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

NOS2 Gene

protein-coding   GIFtS: 70
GCID: GC17M026083

Nitric Oxide Synthase 2, Inducible

(Previous names: nitric oxide synthase 2A (inducible, hepatocytes))
(Previous symbol: NOS2A)
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 2, Inducible1 2     NOS Type II2 3
NOS2A1 2 3 5     EC 1.14.13.393 8
Nitric Oxide Synthase 2A (Inducible, Hepatocytes)1 2     INOS2
Hepatocyte NOS2 3     NOS2
Inducible NO Synthase2 3     Nitric Oxide Synthase, Inducible2
Inducible NOS2 3     Nitric Oxide Synthase, Macrophage2
Peptidyl-Cysteine S-Nitrosylase NOS22 3     NOS, Type II2
HEP-NOS2 3     iNOS3

External Ids:    HGNC: 78731   Entrez Gene: 48432   Ensembl: ENSG000000071717   OMIM: 1637305   UniProtKB: P352283   

Export aliases for NOS2 gene to outside databases

Previous GC identifers: GC17M023108 GC17M022290


(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 NOS2 Gene:
Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including
neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which
is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three
related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. (provided by RefSeq,
Jul 2008)

GeneCards Summary for NOS2 Gene: 
NOS2 (nitric oxide synthase 2, inducible) is a protein-coding gene. Diseases associated with NOS2 include virilizing ovarian tumor, and pityriasis lichenoides, and among its related super-pathways are Immune response IL-12-induced IFN-gamma production and Bacterial infections in CF airways. GO annotations related to this gene include calmodulin binding and protein homodimerization activity. An important paralog of this gene is NOS3.

UniProtKB/Swiss-Prot: NOS2_HUMAN, P35228
Function: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In
macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates
cysteine S-nitrosylation of cytoplasmic target proteins such COX2

summary for NOS2 Gene:
Inducible nitric oxide synthase (iNOS), along with neuronal nitric oxide synthase (nNOS) and endothelial
nitric oxide synthase (eNOS), catalyze the generation of nitric oxide and L-citrulline from L-arginine and
molecular oxygen. It displays high affinity for Ca2+/calmodulin, thus appears to be constitutively active.
Tetrahydrobiopterin, flavin adenine dinucleotide, flavin mononucleotide and NADPH co-factors are required
for catalytic activity. iNOS gene expression is regulated by various pathways including NF-kappaB, IFN-gamma
(signaling through the JAK-STAT cascade) and HIF-1, which induce expression, and TGF-beta and interleukins
-4, -10 and -13, which inhibit expression. Post-translational regulation occurs by prevention of iNOS
homodimerization by NAP110. iNOS has roles in the innate immune system and displays antibacterial, antiviral
and antifungal activity. The human gene encoding iNOS is localized to chromosome 17q11.2-q12.

Gene Wiki entry for NOS2 (Nitric oxide synthase 2) 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_000017.10  NC_018928.2  NT_010799.15  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the NOS2 gene promoter:
         p300   MyoD   IRF-1   HNF-3beta   HNF-4alpha1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): NOS2 promoter sequence
   Search SABiosciences Chromatin IP Primers for NOS2

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NOS2


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

Entrez Gene cytogenetic band: 17q11.2-q12   Ensembl cytogenetic band:  17q11.2   HGNC cytogenetic band: 17q11.2-q12

NOS2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOS2 gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17M026083:  view genomic region     (about GC identifiers)

Start:
26,083,792 bp from pter      End:
26,127,555 bp from pter
Size:
43,764 bases      Orientation:
minus strand

(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: NOS2_HUMAN, P35228 (See protein sequence)
Recommended Name: Nitric oxide synthase, inducible  
Size: 1153 amino acids; 131117 Da
Cofactor: Heme group (By similarity)
Cofactor: Binds 1 FAD (By similarity)
Cofactor: Binds 1 FMN (By similarity)
Cofactor: Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme (By similarity)
Subunit: Homodimer. Binds SLC9A3R1
6/7 PDB 3D structures from and Proteopedia for NOS2 (see all 7):
1NSI (3D)        2LL6 (3D)        2NSI (3D)        3E7G (3D)        3EJ8 (3D)        3HR4 (3D)    
Secondary accessions: A1L3U5 B7ZLY2 O60757 O94994 Q16263 Q16692 Q4TTS5 Q9UD42
Alternative splicing: 2 isoforms:  P35228-1   P35228-2   

