Nitric oxide synthase, endothelial - Mus musculus (Mouse)

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P70313 (NOS3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 137. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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 names

Name:	Nos3
Synonyms:	Ecnos

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1202 AA.
Sequence status	Complete.
Protein existence	Evidence 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. May play a significant role in normal and abnormal limb development. Ref.3
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	Membrane › caveola By similarity. Cytoplasm › cytoskeleton 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.
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 By similarity.
Sequence similarities	Belongs to the NOS family. Contains 1 FAD-binding FR-type domain. Contains 1 flavodoxin-like domain.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Cytoskeleton Golgi apparatus Membrane
Ligand	Calcium Calmodulin-binding FAD FMN Heme Iron Metal-binding NADP Zinc
Molecular function	Oxidoreductase
PTM	Lipoprotein Myristate Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from mutant phenotype PubMed 15016731. Source: MGI arginine catabolic process Inferred from electronic annotation. Source: Compara blood vessel remodeling Inferred from mutant phenotype PubMed 9466966. Source: BHF-UCL endothelial cell migration Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from mutant phenotype PubMed 11732991. Source: MGI lipopolysaccharide-mediated signaling pathway Inferred from mutant phenotype PubMed 15647265. Source: MGI lung development Inferred from mutant phenotype PubMed 15016731. Source: MGI negative regulation of blood pressure Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of calcium ion transport Inferred from mutant phenotype PubMed 12074580. Source: MGI negative regulation of cell proliferation Inferred from mutant phenotype PubMed 9466966. Source: BHF-UCL negative regulation of hydrolase activity Inferred from mutant phenotype PubMed 12074580. Source: MGI negative regulation of muscle hyperplasia Inferred from mutant phenotype PubMed 9466966. Source: BHF-UCL negative regulation of potassium ion transport Inferred from mutant phenotype PubMed 12074580. Source: MGI nitric oxide biosynthetic process Inferred from mutant phenotype PubMed 15647265. Source: MGI nitric oxide mediated signal transduction Inferred from Biological aspect of Ancestor. Source: RefGenome ovulation from ovarian follicle Inferred from mutant phenotype PubMed 11779605. Source: MGI positive regulation of angiogenesis Inferred from mutant phenotype PubMed 9616228. Source: BHF-UCL 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 regulation of blood vessel size Inferred from mutant phenotype PubMed 9466966. Source: BHF-UCL regulation of sodium ion transport Inferred from mutant phenotype PubMed 12074580. Source: MGI regulation of systemic arterial blood pressure by endothelin Inferred from electronic annotation. Source: Compara regulation of the force of heart contraction by chemical signal Inferred from genetic interaction PubMed 18951881. Source: MGI response to fluid shear stress Inferred from electronic annotation. Source: Compara smooth muscle hyperplasia Inferred from mutant phenotype PubMed 9466966. Source: BHF-UCL
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell caveola Inferred from electronic annotation. Source: UniProtKB-SubCell cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Inferred from Biological aspect of Ancestor. Source: RefGenome nucleus Inferred from direct assay PubMed 11732991. Source: MGI
Molecular_function	FMN binding Inferred from electronic annotation. Source: InterPro NADP binding Inferred from electronic annotation. Source: InterPro NADPH-hemoprotein reductase activity Inferred from Biological aspect of Ancestor. Source: RefGenome arginine binding Inferred from electronic annotation. Source: Compara 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 mutant phenotype PubMed 15647265. Source: MGI tetrahydrobiopterin binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1202

1202

Nitric oxide synthase, endothelial

PRO_0000170944

Regions

Domain

519 – 702

184

Flavodoxin-like

Domain

755 – 1001

247

FAD-binding FR-type

Nucleotide binding

648 – 679

FMN By similarity

Nucleotide binding

792 – 803

FAD By similarity

Nucleotide binding

934 – 944

FAD By similarity

Nucleotide binding

1009 – 1027

NADP By similarity

Nucleotide binding

1107 – 1122

NADP By similarity

Region

97 – 485

389

Interaction with NOSIP By similarity

Region

490 – 509

Calmodulin-binding Potential

Compositional bias

31 – 68

Pro-rich

Sites

Metal binding

Zinc By similarity

Metal binding

Zinc By similarity

Metal binding

183

Iron (heme axial ligand) By similarity

Amino acid modifications

Modified residue

140

Phosphoserine By similarity

Modified residue

494

Phosphothreonine; by AMPK By similarity

Modified residue

632

Phosphoserine By similarity

Modified residue

1174

Phosphothreonine Ref.4

Modified residue

1176

Phosphoserine; by AMPK Probable

Lipidation

N-myristoyl glycine By similarity

Lipidation

S-palmitoyl cysteine By similarity

Lipidation

S-palmitoyl cysteine By similarity

Experimental info

Sequence conflict

P → A in AAC52766. Ref.1

Sequence conflict

298

P → S in AAC52766. Ref.1

Sequences

Sequence

Length

Mass (Da)

Tools

P70313 [UniParc].

