Reviewed, UniProtKB/Swiss-Prot Q62600 (NOS3_RAT)

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

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

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 transcript 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	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.
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.
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	aging Inferred from expression pattern. Source: RGD negative regulation of smooth muscle cell proliferation Inferred from mutant phenotype. Source: RGD nitric oxide biosynthetic process Inferred from mutant phenotype. Source: RGD oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to amino acid stimulus Inferred from expression pattern. Source: RGD response to cytokine stimulus Inferred from expression pattern. Source: RGD response to drug Inferred from expression pattern. Source: RGD response to estradiol stimulus Inferred from expression pattern. Source: RGD response to ethanol Inferred from expression pattern. Source: RGD response to hyperoxia Inferred from expression pattern. Source: RGD response to hypoxia Inferred from expression pattern. Source: RGD response to lead ion Inferred from expression pattern. Source: RGD response to lipopolysaccharide Inferred from expression pattern. Source: RGD response to lipoprotein stimulus Inferred from expression pattern. Source: RGD response to organic cyclic substance Inferred from expression pattern. Source: RGD response to peptide hormone stimulus Inferred from expression pattern. Source: RGD
Cellular component	Golgi apparatus Inferred from direct assay. Source: RGD apical part of cell Inferred from direct assay. Source: RGD caveola Inferred from electronic annotation. Source: UniProtKB-SubCell cytoskeleton Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from direct assay. Source: RGD soluble fraction Inferred from direct assay. Source: RGD
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 direct assay. Source: RGD 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_0000170946
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	1009 – 1027	19	NADP By similarity
	Nucleotide binding	1107 – 1122	16	NADP By similarity
	Region	97 – 485	389	Interaction with NOSIP By similarity
	Region	489 – 509	21	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 By similarity
	Modified residue	1176	1	Phosphoserine By similarity
	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	232 – 233	2	QR → PS in AAC34677. Ref.2
	Sequence conflict	249	1	R → S in AAC34677. Ref.2
	Sequence conflict	298 – 304	7	Missing in AAT99567. Ref.3
	Sequence conflict	600	1	P → L in CAA09493. Ref.4
	Sequence conflict	735	1	R → G in AAT99567. Ref.3
	Sequence conflict	739	1	Q → P in AAT99567. Ref.3
	Sequence conflict	748	1	R → G in BAD15356. Ref.1
	Sequence conflict	771	1	S → T in AAT99567. Ref.3
	Sequence conflict	852 – 854	3	CTL → GTV in AAA96141. Ref.5
	Sequence conflict	966	1	G → V in BAD15356. Ref.1
	Sequence conflict	997 – 998	2	SF → FL in AAT99567. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q62600-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 52E905C3134E244D	FASTA	1,202	133,290
	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

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: 15105416] [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: 15808839] [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: 7527874] [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: 7537461] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1018-1080. Strain: Sprague-Dawley. Tissue: Lung.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00206975.
PIR	I51917. I56979.
RefSeq	NP_068610.1.
UniGene	Rn.44265
3D structure databases
HSSP	HSSP built from PDB template 3NOS based on UniProtKB P29474.
SMR	Q62600. Positions 64-479.
ModBase	Search...
PTM databases
PhosphoSite	Q62600.
Genome annotation databases
Ensembl	ENSRNOG00000009348. Rattus norvegicus. [Contig view]
GeneID	24600.
KEGG	rno:24600.
Organism-specific databases
RGD	3186. Nos3.
Phylogenomic databases
HOVERGEN	Q62600.
Enzyme and pathway databases
BRENDA	1.14.13.39. 248.
Gene expression databases
ArrayExpress	Q62600.
GermOnline	ENSRNOG00000009348. Rattus norvegicus.
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
NextBio	603808.

Entry information

Entry name

NOS3_RAT

Accession

Primary (citable) accession number: Q62600
Secondary accession number(s): O88672 , O89041, Q62734, Q68GV6, Q75NE4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 91 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)