Explore the universe of human proteins at neXtProt for NOS2: NX_P35228

Explore proteomics data for NOS2 at MOPED 

Post-translational modifications:

  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P35228

  • 4/43 DME Specific Peptides for NOS2 (P35228) (see all 43)
     VLEEFPS  GWYMGTE  LDITTPP  LQVFDAR 

    NOS2 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    NOS2 Protein Expression
    REFSEQ proteins: NP_000616.3  
    ENSEMBL proteins: 
     ENSP00000327251  
    Reactome Protein details: P35228
    Human Recombinant Protein Products for NOS2: 
    Browse Purified and Recombinant Proteins at EMD Millipore
    Browse R&D Systems for human recombinant proteins
    Enzo Life Sciences proteins for NOS2
    OriGene Purified Protein for NOS2
    OriGene Protein Over-expression Lysate for NOS2
    OriGene MassSpec for NOS2 
    OriGene Custom Protein Services for NOS2
    GenScript Custom Purified and Recombinant Proteins Services for NOS2
    Novus Biologicals NOS2 Protein
    Novus Biologicals NOS2 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates 
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for NOS2 

    Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005622intracellular IDA7544003
    GO:0005634nucleus ISS--
    GO:0005737cytoplasm IDA12085352
    GO:0005777peroxisome IDA12085352
    GO:0005829cytosol TAS--

    NOS2 for ontologies           About GeneDecksing



    NOS2 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of NOS2
    R&D Systems Antibodies for NOS2 (iNOS)
    Browse OriGene Antibodies
    OriGene Custom Antibody Services for NOS2
    GenScript Custom Superior Antibodies Services for NOS2
    Novus Biologicals NOS2 Antibodies
    Abcam antibodies for NOS2
    Cloud-Clone Corp. Antibodies for NOS2 
    ThermoFisher Antibody for NOS2
    LSBio Antibodies in human, mouse, rat for NOS2 

    Assay Products for NOS2: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for NOS2
    R&D Systems ELISAs for NOS2 (iNOS)
    GenScript Custom Assay Services for NOS2
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for NOS2 
    Cloud-Clone Corp. CLIAs for NOS2


    (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: Inducible 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 P35228

    ProtoNet protein and cluster: P35228

    5/6 Blocks protein domains (see all 6):
    IPB001094 Flavodoxin signature
    IPB001433 Oxidoreductase FAD/NAD(P)-binding
    IPB001709 Flavoprotein pyridine nucleotide cytochrome reductase signature
    IPB003097 FAD-binding
    IPB004030 Nitric oxide synthase


    UniProtKB/Swiss-Prot: NOS2_HUMAN, P35228
    Similarity: Belongs to the NOS family
    Similarity: Contains 1 FAD-binding FR-type domain
    Similarity: Contains 1 flavodoxin-like domain


    NOS2 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: NOS2_HUMAN, P35228
    Function: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In
    macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates
    cysteine S-nitrosylation of cytoplasmic target proteins such COX2
    Catalytic activity: 2 L-arginine + 3 NADPH + 4 O(2) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H(2)O
    Enzyme regulation: Regulated by calcium/calmodulin. Aspirin inhibits expression and function of this enzyme and
    effects may be exerted at the level of translational/post-translational modification and directly on the
    catalytic activity (By similarity)
    Induction: By endotoxins and cytokines. Induced by IFNG/IFN-gamma acting synergistically with bacterial
    lipopolysaccharides (LPS), TNF or IL1B/interleukin-1 beta

         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:0003958NADPH-hemoprotein reductase activity IBA--
    GO:0004517nitric-oxide synthase activity IDA7504305
    GO:0005102receptor binding IPI--
    GO:0005506iron ion binding IEA--
    GO:0005515protein binding IPI12855682
         
