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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

NOS3 Gene

protein-coding   GIFtS: 74
GCID: GC07P150688

Nitric Oxide Synthase 3 (Endothelial Cell)

Microbiology & Infectious Diseases Congress
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Nitric Oxide Synthase 3 (Endothelial Cell)1 2     eNOS2 3
Constitutive NOS2 3     NOS Type III2 3
Endothelial NOS2 3     EC 1.14.13.393 8
EC-NOS2 3     Endothelial Nitric Oxide Synthase1
NOSIII2 3     ECNOS2
cNOS2 3     Nitric Oxide Synthase, Endothelial2

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 Gene:
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)

GeneCards Summary for NOS3 Gene: 
NOS3 (nitric oxide synthase 3 (endothelial cell)) is a protein-coding gene. Diseases associated with NOS3 include brain aneurysm, and acute chest syndrome, and among its related super-pathways are ACE Inhibitor Pathway and Metabolic pathways. GO annotations related to this gene include calmodulin binding and heme binding. An important paralog of this gene is POR.

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 Gene:
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) Gene


(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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000007.13  NC_018918.2  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 UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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 Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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

Explore proteomics data for NOS3 at MOPED 

Post-translational modifications:

  • UniProtKB: 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 activity
  • View modification sites using PhosphoSitePlus
  • 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 MOPED1, PaxDb2 and MAXQB3 :    About this image 

    NOS3 Protein Expression
    REFSEQ proteins (4 alternative transcripts): 
    NP_000594.2  NP_001153581.1  NP_001153582.1  NP_001153583.1  

    ENSEMBL proteins: 
     ENSP00000297494   ENSP00000417143   ENSP00000420215   ENSP00000420551   ENSP00000418245  
    Reactome Protein details: P29474
    Human Recombinant Protein Products for NOS3: 
    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 for NOS3
    OriGene Protein Over-expression Lysate for NOS3
    OriGene MassSpec for 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 Sino Biological Cell Lysates 
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for NOS3 

    Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane TAS--
    GO:0005634nucleus ISS--
    GO:0005737cytoplasm IDA9794441
    GO:0005829cytosol TAS--
    GO:0005856cytoskeleton IEA--

    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
    Abcam antibodies for NOS3
    Cloud-Clone Corp. Antibodies for NOS3 
    ThermoFisher Antibody for NOS3
    LSBio Antibodies in human, mouse, rat for NOS3 

    Assay Products for NOS3: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for NOS3
    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
    Cloud-Clone Corp. ELISAs for NOS3 
    Cloud-Clone Corp. CLIAs for NOS3


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    IUPHAR Guide to PHARMACOLOGY protein family classification: Endothelial NOS 
    Nitric oxide synthases

    5/11 InterPro protein domains (see all 11):
     IPR026009 NOS
     IPR017927 Fd_Rdtase_FAD-bd
     IPR001094 Flavdoxin
     IPR008254 Flavodoxin/NO_synth
     IPR001433 OxRdtase_FAD/NAD-bd

    Graphical View of Domain Structure for InterPro Entry P29474

    ProtoNet protein and cluster: P29474

    5/7 Blocks protein domains (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


    NOS3 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    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, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    Molecular Function:

         UniProtKB/Swiss-Prot Summary: 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

         Gene Ontology (GO): 5/14 molecular function terms (GO ID links to tree view) (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003785actin monomer binding IPI17502619
    GO:0003958NADPH-hemoprotein reductase activity IBA--
    GO:0004517nitric-oxide synthase activity IDA1378832
    GO:0005506iron ion binding IEA--
    GO:0005515protein binding IPI11149895
         
    NOS3 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for NOS3:
     Decreased influenza A virus in  Increased G1 DNA content 

         15/23 MGI mutant phenotypes (inferred from 8 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

    Animal Models:
         MGI mouse knock-outs for NOS3: Nos3tm1.1Taka Nos3tm1Weo Nos3tm1Plh Nos3tm1Gdk Nos3tm1Unc

       inGenious Targeting Laboratory - Custom generated mouse model solutions for NOS3 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for NOS3

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NOS3 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NOS3 

    miRNA
    Products:
        
    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 plasmidNOS3 3' UTR sequence
    Inhib. RNA
    Products:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for NOS3
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat NOS3

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for NOS3
    Sirion Biotech Customized adenovirus for overexpression of NOS3

    Clone
    Products:
         
    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene clones in human, mouse for NOS3 (see all 20)
    OriGene ORF clones in mouse, rat for NOS3
    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
    Sirion Biotech Customized lentivirus for stable overexpression of NOS3 
                         Customized lentivirus expression plasmids for stable overexpression of 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


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, 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 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for NOS3 About   (see all 50)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics
    ACE Inhibitor Pathway0.85
    ACE Inhibitor Pathway, Pharmacodynamics0.85
    Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics0.85
    2Metabolism
    Metabolism0.40
    Metabolic pathways0.40
    3Development VEGF signaling via VEGFR2 - generic cascades
    Development VEGF signaling via VEGFR2 - generic cascades0.75
    VEGF - VEGF R2 Signaling Pathways 0.39
    4Development PDGF signaling via STATs and NF-kB
    Angiopoietin-TIE2 Signaling0.36
    Angiopoietin receptor Tie2-mediated signaling0.32
    5Activation of cAMP-Dependent PKA
    Activation of cAMP-Dependent PKA0.77
    Activation of PKA through GPCR0.71
    cAMP Pathway0.77
    PKA Signaling0.56

    Pathways by source                                                                                                                                                                 See SuperPaths
    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

    1 R&D Systems Pathway for NOS3
        VEGF - VEGF R2 Signaling Pathways

    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
    Myometrial Relaxation and Contraction Pathways
    AGE/RAGE pathway
    Endothelin

    5/13        Reactome Pathways for NOS3 (see all 13)
        Hemostasis
    Phagosomal maturation (early endosomal stage)
    eNOS activation and regulation
    Metabolism
    Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation

    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

    5/7         Kegg Pathways  (Kegg details for NOS3) (see all 7):
        Arginine and proline metabolism
    Metabolic pathways
    Calcium signaling pathway
    HIF-1 signaling pathway
    PI3K-Akt signaling pathway


    NOS3 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM 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 (P294741, 2, 3 ENSP000002974944) via UniProtKB, MINT, STRING, and/or I2D (see all 66)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    NOSTRINQ8IVI91, 2, 3, ENSP000003189214EBI-1391623,EBI-1391643 MINT-7213409 MINT-7213465 I2D: score=2 STRING: ENSP00000318921
    ST13P505021, 3EBI-1391623,EBI-357285 I2D: score=1 
    CALM1P621583, ENSP000003494674I2D: score=4 STRING: ENSP00000349467
    CALM2P621583I2D: score=4 
    CALM3P621583I2D: score=4 
    About this table

    Gene Ontology (GO): 5/37 biological process terms (GO ID links to tree view) (see all 37):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001525angiogenesis IEA--
    GO:0001542ovulation from ovarian follicle IEA--
    GO:0001701in utero embryonic development IEA--
    GO:0001974blood vessel remodeling ISS--
    GO:0002028regulation of sodium ion transport IEA--

    NOS3 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, 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
    CompoundAction CAS #
    L-NIO dihydrochloridePotent eNOS inhibitor[36889-13-1]

    10/12 HMDB Compounds for NOS3 (see all 12)    About this table
    CompoundSynonyms CAS #PubMed Ids
    Dihydrobiopterin(S-(R*,S*))-2-amino-6-(1,2-dihydroxypropyl)-7,8-dihydro-4(1H)-Pteridinone (see all 15)6779-87-915470159
    Tetrahydrobiopterin(1R,2S)-(2-Amino-3,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)-1,2-propandiol (see all 11)17528-72-217420345
    CalciumCa (see all 2)7440-70-2--
    Citrulline(2S)-2-amino-5-(carbamoylamino)pentanoic acid (see all 55)372-75-8--
    FAD1H-Purin-6-amine flavin dinucleotide (see all 21)146-14-5--
    Flavin MononucleotideFMN (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--
    NADPAdenine-nicotinamide dinucleotide phosphate (see all 18)53-59-8--
    NADPH2'-(dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide (see all 23)53-57-6--

    10/42 DrugBank Compounds for NOS3 (see all 42)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    Tetrahydrobiopterin5,6,7,8 Tetrahydrobiopterin (see all 3)17528-72-2targetcofactor11009561 10749876 10924132 10995244 10075731 12003347
    L-Arginine(S)-2-Amino-5-guanidinovaleric acid (see all 4)74-79-3target--16690332 16720041 16729278 16682803 16717106
    L-Citrulline2-Amino-5-uredovaleric acid (see all 8)372-75-8target--10440125 10749853 10460702 10690351 10403604
    Miconazole-- 22916-47-8targetinhibitor7536941 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-- 1779-81-3target--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 inferred 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)

    10/11 PharmGKB related drug/compound annotations for NOS3 gene (see all 11)    About this table
    Drug/compound PharmGKB Annotation
    AntihypertensivesCA  
    Antihypertensives And Diuretics In CombinationCA  
    Beta Blocking AgentsCA  
    aspirinCA  
    clopidogrelCA  
    cyclophosphamideCA  
    diureticsCA  
    doxorubicinCA  
    fluorouracilCA  
    hmg coa reductase inhibitorsCA  

    Search CenterWatch for drugs/clinical trials and news about NOS3

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, 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, Sirion Biotech, 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
    10 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000297494(uc003wif.3 uc011kuy.2) ENST00000461406 ENST00000484524(uc011kuz.2)
    ENST00000467517(uc011kvb.2 uc011kva.2) ENST00000460603 ENST00000473057
    ENST00000475017 ENST00000468293 ENST00000477227 ENST00000475454
    Congresses - knowledge worth sharing:  
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    Additional mRNA 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 

    9 DOTS entries:

    DT.97810187  DT.313642  DT.40126949  DT.97845228  DT.75180420  DT.97765741  DT.97845230  DT.100778681 
    DT.95321333 

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

    AA954011 BC063294 AF400594 BM768070 BC069465 BM741457 BM821409 AW168483 
    BM784967 CA423531 BM766305 BM791714 AW298145 AA992377 BM747155 NM_000603 
    M95296 BM790057 BM851583 BQ712348 CR596138 T28178 BM783934 BF060748 

    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)      NOS3 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: GAGCTGGACG
    NOS3 Expression
    About this image


    NOS3 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/15 selected tissues (see all 15) fully expand
     
     Endothelium (Cardiovascular System)    fully expand to see all 18 entries
             Arterial Endothelial Cells Paired Dorsal Aorta
             PureStem endothelial progenitor 30-SM2-1
             Endothelial-like cells ( Generation of endothelial progenitor cells and smooth muscle...
             Human Cardiac Microvascular Endothelial Cells (HCMEC)   
     
     Blood (Hematopoietic System)    fully expand to see all 4 entries
             Bone marrow-derived CD34+ stem cells (ACT34)
             mouse/organ system/cardiovascular system   
     
     Umbilical Cord (Extraembryonic Tissues)    fully expand to see all 4 entries
             Human Umbilical Mesenchymal Stem Cells (HUMSC)   
     
     Heart (Cardiovascular System)    fully expand to see all 3 entries
             Human Cardiac Microvascular Endothelial Cells (HCMEC)   
             mouse/organ system/cardiovascular system   
     
     Adipose (Muscoskeletal System)    fully expand to see all 2 entries
             Body Subcutaneous White Adipose

    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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    (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 common ancestor of animals and fungi.

    Orthologs for NOS3 gene from 5/12 species (see all 12)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Nos31 , 5 nitric oxide synthase 3, endothelial cell1, 5 88.46(n)1
    94.73(a)1
      5 (11.32 cM)5
    181271  NM_008713.41  NP_032739.31 
     243648105 
    chicken
    (Gallus gallus)
    Aves NOS36
    nitric oxide synthase 3 (endothelial cell)
    69(a)
    1 ↔ 1
    2(309959-322560)
    lizard
    (Anolis carolinensis)
    Reptilia NOS36
    Nitric oxide synthase
    71(a)
    1 ↔ 1
    GL343807.1(16588-55860)
    fruit fly
    (Drosophila melanogaster)
    Insecta Nos3 imaginal disc development calmodulin
    binding
    47(a)   2 32B1   --
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes NCP16
    NADP-cytochrome P450 reductase; involved in ergost...
    23(a)
    1 → many
    VIII(190543-192618)


    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 4 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, 4UniProtKB, 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


    10/675 SNPs in NOS3 are shown (see all 675)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 7 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0363044
    A colorectal cancer sample4--see VAR_0363042 R Q mis40--------
    VAR_0363034
    A colorectal cancer sample4--see VAR_0363032 R C mis40--------
    rs17999831,2,4
    C,F,A,Hpathogenic1150025703(+) GATGAG/TCCCCC 8 E D mis1 ese341Minor allele frequency- T:0.27MN NS EA NA WA CSA EU 13917
    rs1881455701,2
    --150015535(+) GCCCTG/TCAGAG 1 -- us2k10--------
    rs599458571,2
    C,F--150015599(+) ATGGAG/AGGGGC 1 -- us2k11Minor allele frequency- A:0.03WA 118
    rs1809467191,2
    --150015616(+) CACAGA/GGCACA 1 -- us2k10--------
    rs1854120401,2
    --150015619(+) AGGGCA/GCAGCC 1 -- us2k10--------
    rs1394023721,2
    C--150015629(+) CCTCCA/CCAGGG 1 -- us2k10--------
    rs768986941,2
    C,F--150015673(+) CTTACC/TCCTGG 1 -- us2k11Minor allele frequency- T:0.06WA 118
    rs105315861,2
    C--150015711(+) AAACACA/-GCCAC 1 -- us2k11Minor allele frequency- -:0.00NS 528

    HapMap Linkage Disequilibrium report for NOS3 (150688083 - 150711687 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 10/11 variations for NOS3 (see all 11):    About this table     
    Variant IDTypeSubtypePubMed ID
    esv2735394CNV Deletion23290073
    nsv889474CNV Loss21882294
    nsv889473CNV Loss21882294
    nsv889470CNV Loss21882294
    dgv7544n71CNV Loss21882294
    esv274999CNV Loss21479260
    nsv889465CNV Loss21882294
    nsv889471CNV Loss21882294
    dgv7543n71CNV Loss21882294
    nsv889472CNV Loss21882294


    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, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section
    OMIM gene information: 163729   
    OMIM disorders: 104300  145500  189800  601367  
    20/246 diseases for NOS3 (see all 246):    About MalaCards
    brain aneurysm    acute chest syndrome    adiponectin deficiency    hemifacial spasm
    polycystic kidney disease, type 1    central sleep apnea    carotid artery thrombosis    nonarteritic anterior ischemic optic neuropathy
    ischemic optic neuropathy    placenta accreta    thromboangiitis obliterans    spermatic cord torsion
    endotheliitis    sleep apnea    spinal cord ischemia    aortic coarctation
    ischemia    intracranial aneurysm    acute mountain sickness    resting heart rate

    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     Liver cirrhosis     Diabetic retinopathy

    NOS3 for disorders           About GeneDecksing


    Congresses - knowledge worth sharing:  
    The International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD) 9 - 13 March 2014
    Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

    10/96 Novoseek inferred 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 3294):
    (articles sorted by number of sources associating them with NOS3)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. In-vivo effects of Glu298Asp endothelial nitric oxide synthase polymorphism. (PubMed id 11740345)1, 2, 4 Sofowora G.... Wood A.J. (2001)
    2. Molecular cloning and characterization of human endothelial nitric oxide synthase. (PubMed id 1379542)1, 2, 3 Marsden P.A.... Michel T. (1992)
    3. The -786T>C promoter polymorphism of the NOS3 gene is associated with prostate cancer progression. (PubMed id 18823560)1, 4, 9 Marangoni K....Goulart L.R. (2008)
    4. 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)
    5. 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)
    6. 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)
    7. Influence of nitric oxide synthase gene polymorphisms on the risk of cardiovascular events in rheumatoid arthritis. (PubMed id 19327239)1, 4, 9 Gonzalez-Gay M.A....Martin J. (2009)
    8. Association of VEGF and eNOS gene polymorphisms in type 2 diabetic retinopathy. (PubMed id 16636650)1, 4, 9 Suganthalakshmi B....Sundaresan P. (2006)
    9. Genetic analysis of caveolin-1 and eNOS genes in colorectal cancer. (PubMed id 16820915)1, 4, 9 Conde M.C....Royo J.L. (2006)
    10. 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)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    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)
    About This Section
      --

    (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
    NameDescription
    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
    GeneReviewshttp://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NOS3
    SeattleSNPshttp://pga.gs.washington.edu/data/nos3/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    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



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
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    About This Section

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    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 3 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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