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P70313

- NOS3_MOUSE

UniProt

P70313 - NOS3_MOUSE

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Protein

Nitric oxide synthase, endothelial

Gene

Nos3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi93 – 931ZincBy similarity
Metal bindingi98 – 981ZincBy similarity
Metal bindingi183 – 1831Iron (heme axial ligand)By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi648 – 67932FMNPROSITE-ProRule annotationAdd
BLAST
Nucleotide bindingi792 – 80312FADBy similarityAdd
BLAST
Nucleotide bindingi934 – 94411FADBy similarityAdd
BLAST
Nucleotide bindingi1009 – 102719NADPBy similarityAdd
BLAST
Nucleotide bindingi1107 – 112216NADPBy similarityAdd
BLAST

GO - Molecular functioni

  1. arginine binding Source: Ensembl
  2. flavin adenine dinucleotide binding Source: InterPro
  3. FMN binding Source: InterPro
  4. heme binding Source: InterPro
  5. iron ion binding Source: InterPro
  6. NADP binding Source: InterPro
  7. NADPH-hemoprotein reductase activity Source: RefGenome
  8. nitric-oxide synthase activity Source: MGI
  9. tetrahydrobiopterin binding Source: Ensembl

GO - Biological processi

  1. angiogenesis Source: MGI
  2. arginine catabolic process Source: Ensembl
  3. blood vessel remodeling Source: BHF-UCL
  4. endothelial cell migration Source: Ensembl
  5. in utero embryonic development Source: MGI
  6. lipopolysaccharide-mediated signaling pathway Source: MGI
  7. lung development Source: MGI
  8. negative regulation of blood pressure Source: RefGenome
  9. negative regulation of calcium ion transport Source: MGI
  10. negative regulation of cell proliferation Source: BHF-UCL
  11. negative regulation of hydrolase activity Source: MGI
  12. negative regulation of muscle hyperplasia Source: BHF-UCL
  13. negative regulation of potassium ion transport Source: MGI
  14. nitric oxide biosynthetic process Source: MGI
  15. nitric oxide mediated signal transduction Source: RefGenome
  16. ovulation from ovarian follicle Source: MGI
  17. positive regulation of angiogenesis Source: BHF-UCL
  18. positive regulation of guanylate cyclase activity Source: RefGenome
  19. positive regulation of vasodilation Source: RefGenome
  20. regulation of blood vessel size Source: BHF-UCL
  21. regulation of sodium ion transport Source: MGI
  22. regulation of systemic arterial blood pressure by endothelin Source: Ensembl
  23. regulation of the force of heart contraction by chemical signal Source: MGI
  24. response to fluid shear stress Source: Ensembl
  25. smooth muscle hyperplasia Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

Calcium, Calmodulin-binding, FAD, Flavoprotein, FMN, Heme, Iron, Metal-binding, NADP, Zinc

Enzyme and pathway databases

ReactomeiREACT_198345. Phagosomal maturation (early endosomal stage).
REACT_199047. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
REACT_215995. NOSTRIN mediated eNOS trafficking.
REACT_221264. eNOS activation.
REACT_226405. NOSIP mediated eNOS trafficking.
REACT_245499. Nitric oxide stimulates guanylate cyclase.
REACT_261840. VEGFR2 mediated vascular permeability.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Nos3
Synonyms:Ecnos
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 5

Organism-specific databases

MGIiMGI:97362. Nos3.

Subcellular locationi

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

GO - Cellular componenti

  1. caveola Source: Ensembl
  2. cytoplasm Source: MGI
  3. cytoskeleton Source: UniProtKB-KW
  4. cytosol Source: RefGenome
  5. Golgi apparatus Source: UniProtKB-KW
  6. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 12021201Nitric oxide synthase, endothelialPRO_0000170944Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-myristoyl glycineBy similarity
Lipidationi15 – 151S-palmitoyl cysteineBy similarity
Lipidationi26 – 261S-palmitoyl cysteineBy similarity
Modified residuei140 – 1401PhosphoserineBy similarity
Modified residuei494 – 4941Phosphothreonine; by AMPKBy similarity
Modified residuei632 – 6321PhosphoserineBy similarity
Modified residuei1174 – 11741Phosphothreonine1 Publication
Modified residuei1176 – 11761Phosphoserine; by AMPKCurated

Post-translational modificationi

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).By similarity

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP70313.
PRIDEiP70313.

PTM databases

PhosphoSiteiP70313.

Expressioni

Gene expression databases

BgeeiP70313.
CleanExiMM_NOS3.
ExpressionAtlasiP70313. baseline and differential.
GenevestigatoriP70313.

Interactioni

Subunit structurei

Homodimer. Interacts with NOSIP and NOSTRIN (By similarity).By similarity

Protein-protein interaction databases

BioGridi201807. 1 interaction.
DIPiDIP-31086N.
IntActiP70313. 1 interaction.
STRINGi10090.ENSMUSP00000030834.

Structurei

3D structure databases

ProteinModelPortaliP70313.
SMRiP70313. Positions 66-480, 491-1176.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini519 – 702184Flavodoxin-likePROSITE-ProRule annotationAdd
BLAST
Domaini755 – 1001247FAD-binding FR-typePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni97 – 485389Interaction with NOSIPBy similarityAdd
BLAST
Regioni490 – 50920Calmodulin-bindingSequence AnalysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi31 – 6838Pro-richAdd
BLAST

Sequence similaritiesi

Belongs to the NOS family.Curated
Contains 1 FAD-binding FR-type domain.PROSITE-ProRule annotation
Contains 1 flavodoxin-like domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG4362.
GeneTreeiENSGT00620000087711.
HOGENOMiHOG000220884.
HOVERGENiHBG000159.
InParanoidiP70313.
KOiK13242.
OMAiWGKLQVF.
OrthoDBiEOG79SDW7.
TreeFamiTF324410.

Family and domain databases

Gene3Di1.20.990.10. 1 hit.
3.40.50.360. 2 hits.
3.90.340.10. 1 hit.
InterProiIPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR012144. NOS_euk.
IPR004030. NOS_N.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamiPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
PF02898. NO_synthase. 1 hit.
[Graphical view]
PIRSFiPIRSF000333. NOS. 1 hit.
PRINTSiPR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMiSSF52218. SSF52218. 1 hit.
SSF56512. SSF56512. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
PS60001. NOS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P70313-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSQ APAPPSPTRP
60 70 80 90 100
APDHSPPLTR PPDGPRFPRV KNWEVGSITY DTLSAQAQQD GPCTSRRCLG
110 120 130 140 150
SLVFPRKLQS RPTQGPSPTE QLLGQARDFI NQYYNSIKRS GSQAHEQRLQ
160 170 180 190 200
EVEAEVAATG TYQLRESELV FGAKQAWRNA PRCVGRIQWG KLQVFDARDC
210 220 230 240 250
RTAQEMFTYI CNHIKYATNR GNLRSAITVF PQRCPGRGDF RIWNSQLIRY
260 270 280 290 300
AGYRQQDGSV RGDPANVEIT ELCIQHGWTP GNGRFDVLPL LLQAPDEPPE
310 320 330 340 350
LFTLPPEMVL EVPLEHPTLE WFAALGLRWY ALPAVSNMLL EIGGLEFPAA
360 370 380 390 400
PFSGWYMSSE IGMRDLCDPH RYNILEDVAV CMDLDTRTTS SLWKDKAAVE
410 420 430 440 450
INVAVLHSYQ LAKVTIVDHH AATASFMKHL ENEQKARGGC PADWAWIVPP
460 470 480 490 500
ISGSLTPVFH QEMVNYFLSP AFRYQPDPWK GSAAKGAGIT RKKTFKEVAN
510 520 530 540 550
AVKISASLMG TVMAKRVKAT ILYGSETGRA QSYAQQLGRL FRKAFDPRVL
560 570 580 590 600
CMDEYDVVSL EHEALVLVVT STFGNGDPPE NGESFAAALM EMSGPYNSSP
610 620 630 640 650
RPEQHKSYKI RFNSVSCSDP LVSSWRRKRK ESSNTDSAGA LGTLRFCVFG
660 670 680 690 700
LGSRAYPHFC AFARAVDTRL EELGGERLLQ LGQGDELCGQ EEAFRGWAQA
710 720 730 740 750
AFQAACETFC VGEDAKAAAR DIFSPKRSWK RQRYRLSTQA ESLQLLPGLT
760 770 780 790 800
HVHRRKMFQA TILSVENLQS SKSTRATILV RLDTGGQEGL QYQPGDHIGV
810 820 830 840 850
CPPNRPGLVE ALLSRVEDPP PSTEPVAVEQ LEKGSPGGPP PGWVRDPRLP
860 870 880 890 900
PCTLRQALTY FLDITSPPSP RLLRLLSTLA EESSEQQELE ALSQDPRRYE
910 920 930 940 950
EWKWFSCPTL LEVLEQFPSV ALPAPLILTQ LPLLQPRYYS VSSAPSAHPG
960 970 980 990 1000
EIHLTIAVLA YRTQDGLGPL HYGVCSTWMS QLKAGDPVPC FIRGAPSFRL
1010 1020 1030 1040 1050
PPDPNLPCIL VGPGTGIAPF RGFWQDRLHD IEIKGLQPAP MTLVFGCRCS
1060 1070 1080 1090 1100
QLDHLYRDEV LDAQQRGVFG QVLTAFSRDP GSPKTYVQDL LRTELAAEVH
1110 1120 1130 1140 1150
RVLCLEQGHM FVCGDVTMAT SVLQTVQRIL ATEGGMELDE AGDVIGVLRD
1160 1170 1180 1190 1200
QQRYHEDIFG LTLRTQEVTS RIRTQSFSLQ ERQLRGAVPW SFDPPGPEIP

GS
Length:1,202
Mass (Da):132,916
Last modified:July 27, 2011 - v4
Checksum:iE1F65C43601F0937
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti50 – 501P → A in AAC52766. (PubMed:8764825)Curated
Sequence conflicti298 – 2981P → S in AAC52766. (PubMed:8764825)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U53142 mRNA. Translation: AAC52766.1.
BC052636 mRNA. Translation: AAH52636.1.
AF045940 Genomic DNA. Translation: AAC02553.1.
CCDSiCCDS19117.1.
PIRiS71424.
RefSeqiNP_032739.3. NM_008713.4.
UniGeneiMm.258415.

Genome annotation databases

EnsembliENSMUST00000030834; ENSMUSP00000030834; ENSMUSG00000028978.
GeneIDi18127.
KEGGimmu:18127.
UCSCiuc008wrd.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U53142 mRNA. Translation: AAC52766.1 .
BC052636 mRNA. Translation: AAH52636.1 .
AF045940 Genomic DNA. Translation: AAC02553.1 .
CCDSi CCDS19117.1.
PIRi S71424.
RefSeqi NP_032739.3. NM_008713.4.
UniGenei Mm.258415.

3D structure databases

ProteinModelPortali P70313.
SMRi P70313. Positions 66-480, 491-1176.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 201807. 1 interaction.
DIPi DIP-31086N.
IntActi P70313. 1 interaction.
STRINGi 10090.ENSMUSP00000030834.

Chemistry

ChEMBLi CHEMBL2643.

PTM databases

PhosphoSitei P70313.

Proteomic databases

PaxDbi P70313.
PRIDEi P70313.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000030834 ; ENSMUSP00000030834 ; ENSMUSG00000028978 .
GeneIDi 18127.
KEGGi mmu:18127.
UCSCi uc008wrd.2. mouse.

Organism-specific databases

CTDi 4846.
MGIi MGI:97362. Nos3.

Phylogenomic databases

eggNOGi COG4362.
GeneTreei ENSGT00620000087711.
HOGENOMi HOG000220884.
HOVERGENi HBG000159.
InParanoidi P70313.
KOi K13242.
OMAi WGKLQVF.
OrthoDBi EOG79SDW7.
TreeFami TF324410.

Enzyme and pathway databases

Reactomei REACT_198345. Phagosomal maturation (early endosomal stage).
REACT_199047. Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation.
REACT_215995. NOSTRIN mediated eNOS trafficking.
REACT_221264. eNOS activation.
REACT_226405. NOSIP mediated eNOS trafficking.
REACT_245499. Nitric oxide stimulates guanylate cyclase.
REACT_261840. VEGFR2 mediated vascular permeability.

Miscellaneous databases

NextBioi 293352.
PROi P70313.
SOURCEi Search...

Gene expression databases

Bgeei P70313.
CleanExi MM_NOS3.
ExpressionAtlasi P70313. baseline and differential.
Genevestigatori P70313.

Family and domain databases

Gene3Di 1.20.990.10. 1 hit.
3.40.50.360. 2 hits.
3.90.340.10. 1 hit.
InterProi IPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR012144. NOS_euk.
IPR004030. NOS_N.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view ]
Pfami PF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
PF02898. NO_synthase. 1 hit.
[Graphical view ]
PIRSFi PIRSF000333. NOS. 1 hit.
PRINTSi PR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMi SSF52218. SSF52218. 1 hit.
SSF56512. SSF56512. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEi PS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
PS60001. NOS. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1174, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiNOS3_MOUSE
AccessioniPrimary (citable) accession number: P70313
Secondary accession number(s): O55056, Q7TSV7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: November 26, 2014
This is version 152 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3