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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

NOS3 Gene

protein-coding GIFtS: 72
GCID: GC07P150688

nitric oxide synthase 3 (endothelial cell)

Explore 269 diseases affiliated with
NOS3 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Nitric Oxide Synthase 3 (Endothelial Cell)¹ ²		NOSIII² ³
ENOS¹		CNOS¹
ECNOS¹ ²		NOS Type III² ³
Constitutive NOS² ³		EC 1.14.13.39³ ⁸
Endothelial NOS² ³		Nitric Oxide Synthase, Endothelial²
EC-NOS² ³

External Ids:	HGNC: 7876¹	Entrez Gene: 4846²	Ensembl: ENSG00000164867⁷	OMIM: 163729⁵	UniProtKB: P29474³

Export aliases for NOS3 gene to outside databases

Previous GC identifers: GC07P148937 GC07P150005 GC07P150082 GC07P150079 GC07P150125 GC07P150319 GC07P144500

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for NOS3:

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. Multiple transcript

variants encoding different isoforms have been found for this gene. (provided by RefSeq, May 2009)

UniProtKB/Swiss-Prot: NOS3_HUMAN, P29474

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

Function: Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming

heterodimers with isoform 1

summary for NOS3:

Endothelial nitric oxide synthase (eNOS), along with inducible nitric oxide synthase (iNOS) and neuronal

nitric oxide synthase (nNOS), catalyze the generation of nitric oxide and L-citrulline from L-arginine and

molecular oxygen. It is activated at concentrations of calcium greater than 100 nM and requires

tetrahydrobiopterin, flavin adenine dinucleotide, flavin mononucleotide and NADPH for catalytic activity.

eNOS is tightly regulated by co- and post-translational lipid modifications, phosphorylation by Akt/PKB, PKA

and AMPK and protein-protein interactions. Negative protein-protein interactions are mediated by Hsp90 and

Cav-1 in the Golgi and by NOSIP and NOSTRIN at the plasma membrane, whilst dynamin, porin and soluble

guanylyl cyclase are positive regulators of eNOS activity. eNOS is a critical mediator of cardiovascular

homeostasis through regulation of the diameter of blood vessels and maintenance of an antiproliferative and

antiapoptotic environment in the vasculature. The human gene encoding eNOS is localized to chromosome 7q36.

Gene Wiki entry for NOS3 (Endothelial NOS)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000007.13 NC_018918.1 NT_007914.15 NT_079596.2

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the NOS3 gene promoter:
NF-1 NF-1/L PPAR-gamma1 AP-1 NRSF form 1 PPAR-gamma2 NRSF form 2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 6): NOS3 promoter sequence

Search SABiosciences Chromatin IP Primers for NOS3

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NOS3

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 7q36 Ensembl cytogenetic band: 7q36.1 HGNC cytogenetic band: 7q36

NOS3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOS3 gene location

GeneLoc information about chromosome 7 GeneLoc Exon Structure

GeneLoc location for GC07P150688: view genomic region (about GC identifiers)

Start:	150,688,083 bp from pter	End:	150,711,687 bp from pter
Size:	23,605 bases	Orientation:	plus strand

1 alternative location:

Chr7+,CRA_TCAG 150,017,398-150,041,276

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: NOS3_HUMAN, P29474 (See protein sequence)

Recommended Name: Nitric oxide synthase, endothelial

Size: 1203 amino acids; 133289 Da

Cofactor: Heme group

Cofactor: Binds 1 FAD

Cofactor: Binds 1 FMN

Cofactor: Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme

Subunit: Homodimer. Interacts with NOSIP and NOSTRIN

Subcellular location: Cell membrane. Membrane, caveola. Cytoplasm, cytoskeleton. 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

6/8 PDB 3D structures from and Proteopedia for NOS3 (see all 8):

1M9J (3D)

1M9K (3D)

1M9M (3D)

1M9Q (3D)

1M9R (3D)

2LL7 (3D)

Secondary accessions: A0S0A7 A0S0A8 A8KA63 B2RCQ1 E9PFR2 Q13662 Q14251 Q14434 Q548C1 Q6GSL5 Q9UDC6

Alternative splicing: 3 isoforms: P29474-1 P29474-2 P29474-3 (Lacks eNOS activity)

Explore the universe of human proteins at neXtProt for NOS3: NX_P29474

Post-translational modifications:

Phosphorylation by AMPK at Ser-1177 in the presence of Ca(2+)-calmodulin (CaM) activates activity. In absence of

Ca(2+)-calmodulin, AMPK also phosphorylates Thr-495, resulting in inhibition of activity (By similarity).

