF PQRCPGRGDF 

       250        260        270        280        290        300 
RIWNSQLIRY AGYRQQDGSV RGDPANVEIT ELCIQHGWTP GNGRFDVLPL LLQAPDEPPE 

       310        320        330        340        350        360 
LFTLPPEMVL EVPLEHPTLE WFAALGLRWY ALPAVSNMLL EIGGLEFPAA PFSGWYMSSE 

       370        380        390        400        410        420 
IGMRDLCDPH RYNILEDVAV CMDLDTRTTS SLWKDKAAVE INVAVLHSYQ LAKVTIVDHH 

       430        440        450        460        470        480 
AATASFMKHL ENEQKARGGC PADWAWIVPP ISGSLTPVFH QEMVNYFLSP AFRYQPDPWK 

       490        500        510        520        530        540 
GSAAKGAGIT RKKTFKEVAN AVKISASLMG TVMAKRVKAT ILYGSETGRA QSYAQQLGRL 

       550        560        570        580        590        600 
FRKAFDPRVL CMDEYDVVSL EHEALVLVVT STFGNGDPPE NGESFAAALM EMSGPYNSSP 

       610        620        630        640        650        660 
RPEQHKSYKI RFNSVSCSDP LVSSWRRKRK ESSNTDSAGA LGTLRFCVFG LGSRAYPHFC 

       670        680        690        700        710        720 
AFARAVDTRL EELGGERLLQ LGQGDELCGQ EEAFRGWAQA AFQAACETFC VGEDAKAAAR 

       730        740        750        760        770        780 
DIFSPKRSWK RQRYRLSTQA ESLQLLPGLT HVHRRKMFQA TILSVENLQS SKSTRATILV 

       790        800        810        820        830        840 
RLDTGGQEGL QYQPGDHIGV CPPNRPGLVE ALLSRVEDPP PSTEPVAVEQ LEKGSPGGPP 

       850        860        870        880        890        900 
PGWVRDPRLP PCTLRQALTY FLDITSPPSP RLLRLLSTLA EESSEQQELE ALSQDPRRYE 

       910        920        930        940        950        960 
EWKWFSCPTL LEVLEQFPSV ALPAPLILTQ LPLLQPRYYS VSSAPSAHPG EIHLTIAVLA 

       970        980        990       1000       1010       1020 
YRTQDGLGPL HYGVCSTWMS QLKAGDPVPC FIRGAPSFRL PPDPNLPCIL VGPGTGIAPF 

      1030       1040       1050       1060       1070       1080 
RGFWQDRLHD IEIKGLQPAP MTLVFGCRCS QLDHLYRDEV LDAQQRGVFG QVLTAFSRDP 

      1090       1100       1110       1120       1130       1140 
GSPKTYVQDL LRTELAAEVH RVLCLEQGHM FVCGDVTMAT SVLQTVQRIL ATEGGMELDE 

      1150       1160       1170       1180       1190       1200 
AGDVIGVLRD QQRYHEDIFG LTLRTQEVTS RIRTQSFSLQ ERQLRGAVPW SFDPPGPEIP 


GS 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of murine endothelial constitutive nitric oxide synthase."
Gnanapandithen K., Chen Z., Kau C.-L., Gorczynski R.M., Marsden P.A.
Biochim. Biophys. Acta 1308:103-106(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal heart.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Colon.
[3]"Limb reduction defects in endothelial nitric oxide synthase-deficient mice."
Gregg A.R., Schauer A., Shi O., Liu Z., Lee C.G.L., O'Brien W.E.
Am. J. Physiol. 275:H2319-H2324(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-54, FUNCTION.
[4]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1174, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U53142 mRNA. Translation: AAC52766.1.
BC052636 mRNA. Translation: AAH52636.1.
AF045940 Genomic DNA. Translation: AAC02553.1.
PIRS71424.
RefSeqNP_032739.3. NM_008713.4.
UniGeneMm.258415.

3D structure databases

ProteinModelPortalP70313.
SMRP70313. Positions 66-480, 491-1176.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201807. 1 interaction.
DIPDIP-31086N.
IntActP70313. 1 interaction.
STRING10090.ENSMUSP00000030834.

Chemistry

BindingDBP70313.
ChEMBLCHEMBL2643.

PTM databases

PhosphoSiteP70313.

Proteomic databases

PaxDbP70313.
PRIDEP70313.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000030834; ENSMUSP00000030834; ENSMUSG00000028978.
GeneID18127.
KEGGmmu:18127.
UCSCuc008wrd.2. mouse.

Organism-specific databases

CTD4846.
MGIMGI:97362. Nos3.

Phylogenomic databases

eggNOGCOG4362.
GeneTreeENSGT00620000087711.
HOGENOMHOG000220884.
HOVERGENHBG000159.
InParanoidQ7TSV7.
KOK13242.
OMAWGKLQVF.
OrthoDBEOG79SDW7.
TreeFamTF324410.

Gene expression databases

ArrayExpressP70313.
BgeeP70313.
CleanExMM_NOS3.
GenevestigatorP70313.

Family and domain databases

Gene3D1.20.990.10. 1 hit.
3.90.340.10. 1 hit.
InterProIPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR004030. NO_synthase_oxygenase_dom.
IPR012144. NOS_euk.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PANTHERPTHR19384:SF5. PTHR19384:SF5. 1 hit.
PfamPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
PF02898. NO_synthase. 1 hit.
[Graphical view]
PIRSFPIRSF000333. NOS. 1 hit.
PRINTSPR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMSSF56512. SSF56512. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
PS60001. NOS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio293352.
PROP70313.
SOURCESearch...

Entry information

Entry nameNOS3_MOUSE
AccessionPrimary (citable) accession number: P70313
Secondary accession number(s): O55056, Q7TSV7
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 146 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot