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P29474 (NOS3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 177. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1203 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. Ref.7

Isoform eNOS13C:Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1. Ref.7

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. Ref.20 Ref.21

Subunit structure

Homodimer. Interacts with NOSIP and NOSTRIN. Ref.20 Ref.21

Subcellular location

Cell membrane. Membranecaveola. Cytoplasmcytoskeleton. Golgi apparatus. 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. Ref.20 Ref.21 Ref.23 Ref.24

Tissue specificity

Platelets, placenta, liver and kidney. Ref.19

Post-translational modification

Phosphorylation by AMPK at Ser-1177 in the presence of Ca2+-calmodulin (CaM) activates activity. In absence of Ca2+-calmodulin, AMPK also phosphorylates Thr-495, resulting in inhibition of activity By similarity. Phosphorylation of Ser-114 by CDK5 reduces activity.

Polymorphism

Variation in NOS3 seem to be associated with susceptibility to coronary spasm.

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
   Coding sequence diversityAlternative splicing
Polymorphism
   LigandCalcium
Calmodulin-binding
FAD
Flavoprotein
FMN
Heme
Iron
Metal-binding
NADP
Zinc
   Molecular functionOxidoreductase
   PTMLipoprotein
Myristate
Palmitate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: Ensembl

arginine catabolic process

Inferred from direct assay Ref.1PubMed 7488039. Source: BHF-UCL

blood coagulation

Traceable author statement. Source: Reactome

blood vessel remodeling

Inferred from sequence or structural similarity. Source: BHF-UCL

endothelial cell migration

Inferred from mutant phenotype PubMed 8999856. Source: BHF-UCL

in utero embryonic development

Inferred from electronic annotation. Source: Ensembl

interaction with host

Traceable author statement. Source: Reactome

lipopolysaccharide-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

lung development

Inferred from electronic annotation. Source: Ensembl

mitochondrion organization

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of blood pressure

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of calcium ion transport

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of hydrolase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of muscle hyperplasia

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of platelet activation

Non-traceable author statement PubMed 7504210. Source: BHF-UCL

negative regulation of potassium ion transport

Inferred from electronic annotation. Source: Ensembl

nitric oxide biosynthetic process

Inferred from direct assay Ref.1PubMed 7488039. Source: BHF-UCL

nitric oxide mediated signal transduction

Inferred from Biological aspect of Ancestor. Source: RefGenome

nitric oxide metabolic process

Traceable author statement. Source: Reactome

ovulation from ovarian follicle

Inferred from electronic annotation. Source: Ensembl

phagosome maturation

Traceable author statement. Source: Reactome

positive regulation of angiogenesis

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of guanylate cyclase activity

Inferred from mutant phenotype PubMed 17502619. Source: BHF-UCL

positive regulation of vasodilation

Non-traceable author statement PubMed 18048451. Source: BHF-UCL

regulation of blood pressure

Non-traceable author statement PubMed 7504210. Source: BHF-UCL

regulation of blood vessel size

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of nitric-oxide synthase activity

Traceable author statement. Source: Reactome

regulation of sodium ion transport

Inferred from electronic annotation. Source: Ensembl

regulation of systemic arterial blood pressure by endothelin

Inferred from mutant phenotype PubMed 8999856. Source: BHF-UCL

regulation of the force of heart contraction by chemical signal

Inferred from electronic annotation. Source: Ensembl

response to fluid shear stress

Inferred from expression pattern PubMed 10376603. Source: BHF-UCL

response to heat

Non-traceable author statement PubMed 18048451. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

smooth muscle hyperplasia

Inferred from sequence or structural similarity. Source: BHF-UCL

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

caveola

Inferred from direct assay PubMed 17502619PubMed 17848177. Source: BHF-UCL

cytoplasm

Inferred from direct assay PubMed 9794441. Source: BHF-UCL

cytoskeleton

Inferred from electronic annotation. Source: UniProtKB-SubCell

cytosol

Traceable author statement. Source: Reactome

endocytic vesicle membrane

Traceable author statement. Source: Reactome

nucleus

Inferred from sequence or structural similarity. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionFMN binding

Non-traceable author statement PubMed 7488039. Source: BHF-UCL

NADP binding

Non-traceable author statement PubMed 7488039. Source: BHF-UCL

NADPH-hemoprotein reductase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

actin monomer binding

Inferred from physical interaction PubMed 17502619. Source: BHF-UCL

arginine binding

Inferred from direct assay PubMed 7488039. Source: BHF-UCL

cadmium ion binding

Non-traceable author statement PubMed 7488039. Source: BHF-UCL

flavin adenine dinucleotide binding

Non-traceable author statement PubMed 7488039. Source: BHF-UCL

heme binding

Inferred from direct assay PubMed 7488039. Source: BHF-UCL

iron ion binding

Inferred from electronic annotation. Source: InterPro

nitric-oxide synthase activity

Inferred from direct assay Ref.1PubMed 7488039. Source: BHF-UCL

protein binding

Inferred from physical interaction Ref.20PubMed 12855682. Source: UniProtKB

tetrahydrobiopterin binding

Inferred from direct assay PubMed 7488039. Source: BHF-UCL

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P29474-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform eNOS13C (identifier: P29474-2)

The sequence of this isoform differs from the canonical sequence as follows:
     584-625: ESFAAALMEM...ISCSDPLVSS → EGLTLWPRLE...VGTTGACHDA
     626-1203: Missing.
Note: Lacks eNOS activity.
Isoform eNOS13B (identifier: P29474-3)

The sequence of this isoform differs from the canonical sequence as follows:
     585-614: SFAAALMEMSGPYNSSPRPEQHKSYKIRFN → RWGFAMLPRLVSNSWVQAIHLPRPPKVLRL
     615-1203: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 12031202Nitric oxide synthase, endothelial
PRO_0000170943

Regions

Domain520 – 703184Flavodoxin-like
Domain756 – 1002247FAD-binding FR-type
Nucleotide binding649 – 68032FMN By similarity
Nucleotide binding793 – 80412FAD By similarity
Nucleotide binding935 – 94511FAD By similarity
Nucleotide binding1010 – 102819NADP By similarity
Nucleotide binding1108 – 112316NADP By similarity
Region98 – 486389Interaction with NOSIP
Region491 – 51020Calmodulin-binding Potential

Sites

Metal binding941Zinc
Metal binding991Zinc
Metal binding1841Iron (heme axial ligand)

Amino acid modifications

Modified residue1141Phosphoserine; by CDK5 Ref.25
Modified residue1411Phosphoserine By similarity
Modified residue4951Phosphothreonine; by AMPK Ref.22
Modified residue6331Phosphoserine By similarity
Modified residue11751Phosphothreonine By similarity
Modified residue11771Phosphoserine; by AMPK Ref.22
Lipidation21N-myristoyl glycine By similarity
Lipidation151S-palmitoyl cysteine By similarity
Lipidation261S-palmitoyl cysteine By similarity

Natural variations

Alternative sequence584 – 62542ESFAA…PLVSS → EGLTLWPRLECSSTITAHCS LNLLDSSNPPTSTSQVVGTT GACHDA in isoform eNOS13C.
VSP_042625
Alternative sequence585 – 61430SFAAA…KIRFN → RWGFAMLPRLVSNSWVQAIH LPRPPKVLRL in isoform eNOS13B.
VSP_045495
Alternative sequence615 – 1203589Missing in isoform eNOS13B.
VSP_045496
Alternative sequence626 – 1203578Missing in isoform eNOS13C.
VSP_042626
Natural variant1121R → Q. Ref.12
Corresponds to variant rs3918166 [ dbSNP | Ensembl ].
VAR_031218
Natural variant2981E → D in susceptibility to coronary spasm. Ref.7 Ref.10 Ref.12 Ref.16 Ref.29 Ref.30
Corresponds to variant rs1799983 [ dbSNP | Ensembl ].
VAR_008037
Natural variant4741R → C in a colorectal cancer sample; somatic mutation. Ref.31
VAR_036303
Natural variant6021R → Q in a colorectal cancer sample; somatic mutation. Ref.31
VAR_036304
Natural variant6651R → H.
Corresponds to variant rs7792133 [ dbSNP | Ensembl ].
VAR_061377
Natural variant8271V → M. Ref.12
Corresponds to variant rs3918232 [ dbSNP | Ensembl ].
VAR_031219
Natural variant8851R → M. Ref.12
Corresponds to variant rs3918201 [ dbSNP | Ensembl ].
VAR_031220
Natural variant9821Q → L. Ref.12
Corresponds to variant rs3918234 [ dbSNP | Ensembl ].
VAR_031221

Experimental info

Mutagenesis1141S → A: Reduced nitrite (NO) production. Ref.25
Sequence conflict531S → R in AAA36373. Ref.17
Sequence conflict1681S → G in BAG37648. Ref.10
Sequence conflict4141K → R in BAF85617. Ref.10
Sequence conflict4891G → S in AAD14336. Ref.18
Sequence conflict5671V → W in CAA53950. Ref.5
Sequence conflict11501R → RQ in BAA05652. Ref.6
Sequence conflict11941D → E in CAA53950. Ref.5

Secondary structure

............................................................................... 1203
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: CD9E60FA277B22C6

FASTA1,203133,289
        10         20         30         40         50         60 
MGNLKSVAQE PGPPCGLGLG LGLGLCGKQG PATPAPEPSR APASLLPPAP EHSPPSSPLT 

        70         80         90        100        110        120 
QPPEGPKFPR VKNWEVGSIT YDTLSAQAQQ DGPCTPRRCL GSLVFPRKLQ GRPSPGPPAP 

       130        140        150        160        170        180 
EQLLSQARDF INQYYSSIKR SGSQAHEQRL QEVEAEVAAT GTYQLRESEL VFGAKQAWRN 

       190        200        210        220        230        240 
APRCVGRIQW GKLQVFDARD CRSAQEMFTY ICNHIKYATN RGNLRSAITV FPQRCPGRGD 

       250        260        270        280        290        300 
FRIWNSQLVR YAGYRQQDGS VRGDPANVEI TELCIQHGWT PGNGRFDVLP LLLQAPDEPP 

       310        320        330        340        350        360 
ELFLLPPELV LEVPLEHPTL EWFAALGLRW YALPAVSNML LEIGGLEFPA APFSGWYMST 

       370        380        390        400        410        420 
EIGTRNLCDP HRYNILEDVA VCMDLDTRTT SSLWKDKAAV EINVAVLHSY QLAKVTIVDH 

       430        440        450        460        470        480 
HAATASFMKH LENEQKARGG CPADWAWIVP PISGSLTPVF HQEMVNYFLS PAFRYQPDPW 

       490        500        510        520        530        540 
KGSAAKGTGI TRKKTFKEVA NAVKISASLM GTVMAKRVKA TILYGSETGR AQSYAQQLGR 

       550        560        570        580        590        600 
LFRKAFDPRV LCMDEYDVVS LEHETLVLVV TSTFGNGDPP ENGESFAAAL MEMSGPYNSS 

       610        620        630        640        650        660 
PRPEQHKSYK IRFNSISCSD PLVSSWRRKR KESSNTDSAG ALGTLRFCVF GLGSRAYPHF 

       670        680        690        700        710        720 
CAFARAVDTR LEELGGERLL QLGQGDELCG QEEAFRGWAQ AAFQAACETF CVGEDAKAAA 

       730        740        750        760        770        780 
RDIFSPKRSW KRQRYRLSAQ AEGLQLLPGL IHVHRRKMFQ ATIRSVENLQ SSKSTRATIL 

       790        800        810        820        830        840 
VRLDTGGQEG LQYQPGDHIG VCPPNRPGLV EALLSRVEDP PAPTEPVAVE QLEKGSPGGP 

       850        860        870        880        890        900 
PPGWVRDPRL PPCTLRQALT FFLDITSPPS PQLLRLLSTL AEEPREQQEL EALSQDPRRY 

       910        920        930        940        950        960 
EEWKWFRCPT LLEVLEQFPS VALPAPLLLT QLPLLQPRYY SVSSAPSTHP GEIHLTVAVL 

       970        980        990       1000       1010       1020 
AYRTQDGLGP LHYGVCSTWL SQLKPGDPVP CFIRGAPSFR LPPDPSLPCI LVGPGTGIAP 

      1030       1040       1050       1060       1070       1080 
FRGFWQERLH DIESKGLQPT PMTLVFGCRC SQLDHLYRDE VQNAQQRGVF GRVLTAFSRE 

      1090       1100       1110       1120       1130       1140 
PDNPKTYVQD ILRTELAAEV HRVLCLERGH MFVCGDVTMA TNVLQTVQRI LATEGDMELD 

      1150       1160       1170       1180       1190       1200 
EAGDVIGVLR DQQRYHEDIF GLTLRTQEVT SRIRTQSFSL QERQLRGAVP WAFDPPGSDT 


NSP 

« Hide

Isoform eNOS13C [UniParc].

