NOS3 (nitric oxide synthase 3)

Gene

• Entrez ID: 4846
• Gene name: Nitric oxide synthase 3
• Gene symbol: NOS3
• Synonyms: ECNOS, eNOS
• Chromosome: 7
• Chromosome location: 7q36.1
• Summary: Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1549758	T>A,C	Risk-factor, benign	Missense variant, coding sequence variant, synonymous variant
rs1799983	T>A,G	Pathogenic, risk-factor, benign	Missense variant, coding sequence variant
rs2070744	C>G,T	Protective, risk-factor	Upstream transcript variant, genic upstream transcript variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT007181	hsa-miR-155-5p	Luciferase reporter assay, qRT-PCR, Western blot	23108656
MIRT017773	hsa-miR-335-5p	Microarray	18185580
MIRT053134	hsa-miR-24-3p	Luciferase reporter assay, qRT-PCR, Western blot	23774796
MIRT053134	hsa-miR-24-3p	Immunocytochemistry, Luciferase reporter assay, qRT-PCR, Western blot	25920448
MIRT732952	hsa-miR-200c-3p	Luciferase reporter assay, qRT-PCR, Western blot	27917915
MIRT735516	hsa-miR-543	Luciferase reporter assay, qRT-PCR	26647850
MIRT735517	hsa-miR-335-3p	Luciferase reporter assay, qRT-PCR	26647850

Transcription factors

Transcription factor	Regulation	Reference
ATF2	Repression	16497991
DDIT3	Repression	22265908
GATA2	Activation	10713142
GATA4	Activation	14555463
HDAC1	Unknown	22848708
JUN	Unknown	11382920
KLF2	Activation	22987017
NFKB1	Activation	17081374;17644577
RELA	Activation	17081374
SP1	Activation	10713142;12270858;18624763
SP1	Unknown	15722551
SP3	Activation	14555463

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000139	Component	Golgi membrane	TAS
GO:0001974	Process	Blood vessel remodeling	ISS
GO:0003100	Process	Regulation of systemic arterial blood pressure by endothelin	IMP	8999856
GO:0003180	Process	Aortic valve morphogenesis	ISS
GO:0003180	Process	Aortic valve morphogenesis	TAS	29325903
GO:0003184	Process	Pulmonary valve morphogenesis	ISS
GO:0003203	Process	Endocardial cushion morphogenesis	ISS
GO:0003785	Function	Actin monomer binding	IPI	17502619
GO:0004517	Function	Nitric-oxide synthase activity	IBA	21873635
GO:0004517	Function	Nitric-oxide synthase activity	IDA	1378832, 7488039, 19666465
GO:0004517	Function	Nitric-oxide synthase activity	IMP	23707606
GO:0005515	Function	Protein binding	IPI	11149895, 12446846, 12852865, 12855682, 16234328, 16432212, 17502619, 21163940, 22458338, 23123858, 23397142, 23585225, 25062958, 25241761, 25416956, 32296183, 32814053
GO:0005516	Function	Calmodulin binding	IEA
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	ISS
GO:0005737	Component	Cytoplasm	IDA	9794441
GO:0005737	Component	Cytoplasm	ISS
GO:0005794	Component	Golgi apparatus	IDA	25131610
GO:0005829	Component	Cytosol	IBA	21873635
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	IEA
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	IDA	25131610
GO:0005886	Component	Plasma membrane	TAS
GO:0005901	Component	Caveola	IDA	17502619, 17848177
GO:0006527	Process	Arginine catabolic process	IBA	21873635
GO:0006527	Process	Arginine catabolic process	IDA	1378832, 7488039
GO:0006809	Process	Nitric oxide biosynthetic process	IBA	21873635
GO:0006809	Process	Nitric oxide biosynthetic process	IDA	1378832, 7488039
GO:0007005	Process	Mitochondrion organization	ISS
GO:0007263	Process	Nitric oxide mediated signal transduction	IBA	21873635
GO:0008217	Process	Regulation of blood pressure	NAS	7504210
GO:0008285	Process	Negative regulation of cell population proliferation	ISS
GO:0009408	Process	Response to heat	NAS	18048451
GO:0009725	Process	Response to hormone	IBA	21873635
GO:0010181	Function	FMN binding	IBA	21873635
GO:0010181	Function	FMN binding	NAS	7488039
GO:0010544	Process	Negative regulation of platelet activation	NAS	7504210
GO:0010628	Process	Positive regulation of gene expression	ISS	23583836
GO:0012506	Component	Vesicle membrane	IBA	21873635
GO:0014740	Process	Negative regulation of muscle hyperplasia	ISS
GO:0014806	Process	Smooth muscle hyperplasia	ISS
GO:0016491	Function	Oxidoreductase activity	IBA	21873635
GO:0016709	Function	Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen	IBA	21873635
GO:0019430	Process	Removal of superoxide radicals	IDA	19666465
GO:0020037	Function	Heme binding	IDA	7488039
GO:0030666	Component	Endocytic vesicle membrane	TAS
GO:0031284	Process	Positive regulation of guanylate cyclase activity	IBA	21873635
GO:0031284	Process	Positive regulation of guanylate cyclase activity	IMP	17502619
GO:0031284	Process	Positive regulation of guanylate cyclase activity	ISS
GO:0031644	Process	Regulation of nervous system process	ISS
GO:0032496	Process	Response to lipopolysaccharide	IBA	21873635
GO:0034405	Process	Response to fluid shear stress	IEP	10376603
GO:0034617	Function	Tetrahydrobiopterin binding	IDA	7488039
GO:0034618	Function	Arginine binding	IDA	7488039
GO:0042311	Process	Vasodilation	NAS	7504210, 18048451
GO:0043536	Process	Positive regulation of blood vessel endothelial cell migration	IDA	23802567
GO:0043542	Process	Endothelial cell migration	IMP	8999856
GO:0045454	Process	Cell redox homeostasis	TAS
GO:0045747	Process	Positive regulation of Notch signaling pathway	IC	23583836
GO:0045766	Process	Positive regulation of angiogenesis	IDA	23802567
GO:0045766	Process	Positive regulation of angiogenesis	ISS
GO:0045776	Process	Negative regulation of blood pressure	IBA	21873635
GO:0046870	Function	Cadmium ion binding	NAS	7488039
GO:0048873	Process	Homeostasis of number of cells within a tissue	ISS
GO:0050660	Function	Flavin adenine dinucleotide binding	IBA	21873635
GO:0050660	Function	Flavin adenine dinucleotide binding	NAS	7488039
GO:0050661	Function	NADP binding	NAS	7488039
GO:0050999	Process	Regulation of nitric-oxide synthase activity	TAS
GO:0070168	Process	Negative regulation of biomineral tissue development	ISS
GO:0097746	Process	Blood vessel diameter maintenance	ISS
GO:1902042	Process	Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	ISS