    NOS2 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for NOS2:
     Decreased viability after Chla  Increased gamma-H2AX phosphory 

         15/23 MGI mutant phenotypes (inferred from 3 alleles(MGI details for Nos2) (see all 23):
     adipose tissue  behavior/neurological  cardiovascular system  cellular  craniofacial 
     digestive/alimentary  endocrine/exocrine gland  growth/size  hematopoietic system  homeostasis/metabolism 
     immune system  integument  liver/biliary system  mortality/aging  muscle 

    NOS2 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for NOS2: Nos2tm1Mrl Nos2tm1Lau Nos2tm1Liew

       inGenious Targeting Laboratory - Custom generated mouse model solutions for NOS2 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for NOS2

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for NOS2 
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for NOS2 

    miRNA
    Products:
        
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat NOS2
    2 QIAGEN miScript miRNA Assays for microRNAs that regulate NOS2:
    hsa-miR-485-3p hsa-miR-323-5p
    SwitchGear 3'UTR luciferase reporter plasmidNOS2 3' UTR sequence
    Inhib. RNA
    Products:
        
    Browse for Gene Knock-down Tools from EMD Millipore
    OriGene RNAi products in human, mouse, rat for NOS2
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat NOS2

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for NOS2
    Sirion Biotech Customized adenovirus for overexpression of NOS2

    Clone
    Products:
         
    Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene clones in human, mouse for NOS2 (see all 7)
    OriGene ORF clones in mouse, rat for NOS2
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: NOS2 (NM_000625)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOS2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOS2
    Sirion Biotech Customized lentivirus for stable overexpression of NOS2 
                         Customized lentivirus expression plasmids for stable overexpression of NOS2 

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for NOS2
    Search LifeMap BioReagents cell lines for NOS2
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOS2


    (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 NOS2 About   (see all 37)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Immune response IL-12-induced IFN-gamma production
    Immune response IL-12-induced IFN-gamma production0.88
    IL12-mediated signaling events0.33
    2Immune response Bacterial infections in normal airways
    Immune response Bacterial infections in normal airways0.78
    Bacterial infections in CF airways0.78
    3Nitric oxide stimulates guanylate cyclase
    Nitric oxide stimulates guanylate cyclase0.75
    Platelet homeostasis0.34
    4Insulin receptor recycling
    Latent infection of Homo sapiens with Mycobacterium tuberculosis0.64
    Phagosomal maturation (early endosomal stage)0.64
    5Toll Comparative Pathway
    Immune response MIF in innate immunity response0.46
    Immune response IL-1 signaling pathway0.41

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    5/6 EMD Millipore Pathways for NOS2 (see all 6)
        Immune response IL-12-induced IFN-gamma production
    G-protein signaling Rac2 regulation pathway
    Immune response MIF-mediated glucocorticoid regulation
    Immune response MIF in innate immunity response
    Immune response CCR3 signaling in eosinophils


    5/11 GeneGo (Thomson Reuters) Pathways for NOS2 (see all 11)
        Immune response MIF-mediated glucocorticoid regulation
    Immune response Bacterial infections in normal airways
    Immune response MIF in innate immunity response
    Development VEGF signaling via VEGFR2 - generic cascades
    Mechanisms of CFTR activation by S-nitrosoglutathione (normal and CF)

    5/11 BioSystems Pathways for NOS2 (see all 11)
        Type II interferon signaling (IFNG)
    Spinal Cord Injury
    AGE/RAGE pathway
    Prolactin Signaling Pathway
    citrulline-nitric oxide cycle

    5/6        Reactome Pathways for NOS2 (see all 6)
        Hemostasis
    Phagosomal maturation (early endosomal stage)
    Latent infection of Homo sapiens with Mycobacterium tuberculosis
    Platelet homeostasis
    Nitric oxide stimulates guanylate cyclase

    2 PharmGKB Pathways for NOS2
        Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics
    Doxorubicin Pathway, Pharmacokinetics

    5/14         Kegg Pathways  (Kegg details for NOS2) (see all 14):
        Arginine and proline metabolism
    Metabolic pathways
    Calcium signaling pathway
    HIF-1 signaling pathway
    Peroxisome