Checksum: 057DDC37143265B6
Show »

FASTA62968,980
Isoform eNOS13B [UniParc].

Checksum: A567DB899BD1372E
Show »

FASTA61467,876

References

« Hide 'large scale' references
[1]"Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase."
Janssens S.P., Shimouchi A., Quertermous T., Bloch D.B., Bloch K.D.
J. Biol. Chem. 267:14519-14522(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]Erratum
Janssens S.P., Shimouchi A., Quertermous T., Bloch D.B., Bloch K.D.
J. Biol. Chem. 267:22694-22694(1992)
[3]"Molecular cloning and characterization of human endothelial nitric oxide synthase."
Marsden P.A., Schappert K.T., Chen H.S., Flowers M., Sundell C.L., Wilcox J.N., Lamas S., Michel T.
FEBS Lett. 307:287-293(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene."
Marsden P.A., Heng H.H.Q., Scherer S.W., Stewart R.J., Hall A.V., Shi X.-M., Tsui L.-C., Schappert K.T.
J. Biol. Chem. 268:17478-17488(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Gene structure, polymorphism and mapping of the human endothelial nitric oxide synthase gene."
Nadaud S.A., Bonnardeaux A., Lathrop M., Soubrier F.
Biochem. Biophys. Res. Commun. 198:1027-1033(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[6]"Cloning and structural characterization of the human endothelial nitric-oxide-synthase gene."
Miyahara K., Kawamoto T., Sase K., Yui Y., Toda K., Yang L.X., Hattori R., Aoyama T., Yamamoto Y., Doi Y., Ogoshi S., Hashimoto K., Kawai C., Sasayama S., Shizuta Y.
Eur. J. Biochem. 223:719-726(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]"Alternative splicing in intron 13 of the human eNOS gene: a potential mechanism for regulating eNOS activity."
Lorenz M., Hewing B., Hui J., Zepp A., Baumann G., Bindereif A., Stangl V., Stangl K.
FASEB J. 21:1556-1564(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ENOS13B AND ENOS13C), ALTERNATIVE SPLICING, FUNCTION (ISOFORM ENOS13C), VARIANT ASP-298.
[8]Liao J.K.
Submitted (DEC-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Umbilical vein.
[9]"The role of phosphatidylinositol-3-oh kinase in platelet-derived nitric oxide release and platelet disaggregation."
Zhang Y., Freedman J.E.
Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Platelet.
[10]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASP-298.
Tissue: Hippocampus and Trachea.
[11]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Spleen.
[12]SeattleSNPs variation discovery resource
Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-112; ASP-298; MET-827; MET-885 AND LEU-982.
[13]NHLBI resequencing and genotyping service (RS&G)
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[14]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[15]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[16]"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] (ISOFORM 1), VARIANT ASP-298.
Tissue: Placenta.
[17]"Isolation and chromosomal localization of the human endothelial nitric oxide synthase (NOS3) gene."
Robinson L.J., Weremowicz S., Morton C.C., Michel T.
Genomics 19:350-357(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-53.
Tissue: Placenta.
[18]"Expression of constitutive endothelial nitric oxide synthase in human blood platelets."
Sase K., Michel T.
Life Sci. 57:2049-2055(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 411-528 (ISOFORM 1/ENOS13C).
Tissue: Platelet.
[19]"Purification and characterization of the constitutive nitric oxide synthase from human placenta."
Garvey E.P., Tuttle J.V., Covington K., Merrill B.M., Wood E.R., Baylis S.A., Charles I.G.
Arch. Biochem. Biophys. 311:235-241(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 167-175; 531-540; 835-845; 876-881; 886-898; 1001-1005 AND 1068-1080, TISSUE SPECIFICITY.
