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NOS3 Gene

protein-coding   GIFtS: 75
GCID: GC07P150688

Nitric Oxide Synthase 3 (Endothelial Cell)

  See NOS3-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)
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Aliases
Nitric Oxide Synthase 3 (Endothelial Cell)1 2     EC 1.14.13.393 8
Constitutive NOS2 3     Endothelial Nitric Oxide Synthase1
Endothelial NOS2 3     ECNOS2
EC-NOS2 3     Nitric Oxide Synthase 3 Transcript Variant ENOS-Delta202
NOSIII2 3     Nitric Oxide Synthase 3 Transcript Variant ENOS-Delta20-212
cNOS2 3     Nitric Oxide Synthase 3 Transcript Variant ENOS-Delta212
eNOS2 3     Nitric Oxide Synthase, Endothelial2
NOS Type III2 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, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 hypertension, and stroke, ischemic. 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 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000007.13  NT_007933.16  NC_018918.2  
Regulatory elements:
   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 Chromatin IP Primers for NOS3

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing 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, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, 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, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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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
Selected PDB 3D structures from and Proteopedia for NOS3 (see all 9):
1M9J (3D)        1M9K (3D)        1M9M (3D)        1M9Q (3D)        1M9R (3D)        1NIW (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: 

  • 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
  • Ubiquitination2 at Lys1035
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for NOS3 (P29474) (see all 40)
     AVLHSYQ  VFGLGSR  LQVFDAR  GQEEAFR 


    See NOS3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    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

    NOS3 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 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

     
    Search eBioscience for Proteins for NOS3 

    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)
    OriGene Antibodies for NOS3
    OriGene Custom Antibody Services for NOS3
    Novus Biologicals NOS3 Antibodies
    Abcam antibodies for NOS3 (P29474, P29475, P35228)
    Cloud-Clone Corp. Antibodies for NOS3
    ThermoFisher Antibody for NOS3
    LSBio Antibodies in human, mouse, rat for NOS3

    NOS3 Assay Products:

    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
    Search eBioscience for ELISAs for NOS3 


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

    Selected InterPro protein domains (see all 10):
     IPR017927 Fd_Rdtase_FAD-bd
     IPR001094 Flavdoxin
     IPR008254 Flavodoxin/NO_synth
     IPR012144 NOS_euk
     IPR004030 NO_synthase_oxygenase_dom

    Graphical View of Domain Structure for InterPro Entry P29474

    ProtoNet protein and cluster: P29474

    Selected 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


    Find genes that share domains with NOS3           About GenesLikeMe


    (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,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    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): Selected molecular function terms (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
         
    Find genes that share ontologies with NOS3           About GenesLikeMe


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

         Selected MGI mutant phenotypes (inferred from 8 alleles(MGI details for Nos3) (see all 22):
     adipose tissue  behavior/neurological  cardiovascular system  cellular  digestive/alimentary 
     endocrine/exocrine gland  growth/size/body  hematopoietic system  homeostasis/metabolism  immune system 
     limbs/digits/tail  liver/biliary system  mortality/aging  muscle  nervous system 

    Find genes that share phenotypes with NOS3           About GenesLikeMe

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

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for NOS3
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models 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:
        
    miRTarBase miRNAs that target NOS3:
    hsa-mir-155-5p (MIRT007181), hsa-mir-335-5p (MIRT017773)

    Block miRNA regulation of human, mouse, rat NOS3 using miScript Target Protectors
    4 qRT-PCR 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:
        
    OriGene RNAi products in human, mouse, rat for NOS3
    Predesigned siRNA for gene silencing in human, mouse, rat NOS3

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for NOS3

    Clone
    Products:
         
    OriGene clones in human, mouse for NOS3 (see all 24)
    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
    Addgene plasmids for NOS3 

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for NOS3
    Browse ESI BIO Cell Lines and PureStem Progenitors for NOS3 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOS3

    Flow Cytometry
    Products:
       

     
    eBioscience FlowRNA Probe Sets ( VA1-11705) for NOS3 


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    NOS3_HUMAN, P29474: 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
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton5
    golgi apparatus5
    plasma membrane5
    cytosol4
    extracellular3
    nucleus3
    endoplasmic reticulum2
    mitochondrion2
    peroxisome2

    Gene Ontology (GO): Selected cellular component terms (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--

    Find genes that share ontologies with NOS3           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to 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 QIAGEN, 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 Apr 2014 via Entrez Gene).
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    SuperPaths for NOS3 About   (see all 50)  
    See pathways by source

    SuperPathContained pathways About
    1Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics
    Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics0.37
    ACE Inhibitor Pathway0.00
    ACE Inhibitor Pathway, Pharmacodynamics0.00
    2Arginine and proline metabolism
    Arginine and proline metabolism
    citrulline-nitric oxide cycle0.00
    superpathway of citrulline metabolism0.00
    3Metabolism
    Metabolism0.38
    Metabolic pathways0.38
    4Immune response IL 23 signaling pathway
    Angiopoietin-TIE2 Signaling0.36
    Angiopoietin receptor Tie2-mediated signaling0.32
    5Immune response Fc epsilon RI pathway
    VEGF signaling pathway0.39
    VEGF - VEGF R2 Signaling Pathways0.35


    Find genes that share SuperPaths with NOS3           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

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

    Selected Downloadable PowerPoint Slides of GeneGlobe 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

    Selected 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

    Selected BioSystems Pathways for NOS3 (see all 15)
        ACE Inhibitor Pathway
    Myometrial Relaxation and Contraction Pathways
    Angiogenesis
    AGE/RAGE pathway
    Effects of nitric oxide

    Selected Reactome Pathways for NOS3 (see all 6)
        NOSTRIN mediated eNOS trafficking
    Phagosomal maturation (early endosomal stage)
    eNOS activation
    Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation
    Nitric oxide stimulates guanylate cyclase

    Selected 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

    Selected Kegg Pathways  (Kegg details for NOS3) (see all 8):
        Arginine and proline metabolism
    Metabolic pathways
    Calcium signaling pathway
    HIF-1 signaling pathway
    PI3K-Akt signaling pathway

        Pathway & Disease-focused RT2 Profiler 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

    Interactions:

        GeneGlobe Interaction Network for NOS3

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

    Selected Interacting proteins for NOS3 (P294741, 2, 3 ENSP000002974944) via UniProtKB, MINT, STRING, and/or I2D (see all 102)
    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): Selected biological process terms (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--

    Find genes that share ontologies with NOS3           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Enzo Life Sciences drugs & compounds for NOS3
      Browse compounds at ApexBio 

    Compounds for NOS3 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    L-NIO dihydrochloridePotent eNOS inhibitor[36889-13-1]

    Selected 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--

    Selected 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

    Selected 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)

    Selected 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  



    Find genes that share compounds with NOS3           About GenesLikeMe



    (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,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    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
    miRNA
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    hsa-miR-4324 hsa-miR-875-3p hsa-miR-4261 hsa-miR-1303
    SwitchGear 3'UTR luciferase reporter plasmidNOS3 3' UTR sequence
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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 

    Selected AceView cDNA sequences (see all 105):

    BQ712348 CR596138 BM747155 AA954011 CA423531 AA992377 BM790057 BM546712 
    BM783934 BG741096 BM756290 BM823046 NM_000603 BF060748 AF400594 BM791714 
    BC063294 BM784967 AW298145 T28178 BC069465 BM766305 BM768070 M95296 

    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™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    NOS3 expression in normal human tissues (normalized intensities)
    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
     selected tissues (see all 4) fully expand
     
     Endothelium (Cardiovascular System)    fully expand to see all 6 entries
             eNOS-transfected endothelial progenitor cells
             Endothelial-like cells
     
     Blood (Hematopoietic System)
             Bone marrow-derived CD34+ stem cells (ACT34)
     
     Adipose (Muscoskeletal System)    fully expand to see all 2 entries
             Body Subcutaneous White Adipose
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
    NOS3 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    NOS3 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.647092

    UniProtKB/Swiss-Prot: NOS3_HUMAN, P29474
    Tissue specificity: Platelets, placenta, liver and kidney

        Pathway & Disease-focused RT2 Profiler 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)
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    This gene was present in the common ancestor of animals and fungi.

    Orthologs for NOS3 gene from Selected species (see all 13)    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 INOS6
    Gallus gallus nitric oxide synthase 2, inducible (...
    49(a)
    many ↔ many
    19(9192393-9211569) ENSGALG00000005693
    lizard
    (Anolis carolinensis)
    Reptilia NOS36
    nitric oxide synthase 3 (endothelial cell)
    71(a)
    1 ↔ 1
    GL343807.1(16588-55860)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia nos31 nitric oxide synthase 3 (endothelial cell) 66.96(n)
    67.8(a)
      100486016  NM_001256229.1  NP_001243158.1 
    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...
    25(a)
    1 → many
    VIII(190543-192618) YHR042W


    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)
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    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

    Find genes that share paralogs with NOS3           About GenesLikeMe



    (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), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    NOS3_HUMAN, P29474: Variation in NOS3 seem to be associated with susceptibility to coronary spasm


    Selected SNPs for NOS3 (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) Selected 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

    Site Specific Mutation Identification with 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.)
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    OMIM gene information: 163729   
    OMIM disorders: 104300  145500  189800  601367  
    Selected diseases for NOS3 (see all 36):    
    About MalaCards
    hypertension    stroke, ischemic    coronary artery spasm 1    acute chest syndrome
    placental abruption    alzheimer disease type 2    pre-eclampsia    adiponectin deficiency
    polycystic kidney disease, type 1    hemifacial spasm    placenta accreta    central sleep apnea
    arteritic anterior ischemic optic neuropathy    carotid artery thrombosis    non-arteritic anterior ischemic optic neuropathy    thromboangiitis obliterans
    renal artery disease    acute mountain sickness    mitral valve disease    anterior ischemic optic neuropathy

    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

    Find genes that share disorders with NOS3           About GenesLikeMe

    Selected 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)
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    PubMed articles for NOS3 gene, integrated from 10 sources (see all 3342):
    (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. (Pharmacogenetics 2001)
    2. Molecular cloning and characterization of human endothelial nitric oxide synthase. (PubMed id 1379542)1, 2, 3 Marsden P.A.... Michel T. (FEBS Lett. 1992)
    3. The -786T&gt;C promoter polymorphism of the NOS3 gene is associated with prostate cancer progression. (PubMed id 18823560)1, 4, 9 Marangoni K....Goulart L.R. (BMC Cancer 2008)
    4. Evidence for association of a common variant of the endothelial nitric oxide synthase gene (Glu298--&gt;Asp polymorphism) to the presence, extent, and severity of coronary artery disease. (PubMed id 12010932)1, 4, 9 Colombo M.G....Biagini A. (Heart 2002)
    5. Prevalence of endothelial nitric oxide synthase gene polymorphisms in patients with atopic asthma. (PubMed id 12190658)1, 4, 9 HollA! L.I....VA!cha J. (Clin. Exp. Allergy 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. (Neurology 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. (Clin. Exp. Rheumatol. 2009)
    8. Association of VEGF and eNOS gene polymorphisms in type 2 diabetic retinopathy. (PubMed id 16636650)1, 4, 9 Suganthalakshmi B....Sundaresan P. (Mol. Vis. 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. (Oncol. Rep. 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. (Proc. Natl. Acad. Sci. U.S.A. 2002)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     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)
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    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, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    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/books/NBK1116/?term=NOS3[genesymbol]
    SeattleSNPshttp://pga.gs.washington.edu/data/nos3/

    (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



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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