Reviewed, UniProtKB/Swiss-Prot P70313 (NOS3_MOUSE)

Names and origin

Protein names

Recommended name:
    Nitric oxide synthase, endothelial
    EC=1.14.13.39
Alternative name(s):
    Endothelial NOS
      Short name=eNOS
    EC-NOS
    NOS type III
      Short name=NOSIII
    Constitutive NOS
      Short name=cNOS

Gene names

Name:	Nos3
Synonyms:	Ecnos

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1202 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
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.2
Catalytic activity	L-arginine + n NADPH + n H+ + m O2 = citrulline + nitric oxide + n NADP+.
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.
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
Gene Ontology (GO)
Biological process	angiogenesis Inferred from mutant phenotype. Source: MGI blood vessel remodeling Inferred from mutant phenotype. Source: UniProtKB lipopolysaccharide-mediated signaling pathway Inferred from mutant phenotype. Source: MGI lung development Inferred from mutant phenotype. Source: MGI negative regulation of calcium ion transport Inferred from mutant phenotype. Source: MGI negative regulation of hydrolase activity Inferred from mutant phenotype. Source: MGI negative regulation of muscle hyperplasia Inferred from mutant phenotype. Source: UniProtKB negative regulation of potassium ion transport Inferred from mutant phenotype. Source: MGI nitric oxide biosynthetic process Inferred from mutant phenotype. Source: MGI ovulation from ovarian follicle Inferred from mutant phenotype. Source: MGI oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of angiogenesis Inferred from mutant phenotype. Source: UniProtKB regulation of blood vessel size Inferred from mutant phenotype. Source: UniProtKB regulation of sodium ion transport Inferred from mutant phenotype. Source: MGI smooth muscle hyperplasia Inferred from mutant phenotype. Source: UniProtKB
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
Molecular function	FAD binding Inferred from electronic annotation. Source: InterPro FMN binding Inferred from electronic annotation. Source: InterPro NADP or NADPH binding Inferred from electronic annotation. Source: InterPro calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW calmodulin binding Inferred from electronic annotation. Source: UniProtKB-KW electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro nitric-oxide synthase activity Inferred from mutant phenotype. Source: MGI zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 1202	1201	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	32	FMN By similarity
	Nucleotide binding	792 – 803	12	FAD By similarity
	Nucleotide binding	934 – 944	11	FAD By similarity
	Nucleotide binding	1009 – 1027	19	NADP By similarity
	Nucleotide binding	1107 – 1122	16	NADP By similarity
	Region	97 – 485	389	Interaction with NOSIP By similarity
	Region	490 – 509	20	Calmodulin-binding Potential
	Compositional bias	31 – 68	38	Pro-rich
Sites
	Metal binding	93	1	Zinc By similarity
	Metal binding	98	1	Zinc By similarity
	Metal binding	183	1	Iron (heme axial ligand) By similarity
Amino acid modifications
	Modified residue	80	1	Phosphotyrosine By similarity
	Modified residue	494	1	Phosphothreonine By similarity
	Modified residue	632	1	Phosphoserine By similarity
	Modified residue	1174	1	Phosphothreonine Ref.3
	Modified residue	1176	1	Phosphoserine Ref.3
	Lipidation	2	1	N-myristoyl glycine By similarity
	Lipidation	15	1	S-palmitoyl cysteine By similarity
	Lipidation	26	1	S-palmitoyl cysteine By similarity
Experimental info
	Sequence conflict	50	1	A → P in AAC02553. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P70313-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 8570874AA59643B2	FASTA	1,202	132,880
	10 20 30 40 50 60 MGNLKSVGQE PGPPCGLGLG LGLGLCGKQG PASPAPEPSQ APAPPSPTRA 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 LLQAPDESPE 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

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: 8764825] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal heart.
[2]	"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: 9843834] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-54, FUNCTION.
[3]	"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: 17242355] [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
EMBLGenBankDDBJ	U53142 mRNA. Translation: AAC52766.1. AF045940 Genomic DNA. Translation: AAC02553.1.
IPI	IPI00555127.
PIR	S71424.
RefSeq	NP_032739.3.
UniGene	Mm.258415
3D structure databases
HSSP	HSSP built from PDB template 1M9M based on UniProtKB P29474.
SMR	P70313. Positions 64-479.
ModBase	Search...
Protein-protein interaction databases
STRING	P70313.
PTM databases
PhosphoSite	P70313.
Proteomic databases
PRIDE	P70313.
Genome annotation databases
Ensembl	ENSMUST00000030834; ENSMUSP00000030834; ENSMUSG00000028978; Mus musculus. [Genome view]
GeneID	18127.
KEGG	mmu:18127.
Organism-specific databases
MGI	MGI:97362. Nos3.
Phylogenomic databases
HOGENOM	P70313.
HOVERGEN	P70313.
Enzyme and pathway databases
BRENDA	1.14.13.39. 244.
Gene expression databases
ArrayExpress	P70313.
Bgee	P70313.
CleanEx	MM_NOS3.
Genevestigator	P70313.
GermOnline	ENSMUSG00000028978. Mus musculus.
Family and domain databases
InterPro	IPR003097. FAD-binding_1. IPR017927. Fd_Rdtase_FAD-bd. IPR001094. Flavdoxin-like. IPR008254. Flavodoxin/NO_synth. IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase. IPR012144. Nitric-oxide_synthase. IPR004030. NO_synthase_oxygenase_reg. IPR001433. OxRdtase_FAD/NAD_bd. [Graphical view]
Gene3D	G3DSA:3.90.340.10. NO_synthase_oxygenase_reg. 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.
PROSITE	PS51384. FAD_FR. 1 hit. PS50902. FLAVODOXIN_LIKE. 1 hit. PS60001. NOS. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

NOS3_MOUSE

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	January 23, 2007
Last modified:	October 13, 2009
This is version 104 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)