Tissue: Placenta.
[20]"NOSIP, a novel modulator of endothelial nitric oxide synthase activity."
Dedio J., Koenig P., Wohlfart P., Schroeder C., Kummer W., Mueller-Esterl W.
FASEB J. 15:79-89(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NOSIP, ENZYME REGULATION, SUBCELLULAR LOCATION.
[21]"NOSTRIN: a protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase."
Zimmermann K., Opitz N., Dedio J., Renne C., Mueller-Esterl W., Oess S.
Proc. Natl. Acad. Sci. U.S.A. 99:17167-17172(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NOSTRIN, ENZYME REGULATION, SUBCELLULAR LOCATION.
[22]"Endothelial thrombomodulin induces Ca2+ signals and nitric oxide synthesis through epidermal growth factor receptor kinase and calmodulin kinase II."
David-Dufilho M., Millanvoye-Van Brussel E., Topal G., Walch L., Brunet A., Rendu F.
J. Biol. Chem. 280:35999-36006(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-495 AND SER-1177.
[23]"NOSTRIN functions as a homotrimeric adaptor protein facilitating internalization of eNOS."
Icking A., Matt S., Opitz N., Wiesenthal A., Mueller-Esterl W., Schilling K.
J. Cell Sci. 118:5059-5069(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[24]"Cell cycle-regulated inactivation of endothelial NO synthase through NOSIP-dependent targeting to the cytoskeleton."
Schleicher M., Brundin F., Gross S., Mueller-Esterl W., Oess S.
Mol. Cell. Biol. 25:8251-8258(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[25]"CDK5 phosphorylates eNOS at Ser-113 and regulates NO production."
Lee C.-H., Wei Y.-W., Huang Y.-T., Lin Y.-T., Lee Y.-C., Lee K.-H., Lu P.-J.
J. Cell. Biochem. 110:112-117(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-114, MUTAGENESIS OF SER-114.
[26]"Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation."
Fischmann T.O., Hruza A., Niu X.D., Fossetta J.D., Lunn C.A., Dolphin E., Prongay A.J., Reichert P., Lundell D.J., Narula S.K., Weber P.C.
Nat. Struct. Biol. 6:233-242(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[27]"Conformational changes in nitric oxide synthases induced by chlorzoxazone and nitroindazoles: crystallographic and computational analyses of inhibitor potency."
Rosenfeld R.J., Garcin E.D., Panda K., Andersson G., Aberg A., Wallace A.V., Morris G.M., Olson A.J., Stuehr D.J., Tainer J.A., Getzoff E.D.
Biochemistry 41:13915-13925(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 67-480.
[28]"Anchored plasticity opens doors for selective inhibitor design in nitric oxide synthase."
Garcin E.D., Arvai A.S., Rosenfeld R.J., Kroeger M.D., Crane B.R., Andersson G., Andrews G., Hamley P.J., Mallinder P.R., Nicholls D.J., St-Gallay S.A., Tinker A.C., Gensmantel N.P., Mete A., Cheshire D.R., Connolly S., Stuehr D.J., Aberg A. expand/collapse author list , Wallace A.V., Tainer J.A., Getzoff E.D.
Nat. Chem. Biol. 4:700-707(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 66-492.
[29]"A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese."
Yoshimura M., Yasue H., Nakayama M., Shimasaki Y., Sumida H., Sugiyama S., Kugiyama K., Ogawa H., Ogawa Y., Saito Y., Miyamoto Y., Nakao K.
Hum. Genet. 103:65-69(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SUSCEPTIBILITY TO CORONARY SPASM ASP-298.
[30]"In-vivo effects of Glu298Asp endothelial nitric oxide synthase polymorphism."
Sofowora G., Dishy V., Xie H.G., Imamura H., Nishimi Y., Morales C.R., Morrow J.D., Kim R.B., Stein C.M., Wood A.J.
Pharmacogenetics 11:809-814(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SUSCEPTIBILITY TO CORONARY SPASM ASP-298.
[31]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] CYS-474 AND GLN-602.
+Additional computationally mapped references.

