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Protein

Nitric oxide synthase, endothelial

Gene

Nos3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Metal bindingi93ZincBy similarity1
Metal bindingi98ZincBy similarity1
Metal bindingi183Iron (heme axial ligand)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi648 – 679FMNPROSITE-ProRule annotationAdd BLAST32
Nucleotide bindingi792 – 803FADBy similarityAdd BLAST12
Nucleotide bindingi934 – 944FADBy similarityAdd BLAST11
Nucleotide bindingi1009 – 1027NADPBy similarityAdd BLAST19
Nucleotide bindingi1107 – 1122NADPBy similarityAdd BLAST16

GO - Molecular functioni

GO - Biological processi

  • angiogenesis Source: MGI
  • aortic valve morphogenesis Source: BHF-UCL
  • arginine catabolic process Source: MGI
  • blood vessel remodeling Source: BHF-UCL
  • cellular response to mechanical stimulus Source: MGI
  • cellular response to transforming growth factor beta stimulus Source: MGI
  • endocardial cushion morphogenesis Source: BHF-UCL
  • endothelial cell migration Source: MGI
  • homeostasis of number of cells within a tissue Source: BHF-UCL
  • in utero embryonic development Source: MGI
  • lipopolysaccharide-mediated signaling pathway Source: MGI
  • lung development Source: MGI
  • negative regulation of biomineral tissue development Source: BHF-UCL
  • negative regulation of blood pressure Source: GO_Central
  • negative regulation of calcium ion transport Source: MGI
  • negative regulation of cell proliferation Source: BHF-UCL
  • negative regulation of hydrolase activity Source: MGI
  • negative regulation of muscle hyperplasia Source: BHF-UCL
  • negative regulation of potassium ion transport Source: MGI
  • negative regulation of smooth muscle cell proliferation Source: MGI
  • nitric oxide biosynthetic process Source: MGI
  • nitric oxide mediated signal transduction Source: GO_Central
  • ovulation from ovarian follicle Source: MGI
  • positive regulation of angiogenesis Source: BHF-UCL
  • positive regulation of apoptotic process Source: MGI
  • positive regulation of blood vessel diameter Source: GO_Central
  • positive regulation of blood vessel endothelial cell migration Source: MGI
  • positive regulation of gene expression Source: BHF-UCL
  • positive regulation of guanylate cyclase activity Source: MGI
  • pulmonary valve morphogenesis Source: BHF-UCL
  • regulation of blood vessel size Source: BHF-UCL
  • regulation of sodium ion transport Source: MGI
  • regulation of systemic arterial blood pressure by endothelin Source: MGI
  • regulation of the force of heart contraction by chemical signal Source: MGI
  • removal of superoxide radicals Source: MGI
  • response to estradiol Source: MGI
  • response to fluid shear stress Source: Ensembl
  • signal transduction Source: MGI
  • smooth muscle hyperplasia Source: BHF-UCL
  • ventricular septum morphogenesis Source: BHF-UCL

Keywordsi

Molecular functionCalmodulin-binding, Oxidoreductase
LigandCalcium, FAD, Flavoprotein, FMN, Heme, Iron, Metal-binding, NADP, Zinc

Enzyme and pathway databases

BRENDAi1.14.13.39 3474
ReactomeiR-MMU-1222556 ROS, RNS production in phagocytes
R-MMU-1474151 Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
R-MMU-203615 eNOS activation
R-MMU-203641 NOSTRIN mediated eNOS trafficking
R-MMU-203754 NOSIP mediated eNOS trafficking
R-MMU-392154 Nitric oxide stimulates guanylate cyclase
R-MMU-5218920 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:97362 Nos3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Golgi apparatus, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2643

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001709442 – 1202Nitric oxide synthase, endothelialAdd BLAST1201

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycineBy similarity1
Lipidationi15S-palmitoyl cysteineBy similarity1
Lipidationi26S-palmitoyl cysteineBy similarity1
Modified residuei494Phosphothreonine; by AMPKBy similarity1
Modified residuei614PhosphoserineCombined sources1
Modified residuei632PhosphoserineBy similarity1
Modified residuei637PhosphoserineBy similarity1
Modified residuei835PhosphoserineBy similarity1
Modified residuei1174PhosphothreonineCombined sources1
Modified residuei1176Phosphoserine; by AMPKCombined sourcesCurated1
Modified residuei1178PhosphoserineCombined sources1

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

MaxQBiP70313
PaxDbiP70313
PRIDEiP70313

PTM databases

iPTMnetiP70313
PhosphoSitePlusiP70313
SwissPalmiP70313

Expressioni

Gene expression databases

BgeeiENSMUSG00000028978
CleanExiMM_NOS3
ExpressionAtlasiP70313 baseline and differential
GenevisibleiP70313 MM

Interactioni

Subunit structurei

Homodimer. Interacts with NOSIP and NOSTRIN (By similarity). Interacts with HSP90AB1 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201807, 2 interactors
DIPiDIP-31086N
IntActiP70313, 3 interactors
STRINGi10090.ENSMUSP00000030834

Chemistry databases

BindingDBiP70313

Structurei

3D structure databases

ProteinModelPortaliP70313
SMRiP70313
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini519 – 702Flavodoxin-likePROSITE-ProRule annotationAdd BLAST184
Domaini755 – 1001FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST247

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni97 – 485Interaction with NOSIPBy similarityAdd BLAST389
Regioni490 – 509Calmodulin-bindingSequence analysisAdd BLAST20

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi31 – 68Pro-richAdd BLAST38

Sequence similaritiesi

Belongs to the NOS family.Curated

Phylogenomic databases

eggNOGiKOG1158 Eukaryota
COG0369 LUCA
COG4362 LUCA
GeneTreeiENSGT00840000129757
HOGENOMiHOG000220884
HOVERGENiHBG000159
InParanoidiP70313
KOiK13242
OMAiWEVGSIT
OrthoDBiEOG091G10Z0
TreeFamiTF324410

Family and domain databases

Gene3Di1.20.990.10, 1 hit
3.40.50.360, 1 hit
3.40.50.80, 1 hit
InterProiView protein in InterPro
IPR003097 FAD-binding_1
IPR017927 Fd_Rdtase_FAD-bd
IPR001094 Flavdoxin-like
IPR008254 Flavodoxin/NO_synth
IPR001709 Flavoprot_Pyr_Nucl_cyt_Rdtase
IPR029039 Flavoprotein-like_sf
IPR039261 FNR_nucleotide_bd
IPR023173 NADPH_Cyt_P450_Rdtase_alpha
IPR012144 NOS_euk
IPR004030 NOS_N
IPR036119 NOS_N_sf
IPR001433 OxRdtase_FAD/NAD-bd
IPR017938 Riboflavin_synthase-like_b-brl
PfamiView protein in Pfam
PF00667 FAD_binding_1, 1 hit
PF00258 Flavodoxin_1, 1 hit
PF00175 NAD_binding_1, 1 hit
PF02898 NO_synthase, 1 hit
PIRSFiPIRSF000333 NOS, 1 hit
PRINTSiPR00369 FLAVODOXIN
PR00371 FPNCR
SUPFAMiSSF52218 SSF52218, 1 hit
SSF52343 SSF52343, 1 hit
SSF56512 SSF56512, 1 hit
SSF63380 SSF63380, 1 hit
PROSITEiView protein in PROSITE
PS51384 FAD_FR, 1 hit
PS50902 FLAVODOXIN_LIKE, 1 hit
PS60001 NOS, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti50P → A in AAC52766 (PubMed:8764825).Curated1
Sequence conflicti298P → S in AAC52766 (PubMed:8764825).Curated1

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

Similar proteinsi

Entry informationi

Entry nameiNOS3_MOUSE
AccessioniPrimary (citable) accession number: P70313
Secondary accession number(s): O55056, Q7TSV7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: July 18, 2018
This is version 186 of the entry and version 4 of the sequence. See 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

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