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NOS2 Gene(Protein Coding)

Nitric Oxide Synthase 2

GCID:
GC17M027756
GIFtS:
72
Genes Participants
UDN Logo

Aliases for NOS2 Gene

Aliases for NOS2 Gene

  • Nitric Oxide Synthase 2 2 3 5
  • Nitric Oxide Synthase 2A (Inducible, Hepatocytes) 2 3
  • Peptidyl-Cysteine S-Nitrosylase NOS2 3 4
  • Nitric Oxide Synthase 2, Inducible 2 3
  • Inducible NO Synthase 3 4
  • Hepatocyte NOS 3 4
  • Inducible NOS 3 4
  • EC 1.14.13.39 4 63
  • NOS Type II 3 4
  • HEP-NOS 3 4
  • NOS2A 3 4
  • INOS 3 4
  • Nitric Oxide Synthase, Macrophage 3
  • NOS, Type II 3
  • NOS 3

External Ids for NOS2 Gene

Previous HGNC Symbols for NOS2 Gene

  • NOS2A

Previous GeneCards Identifiers for NOS2 Gene

  • GC17M023108
  • GC17M026083
  • GC17M022290

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) is a Protein Coding gene. Diseases associated with NOS2 include Malaria and Pityriasis Lichenoides. Among its related pathways are ERK Signaling and Arginine biosynthesis. GO annotations related to this gene include protein homodimerization activity and oxidoreductase activity. 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 (PubMed:7531687, PubMed:7544004). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (By similarity). 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 (PubMed:25417112). Involved in inflammation, enhances the synthesis of proinflammatory mediators such as IL6 and IL8 (PubMed:19688109).

Gene Wiki entry for NOS2 Gene

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

Genomics for NOS2 Gene

Products:

  1. Regulatory Element

Regulatory Elements for NOS2 Gene

Enhancers for NOS2 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around NOS2 on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the NOS2 gene promoter:

Genomic Location for NOS2 Gene

Chromosome:
17
Start:
27,756,766 bp from pter
End:
27,804,341 bp from pter
Size:
47,576 bases
Orientation:
Minus strand

Genomic View for NOS2 Gene

Genes around NOS2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NOS2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NOS2 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for NOS2 Gene

Proteins for NOS2 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

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

    Protein Symbol:
    P35228-NOS2_HUMAN
    Recommended name:
    Nitric oxide synthase, inducible
    Protein Accession:
    P35228
    Secondary Accessions:
    • A1L3U5
    • B7ZLY2
    • O60757
    • O94994
    • Q16263
    • Q16692
    • Q4TTS5
    • Q9UD42

    Protein attributes for NOS2 Gene

    Size:
    1153 amino acids
    Molecular mass:
    131117 Da
    Cofactor:
    Name=5,6,7,8-tetrahydrobiopterin; Xref=ChEBI:CHEBI:15372;
    Cofactor:
    Name=FAD; Xref=ChEBI:CHEBI:57692;
    Cofactor:
    Name=FMN; Xref=ChEBI:CHEBI:58210;
    Cofactor:
    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

    UniProtKB/Swiss-Prot:

neXtProt entry for NOS2 Gene

Proteomics data for NOS2 Gene at MOPED

Protein Expression for NOS2 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for NOS2 Gene

P35228:

Post-translational modifications for NOS2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for NOS2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Domains & Families for NOS2 Gene

Gene Families for NOS2 Gene

IUPHAR :

Protein Domains for NOS2 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for NOS2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P35228

UniProtKB/Swiss-Prot:

NOS2_HUMAN :
  • Contains 1 FAD-binding FR-type domain.
  • Belongs to the NOS family.
Domain:
  • Contains 1 FAD-binding FR-type domain.
  • Contains 1 flavodoxin-like domain.
Family:
  • Belongs to the NOS family.
genes like me logo Genes that share domains with NOS2: view

Function for NOS2 Gene

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  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
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  6. Cell Line
  7. Flow Cytometry

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 (PubMed:7531687, PubMed:7544004). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (By similarity). 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 (PubMed:25417112). Involved in inflammation, enhances the synthesis of proinflammatory mediators such as IL6 and IL8 (PubMed:19688109).
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:0005506 iron ion binding IEA --
genes like me logo Genes that share ontologies with NOS2: view

Phenotypes for NOS2 Gene

MGI mutant phenotypes for NOS2:
inferred from 3 alleles
GenomeRNAi human phenotypes for NOS2:
genes like me logo Genes that share phenotypes with NOS2: view

Animal Models for NOS2 Gene

MGI Knock Outs for NOS2:

Animal Model Products

miRNA for NOS2 Gene

miRTarBase miRNAs that target NOS2

Inhibitory RNA Products

Flow Cytometry Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NOS2 Gene

Localization for NOS2 Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for NOS2 Gene COMPARTMENTS Subcellular localization image for NOS2 gene
Compartment Confidence
peroxisome 5
cytosol 4
nucleus 4
cytoskeleton 2
extracellular 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for NOS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005777 peroxisome IDA 12085352
genes like me logo Genes that share ontologies with NOS2: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for NOS2 Gene

Pathways & Interactions for NOS2 Gene

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

SIGNOR curated interactions for NOS2 Gene

Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for NOS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001666 response to hypoxia IEA --
GO:0002227 innate immune response in mucosa NAS 18390757
GO:0006527 arginine catabolic process IDA 7504305
GO:0006801 superoxide metabolic process ISS --
GO:0006809 nitric oxide biosynthetic process IEA,IDA 7504305
genes like me logo Genes that share ontologies with NOS2: view

Drugs & Compounds for NOS2 Gene

Products:

  1. Drug

(105) Drugs for NOS2 Gene - From: DrugBank, PharmGKB, ApexBio, DGIdb, FDA Approved Drugs, IUPHAR, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Dexamethasone Approved, Investigational Pharma Agonist, Target, negative modulator 1950
Citrulline Approved Nutra Full agonist, Agonist, Target 0
Miconazole Approved, Investigational Pharma Antagonist, Pore Blocker, Target, inhibitor 3525
L-Arginine Approved Nutra Full agonist, Agonist, Target 0
Nitric Oxide Approved Pharma 576

(78) Additional Compounds for NOS2 Gene - From: Novoseek, HMDB, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
nadph
  • 2'-(Dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide
  • 2'-(Dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-beta-delta-ribofuranosylnicotinamide
  • Adenosine 5'-(trihydrogen diphosphate) 2'-(dihydrogen phosphate) P'-5'-ester with 1,4-dihydro-1-beta-D-ribofuranosyl-3-pyridinecarboxamide
  • Adenosine 5'-(trihydrogen diphosphate) 2'-(dihydrogen phosphate) P'-5'-ester with 1,4-dihydro-1-beta-delta-ribofuranosyl-3-pyridinecarboxamide
  • b-NADPH
 53-57-6
oxygen
  • Dioxygen
  • Molecular oxygen
  • O2
  • Oxygen
  • Oxygen molecule
 7782-44-7
Hydrogen Ion
  • Hydrogen cation
  • Hydron
  • Proton
N-(o)-Hydroxyarginine
  • N-(G)-Hydroxyarginine
  • N-(Omega)-Hydroxyarginine
NADP
  • Adenine-nicotinamide dinucleotide phosphate
  • b-NADP
  • b-Nicotinamide adenine dinucleotide phosphate
  • b-TPN
  • beta-NADP
 53-59-8

(5) Tocris Compounds for NOS2 Gene

Compound Action Cas Number
(S)-Methylisothiourea sulfate Highly selective iNOS inhibitor 867-44-7
Aminoguanidine hydrochloride Irreversible iNOS inhibitor 1937-19-5
AMT hydrochloride Potent, selective iNOS inhibitor 21463-31-0
EIT hydrobromide Selective iNOS inhibitor, acts arginine binding site 1071-37-0
L-NIO dihydrochloride NOS inhibitor 159190-44-0

(1) ApexBio Compounds for NOS2 Gene

Compound Action Cas Number
1400W dihydrochloride INOS inhibitor,potent and highly selective 214358-33-5
genes like me logo Genes that share compounds with NOS2: view

Drug Products

Transcripts for NOS2 Gene

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  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for NOS2 Gene

(6) REFSEQ mRNAs :
(14) Additional mRNA sequences :
(75) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for NOS2 Gene

Nitric oxide synthase 2, inducible:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

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
SP1:
SP2:
SP3:

Relevant External Links for NOS2 Gene

GeneLoc Exon Structure for
NOS2
ECgene alternative splicing isoforms for
NOS2

Expression for NOS2 Gene

Products:

  1. Primer

mRNA expression in normal human tissues for NOS2 Gene

mRNA expression in normal human tissues for NOS2 Gene
mRNA expression by BioGPS for NOS2 GenemRNA expression by GTEx 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 (x8.6), Colon - Transverse (x7.9), and Brain - Cortex (x5.0).

Protein differential expression in normal tissues from HIPED for NOS2 Gene

This gene is overexpressed in Monocytes (35.0), Heart (13.8), and Neutrophil (9.1).

Integrated Proteomics: protein expression in normal tissues and cell lines 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

P35228-NOS2_HUMAN
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 expression patterns with NOS2: view

Protein tissue co-expression partners for NOS2 Gene

Primer Products

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
cow
(Bos Taurus)
 Mammalia NOS2 35
  • 87.85 (n)
  • 86.81 (a)
INOS 36
  • 86 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia NOS2 35
  • 87.38 (n)
  • 87.15 (a)
NOS2 36
  • 87 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia Nos2 35
  • 82.4 (n)
  • 81.21 (a)
Nos2 16
Nos2 36
  • 81 (a)
 OneToOne
chimpanzee
(Pan troglodytes)
 Mammalia NOS2 35
  • 99.48 (n)
  • 99.39 (a)
NOS2 36
  • 99 (a)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia LOC497963 35
  • 82.52 (n)
  • 81.21 (a)
oppossum
(Monodelphis domestica)
 Mammalia NOS2 36
  • 75 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia NOS2 36
  • 74 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves NOS2 35
  • 68.43 (n)
  • 70.46 (a)
NOS2 36
  • 58 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia NOS2 36
  • 56 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia nos2 35
  • 65.96 (n)
  • 65.96 (a)
zebrafish
(Danio rerio)
 Actinopterygii nos2b 35
  • 61.56 (n)
  • 60.63 (a)
nos2a 36
  • 58 (a)
 OneToMany
nos2b 36
  • 59 (a)
 OneToMany
fruit fly
(Drosophila melanogaster)
 Insecta Nos 36
  • 38 (a)
 OneToMany
baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes NCP1 36
  • 24 (a)
 OneToMany
sea squirt
(Ciona savignyi)
 Ascidiacea CSA.5751 36
  • 47 (a)
 OneToMany
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

ENSEMBL:
Gene Tree for NOS2 (if available)
TreeFam:
Gene Tree for NOS2 (if available)

Paralogs for NOS2 Gene

Paralogs for NOS2 Gene

(2) SIMAP similar genes for NOS2 Gene using alignment to 1 proteins:

Pseudogenes.org Pseudogenes for NOS2 Gene

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

Variants for NOS2 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for NOS2 Gene

NOS2_HUMAN-P35228
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
rs2297518 - 27,769,571(+) AGAGC(A/G)ATTTC reference, missense
rs3730017 - 27,782,076(-) CTGCC(C/T)GGGAA reference, missense, utr-variant-5-prime
rs28944173 - 27,766,517(-) GTCCG(A/G)CATCC reference, missense
rs28944201 - 27,760,164(-) GAGGC(C/T)GCATG reference, missense
VAR_036302 A breast cancer sample

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

Variation tolerance for NOS2 Gene

Residual Variation Intolerance Score: 17.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 9.85; 89.64% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for NOS2 Gene

Human Gene Mutation Database (HGMD)
NOS2

Disorders for NOS2 Gene

MalaCards: The human disease database

(37) MalaCards diseases for NOS2 Gene - From: OMIM, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
malaria
  • malaria, severe
pityriasis lichenoides
mycetoma
  • madura foot
borderline leprosy
  • borderline leprosy [group b]
collagenous colitis
  • microscopic colitis, collagenous type
- elite association - COSMIC cancer census association via MalaCards
Search NOS2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for NOS2

Genetic Association Database (GAD)
NOS2
Human Genome Epidemiology (HuGE) Navigator
NOS2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
NOS2
genes like me logo Genes that share disorders with NOS2: view

No data available for UniProtKB/Swiss-Prot and Genatlas 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 67
  2. IL-4 stimulates the expression of CXCL-8, E-selectin, VEGF, and inducible nitric oxide synthase mRNA by equine pulmonary artery endothelial cells. (PMID: 17494951) Huang H. … Lavoie J.P. (Am. J. Physiol. Lung Cell Mol. Physiol. 2007) 23 25 26
  3. Antifungal imidazoles block assembly of inducible NO synthase into an active dimer. (PMID: 9873034) Sennequier N. … Stuehr D.J. (J. Biol. Chem. 1999) 23 25 26
  4. Nitric oxide synthase isoenzyme expression and activity in peripheral lung tissue of patients with chronic obstructive pulmonary disease. (PMID: 19797159) Brindicci C. … Ito K. (Am. J. Respir. Crit. Care Med. 2010) 3 23
  5. Transient hyperoxic reoxygenation reduces cytochrome C oxidase activity by increasing superoxide dismutase and nitric oxide. (PMID: 20086011) Arab A. … Hehrlein C. (J. Biol. Chem. 2010) 3 23

Products for NOS2 Gene

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