    NOS2 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for NOS2

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

    5/60 Interacting proteins for NOS2 (P352283 ENSP000003272514) via UniProtKB, MINT, STRING, and/or I2D (see all 60)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CALM2P621583, ENSP000002722984I2D: score=1 STRING: ENSP00000272298
    CALM1P621583, ENSP000003494674I2D: score=1 STRING: ENSP00000349467
    CALM3P621583I2D: score=1 
    ACTN4O437073, ENSP000002526994I2D: score=4 STRING: ENSP00000252699
    RAC2P151533, ENSP000002490714I2D: score=4 STRING: ENSP00000249071
    About this table

    Gene Ontology (GO): 5/27 biological process terms (GO ID links to tree view) (see all 27):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001666response to hypoxia IEA--
    GO:0001912positive regulation of leukocyte mediated cytotoxicity TAS10450191
    GO:0002227innate immune response in mucosa NAS18390757
    GO:0006527arginine catabolic process IDA7504305
    GO:0006801superoxide metabolic process ISS--

    NOS2 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

    NOS2 for compounds           About GeneDecksing

    EMD Millipore small molecules for NOS2:
    Small Molecule - inhibitor
    Enzo Life Sciences drugs & compounds for NOS2

    Compounds for NOS2 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    BYK 191023 dihydrochloridePotent and selective inhibitor of iNOS[608880-48-4]
    L-NIL hydrochlorideSelective iNOS inhibitor[150403-89-7]
    1400W dihydrochloride Potent, highly selective iNOS inhibitor [180001-34-7]
    AMT hydrochloride Potent, selective iNOS inhibitor [21463-31-0]
    (S)-Methylisothiourea sulfateHighly selective iNOS inhibitor[867-44-7]

    10 HMDB Compounds for NOS2    About this table
    CompoundSynonyms CAS #PubMed Ids
    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--
    Nitric oxideMononitrogen monoxide (see all 9)10102-43-9--
    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--

    10/40 DrugBank Compounds for NOS2 (see all 40)    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    L-Arginine(S)-2-Amino-5-guanidinovaleric acid (see all 4)74-79-3target--17513447 17340133 16778961 17362916 17363779
    L-Citrulline2-Amino-5-uredovaleric acid (see all 8)372-75-8target--12745988 10906994 11742852 10906995 10944418
    Aminoguanidine-- 79-17-4targetinhibitor17139284 11752352 17016423 10592235
    DexamethasoneDesametasone (see all 9)50-02-2targetnegative modulator17494951 17503181 11752352 17379310
    Miconazole-- 22916-47-8targetinhibitor7536941 7518297 7683652 9873034
    Triflusal-- --targetagonist9551715 19465361 16939630 10998082
    3-Bromo-7-Nitroindazole-- --target--17139284 17016423 10592235
    4r-Fluoro-N6-Ethanimidoyl-L-Lysine-- --target--17139284 17016423 10592235
    5-Nitroindazole-- --target--17139284 17016423 10592235
    6-Nitroindazole-- --target--17139284 17016423 10592235

    5 IUPHAR Ligands for NOS2 (Inducible NOS)    About this table 
    LigandTypeActionAffinityPubmed IDs
    1400W
    InhibitorInhibition8.29030556
    2-amino-4-methylpyridine
    InhibitorInhibition7.48937711
    PIBTU
    InhibitorInhibition7.37523409
    NIL
    InhibitorInhibition5.57525961
    aminoguanidine
    InhibitorInhibition5.51378415

    10/124 Novoseek inferred chemical compound relationships for NOS2 gene (see all 124)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    nitric oxide 97.5 18892 11680730 (10), 11342896 (8), 16957516 (8), 18554637 (8) (see all 99)
    citrulline 87.5 279 20148434 (3), 20148433 (3), 8561501 (3), 7527657 (2) (see all 99)
    l-nmma 87.3 488 9503327 (4), 12810424 (3), 17724209 (3), 18090547 (3) (see all 99)
    arginine 86.4 1048 16245240 (5), 11275358 (5), 8639550 (5), 7664438 (4) (see all 99)
    peroxynitrite 86.2 233 11788351 (4), 9180331 (3), 10383909 (3), 9122229 (3) (see all 99)
    aminoguanidine 84.9 363 9538001 (5), 16553284 (4), 18790185 (4), 11062159 (3) (see all 99)
    adma 83.5 234 8743168 (5), 15325021 (4), 19682580 (4), 10802528 (3) (see all 99)
    tetrahydrobiopterin 79.4 94 15565652 (2), 14609340 (2), 16052472 (2), 16172396 (2) (see all 67)
    cgmp 78.8 303 18606420 (5), 10802528 (4), 11181408 (4), 8633049 (4) (see all 99)
    n(g)-nitro-l-arginine methyl ester 76.8 176 11891189 (2), 7684763 (1), 7673269 (1), 8991992 (1) (see all 99)

    Search CenterWatch for drugs/clinical trials and news about NOS2

    (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 NOS2 gene (2 alternative transcripts): 
    NM_000625.4  NM_153292.1  

    Unigene Cluster for NOS2:

    Nitric oxide synthase 2, inducible
    Hs.709191  [show with all ESTs]
    Unigene Representative Sequence: NM_000625
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000313735(uc002gzu.3 uc010wab.1 uc010crh.1)
    Congresses - knowledge worth sharing:  
    European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

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    Additional mRNA sequence: 

    AB022318.1 AF068236.1 AK304252.1 BC130283.1 BC144126.1 D26525.1 L09210.1 L24553.1 
    S75615.1 S76479.1 U05810.1 U20141.1 U31511.1 X73029.1 

    2 DOTS entries:

    DT.412801  DT.95333286 

    24/75 AceView cDNA sequences (see all 75):

    NM_000625 L24553 AI991263 X73029 AI738789 CD609259 BE073577 S76479 
    BE073638 AI797675 S75615 BM834810 AW297448 U31511 AW449618 AI953734 
    AW445097 NM_153292 U20141 U05810 CD609228 BG099280 CD609248 AA877840 

    GeneLoc Exon Structure

    3 Alternative Splicing Database (ASD) splice patterns (SP) for NOS2    About this scheme

    ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25 ^
    SP1:                    -                                                                                                                                       
    SP2:                    -                                                                                                                                       
    SP3:                                      -                                                                                                                     

    ExUns: 26 ^ 27 ^ 28
    SP1:                  
    SP2:                  
    SP3:                  


    ECgene alternative splicing isoforms for NOS2

    (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

    NOS2 expression in normal human tissues (normalized intensities)      NOS2 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AATTGCATTT
    NOS2 Expression
    About this image


    NOS2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database 
     5/4 selected tissues (see all 4) fully expand
     
     Cartilage (Muscoskeletal System)    fully expand to see all 2 entries
             HyStem+BMP4-induced 4D20.8 cells
             fetal cartilage   
     
     Bone (Muscoskeletal System)
             HyStem+BMP4-induced 4D20.8 cells
     
     Brain (Nervous System)
             N2/LSB induced-cells ( Generation of midbrain dopaminergic, forebrain and hypothalamic...
     
     Colon (Gastrointestinal Tract)

    See NOS2 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for NOS2

    SOURCE GeneReport for Unigene cluster: Hs.709191

    UniProtKB/Swiss-Prot: NOS2_HUMAN, P35228
    Tissue specificity: Expressed in the liver, retina, bone cells and airway epithelial cells of the lung. Not
    expressed in the platelets

        SABiosciences Expression via Pathway-Focused PCR Arrays including NOS2 (see all 14): 
              Insulin Signaling Pathway in human mouse rat
              G-Protein-Coupled Receptor Signaling PathwayFinder in human mouse rat
              Oxidative Stress in human mouse rat
              Nitric Oxide Signaling Pathway in human mouse rat
              Skeletal Muscle: Myogenesis & Myopathy 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 NOS2 gene from 6/14 species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Nos21 , 5 nitric oxide synthase 2, inducible1, 5 82.4(n)1
    81.21(a)1
      11 (46.74 cM)5
    181261  NM_010927.31  NP_035057.11 
     789207875 
    chicken
    (Gallus gallus)
    Aves NOS21 nitric oxide synthase 2, inducible 68.43(n)
    70.46(a)
      395807  NM_204961.1  NP_990292.1 
    lizard
    (Anolis carolinensis)
    Reptilia NOS26
    nitric oxide synthase 2, inducible
    56(a)
    1 ↔ 1
    GL343729.1(116369-178014)
    zebrafish
    (Danio rerio)
    Actinopterygii nos2b1 nitric oxide synthase 2b, inducible 61.56(n)
    60.63(a)
      563654  NM_001113501.1  NP_001106973.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Nos6
    CG148826
    --
    38(a)
    24(a)
    1 ↔ many
    possible ortholog
    2L(10804269-10838448)
    3R(12268966-12270526)
    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 NOS2 (if available)
    TreeFam Gene Tree for NOS2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for NOS2 gene
    NOS32  POR2  MTRR2  NOS12  
    2 SIMAP similar genes for NOS2 using alignment to 1 protein entry:     NOS2_HUMAN(see first protein):
    NOS1    NOS3

    NOS2 for paralogs           About GeneDecksing


    5/15 Pseudogenes.org Pseudogenes for NOS2 (see all 15)
    PGOHUM00000247699 PGOHUM00000248028 PGOHUM00000250807 PGOHUM00000237000 PGOHUM00000237005


    (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: NOS2_HUMAN, P35228
    Polymorphism: Note=Genetic variations in NOS2 are involved in resistance to malaria [MIM:611162]


    10/1440 SNPs in NOS2 are shown (see all 1440)    About this table     
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0363024
    A breast cancer sample4--see VAR_0363022 A S mis40--------
    rs596857461,2
    C--26088338(+) CACGG-/CCCTCC 1 -- int13Minor allele frequency- C:0.00NA CSA 8
    rs58198211,2
    C,F--26106756(+) CAGAAA/-GCTGG 1 -- int17Minor allele frequency- -:0.31NS NA CSA 178
    rs1123369321,2
    C--26115222(+) GCGTGCACA/-  
            
    CACAC
    1 -- int11Minor allele frequency- -:0.50CSA 2
    rs594313571,2
    C,F--26115249(+) CACAC-/AC/ACAC/ACACAC
    ACAC
    /ACACACACACAC
    GAATG
    2 -- int1 cds12NA 4
    rs349927771,2
    C--26119841(+) CTACAA/-AAAAA 1 -- int11Minor allele frequency- -:0.00NA 2
    rs289987991,2
    C,F--26126131(-) GGGGGG/-TTCAT 1 -- int16Minor allele frequency- -:0.07NS NA 184
    rs358348121,2
    C--26126817(+) AAAAA-/AGAAAG 1 -- int11Minor allele frequency- A:0.50NA 2
    rs1462260231,2
    --26143243(+) TCCTTA/GGCCTG 1 -- ds50010--------
    rs1154286341,2
    F--26143250(+) CCTGCT/ACCAAA 1 -- ds50011Minor allele frequency- A:0.01WA 118

    HapMap Linkage Disequilibrium report for NOS2 (26083792 - 26127555 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for NOS2:    About this table     
    Variant IDTypeSubtypePubMed ID
    esv2715781CNV Deletion23290073
    nsv9533CNV Gain18304495
    esv28579CNV Gain19812545
    dgv943e1CNV Complex17122850


    Human Gene Mutation Database (HGMD): NOS2

    Locus Specific Mutation Databases (LSDB): NOS2
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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: 163730   
    OMIM disorders: 145500  611162  
    20/358 diseases for NOS2 (see all 358):    About MalaCards
    virilizing ovarian tumor    pityriasis lichenoides    bladder carcinoma in situ    borderline leprosy
    peyronie's disease    peyronies disease    collagenous colitis    trigonitis
    lymphocytic colitis    internal hemorrhoid    cytokine receptor deficiency    hemorrhoid
    warthin tumor    idiopathic achalasia    myocarditis    colonic disease
    retinal vasculitis    lip cancer    microscopic colitis    choledochal cyst

