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Q62600 (NOS3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Nos3
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1202 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

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

Cofactor

Heme group.

Binds 1 FAD.

Binds 1 FMN.

Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.

Enzyme regulation

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

Subunit structure

Homodimer. Interacts with NOSIP and NOSTRIN By similarity.

Subcellular location

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.

Tissue specificity

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 stage

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

Post-translational modification

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.

Sequence similarities

Belongs to the NOS family.

Contains 1 FAD-binding FR-type domain.

Contains 1 flavodoxin-like domain.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Cytoskeleton
Golgi apparatus
Membrane
   LigandCalcium
Calmodulin-binding
FAD
Flavoprotein
FMN
Heme
Iron
Metal-binding
NADP
Zinc
   Molecular functionOxidoreductase
   PTMLipoprotein
Myristate
Palmitate
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaging

Inferred from expression pattern PubMed 18386218. Source: RGD

bone development

Inferred from expression pattern PubMed 10352094. Source: RGD

cellular response to cAMP

Inferred from expression pattern PubMed 8621775. Source: RGD

cellular response to growth factor stimulus

Inferred from expression pattern PubMed 18023142. Source: RGD

cellular response to heat

Inferred from expression pattern PubMed 15475520. Source: RGD

cellular response to magnesium ion

Inferred from expression pattern PubMed 15919495. Source: RGD

cellular response to organic cyclic compound

Inferred from expression pattern PubMed 18006476. Source: RGD

cellular response to transforming growth factor beta stimulus

Inferred from mutant phenotype PubMed 21191994. Source: RGD

cellular response to tumor necrosis factor

Inferred from expression pattern PubMed 22566503. Source: RGD

female pregnancy

Inferred from expression pattern PubMed 15642797PubMed 20630934. Source: RGD

negative regulation of blood pressure

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of smooth muscle cell proliferation

Inferred from mutant phenotype PubMed 12388111PubMed 14871555. Source: RGD

nitric oxide biosynthetic process

Inferred from mutant phenotype PubMed 12388111. Source: RGD

nitric oxide mediated signal transduction

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of apoptotic process

Inferred from mutant phenotype PubMed 21191994. Source: RGD

positive regulation of guanylate cyclase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of vasodilation

Inferred from Biological aspect of Ancestor. Source: RefGenome

response to activity

Inferred from expression pattern PubMed 19793134. Source: RGD

response to amino acid

Inferred from expression pattern PubMed 17535904. Source: RGD

response to axon injury

Inferred from expression pattern PubMed 15735325. Source: RGD

response to candesartan

Inferred from expression pattern PubMed 20535114. Source: RGD

response to corticosterone

Inferred from expression pattern PubMed 11304519. Source: RGD

response to cytokine

Inferred from expression pattern PubMed 17591083. Source: RGD

response to drug

Inferred from expression pattern PubMed 18390819. Source: RGD

response to estradiol

Inferred from direct assay PubMed 20233295. Source: RGD

response to ethanol

Inferred from expression pattern PubMed 18284813. Source: RGD

response to fructose

Inferred from expression pattern PubMed 12154112. Source: RGD

response to hyperoxia

Inferred from expression pattern PubMed 17937862. Source: RGD

response to hypoxia

Inferred from expression pattern PubMed 17947499. Source: RGD

response to ketone

Inferred from expression pattern PubMed 19717731. Source: RGD

response to lead ion

Inferred from expression pattern PubMed 17403586PubMed 19524414. Source: RGD

response to lipopolysaccharide

Inferred from expression pattern PubMed 18031380. Source: RGD

response to lipoprotein particle

Inferred from expression pattern PubMed 17918268. Source: RGD

response to mechanical stimulus

Inferred from expression pattern PubMed 19329460. Source: RGD

response to metal ion

Inferred from expression pattern PubMed 19446049. Source: RGD

response to organic cyclic compound

Inferred from expression pattern PubMed 17850874. Source: RGD

response to peptide

Inferred from expression pattern PubMed 15525466. Source: RGD

response to peptide hormone

Inferred from expression pattern PubMed 17895290. Source: RGD

response to salt

Inferred from expression pattern PubMed 21746791. Source: RGD

response to statin

Inferred from expression pattern PubMed 23091284. Source: RGD

retina development in camera-type eye

Inferred from expression pattern PubMed 16639026. Source: RGD

signal transduction

Inferred from mutant phenotype PubMed 12388111. Source: RGD

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 17574745. Source: RGD

apical part of cell

Inferred from direct assay PubMed 17123860. Source: RGD

caveola

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytoplasm

Inferred from direct assay PubMed 11943139. Source: BHF-UCL

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Inferred from direct assay PubMed 17892502. Source: RGD

membrane raft

Inferred from direct assay PubMed 15007069. Source: RGD

mitochondrion

Inferred from direct assay PubMed 21448354. Source: RGD

nucleolus

Inferred from direct assay PubMed 17574745. Source: RGD

nucleus

Inferred from direct assay PubMed 11943139. Source: BHF-UCL

plasma membrane

Inferred from direct assay PubMed 17892502. Source: RGD

sarcolemma

Inferred from direct assay PubMed 9111020. Source: RGD

vesicle membrane

Inferred from direct assay PubMed 21448354. Source: RGD

   Molecular_functionFMN binding

Inferred from electronic annotation. Source: InterPro

Hsp90 protein binding

Inferred from direct assay PubMed 15475520. Source: RGD

NADP binding

Inferred from electronic annotation. Source: InterPro

NADPH-hemoprotein reductase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

actin binding

Inferred from direct assay PubMed 15858215. Source: RGD

beta-catenin binding

Inferred from physical interaction PubMed 15858215. Source: RGD

cadherin binding

Inferred from physical interaction PubMed 15858215. Source: RGD

calmodulin binding

Inferred from direct assay PubMed 7545663. Source: RGD

flavin adenine dinucleotide binding

Inferred from electronic annotation. Source: InterPro

heme binding

Inferred from electronic annotation. Source: InterPro

iron ion binding

Inferred from electronic annotation. Source: InterPro

nitric-oxide synthase activity

Inferred from direct assay PubMed 12388111. Source: RGD

nitric-oxide synthase binding

Inferred from physical interaction PubMed 15858215. Source: RGD

protein binding

Inferred from physical interaction PubMed 22004458. Source: IntAct

scaffold protein binding

Inferred from physical interaction PubMed 12566108PubMed 15007069. Source: RGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CALMP621572EBI-7052018,EBI-397403From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 12021201Nitric oxide synthase, endothelial
PRO_0000170946

Regions

Domain519 – 702184Flavodoxin-like
Domain755 – 1001247FAD-binding FR-type
Nucleotide binding648 – 67932FMN By similarity
Nucleotide binding792 – 80312FAD By similarity
Nucleotide binding1009 – 102719NADP By similarity
Nucleotide binding1107 – 112216NADP By similarity
Region97 – 485389Interaction with NOSIP By similarity
Region489 – 50921Calmodulin-binding Potential
Compositional bias31 – 6838Pro-rich

Sites

Metal binding931Zinc By similarity
Metal binding981Zinc By similarity
Metal binding1831Iron (heme axial ligand) By similarity

Amino acid modifications

Modified residue1401Phosphoserine By similarity
Modified residue4941Phosphothreonine; by AMPK Ref.8
Modified residue6321Phosphoserine By similarity
Modified residue11741Phosphothreonine By similarity
Modified residue11761Phosphoserine; by AMPK Ref.8
Lipidation21N-myristoyl glycine By similarity
Lipidation151S-palmitoyl cysteine By similarity
Lipidation261S-palmitoyl cysteine By similarity

Experimental info

Sequence conflict232 – 2332QR → PS in AAC34677. Ref.2
Sequence conflict2491R → S in AAC34677. Ref.2
Sequence conflict298 – 3047Missing in AAT99567. Ref.3
Sequence conflict6001P → L in CAA09493. Ref.4
Sequence conflict7351R → G in AAT99567. Ref.3
Sequence conflict7391Q → P in AAT99567. Ref.3
Sequence conflict7481R → G in BAD15356. Ref.1
Sequence conflict7711S → T in AAT99567. Ref.3
Sequence conflict852 – 8543CTL → GTV in AAA96141. Ref.5
Sequence conflict9661G → V in BAD15356. Ref.1
Sequence conflict997 – 9982SF → FL in AAT99567. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q62600 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 52E905C3134E244D

FASTA1,202133,290
        10         20         30         40         50         60 
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSQ APVPPSPTRP APDHSPPLTR 

        70         80         90        100        110        120 
PPDGPKFPRV KNWEVGSITY DTLSAQAQQD GPCTPRRCLG SLVFPRKLQS RPTQGPSPTE 

       130        140        150        160        170        180 
QLLGQARDFI NQYYNSIKRS GSQAHEQRLQ EVEAEVVATG TYQLRESELV FGAKQAWRNA 

       190        200        210        220        230        240 
PRCVGRIQWG KLQVFDARDC RTAQEMFTYI CNHIKYATNR GNLRSAITVF PQRYAGRGDF 

       250        260        270        280        290        300 
RIWNSQLVRY AGYRQQDGSV RGDPANVEIT ELCIQHGWTP GNGRFDVLPL LLQAPDEPPE 

       310        320        330        340        350        360 
LFTLPPELVL EVPLEHPTLE WFAALGLRWY ALPAVSNMLL EIGGLEFPAA PFSGWYMSSE 

       370        380        390        400        410        420 
IGMRDLCDPH RYNILEDVAV CMDLDTRTTS SLWKDKAAVE INVAVLYSYQ LAKVTIVDHH 

       430        440        450        460        470        480 
AATASFMKHL ENEQKARGGC PADWAWIVPP ISGSLTPVFH QEMVNYFLSP AFRYQPDPWK 

       490        500        510        520        530        540 
GSAAKGTGIT RKKTFKEVAN AVKISASLMG TVMAKRVKAT ILYGSETGRA QSYAQQLGRL 

       550        560        570        580        590        600 
FRKAFDPRVL CMDEYDVVSL EHEALVLVVT STFGNGDPPE NGESFAAALM EMSGPYNSSP 

       610        620        630        640        650        660 
RPEQHKSYKI RFNSVSCSDP LVSSWRRKRK ESSNTDSAGA LGTLRFCVFG LGSRAYPHFC 

       670        680        690        700        710        720 
AFARAVDTRL EELGGERLLQ LGQGDELCGQ EEAFRGWAQA AFQAACETFC VGEDAKAAAR 

       730        740        750        760        770        780 
DIFSPKRSWK RQRYRLSTQA ESLQLLPRLT HVHRRKMFQA TILSVENLQS SKSTRATILV 

       790        800        810        820        830        840 
RLDTGSQEGL QYQPGDHIGV CPPNRPGLVE ALLSRVEDPP PSTEPVAVEQ LEKGSPGGPP 

       850        860        870        880        890        900 
PGWVRDPRLP PCTLRQALTY FLDITSPPSP RLLRLLSTLA EESSEQQELE ALSQDPRRYE 

       910        920        930        940        950        960 
EWKWFRCPTL LEVLEQFPSV ALPAPLILTQ LPLLQPRYYS VSSAPSAHPG EIHLTVAVLA 

       970        980        990       1000       1010       1020 
YRTQDGLGPL HYGVCSTWMS QLKAGDPVPC FIRGAPSFRL PPDPNLPCIL VGPGTGIAPF 

      1030       1040       1050       1060       1070       1080 
RGFWQDRLHD IEIKGLQPAP MTLVFGCRCS QLDHLYRDEV LDAQQRGVFG QVLTAFSRDP 

      1090       1100       1110       1120       1130       1140 
GSPKTYVQDL LRTELAAEVH RVLCLEQGHM FVCGDVTMAT SVLQTVQRIL ATEGSMELDE 

      1150       1160       1170       1180       1190       1200 
AGDVIGVLRD QQRYHEDIFG LTLRTQEVTS RIRTQSFSLQ ERQLRGAVPW SFDPPTQETP 


GS 

« Hide

References

[1]"NIDD, a novel DHHC-containing protein, targets neuronal nitric-oxide synthase (nNOS) to the synaptic membrane through a PDZ-dependent interaction and regulates nNOS activity."
Saitoh F., Tian Q.B., Okano A., Sakagami H., Kondo H., Suzuki T.
J. Biol. Chem. 279:29461-29468(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Downregulation of endothelial nitric oxide synthase (NOS III) in rat aorta following in-vivo hypoxia."
Toporsian M., Govindaraju K., Nagi M., Eidelman D., Thibault G., Ward M.E.
Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-288.
Strain: Sprague-Dawley.
[3]"Increased resistance to myocardial ischemia in the Brown Norway vs. Dahl S rat: role of nitric oxide synthase and Hsp90."
Shi Y., Hutchins W., Ogawa H., Chang C.-C., Pritchard K.A. Jr., Zhang C., Khampang P., Lazar J., Jacob H.J., Rafiee P., Baker J.E.
J. Mol. Cell. Cardiol. 38:625-635(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-1202.
Strain: SS/JrHsdMcwi.
Tissue: Heart.
[4]"Cloning and expression of the rat endothelial nitric oxide synthase."
Seidel B., Jiang L., Wolf G.
Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 473-672 AND 951-1192.
Tissue: Brain.
[5]"Differential expression and induction of mRNAs encoding two inducible nitric oxide synthases in rat kidney."
Mohaupt M.G., Elzie J.L., Ahn K.Y., Clapp W.L., Wilcox C.S., Kone B.C.
Kidney Int. 46:653-665(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 633-862.
Strain: Sprague-Dawley.
[6]"Endothelin-1, endothelin receptors and ecNOS mRNA expression in vital organs during traumatic shock in rats."
Minchenko A.G., Armstead V.E., Opentanova I.L., Lefer A.M.
Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1015-1132.
Strain: Sprague-Dawley.
Tissue: Lung.
[7]"Constitutive endothelial nitric oxide synthase gene expression is regulated during lung development."
Kawai N., Bloch D.B., Filippov G., Rabkina D., Suen H.C., Losty P.D., Janssens S.P., Zapol W.M., de la Monte S., Bloch K.D.
Am. J. Physiol. 268:L589-L595(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1018-1080.
Strain: Sprague-Dawley.
Tissue: Lung.
[8]"AMP-activated protein kinase phosphorylation of endothelial NO synthase."
Chen Z.P., Mitchelhill K.I., Michell B.J., Stapleton D., Rodriguez-Crespo I., Witters L.A., Power D.A., Ortiz de Montellano P.R., Kemp B.E.
FEBS Lett. 443:285-289(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-494 AND SER-1176.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRI51917.
I56979.
RefSeqNP_068610.1. NM_021838.2.
UniGeneRn.44265.

3D structure databases

ProteinModelPortalQ62600.
SMRQ62600. Positions 66-480, 728-1161.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-41833N.
IntActQ62600. 2 interactions.
MINTMINT-202608.

Chemistry

BindingDBQ62600.
ChEMBLCHEMBL1075230.

PTM databases

PhosphoSiteQ62600.

Proteomic databases

PRIDEQ62600.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID24600.
KEGGrno:24600.

Organism-specific databases

CTD4846.
RGD3186. Nos3.

Phylogenomic databases

eggNOGCOG4362.
HOGENOMHOG000220884.
HOVERGENHBG000159.
InParanoidQ62600.
KOK13242.
PhylomeDBQ62600.

Enzyme and pathway databases

SABIO-RKQ62600.

Gene expression databases

GenevestigatorQ62600.

Family and domain databases

Gene3D1.20.990.10. 1 hit.
3.40.50.360. 2 hits.
3.90.340.10. 1 hit.
InterProIPR003097. 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.
IPR004030. NO_synthase_oxygenase_dom.
IPR012144. NOS_euk.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
PF02898. NO_synthase. 1 hit.
[Graphical view]
PIRSFPIRSF000333. NOS. 1 hit.
PRINTSPR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMSSF52218. SSF52218. 1 hit.
SSF56512. SSF56512. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
PS60001. NOS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio603808.

Entry information

Entry nameNOS3_RAT
AccessionPrimary (citable) accession number: Q62600
Secondary accession number(s): O88672 expand/collapse secondary AC list , O89041, Q62734, Q68GV6, Q75NE4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2007
Last modified: June 11, 2014
This is version 137 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families