Other IDs

• MIM: 163729
• HGNC: 7876
• e!Ensembl: ENSG00000164867

Protein

• UniProt ID: P29474
• Protein name: Nitric oxide synthase, endothelial (EC 1.14.13.39) (Constitutive NOS) (cNOS) (EC-NOS) (Endothelial NOS) (eNOS) (NOS type III) (NOSIII)
• Protein 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.; [Isoform eNOS13C]: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.
• PDB: 1M9J, 1M9K, 1M9M, 1M9Q, 1M9R, 1NIW, 2LL7, 2MG5, 2N8J, 3EAH, 3NOS, 4D1O, 4D1P, 5UO8, 5UO9, 5UOA, 5UOB, 5UOC, 5VVB, 5VVC, 5VVD, 5XOF, 6AV6, 6AV7, 6CIE, 6CIF, 6NH1, 6NH2, 6NH3, 6NH4, 6NH5, 6NH6, 6NH7, 6NH8, 6NHF, 6POU, 6POV, 6POW, 6POX, 6POY, 6POZ, 6PP0, 6PP1, 6PP2, 6PP3, 6PP4
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02898	NO_synthase	119 → 481	Nitric oxide synthase, oxygenase domain	Domain
  PF00258	Flavodoxin_1	522 → 698	Flavodoxin	Domain
  PF00667	FAD_binding_1	751 → 979	FAD binding domain	Domain
  PF00175	NAD_binding_1	1011 → 1125	Oxidoreductase NAD-binding domain	Domain

• Sequence:

  MGNLKSVAQEPGPPCGLGLGLGLGLCGKQGPATPAPEPSRAPASLLPPAPEHSPPSSPLT
  QPPEGPKFPRVKNWEVGSITYDTLSAQAQQDGPCTPRRCLGSLVFPRKLQGRPSPGPPAP
  EQLLSQARDFINQYYSSIKRSGSQAHEQRLQEVEAEVAATGTYQLRESELVFGAKQAWRN
  APRCVGRIQWGKLQVFDARDCRSAQEMFTYICNHIKYATNRGNLRSAITVFPQRCPGRGD
  FRIWNSQLVRYAGYRQQDGSVRGDPANVEITELCIQHGWTPGNGRFDVLPLLLQAPDDPP
  ELFLLPPELVLEVPLEHPTLEWFAALGLRWYALPAVSNMLLEIGGLEFPAAPFSGWYMST
  EIGTRNLCDPHRYNILEDVAVCMDLDTRTTSSLWKDKAAVEINVAVLHSYQLAKVTIVDH
  HAATASFMKHLENEQKARGGCPADWAWIVPPISGSLTPVFHQEMVNYFLSPAFRYQPDPW
  KGSAAKGTGITRKKTFKEVANAVKISASLMGTVMAKRVKATILYGSETGRAQSYAQQLGR
  LFRKAFDPRVLCMDEYDVVSLEHETLVLVVTSTFGNGDPPENGESFAAALMEMSGPYNSS
  PRPEQHKSYKIRFNSISCSDPLVSSWRRKRKESSNTDSAGALGTLRFCVFGLGSRAYPHF
  CAFARAVDTRLEELGGERLLQLGQGDELCGQEEAFRGWAQAAFQAACETFCVGEDAKAAA
  RDIFSPKRSWKRQRYRLSAQAEGLQLLPGLIHVHRRKMFQATIRSVENLQSSKSTRATIL
  VRLDTGGQEGLQYQPGDHIGVCPPNRPGLVEALLSRVEDPPAPTEPVAVEQLEKGSPGGP
  PPGWVRDPRLPPCTLRQALTFFLDITSPPSPQLLRLLSTLAEEPREQQELEALSQDPRRY
  EEWKWFRCPTLLEVLEQFPSVALPAPLLLTQLPLLQPRYYSVSSAPSTHPGEIHLTVAVL
  AYRTQDGLGPLHYGVCSTWLSQLKPGDPVPCFIRGAPSFRLPPDPSLPCILVGPGTGIAP
  FRGFWQERLHDIESKGLQPTPMTLVFGCRCSQLDHLYRDEVQNAQQRGVFGRVLTAFSRE
  PDNPKTYVQDILRTELAAEVHRVLCLERGHMFVCGDVTMATNVLQTVQRILATEGDMELD
  EAGDVIGVLRDQQRYHEDIFGLTLRTQEVTSRIRTQSFSLQERQLRGAVPWAFDPPGSDT
  NSP

• Sequence length: 1203