Phosphorylation of Ser-114 by CDK5 reduces activity¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P29474

4/40 DME Specific Peptides for NOS3 (P29474) (see all 40)

AVLHSYQ

VFGLGSR

LQVFDAR

GQEEAFR

NOS3 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (4 alternative transcripts):

NP_000594.2 NP_001153581.1 NP_001153582.1 NP_001153583.1

ENSEMBL proteins:

ENSP00000297494 ENSP00000418338 ENSP00000417143 ENSP00000420215 ENSP00000420551

ENSP00000418245

Reactome Protein details: P29474
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Enzo Life Sciences proteins for NOS3
	OriGene Purified Protein: NOS3 OriGene Protein Over-expression Lysate: NOS3 OriGene Custom Protein Services for NOS3
	GenScript Custom Purified and Recombinant Proteins Services for NOS3
	Novus Biologicals NOS3 Protein Novus Biologicals NOS3 Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for NOS3

Gene Ontology (GO): 5/12 cellular component terms (GO ID links to tree view) (see all 12): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000139	Golgi membrane	TAS	--
GO:0005625	soluble fraction	--	--
GO:0005634	nucleus	ISS	--
GO:0005730	nucleolus	--	--
GO:0005737	cytoplasm	IDA	9794441

NOS3 for ontologies About GeneDecksing

NOS3 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of NOS3
	R&D Systems Antibodies for NOS3 (eNOS)
	Cell Signaling Technology (CST) Antibodies for NOS3 (eNOS)
	Browse OriGene Antibodies OriGene Custom Antibody Services for NOS3
	GenScript Custom Superior Antibodies Services for NOS3
	Novus Biologicals NOS3 Antibodies
	Search for Antibodies for NOS3 at Abcam
	Uscn Antibodies for NOS3
	ThermoFisher Antibody for NOS3

Assay Products for NOS3:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for NOS3 (eNOS) (see all)
	GenScript Custom Assay Services for NOS3
	Cell Signaling Technology (CST) Sandwich ELISA Kits for NOS3 (eNOS)
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for NOS3

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

NOS3 for domains About GeneDecksing

5/11 InterPro domains/families (see all 11):

IPR026009 NOS

IPR017927 Fd_Rdtase_FAD-bd

IPR001094 Flavdoxin

IPR008254 Flavodoxin/NO_synth

IPR012144 NOS_met

Graphical View of Domain Structure for InterPro Entry P29474

ProtoNet protein and cluster: P29474

5/7 Blocks protein families (see all 7):

IPB001094 Flavodoxin signature

IPB001226 Flavodoxin

IPB001433 Oxidoreductase FAD/NAD(P)-binding

IPB001709 Flavoprotein pyridine nucleotide cytochrome reductase signature

IPB003097 FAD-binding

UniProtKB/Swiss-Prot: NOS3_HUMAN, P29474

Similarity: Belongs to the NOS family

Similarity: Contains 1 FAD-binding FR-type domain

Similarity: Contains 1 flavodoxin-like domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: NOS3_HUMAN, P29474

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

Function: Isoform eNOS13C: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming

heterodimers with isoform 1

Catalytic activity: 2 L-arginine + 3 NADPH + 4 O(2) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H(2)O

Enzyme regulation: Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN

Genatlas biochemistry entry for NOS3:

nitric oxide synthase 3,constitutively expressed,endothelial,also expressed in cardiac myocytes,regulating vascular

tone,overexpressed in squamous hyperplasia,dysplasia and squamous cell carcinoma of the head and neck,putative

susceptibility factor for late onset Alzheimer disease

Enzyme Number (IUBMB): EC 1.14.13.39¹ ²

miRNA Products:		OriGene 3'-UTR Clone (see all 4): NOS3 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat NOS3
		4 QIAGEN miScript miRNA Assays for microRNAs that regulate NOS3:
		hsa-miR-4324 hsa-miR-875-3p hsa-miR-4261 hsa-miR-1303
		SwitchGear 3'UTR luciferase reporter plasmid: NOS3 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for NOS3 (see all 7) OriGene shRNA RFP: NOS3 OriGene siRNA: NOS3
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat NOS3

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for NOS3

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for NOS3 (see all 7) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for NOS3 (see all 4) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 4): NOS3 (NM_000603)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOS3
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOS3

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for NOS3
		Search LifeMap BioReagents cell lines for NOS3

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOS3

Gene Ontology (GO): 5/13 molecular function terms (GO ID links to tree view) (see all 13): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003785	actin monomer binding	IPI	17502619
GO:0003958	NADPH-hemoprotein reductase activity	IBA	--
GO:0004517	nitric-oxide synthase activity	IDA	1378832
GO:0005506	iron ion binding	IEA	--
GO:0005515	protein binding	IPI	12852865

NOS3 for ontologies About GeneDecksing

2 GenomeRNAi human phenotypes for NOS3:

Decreased influenza A virus in

Increased G1 DNA content

Animal Models:
Mouse knock-outs for NOS3: Nos3^tm1.1Taka Nos3^tm1Weo Nos3^tm1Plh Nos3^tm1Gdk Nos3^tm1Unc
15/23 MGI mutant phenotypes (inferred from 6 alleles) (MGI details for Nos3) (see all 23):

adipose tissue	behavior/neurological	cardiovascular system	cellular	digestive/alimentary
embryogenesis	endocrine/exocrine gland	growth/size	hematopoietic system	homeostasis/metabolism
immune system	limbs/digits/tail	liver/biliary system	mortality/aging	muscle

NOS3 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/46 super-pathways (see all 46) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Metabolism of nitric oxide

Metabolism of nitric oxide	1.00	eNOS activation	0.41
eNOS activation and regulation	1.00	NOSTRIN mediated translocation of eNOS from plasma membrane	0.29
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation	0.59	NOSTRIN mediated eNOS trafficking	0.29

Activation of cAMP-Dependent PKA

	Activation of cAMP-Dependent PKA	1.00			Activation of PKA through GPCR	0.71
	cAMP Pathway	0.77			PKA Signaling	0.56

eNOS:NOSIP translocation from caveolae to intracellular compartments

	eNOS:NOSIP translocation from caveolae to intracellular compartments	1.00			eNOS translocation from Golgi to Caveolae	0.50
	NOSIP mediated eNOS trafficking	1.00

Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics

	Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics	1.00			ACE Inhibitor Pathway	0.85
	ACE Inhibitor Pathway, Pharmacodynamics	1.00

Development VEGF signaling via VEGFR2 - generic cascades

Development VEGF signaling via VEGFR2 - generic cascades

1.00

Development_VEGF signaling via VEGFR2 - generic cascades

0.51

Pathway sources
See GeneCards unified pathways
Show all pathways

4 EMD Millipore Pathways for NOS3

	Development EDNRB signaling
	Apoptosis and survival Anti-apoptotic action of membrane-bound ESR1
	Development A2B receptor- action via G-protein alpha s
	Development VEGF signaling via VEGFR2 - generic cascades

5/18 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for NOS3 (see all 18)

	PKA Signaling
	Sertoli-Sertoli Cell Junction Dynamics
	Endothelin-1 Signaling Pathway
	Relaxin Pathway
	Cellular Effects of Sildenafil

2 Cell Signaling Technology (CST) Pathways for NOS3

	Angiogenesis
	PI3K / Akt Signaling

3 Tocris Bioscience Pathways for NOS3

	Akt Pathway
	Apoptosis Pathway
	VEGF Pathway

5/6 GeneGo (Thomson Reuters) Pathways for NOS3 (see all 6)

	Development A2B receptor- action via G-protein alpha s
	Development VEGF signaling via VEGFR2 - generic cascades
	Mechanisms of CFTR activation by S-nitrosoglutathione (normal and CF)
	Development EDNRB signaling
	Apoptosis and survival Anti-apoptotic action of membrane-bound ESR1

5/13 BioSystems Pathways for NOS3 (see all 13)

	ACE Inhibitor Pathway
	Angiogenesis
	AGE/RAGE pathway
	Myometrial Relaxation and Contraction Pathways
	Endothelin

5/16 Reactome Pathways for NOS3 (see all 16)

	Phagosomal maturation (early endosomal stage)
	Metabolism
	Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
	Platelet homeostasis
	NOSTRIN mediated translocation of eNOS from plasma membrane

5/6 PharmGKB Pathways for NOS3 (see all 6)

	ACE Inhibitor Pathway, Pharmacodynamics
	Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics
	Doxorubicin Pathway (Cancer Cell), Pharmacodynamics
	Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics
	Doxorubicin Pathway, Pharmacokinetics

4 Kegg Pathways (Kegg details for NOS3):

	Arginine and proline metabolism
	Metabolic pathways
	Calcium signaling pathway
	VEGF signaling pathway

NOS3 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for NOS3

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/66 Interacting proteins for NOS3 (P29474^{1, 2, 3} ENSP00000297494⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 66)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
NOSTRIN	Q8IVI9¹^,²^,³, ENSP00000318921⁴	EBI-1391623,EBI-1391643 MINT-7213409 MINT-7213465 I2D: score=2 STRING: ENSP00000318921
ST13	P50502¹^,³	EBI-1391623,EBI-357285 I2D: score=1
CALM1	P62158³, ENSP00000349467⁴	I2D: score=4 STRING: ENSP00000349467
CALM2	P62158³	I2D: score=4
CALM3	P62158³	I2D: score=4

About this table

Gene Ontology (GO): 5/54 biological process terms (GO ID links to tree view) (see all 54): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001525	angiogenesis	IEA	--
GO:0001542	ovulation from ovarian follicle	IEA	--
GO:0001666	response to hypoxia	--	--
GO:0001701	in utero embryonic development	IEA	--
GO:0001974	blood vessel remodeling	ISS	--

NOS3 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

NOS3 for compounds About GeneDecksing

EMD Millipore small molecules for NOS3:
Small Molecule - inhibitor

Enzo Life Sciences drugs & compounds for NOS3

Compounds for NOS3 available from Tocris Bioscience About this table

Compound	Action	CAS #
L-NNA	NOS inhibitor (nNOS = eNOS >> iNOS)	[2149-70-4]
L-NIO dihydrochloride	Potent eNOS inhibitor	[36889-13-1]

10/12 HMDB Compounds for NOS3 (see all 12) About this table

Compound	Synonyms	CAS #	PubMed Ids
Dihydrobiopterin	(S-(R,S))-2-amino-6-(1,2-dihydroxypropyl)-7,8-dihydro-4(1H)-Pteridinone (see all 15)	6779-87-9	15470159
Tetrahydrobiopterin	(1R,2S)-(2-Amino-3,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)-1,2-propandiol (see all 11)	17528-72-2	17420345
Calcium	Ca (see all 2)	7440-70-2	--
Citrulline	(2S)-2-amino-5-(carbamoylamino)pentanoic acid (see all 55)	372-75-8	--
FAD	1H-Purin-6-amine flavin dinucleotide (see all 21)	146-14-5	--
Flavin Mononucleotide	FMN (see all 19)	146-17-8	--
Heme	(protoporphyrinato)iron (see all 19)	14875-96-8	--
L-Arginine	(S)-2-Amino-5-[(aminoiminomethyl)amino]pentanoate (see all 14)	74-79-3	--
NADP	Adenine-nicotinamide dinucleotide phosphate (see all 18)	53-59-8	--
NADPH	2'-(dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide (see all 23)	53-57-6	--

10/41 DrugBank Compounds for NOS3 (see all 41) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Tetrahydrobiopterin	5,6,7,8 Tetrahydrobiopterin (see all 3)	17528-72-2	target	cofactor	11009561 10749876 10924132 10995244 10075731 12003347
L-Arginine	(S)-2-Amino-5-guanidinovaleric acid (see all 4)	74-79-3	target	--	16690332 16720041 16729278 16682803 16717106
L-Citrulline	2-Amino-5-uredovaleric acid (see all 8)	372-75-8	target	--	10440125 10749853 10460702 10690351 10403604
Miconazole	--	22916-47-8	target	inhibitor	7536941 7518297 7683652 9873034
(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin	--	--	target	--	17139284 17016423 10592235
1,2,4-Triazole-Carboxamidine	--	--	target	--	17139284 17016423 10592235
2-Aminothiazoline	--	1779-81-3	target	--	17139284 17016423 10592235
3-Bromo-7-Nitroindazole	--	--	target	--	17139284 17016423 10592235
5,6-Cyclic-Tetrahydropteridine	--	--	target	--	17139284 17016423 10592235
6s-5,6,7,8-Tetrahydrobiopterin	--	--	target	--	17139284 17016423 10592235

10/126 Novoseek chemical compound relationships for NOS3 gene (see all 126) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
nitric oxide	96.3	9182	16036314 (9), 17637430 (8), 10536122 (8), 15640399 (7) (see all 99)
tetrahydrobiopterin	85.2	126	15288120 (3), 20124983 (2), 16940192 (2), 17825498 (2) (see all 80)
citrulline	81.4	64	15288120 (2), 20144727 (2), 7538428 (2), 15522271 (2) (see all 43)
adma	79.7	111	18167189 (3), 18792879 (3), 19297385 (3), 18553936 (3) (see all 56)
arginine	78.9	318	18689498 (5), 16873402 (4), 15465805 (3), 8969188 (3) (see all 99)
peroxynitrite	74.9	69	18047920 (2), 12489993 (2), 16940192 (2), 10997917 (2) (see all 43)
nadph	74	174	16076760 (4), 17496167 (3), 7540756 (3), 17023679 (3) (see all 98)
cgmp	73.1	128	10758392 (4), 16128864 (4), 20144727 (3), 11319157 (3) (see all 68)
superoxide	72.1	325	9689061 (7), 11879202 (7), 9268712 (6), 17827253 (4) (see all 99)
l-nmma	71	46	18553936 (3), 16102116 (2), 17082183 (2), 18516617 (1) (see all 27)

7 PharmGKB related drug/compound annotations for NOS3 gene

Drug/compound	PharmGKB Annotation
Antihypertensives	CA
Antihypertensives And Diuretics In Combination	CA
cyclophosphamide	CA
diuretics	CA
doxorubicin	CA
fluorouracil	CA
methotrexate	CA

About this table

Search CenterWatch for drugs/clinical trials and news about NOS3

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for NOS3 gene (4 alternative transcripts):

NM_000603.4 NM_001160109.1 NM_001160110.1 NM_001160111.1

Unigene Cluster for NOS3:

Nitric oxide synthase 3 (endothelial cell)

Hs.647092 [show with all ESTs]

Unigene Representative Sequence: NM_000603

14 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000297494(uc003wif.3 uc011kuy.2) ENST00000484576 ENST00000461406

ENST00000484524(uc011kuz.2) ENST00000467517(uc011kvb.2 uc011kva.2)

ENST00000460603 ENST00000473057 ENST00000475017 ENST00000468293 ENST00000477227

ENST00000498521 ENST00000475454 ENST00000468870 ENST00000486784

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Additional cDNA sequence:

AF400594.1 AK223636.1 AK225827.1 AK292928.1 AK300390.1 AK302686.1 AK315213.1 BC063294.1

BC069465.1 DQ256129.1 DQ256130.1 DQ256131.1 M93718.1 M95296.1 S80791.1

8 DOTS entries:

DT.97810187 DT.313642 DT.40126949 DT.97845228 DT.75180420 DT.97765741 DT.97845230 DT.95321333

24/105 AceView cDNA sequences (see all 105):

AF400594 BM821409 BM766305 T28178 BQ712348 BM851583 AA954011 AA992377

CA423531 M95296 BF060748 NM_000603 BC063294 BM741457 BM756290 BC069465

BM768070 BG741096 BM823046 BM783934 AW168483 BM747155 BM546712 AW298145

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

NOS3 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: GAGCTGGACG

About this image

NOS3 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

2 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Lateral Plate Mesoderm

Paired Dorsal Aorta

Arterial endothelial cells

Endothelium

Adipose

Visceral White Adipose

Adipose

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 8 LifeMap Cells

Name

Category

Bone marrow-derived CD34+ stem cells (ACT34) (Adult Stem / Progenitor Cell)

Bone

Human umbilical vein endothelial cells (HUVEC) (Primary Cell)

Endothelium

PureStem™ endothelial progenitor 30-MV2-12 (Embryonic Progenitor Cell)

Blood, Endothelium

PureStem™ endothelial Progenitor 30-SM2-3 (Embryonic Progenitor Cell)

Blood, Endothelium

PureStem™ endothelial progenitor 30-SM2-1 (Embryonic Progenitor Cell)

Endothelium

PureStem™ endothelial progenitor 30-MV2-14 (Embryonic Progenitor Cell)

Endothelium

Mixed endothelial progenitors cells (Differentiation of h...)

Endothelial-like cells (Generation of endoth...)

See NOS3 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for NOS3

SOURCE GeneReport for Unigene cluster: Hs.647092

UniProtKB/Swiss-Prot: NOS3_HUMAN, P29474

Tissue specificity: Platelets, placenta, liver and kidney

SABiosciences Expression via Pathway-Focused PCR Arrays including NOS3 (see all 11):

Cell Surface Markers in human mouse rat

Nitric Oxide Signaling Pathway in human mouse rat

VEGF Signaling in human mouse rat

Hypoxia Signaling Pathway in human mouse rat

Angiogenesis in human mouse rat

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In Situ
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the last universal common ancestor (LUCA).

Orthologs for NOS3 gene from 8/28 species (see all 28) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	NDOR1⁶	Uncharacterized protein	25(a)	possible ortholog	17(1342843-1359837)
lizard (Anolis carolinensis)	Reptilia	NOS3⁶ NDOR1⁶	--	71(a) 25(a)	1 ↔ 1 possible ortholog	GL343807.1(16588-55581) GL344097.1(1892-21914)
zebrafish (Danio rerio)	Actinopterygii	ndor1⁶	NADPH dependent diflavin oxidoreductase 1	24(a)	possible ortholog	5(34108136-34116636)
fruit fly (Drosophila melanogaster)	Insecta	Nos³	imaginal disc development calmodulin binding	47(a)		2 32B1 --
worm (Caenorhabditis elegans)	Secernentea	fre-1⁶	Flavin REductase family member (fre-1)	22(a)	possible ortholog	V(20075890-20087702)
thale cress (Arabidopsis thaliana)	eudicotyledons	AT3G02280⁶ ATLFNR1⁶ (see all 5)	ferredoxin--NADP+ reductase (see all 5)	24(a) 18(a) (see all 5)	possible ortholog possible ortholog (see all 5)	3(453421-457841) 5(26450964-26453199)
rice (Oryza sativa)	Liliopsida	-- -- (see all 5)	NADPH reductase, putative, expressed ferredoxin--NADP reductase, chloroplast precursor,... (see all 5)	23(a) 18(a) (see all 5)	possible ortholog possible ortholog (see all 5)	1(30592390-30597478) 6(478179-480670)
E. coli (Escherichia coli)	Gamma proteobacteria	cysJ⁶	sulfite reductase, alpha subunit, flavoprotein	25(a)	possible ortholog	Chromosome(2888121-2889920)

ENSEMBL Gene Tree for NOS3 (if available)
TreeFam Gene Tree for NOS3 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for NOS3 gene

POR² NOS2² MTRR² NOS1²

3 SIMAP similar genes for NOS3 using alignment to 5 protein entries: NOS3_HUMAN (see all proteins):

NOS1 NOS2 POR

NOS3 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

UniProtKB/Swiss-Prot: NOS3_HUMAN, P29474

Polymorphism: Variation in NOS3 seem to be associated with susceptibility to coronary spasm

SNP ID	Valid	Clinical significance	Chr 7 pos	Sequence	#	AA Chg	Type	More	#	Pop	Total sample
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs59945857^1,2	C,F,	--	150015599(+)	`ATGGAG/AGGGGC`	1	--	us2k¹		1	WA	118
rs76898694^1,2	C,F,	--	150015673(+)	`CTTACC/TCCTGG`	1	--	us2k¹		1	WA	118
rs112503436^1,2	C,	--	150016549(+)	`GAGGAA/GCTGAC`	1	--	us2k¹		2	CSA WA	120
rs34204527^1,2	C	--	150016684(+)	`CCTTGA/GGGACA`	1	--	us2k¹		2	NA	4
rs79845382^1,2	C,F,	--	150016982(+)	`GCCCCG/AGGGCT`	1	--	us2k¹		1	WA	118
rs79107117^1,2	F,	--	150017059(+)	`TGTTCC/TCAGCA`	1	--	us2k¹		1	WA	118
rs61647168^1,2	F,	--	150017217(+)	`CACCGT/ACTGAG`	1	--	us2k¹		1	WA	118
rs77017676^1,2	F,	--	150017339(+)	`CAGAGC/TAGGTG`	1	--	us2k¹		1	NA	120
rs80029303^1,2	C,F,	--	150017733(+)	`TGTCAG/AAGGCG`	1	--	int¹		1	WA	118
rs2243310^1,2	F	--	150017741(+)	`CGGAAG/AAGGCG`	1	--	int¹		2	NA	180

HapMap Linkage Disequilibrium report for NOS3 (150688083 - 150711687 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for NOS3: --
Human Gene Mutation Database (HGMD): NOS3

Locus Specific Mutation Databases (LSDB): NOS3

SABiosciences Cancer Mutation PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

NOS3 for disorders           About GeneDecksing

OMIM gene information: 163729
OMIM disorders: 104300  145500  189800  601367
20/269 diseases for NOS3 (see all 269):    About MalaCards

open-angle glaucoma coronary artery spasm 1 alpha 1-antitrypsin deficiency spermatic cord torsion

prinzmetal angina spinal cord ischemia high blood pressure resting heart rate

primary open angle glaucoma hemifacial spasm end stage renal failure leber hereditary optic neuropathy

placenta accreta deep vein thrombosis acute mountain sickness acute chest syndrome

dna topoisomerase i central sleep apnea thromboangiitis obliterans sleep apnea

12 diseases from the University of Copenhagen DISEASES database for NOS3:

Hypertension Atherosclerosis Heart disease Diabetes mellitus

Cerebrovascular accident Portal hypertension Kidney disease Hyperglycemia

Hepatopulmonary syndrome Hyperhomocysteinemia Spermatic cord torsion Liver cirrhosis

10/96 Novoseek disease relationships for NOS3 gene (see all 96) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
atherosclerosis	73.1	132	16595793 (3), 15370069 (3), 17108813 (2), 16364824 (2) (see all 80)
vascular diseases	70.5	56	12504936 (2), 18629615 (2), 11298374 (2), 11812265 (2) (see all 29)
cardiovascular diseases	70	121	17108813 (2), 19407804 (2), 18331440 (2), 15494775 (2) (see all 81)
coronary artery disease	62	133	12010932 (6), 17151815 (3), 16842840 (2), 19466514 (2) (see all 80)
hypertension pulmonary	58.5	55	12904860 (3), 9950892 (3), 9727710 (3), 11371423 (3) (see all 32)
neovascularization	55.6	23	16983080 (2), 14556003 (2), 15162796 (2), 16100571 (1) (see all 13)
preeclampsia	55.5	143	10464002 (6), 12859429 (5), 10806726 (4), 11327094 (4) (see all 50)
erectile dysfunction	53.6	26	10553806 (3), 19466514 (2), 16871271 (2), 16085713 (2) (see all 14)
coronary spasm	53.3	32	10359729 (3), 9737779 (2), 12826928 (2), 16565556 (2) (see all 17)
cerebral vasospasm	53.2	15	18590437 (3), 19246300 (3), 16626096 (1), 15571165 (1) (see all 5)

Genetic Association Database (GAD): NOS3
Human Genome Epidemiology (HuGE) Navigator: NOS3 (891 documents)

Export disorders for NOS3 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for NOS3 gene, integrated from 9 sources (see all 3214):
(articles sorted by number of sources associating them with NOS3)

