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Aliases for NOS2 Gene

Aliases for NOS2 Gene

  • Nitric Oxide Synthase 2, Inducible 2 3
  • Nitric Oxide Synthase 2A (Inducible, Hepatocytes) 2 3
  • Peptidyl-Cysteine S-Nitrosylase NOS2 3 4
  • Inducible NO Synthase 3 4
  • Hepatocyte NOS 3 4
  • Inducible NOS 3 4
  • EC 4 64
  • NOS Type II 3 4
  • HEP-NOS 3 4
  • NOS2A 3 4
  • INOS 3 4
  • Nitric Oxide Synthase, Macrophage 3
  • Nitric Oxide Synthase, Inducible 3
  • NOS, Type II 3
  • NOS2A, 6
  • NOS 3

External Ids for NOS2 Gene

Previous Symbols for NOS2 Gene

  • NOS2A

Summaries for NOS2 Gene

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 borderline leprosy. Among its related pathways are Disease and Pathways in cancer. GO annotations related to this gene include protein homodimerization activity and calmodulin binding. An important paralog of this gene is NOS1.

UniProtKB/Swiss-Prot for NOS2 Gene

  • 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. As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on Cys-247 implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM.

Tocris 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 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NOS2 Gene

Genomics for NOS2 Gene

Genomic Location for NOS2 Gene

27,756,766 bp from pter
27,800,529 bp from pter
43,764 bases
Minus strand

Genomic View for NOS2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for NOS2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NOS2 Gene

Regulatory Elements for NOS2 Gene

Proteins for NOS2 Gene

  • Protein details for NOS2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Nitric oxide synthase, inducible
    Protein Accession:
    Secondary Accessions:
    • A1L3U5
    • B7ZLY2
    • O60757
    • O94994
    • Q16263
    • Q16692
    • Q4TTS5
    • Q9UD42

    Protein attributes for NOS2 Gene

    1153 amino acids
    Molecular mass:
    131117 Da
    Name=5,6,7,8-tetrahydrobiopterin; Xref=ChEBI:CHEBI:15372; Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.;
    Name=FAD; Xref=ChEBI:CHEBI:57692; Note=Binds 1 FAD.;
    Name=FMN; Xref=ChEBI:CHEBI:58210; Note=Binds 1 FMN.;
    Name=heme; Xref=ChEBI:CHEBI:30413;
    Quaternary structure:
    • Homodimer. Binds SLC9A3R1. Interacts with GAPDH; induced by oxidatively-modified low-densitity lipoprotein (LDL(ox)). Interacts with S100A8 and S100A9 to form the iNOS-S100A8/9 transnitrosylase complex.

    Three dimensional structures from OCA and Proteopedia for NOS2 Gene

    Alternative splice isoforms for NOS2 Gene


neXtProt entry for NOS2 Gene

Proteomics data for NOS2 Gene at MOPED

Post-translational modifications for NOS2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NOS2 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for NOS2 Gene

Gene Families for NOS2 Gene


  • Contains 1 FAD-binding FR-type domain.:
    • P35228
  • Contains 1 flavodoxin-like domain.:
    • P35228
  • Belongs to the NOS family.:
    • P35228
genes like me logo Genes that share domains with NOS2: view

Function for NOS2 Gene

Molecular function for NOS2 Gene

UniProtKB/Swiss-Prot CatalyticActivity: 2 L-arginine + 3 NADPH + 4 O(2) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H(2)O
UniProtKB/Swiss-Prot EnzymeRegulation: 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).
UniProtKB/Swiss-Prot 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. As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on Cys-247 implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM.
UniProtKB/Swiss-Prot Induction: By endotoxins and cytokines. Induced by IFNG/IFN-gamma acting synergistically with bacterial lipopolysaccharides (LPS), TNF or IL1B/interleukin-1 beta (PubMed:7528267). Down-regulated by zinc due to inhibition of NF-kappa-B transactivation activity (PubMed:25180171). By oxidatively-modified low-densitity lipoprotein (LDL(ox)) (PubMed:25417112).

Enzyme Numbers (IUBMB) for NOS2 Gene

Gene Ontology (GO) - Molecular Function for NOS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003958 NADPH-hemoprotein reductase activity IBA --
GO:0004517 nitric-oxide synthase activity IDA 7504305
GO:0005102 receptor binding IPI 20178365
GO:0005506 iron ion binding IEA --
GO:0005515 protein binding IPI 12855682
genes like me logo Genes that share ontologies with NOS2: view
genes like me logo Genes that share phenotypes with NOS2: view

Animal Models for NOS2 Gene

MGI Knock Outs for NOS2:

miRNA for NOS2 Gene

miRTarBase miRNAs that target NOS2

No data available for Transcription Factor Targeting and HOMER Transcription for NOS2 Gene

Localization for NOS2 Gene

Subcellular locations from

Jensen Localization Image for NOS2 Gene COMPARTMENTS Subcellular localization image for NOS2 gene
Compartment Confidence
peroxisome 5
cytosol 3
nucleus 3
cytoskeleton 2
extracellular 2
mitochondrion 2
plasma membrane 2
endoplasmic reticulum 1
lysosome 1
vacuole 1

Gene Ontology (GO) - Cellular Components for NOS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IDA 7544003
GO:0005634 nucleus ISS --
GO:0005737 cytoplasm IDA 12085352
GO:0005777 peroxisome IDA 12085352
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with NOS2: view

Pathways for NOS2 Gene

genes like me logo Genes that share pathways with NOS2: view

Gene Ontology (GO) - Biological Process for NOS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001666 response to hypoxia IEA --
GO:0001912 positive regulation of leukocyte mediated cytotoxicity TAS 10450191
GO:0002227 innate immune response in mucosa NAS 18390757
GO:0006527 arginine catabolic process IDA 7504305
GO:0006801 superoxide metabolic process ISS --
genes like me logo Genes that share ontologies with NOS2: view

Compounds for NOS2 Gene

(5) Tocris Compounds for NOS2 Gene

Compound Action Cas Number
(S)-Methylisothiourea sulfate Highly selective iNOS inhibitor [867-44-7]
1400W dihydrochloride Potent, highly selective iNOS inhibitor [180001-34-7]
AMT hydrochloride Potent, selective iNOS inhibitor [21463-31-0]
BYK 191023 dihydrochloride Potent and selective inhibitor of iNOS [608880-48-4]
L-NIL hydrochloride Selective iNOS inhibitor [150403-89-7]

(10) HMDB Compounds for NOS2 Gene

Compound Synonyms Cas Number PubMed IDs
  • Ca
  • (2S)-2-amino-5-(carbamoylamino)pentanoic acid
  • 1H-Purin-6-amine flavin dinucleotide
Flavin Mononucleotide
  • FMN
  • (protoporphyrinato)iron

(5) IUPHAR Ligand for NOS2 Gene

Ligand Type Action Affinity Pubmed IDs
1400W Inhibitor Inhibition 8.2
2-amino-4-methylpyridine Inhibitor Inhibition 7.4
PIBTU Inhibitor Inhibition 7.3
NIL Inhibitor Inhibition 5.5
aminoguanidine Inhibitor Inhibition

(124) Novoseek inferred chemical compound relationships for NOS2 Gene

Compound -log(P) Hits PubMed IDs
nitric oxide 97.5 559
citrulline 87.5 123
l-nmma 87.3 135
arginine 86.4 249
peroxynitrite 86.2 138

(2) PharmGKB related drug/compound annotations for NOS2 Gene

Drug/compound Annotation
isoniazid CA
rifampin CA
genes like me logo Genes that share compounds with NOS2: view

Transcripts for NOS2 Gene

Unigene Clusters for NOS2 Gene

Nitric oxide synthase 2, inducible:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for NOS2 Gene

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

Relevant External Links for NOS2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for NOS2 Gene

mRNA expression in normal human tissues for NOS2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NOS2 Gene

This gene is overexpressed in Small Intestine - Terminal Ileum (8.6), Colon - Transverse (7.9), and Brain - Cortex (5.0).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for NOS2 Gene

SOURCE GeneReport for Unigene cluster for NOS2 Gene Hs.709191

mRNA Expression by UniProt/SwissProt for NOS2 Gene

Tissue specificity: Expressed in the liver, retina, bone cells and airway epithelial cells of the lung. Not expressed in the platelets
genes like me logo Genes that share expressions with NOS2: view

Orthologs for NOS2 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for NOS2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia NOS2 36
  • 99.48 (n)
  • 99.39 (a)
NOS2 37
  • 99 (a)
(Bos Taurus)
Mammalia INOS 37
  • 86 (a)
NOS2 36
  • 87.85 (n)
  • 86.81 (a)
(Canis familiaris)
Mammalia NOS2 36
  • 87.38 (n)
  • 87.15 (a)
NOS2 37
  • 87 (a)
(Mus musculus)
Mammalia Nos2 36
  • 82.4 (n)
  • 81.21 (a)
Nos2 16
Nos2 37
  • 81 (a)
(Monodelphis domestica)
Mammalia NOS2 37
  • 75 (a)
(Ornithorhynchus anatinus)
Mammalia NOS2 37
  • 74 (a)
(Rattus norvegicus)
Mammalia LOC497963 36
  • 82.52 (n)
  • 81.21 (a)
(Gallus gallus)
Aves NOS2 36
  • 68.43 (n)
  • 70.46 (a)
NOS2 37
  • 58 (a)
(Anolis carolinensis)
Reptilia NOS2 37
  • 56 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia nos2 36
  • 65.96 (n)
  • 65.96 (a)
(Danio rerio)
Actinopterygii nos2a 37
  • 58 (a)
nos2b 36
  • 61.56 (n)
  • 60.63 (a)
nos2b 37
  • 59 (a)
fruit fly
(Drosophila melanogaster)
Insecta Nos 37
  • 38 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes NCP1 37
  • 24 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.5751 37
  • 47 (a)
Species with no ortholog for NOS2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for NOS2 Gene

Gene Tree for NOS2 (if available)
Gene Tree for NOS2 (if available)

Paralogs for NOS2 Gene

Paralogs for NOS2 Gene

Selected SIMAP similar genes for NOS2 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with NOS2: view

Variants for NOS2 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for NOS2 Gene

Note=Genetic variations in NOS2 are involved in resistance to malaria [MIM:611162]

Sequence variations from dbSNP and Humsavar for NOS2 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type MAF
rs15782 -- 27,757,009(-) GAGAC(A/G)AAATC utr-variant-3-prime
rs16948 -- 27,797,578(+) ATGCT(C/T)ACACA intron-variant
rs16949 -- 27,797,673(+) GTAGA(C/T)GGGGG intron-variant
rs944722 -- 27,765,011(+) GGAGT(C/T)TCTGT intron-variant
rs944723 -- 27,765,235(+) CACCC(A/G)CCACG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for NOS2 Gene

Variant ID Type Subtype PubMed ID
dgv943e1 CNV Complex 17122850
esv2715781 CNV Deletion 23290073
esv28579 CNV Gain 19812545
nsv9533 CNV Gain 18304495

Relevant External Links for NOS2 Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)
Locus Specific Mutation Databases (LSDB)

Disorders for NOS2 Gene

(2) OMIM Diseases for NOS2 Gene (163730)

(3) University of Copenhagen DISEASES for NOS2 Gene

(96) Novoseek inferred disease relationships for NOS2 Gene

Disease -log(P) Hits PubMed IDs
inflammation 76.7 154
necrosis 75.9 123
tumors 64.1 293
shock septic 63.8 75
sepsis 54.4 101

Relevant External Links for NOS2

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with NOS2: view

No data available for UniProtKB/Swiss-Prot for NOS2 Gene

Publications for NOS2 Gene

  1. Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. (PMID: 7682706) Geller D.A. … Billiar T.R. (Proc. Natl. Acad. Sci. U.S.A. 1993) 2 3 4 23
  2. A new NOS2 promoter polymorphism associated with increased nitric oxide production and protection from severe malaria in Tanzanian and Kenyan children. (PMID: 12433515) Hobbs M.R. … Weinberg J.B. (Lancet 2002) 3 4 23 49
  3. Cloning and functional expression of human inducible nitric oxide synthase (NOS) cDNA from a glioblastoma cell line A-172. (PMID: 7531687) Hokari A. … Esumi H. (J. Biochem. 1994) 3 4 23
  4. Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumor cell line. (PMID: 7692964) Sherman P.A. … Wood E.R. (Biochemistry 1993) 3 4 23
  5. Dedifferentiated human ventricular cardiac myocytes express inducible nitric oxide synthase mRNA but not protein in response to IL-1, TNF, IFNgamma, and LPS. (PMID: 9160867) Luss H. … Billiar T.R. (J. Mol. Cell. Cardiol. 1997) 3 4 23

Products for NOS2 Gene

Sources for NOS2 Gene

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