    3 diseases from the University of Copenhagen DISEASES database for NOS2:
    Vascular disease     Gastrointestinal system disease     Arthritis

    NOS2 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 NOS2 gene (see all 96)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    inflammation 76.7 531 14657339 (3), 17449036 (3), 16537027 (3), 12613978 (3) (see all 99)
    necrosis 75.9 590 16827641 (4), 17452936 (3), 9856818 (3), 10713108 (3) (see all 99)
    tumors 64.1 1265 11156233 (6), 17980097 (6), 16557582 (5), 20338478 (5) (see all 99)
    shock septic 63.8 96 7536056 (4), 12594864 (3), 14654318 (3), 10791377 (3) (see all 58)
    sepsis 54.4 152 12016107 (5), 17997414 (4), 12594864 (3), 10669117 (3) (see all 72)
    atherosclerosis 51.8 77 8683942 (3), 10073969 (3), 10334927 (2), 11139364 (2) (see all 47)
    neurodegenerative diseases 50.5 18 16144552 (1), 7523410 (1), 11246231 (1), 16807879 (1) (see all 11)
    inflammatory bowel diseases 46.6 44 17955236 (2), 12792224 (2), 10102942 (1), 10630438 (1) (see all 28)
    cell damage 46.4 28 11218753 (2), 9377819 (1), 11139364 (1), 11488434 (1) (see all 22)
    ischemia 46.1 102 15327760 (4), 16154689 (4), 11708836 (3), 8787213 (3) (see all 61)

    Genetic Association Database (GAD): NOS2
    Human Genome Epidemiology (HuGE) Navigator: NOS2 (192 documents)

    Export disorders for NOS2 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 NOS2 gene, integrated from 9 sources (see all 4083):
    (articles sorted by number of sources associating them with NOS2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. (PubMed id 7682706)1, 2, 3, 9 Geller D.A....Billiar T.R. (1993)
    2. A new NOS2 promoter polymorphism associated with increased nitric oxide production and protection from severe malaria in Tanzanian and Kenyan children. (PubMed id 12433515)1, 2, 4, 9 Hobbs M.R....Weinberg J.B. (2002)
    3. Dedifferentiated human ventricular cardiac myocytes express inducible nitric oxide synthase mRNA but not protein in response to IL-1, TNF, IFNgamma, and LPS. (PubMed id 9160867)1, 2, 9 Luss H.... Billiar T.R. (1997)
    4. 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)
    5. Malaria severity and human nitric oxide synthase type 2 (NOS2) promoter haplotypes. (PubMed id 19859740)1, 4, 9 Levesque M.C....Weinberg J.B. (2010)
    6. Role of inducible nitric oxide synthase in asthma ris k and lung function growth during adolescence. (PubMed id 19996333)1, 4, 9 Islam T....Gilliland F.D. (2010)
    7. The CCTTT pentanucleotide microsatellite in iNOS promoter influences the clinical outcome in P. falciparum infection. (PubMed id 19153766)1, 4, 9 Dhangadamajhi G....Ranjit M.R. (2009)
    8. Genetic polymorphisms modifying oxidative stress are associated with disease activity in rheumatoid arthritis patients. (PubMed id 19242068)1, 4, 9 Bohanec Grabar P....Dolzan V. (2009)
    9. NO role of NOS2A susceptibility polymorphisms in rheu matoid arthritis. (PubMed id 19635578)1, 4, 9 VaradAc J....Urcelay E. (2009)
    10. Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase. (PubMed id 10409685)1, 2, 9 Li H.... Poulos T.L. (1999)

    (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: 4843 HGNC: 7873 AceView: NOS2A Ensembl:ENSG00000007171 euGenes: HUgn4843
    ECgene: NOS2 Kegg: 4843 H-InvDB: NOS2

    (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 NOS2 Pharmacogenomics, SNPs, Pathways
    NIEHS-SNPshttp://egp.gs.washington.edu/data/nos2a/
    Wikipedia http://en.wikipedia.org/wiki/Nitric_oxide_synthase

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    Patent Information for NOS2 gene:
    Search GeneIP for patents involving NOS2

    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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