Utopia: connect your pdf to the dynamic
world of online information

In-vivo effects of Glu298Asp endothelial nitric oxide synthase polymorphism. (PubMed id 11740345)^{1, 2, 4} Sofowora G.... Wood A.J. (2001)
Molecular cloning and characterization of human endothelial nitric oxide synthase. (PubMed id 1379542)^{1, 2, 3} Marsden P.A.... Michel T. (1992)
Evidence for association of a common variant of the endothelial nitric oxide synthase gene (Glu298-->Asp polymorphism) to the presence, extent, and severity of coronary artery disease. (PubMed id 12010932)^{1, 4, 9} Colombo M.G....Biagini A. (2002)
Prevalence of endothelial nitric oxide synthase gene polymorphisms in patients with atopic asthma. (PubMed id 12190658)^{1, 4, 9} Holla L.I....Vacha J. (2002)
Association of a 27-bp repeat polymorphism in ecNOS gene with ischemic stroke in Chinese patients. (PubMed id 11222793)^{1, 4, 9} Hou L....Harada S. (2001)
NOSTRIN: a protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase. (PubMed id 12446846)^{1, 2, 9} Zimmermann K....Oess S. (2002)
Genetic polymorphisms of oxidative and antioxidant enzymes and arsenic-related hypertension. (PubMed id 16076760)^{1, 4, 9} Hsueh Y.M....Chen C.J. (2005)
Endothelial venodilator response in carriers of genetic polymorphisms involved in NO synthesis and degradation. (PubMed id 15255799)^{1, 4, 9} Fricker R....Haefeli W.E. (2004)
Relations between ACE gene and ecNOS gene polymorphisms and resistive index in type 2 diabetic patients with nephropathy. (PubMed id 11522715)^{1, 4, 9} Taniwaki H....Nishizawa Y. (2001)
An endothelial nitric oxide synthase gene polymorphism is associated with preeclampsia. (PubMed id 12044319)^{1, 4, 9} Tempfer C.B....Gregg A.R. (2001)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 4846	HGNC: 7876	AceView: NOS3	Ensembl:ENSG00000164867	euGenes: HUgn4846
ECgene: NOS3	Kegg: 4846	H-InvDB: NOS3

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for NOS3	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for NOS3	Genetics and Cytogenetics in Oncology and Haematology
Wikipedia	http://en.wikipedia.org/wiki/Nitric_oxide_synthase
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NOS3
SeattleSNPs	http://pga.gs.washington.edu/data/nos3/

Intellectual Property for NOS3 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for NOS3 gene:
Search GeneIP for patents involving NOS3

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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NOS3 Gene

nitric oxide synthase 3 (endothelial cell)

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Microalbuminuria
Genetic Susceptibility
Hyperinsulinemia
essential hypertension
sepsis
Shock Hemorrhagic
Myocardial Ischemia
Atherosclerosis
Ischemia
Neovascularization
Brain Ischemia
Hypercholesterolemia
cell damage
Mood Disorders
Hypertension Pulmonary
bone loss
Coronary Atherosclerosis
Pathological Processes
Chronic myocardial ischemia
Hepatitis B Chronic
RENAL DISEASE
Shock
Coronary Vasospasm
ADPKD
Inflammation
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Microangiopathy Diabetic
SICKLE CELL DISEASE
Hyperhomocysteinemia
Psoriasis
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prostate cancer
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Necrosis
Carotid Atherosclerosis
Preeclampsia
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renal ischemia
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HYPERTENSION ARTERIAL
atopy
Hyperplasia
atherosclerotic plaque
ARTERIAL VESSELS
INFARCT
retinopathy
Infarction Lacunar
Intracranial Aneurysm
Vasospasm
Alzheimers Disease
VASCULAR RING
Erectile Dysfunction
Diabetes Mellitus
Subarachnoid Hemorrhage
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VENOUS OCCLUSION
systemic hypertension
Effects Cardiovascular
Arteriosclerosis
Intrauterine Growth Retardation
Albuminuria
HEART FAILURE
Myocardial Infarction
Uremia
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Hypertension Portal
VARIANT ANGINA
Insulin Resistance
Ascites
Subarachnoid Hemorrhage Aneurysmal
Cerebral Vasospasm
OBESITY
acute chest syndrome
restenosis
Cardiac Hypertrophy
associated conditions
Brain Aneurysm
ventricular hypertrophy
STROKE
Graves Disease
Vascular Diseases
Cerebral Ischemia
chronic liver disease
NIDDM
reactive hyperemia
Sclerosis Systemic
CORONARY SPASM
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NOS3 Gene

nitric oxide synthase 3 (endothelial cell)

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Aliases
for NOS3 gene

Summaries
for NOS3 gene

Genomic Views
for NOS3 gene

Proteins
for NOS3 gene

Protein Domains /
Families
for NOS3 gene

Function
for NOS3 gene

Pathways & Interactions
for NOS3 gene

Drugs & Compounds
for NOS3 gene

Transcripts
for NOS3 gene

Expression
for NOS3 gene

Orthologs
for NOS3 gene

Paralogs
for NOS3 gene

Genomic Variants
for NOS3 gene

Disorders / Diseases
for NOS3 gene

Publications
for NOS3 gene

Intellectual Property
for NOS3 gene

Products
for NOS3 gene