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Protein

Nitric oxide synthase, endothelial

Gene

Nos3

Organism
Rattus norvegicus (Rat)
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.

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:

Activity 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 bindingi1009 – 1027NADPBy similarityAdd BLAST19
Nucleotide bindingi1107 – 1122NADPBy similarityAdd BLAST16

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi1.14.13.39 5301
SABIO-RKiQ62600

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3186 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

ChEMBLiCHEMBL1075230

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001709462 – 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 AMPK1 Publication1
Modified residuei614PhosphoserineBy similarity1
Modified residuei632PhosphoserineBy similarity1
Modified residuei637PhosphoserineBy similarity1
Modified residuei835PhosphoserineBy similarity1
Modified residuei1174PhosphothreonineCombined sources1
Modified residuei1176Phosphoserine; by AMPKCombined sources1 Publication1
Modified residuei1178PhosphoserineBy similarity1

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.1 Publication

Keywords - PTMi

Lipoprotein, Myristate, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ62600
PRIDEiQ62600

PTM databases

iPTMnetiQ62600
PhosphoSitePlusiQ62600
SwissPalmiQ62600

Expressioni

Tissue specificityi

Expressed constitutively by vascular endothelium. Detected in alveolar and serosal epithelial cells as well as in endothelial cells in one day old rat. In adult lung, detected in rare endothelial cells.

Developmental stagei

Detected at high levels in lung during the late fetal and postnatal period and at lower levels in adult.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
CALMP621572EBI-7052018,EBI-397403From Bos taurus.

GO - Molecular functioni

Protein-protein interaction databases

CORUMiQ62600
DIPiDIP-41833N
IntActiQ62600, 2 interactors
MINTiQ62600
STRINGi10116.ENSRNOP00000013058

Chemistry databases

BindingDBiQ62600

Structurei

3D structure databases

ProteinModelPortaliQ62600
SMRiQ62600
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
Regioni489 – 509Calmodulin-bindingSequence analysisAdd BLAST21

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
HOGENOMiHOG000220884
HOVERGENiHBG000159
InParanoidiQ62600
KOiK13242
PhylomeDBiQ62600

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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.iShow all

Q62600-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSQ APVPPSPTRP
60 70 80 90 100
APDHSPPLTR PPDGPKFPRV KNWEVGSITY DTLSAQAQQD GPCTPRRCLG
110 120 130 140 150
SLVFPRKLQS RPTQGPSPTE QLLGQARDFI NQYYNSIKRS GSQAHEQRLQ
160 170 180 190 200
EVEAEVVATG TYQLRESELV FGAKQAWRNA PRCVGRIQWG KLQVFDARDC
210 220 230 240 250
RTAQEMFTYI CNHIKYATNR GNLRSAITVF PQRYAGRGDF RIWNSQLVRY
260 270 280 290 300
AGYRQQDGSV RGDPANVEIT ELCIQHGWTP GNGRFDVLPL LLQAPDEPPE
310 320 330 340 350
LFTLPPELVL EVPLEHPTLE WFAALGLRWY ALPAVSNMLL EIGGLEFPAA
360 370 380 390 400
PFSGWYMSSE IGMRDLCDPH RYNILEDVAV CMDLDTRTTS SLWKDKAAVE
410 420 430 440 450
INVAVLYSYQ LAKVTIVDHH AATASFMKHL ENEQKARGGC PADWAWIVPP
460 470 480 490 500
ISGSLTPVFH QEMVNYFLSP AFRYQPDPWK GSAAKGTGIT 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 ESLQLLPRLT
760 770 780 790 800
HVHRRKMFQA TILSVENLQS SKSTRATILV RLDTGSQEGL 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
EWKWFRCPTL LEVLEQFPSV ALPAPLILTQ LPLLQPRYYS VSSAPSAHPG
960 970 980 990 1000
EIHLTVAVLA 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 ATEGSMELDE AGDVIGVLRD
1160 1170 1180 1190 1200
QQRYHEDIFG LTLRTQEVTS RIRTQSFSLQ ERQLRGAVPW SFDPPTQETP

GS
Length:1,202
Mass (Da):133,290
Last modified:January 23, 2007 - v4
Checksum:i52E905C3134E244D
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F1LQC7F1LQC7_RAT
Nitric oxide synthase
Nos3
1,202Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti232 – 233QR → PS in AAC34677 (Ref. 2) Curated2
Sequence conflicti249R → S in AAC34677 (Ref. 2) Curated1
Sequence conflicti298 – 304Missing in AAT99567 (PubMed:15808839).Curated7
Sequence conflicti600P → L in CAA09493 (Ref. 4) Curated1
Sequence conflicti735R → G in AAT99567 (PubMed:15808839).Curated1
Sequence conflicti739Q → P in AAT99567 (PubMed:15808839).Curated1
Sequence conflicti748R → G in BAD15356 (PubMed:15105416).Curated1
Sequence conflicti771S → T in AAT99567 (PubMed:15808839).Curated1
Sequence conflicti852 – 854CTL → GTV in AAA96141 (PubMed:7527874).Curated3
Sequence conflicti966G → V in BAD15356 (PubMed:15105416).Curated1
Sequence conflicti997 – 998SF → FL in AAT99567 (PubMed:15808839).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB176831 mRNA Translation: BAD15356.1
AF085195 mRNA Translation: AAC34677.1
AY695391 mRNA Translation: AAT99567.1
AJ011115 mRNA Translation: CAA09493.1
AJ011116 mRNA Translation: CAA09494.1
U02534 mRNA Translation: AAA96141.1
AF093837 mRNA Translation: AAC64178.1
U18336 mRNA Translation: AAC52188.1
PIRiI51917
I56979
RefSeqiNP_068610.1, NM_021838.2
UniGeneiRn.44265

Genome annotation databases

GeneIDi24600
KEGGirno:24600

Similar proteinsi

Entry informationi

Entry nameiNOS3_RAT
AccessioniPrimary (citable) accession number: Q62600
Secondary accession number(s): O88672
, O89041, Q62734, Q68GV6, Q75NE4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2007
Last modified: September 12, 2018
This is version 172 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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