Last modified July 27, 2011. Version 4.
Checksum: E1F65C43601F0937
Show »

FASTA

1,202

132,916

        10         20         30         40         50         60 
MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSQ APAPPSPTRP APDHSPPLTR 

        70         80         90        100        110        120 
PPDGPRFPRV KNWEVGSITY DTLSAQAQQD GPCTSRRCLG SLVFPRKLQS RPTQGPSPTE 

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

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

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

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

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

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

       490        500        510        520        530        540 
GSAAKGAGIT 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 ESLQLLPGLT HVHRRKMFQA TILSVENLQS SKSTRATILV 

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

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

       910        920        930        940        950        960 
EWKWFSCPTL LEVLEQFPSV ALPAPLILTQ LPLLQPRYYS VSSAPSAHPG EIHLTIAVLA 

       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 ATEGGMELDE 

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


GS

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1174 AND SER-1176, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U53142 mRNA. Translation: AAC52766.1. BC052636 mRNA. Translation: AAH52636.1. AF045940 Genomic DNA. Translation: AAC02553.1.
IPI	IPI00555127.
PIR	S71424.
RefSeq	NP_032739.3. NM_008713.4.
UniGene	Mm.258415.
3D structure databases
ProteinModelPortal	P70313.
SMR	P70313. Positions 66-480, 491-1176.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-31086N.
IntAct	P70313. 1 interaction.
STRING	10090.ENSMUSP00000030834.
PTM databases
PhosphoSite	P70313.
Proteomic databases
PaxDb	P70313.
PRIDE	P70313.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000030834; ENSMUSP00000030834; ENSMUSG00000028978.
GeneID	18127.
KEGG	mmu:18127.
UCSC	uc008wrd.2. mouse.
Organism-specific databases
CTD	4846.
MGI	MGI:97362. Nos3.
Phylogenomic databases
eggNOG	COG4362.
GeneTree	ENSGT00620000087711.
HOGENOM	HOG000220884.
HOVERGEN	HBG000159.
InParanoid	Q7TSV7.
KO	K13242.
OMA	QWGKLQV.
OrthoDB	EOG4ZS92B.
Gene expression databases
ArrayExpress	P70313.
Bgee	P70313.
CleanEx	MM_NOS3.
Genevestigator	P70313.
GermOnline	ENSMUSG00000028978. Mus musculus.
Family and domain databases
Gene3D	1.20.990.10. 1 hit. 3.90.340.10. 1 hit.
InterPro	IPR003097. FAD-binding_1. IPR017927. Fd_Rdtase_FAD-bd. IPR001094. Flavdoxin. IPR008254. Flavodoxin/NO_synth. IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase. IPR023173. NADPH_Cyt_P450_Rdtase_dom3. IPR004030. NO_synthase_oxygenase_dom. IPR026009. NOS. IPR012144. NOS_met. IPR001433. OxRdtase_FAD/NAD-bd. IPR017938. Riboflavin_synthase-like_b-brl. [Graphical view]
PANTHER	PTHR19384:SF5. PTHR19384:SF5. 1 hit.
Pfam	PF00667. FAD_binding_1. 1 hit. PF00258. Flavodoxin_1. 1 hit. PF00175. NAD_binding_1. 1 hit. PF02898. NO_synthase. 1 hit. [Graphical view]
PIRSF	PIRSF000333. NOS. 1 hit.
PRINTS	PR00369. FLAVODOXIN. PR00371. FPNCR.
SUPFAM	SSF56512. NO_synthase_oxygenase_reg. 1 hit. SSF63380. Riboflavin_synthase_like_b-brl. 1 hit.
PROSITE	PS51384. FAD_FR. 1 hit. PS50902. FLAVODOXIN_LIKE. 1 hit. PS60001. NOS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P70313.
ChEMBL	CHEMBL2643.
NextBio	293352.
SOURCE	Search...

Entry information

Entry name

NOS3_MOUSE

Accession

Primary (citable) accession number: P70313
Secondary accession number(s): O55056, Q7TSV7

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	July 27, 2011
Last modified:	May 29, 2013
This is version 137 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents