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Protein

Nitric oxide synthase, endothelial

Gene

Nos3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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

  • actin monomer binding Source: MGI
  • arginine binding Source: MGI
  • flavin adenine dinucleotide binding Source: InterPro
  • FMN binding Source: InterPro
  • heme binding Source: MGI
  • iron ion binding Source: InterPro
  • NADP binding Source: InterPro
  • nitric-oxide synthase activity Source: MGI
  • scaffold protein binding Source: BHF-UCL
  • tetrahydrobiopterin binding Source: MGI

GO - Biological processi

  • angiogenesis Source: MGI
  • arginine catabolic process Source: MGI
  • blood vessel remodeling Source: BHF-UCL
  • endothelial cell migration Source: MGI
  • in utero embryonic development Source: MGI
  • lipopolysaccharide-mediated signaling pathway Source: MGI
  • lung development Source: MGI
  • 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
  • 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 guanylate cyclase activity Source: MGI
  • positive regulation of vasodilation Source: GO_Central
  • 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 fluid shear stress Source: Ensembl
  • 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

BRENDAi1.14.13.39. 3474.
ReactomeiR-MMU-1222556. ROS, RNS production in response to bacteria.
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:97362. Nos3.

Subcellular locationi

GO - Cellular componenti

  • caveola Source: MGI
  • cytoplasm Source: MGI
  • cytoskeleton Source: UniProtKB-SubCell
  • Golgi apparatus Source: UniProtKB-SubCell
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Golgi apparatus, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2643.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedBy 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 residuei494 – 4941Phosphothreonine; by AMPKBy similarity
Modified residuei614 – 6141PhosphoserineCombined sources
Modified residuei632 – 6321PhosphoserineBy similarity
Modified residuei637 – 6371PhosphoserineBy similarity
Modified residuei835 – 8351PhosphoserineBy similarity
Modified residuei1174 – 11741PhosphothreonineCombined sources
Modified residuei1176 – 11761Phosphoserine; by AMPKCombined sourcesCurated
Modified residuei1178 – 11781PhosphoserineCombined sources

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.
PhosphoSiteiP70313.

Expressioni

Gene expression databases

BgeeiENSMUSG00000028978.
CleanExiMM_NOS3.
ExpressionAtlasiP70313. baseline and differential.
GenevisibleiP70313. MM.

Interactioni

Subunit structurei

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

GO - Molecular functioni

  • actin monomer binding Source: MGI
  • scaffold protein binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi201807. 1 interaction.
DIPiDIP-31086N.
IntActiP70313. 2 interactions.
STRINGi10090.ENSMUSP00000030834.

Chemistry

BindingDBiP70313.

Structurei

3D structure databases

ProteinModelPortaliP70313.
SMRiP70313. Positions 67-479, 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

eggNOGiKOG1158. Eukaryota.
COG0369. LUCA.
COG4362. LUCA.
GeneTreeiENSGT00840000129757.
HOGENOMiHOG000220884.
HOVERGENiHBG000159.
InParanoidiP70313.
KOiK13242.
OMAiWGKLQVF.
OrthoDBiEOG091G10Z0.
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-like.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like_dom.
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.
CCDSiCCDS19117.1.
PIRiS71424.
RefSeqiNP_032739.3. NM_008713.4.
UniGeneiMm.258415.

3D structure databases

ProteinModelPortaliP70313.
SMRiP70313. Positions 67-479, 491-1176.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201807. 1 interaction.
DIPiDIP-31086N.
IntActiP70313. 2 interactions.
STRINGi10090.ENSMUSP00000030834.

Chemistry

BindingDBiP70313.
ChEMBLiCHEMBL2643.

PTM databases

iPTMnetiP70313.
PhosphoSiteiP70313.

Proteomic databases

MaxQBiP70313.
PaxDbiP70313.
PRIDEiP70313.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4846.
MGIiMGI:97362. Nos3.

Phylogenomic databases

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

Enzyme and pathway databases

BRENDAi1.14.13.39. 3474.
ReactomeiR-MMU-1222556. ROS, RNS production in response to bacteria.
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.

Miscellaneous databases

PROiP70313.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000028978.
CleanExiMM_NOS3.
ExpressionAtlasiP70313. baseline and differential.
GenevisibleiP70313. MM.

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-like.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like_dom.
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]
ProtoNetiSearch...

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: September 7, 2016
This is version 169 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.