Web resources

Wikipedia

Nitric oxide synthase entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M93718 mRNA. Translation: AAA36364.1.
M95296 mRNA. Translation: AAA36372.1.
L10709 expand/collapse EMBL AC list , L10693, L10694, L10695, L10696, L10697, L10698, L10699, L10700, L10701, L10702, L10703, L10704, L10705, L10706, L10707, L10708 Genomic DNA. Translation: AAA36365.1.
X76303 expand/collapse EMBL AC list , X76304, X76305, X76306, X76307, X76308, X76309, X76310, X76311, X76312, X76313, X76314, X76315, X76316 Genomic DNA. Translation: CAA53950.1.
D26607 Genomic DNA. Translation: BAA05652.1.
DQ256130 mRNA. Translation: ABB79839.1.
DQ256131 mRNA. Translation: ABB79840.1.
L26914 Genomic DNA. Translation: AAA36374.1.
AF400594 mRNA. Translation: AAK83389.1.
AK292928 mRNA. Translation: BAF85617.1.
AK315213 mRNA. Translation: BAG37648.1.
AK223636 mRNA. Translation: BAD97356.1.
AF519768 Genomic DNA. Translation: AAM74944.1.
EU332855 Genomic DNA. Translation: ABY87544.1.
AC010973 Genomic DNA. No translation available.
CH471173 Genomic DNA. Translation: EAW54069.1.
BC063294 mRNA. Translation: AAH63294.1.
BC069465 mRNA. Translation: AAH69465.1.
L23210 Genomic DNA. Translation: AAA36373.1.
S80791 mRNA. Translation: AAD14336.1.
CCDSCCDS55182.1. [P29474-2]
CCDS55183.1. [P29474-3]
CCDS5912.1. [P29474-1]
PIRA47501.
RefSeqNP_000594.2. NM_000603.4.
NP_001153581.1. NM_001160109.1.
NP_001153582.1. NM_001160110.1.
NP_001153583.1. NM_001160111.1.
XP_006716063.1. XM_006716000.1.
UniGeneHs.647092.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1M9JX-ray2.43A/B67-481[»]
1M9KX-ray2.01A/B67-481[»]
1M9MX-ray1.96A/B67-481[»]
1M9QX-ray2.01A/B67-481[»]
1M9RX-ray2.56A/B67-481[»]
1NIWX-ray2.05B/D/F/H492-511[»]
2LL7NMR-B493-509[»]
2MG5NMR-B495-510[»]
3EAHX-ray2.44A/B66-492[»]
3NOSX-ray2.40A/B66-492[»]
ProteinModelPortalP29474.
SMRP29474. Positions 67-481, 492-1177.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110909. 44 interactions.
DIPDIP-38479N.
IntActP29474. 28 interactions.
MINTMINT-106980.

Chemistry

BindingDBP29474.
ChEMBLCHEMBL2111350.
DrugBankDB00125. L-Arginine.
DB00155. L-Citrulline.
DB01098. Rosuvastatin.
DB00360. Tetrahydrobiopterin.

PTM databases

PhosphoSiteP29474.

Polymorphism databases

DMDM266648.

Proteomic databases

MaxQBP29474.
PaxDbP29474.
PRIDEP29474.

Protocols and materials databases

DNASU4846.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000297494; ENSP00000297494; ENSG00000164867.
ENST00000484524; ENSP00000420215; ENSG00000164867.
GeneID4846.
KEGGhsa:4846.
UCSCuc003wif.3. human. [P29474-1]
uc011kuz.2. human. [P29474-2]

Organism-specific databases

CTD4846.
GeneCardsGC07P150688.
H-InvDBHIX0033558.
HGNCHGNC:7876. NOS3.
HPACAB002168.
MIM163729. gene+phenotype.
neXtProtNX_P29474.
PharmGKBPA254.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4362.
HOGENOMHOG000111088.
HOVERGENHBG000159.
InParanoidP29474.
KOK13242.
OrthoDBEOG79SDW7.
PhylomeDBP29474.
TreeFamTF324410.

Enzyme and pathway databases

BioCycMetaCyc:HS09149-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
REACT_604. Hemostasis.
SignaLinkP29474.

Gene expression databases

ArrayExpressP29474.
BgeeP29474.
CleanExHS_NOS3.
GenevestigatorP29474.

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

ChiTaRSNOS3. human.
EvolutionaryTraceP29474.
GeneWikiEndothelial_NOS.
GenomeRNAi4846.
NextBio18666.
PROP29474.
SOURCESearch...

Entry information

Entry nameNOS3_HUMAN
AccessionPrimary (citable) accession number: P29474
Secondary accession number(s): A0S0A7 expand/collapse secondary AC list , A0S0A8, A8KA63, B2RCQ1, E9PFR2, Q13662, Q14251, Q14434, Q548C1, Q6GSL5, Q9UDC6
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 177 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM