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P70313

- NOS3_MOUSE

UniProt

P70313 - NOS3_MOUSE

Protein

Nitric oxide synthase, endothelial

Gene

Nos3

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 150 (01 Oct 2014)
      Sequence version 4 (27 Jul 2011)
      Previous versions | rss
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    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

    Heme group.
    Binds 1 FAD.
    Binds 1 FMN.
    Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.

    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

    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.

    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: UniProtKB-SubCell
    2. cytoplasm Source: MGI
    3. cytoskeleton Source: UniProtKB-SubCell
    4. cytosol Source: RefGenome
    5. Golgi apparatus Source: UniProtKB-SubCell
    6. nucleus Source: MGI

    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

    ArrayExpressiP70313.
    BgeeiP70313.
    CleanExiMM_NOS3.
    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.
    InParanoidiQ7TSV7.
    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

    MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSQ APAPPSPTRP     50
    APDHSPPLTR PPDGPRFPRV KNWEVGSITY DTLSAQAQQD GPCTSRRCLG 100
    SLVFPRKLQS RPTQGPSPTE QLLGQARDFI NQYYNSIKRS GSQAHEQRLQ 150
    EVEAEVAATG TYQLRESELV FGAKQAWRNA PRCVGRIQWG KLQVFDARDC 200
    RTAQEMFTYI CNHIKYATNR GNLRSAITVF PQRCPGRGDF RIWNSQLIRY 250
    AGYRQQDGSV RGDPANVEIT ELCIQHGWTP GNGRFDVLPL LLQAPDEPPE 300
    LFTLPPEMVL EVPLEHPTLE WFAALGLRWY ALPAVSNMLL EIGGLEFPAA 350
    PFSGWYMSSE IGMRDLCDPH RYNILEDVAV CMDLDTRTTS SLWKDKAAVE 400
    INVAVLHSYQ LAKVTIVDHH AATASFMKHL ENEQKARGGC PADWAWIVPP 450
    ISGSLTPVFH QEMVNYFLSP AFRYQPDPWK GSAAKGAGIT RKKTFKEVAN 500
    AVKISASLMG TVMAKRVKAT ILYGSETGRA QSYAQQLGRL FRKAFDPRVL 550
    CMDEYDVVSL EHEALVLVVT STFGNGDPPE NGESFAAALM EMSGPYNSSP 600
    RPEQHKSYKI RFNSVSCSDP LVSSWRRKRK ESSNTDSAGA LGTLRFCVFG 650
    LGSRAYPHFC AFARAVDTRL EELGGERLLQ LGQGDELCGQ EEAFRGWAQA 700
    AFQAACETFC VGEDAKAAAR DIFSPKRSWK RQRYRLSTQA ESLQLLPGLT 750
    HVHRRKMFQA TILSVENLQS SKSTRATILV RLDTGGQEGL QYQPGDHIGV 800
    CPPNRPGLVE ALLSRVEDPP PSTEPVAVEQ LEKGSPGGPP PGWVRDPRLP 850
    PCTLRQALTY FLDITSPPSP RLLRLLSTLA EESSEQQELE ALSQDPRRYE 900
    EWKWFSCPTL LEVLEQFPSV ALPAPLILTQ LPLLQPRYYS VSSAPSAHPG 950
    EIHLTIAVLA YRTQDGLGPL HYGVCSTWMS QLKAGDPVPC FIRGAPSFRL 1000
    PPDPNLPCIL VGPGTGIAPF RGFWQDRLHD IEIKGLQPAP MTLVFGCRCS 1050
    QLDHLYRDEV LDAQQRGVFG QVLTAFSRDP GSPKTYVQDL LRTELAAEVH 1100
    RVLCLEQGHM FVCGDVTMAT SVLQTVQRIL ATEGGMELDE AGDVIGVLRD 1150
    QQRYHEDIFG LTLRTQEVTS RIRTQSFSLQ ERQLRGAVPW SFDPPGPEIP 1200
    GS 1202
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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

    BindingDBi P70313.
    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 Q7TSV7.
    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.

    Miscellaneous databases

    NextBioi 293352.
    PROi P70313.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P70313.
    Bgeei P70313.
    CleanExi MM_NOS3.
    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

    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: October 1, 2014
    This is version 150 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