Nitric oxide synthase 2 (inducible)

NOS2
Identifiers
Aliases	NOS2, HEP-NOS, NOS, NOS2A, Nitric oxide synthase 2, iNOS
External IDs	OMIM: 163730; MGI: 97361; GeneCards: NOS2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1NSI, 2LL6, 2NSI, 3E7G, 3EJ8, 3HR4, 4CX7, 4NOS
Enzyme activity EC # BRENDA ExPASy KEGG MetaCyc 1.14.13.39 ↗ ↗ ↗ ↗
Gene location (Human) Chr. Chromosome 17 (human) Band 17q11.2 Start 27,756,766 bp End 27,800,529 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 B5|11 46.74 cM Start 78,811,613 bp End 78,851,080 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cartilage tissue olfactory zone of nasal mucosa mucosa of paranasal sinus mucosa of transverse colon rectum appendix testicle prefrontal cortex duodenum right frontal lobe Top expressed in Ileal epithelium jejunum muscle of thigh placenta thymus entorhinal cortex skeletal muscle tissue esophagus neural tube dentate gyrus of hippocampal formation granule cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function FMN binding protein homodimerization activity flavin adenine dinucleotide binding arginine binding tetrahydrobiopterin binding metal ion binding calmodulin binding protein binding heme binding oxidoreductase activity signaling receptor binding nitric-oxide synthase activity NADPH-hemoprotein reductase activity NADP binding Cellular component cytoplasm cytosol cortical cytoskeleton peroxisome intracellular anatomical structure perinuclear region of cytoplasm nucleus peroxisomal matrix plasma membrane vesicle membrane Biological process positive regulation of guanylate cyclase activity response to hypoxia nitric oxide biosynthetic process positive regulation of leukocyte mediated cytotoxicity response to bacterium negative regulation of protein catabolic process regulation of insulin secretion negative regulation of blood pressure regulation of cytokine production involved in inflammatory response positive regulation of killing of cells of other organism negative regulation of gene expression cell redox homeostasis arginine catabolic process prostaglandin secretion response to lipopolysaccharide innate immune response in mucosa regulation of cell population proliferation peptidyl-cysteine S-nitrosylation defense response to bacterium circadian rhythm defense response to Gram-negative bacterium nitric oxide mediated signal transduction cellular response to interferon-gamma regulation of cellular respiration cellular response to lipopolysaccharide superoxide metabolic process cytokine-mediated signaling pathway protein targeting to peroxisome response to hormone Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 4843 18126 Ensembl ENSG00000007171 ENSMUSG00000020826 UniProt P35228 P29477 RefSeq (mRNA) NM_000625 NM_153292 NM_010927 NM_001313921 NM_001313922 RefSeq (protein) NP_000616 NP_001300850 NP_001300851 NP_035057 Location (UCSC) Chr 17: 27.76 – 27.8 Mb Chr 11: 78.81 – 78.85 Mb PubMed search
Wikidata
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Nitric oxide synthase, inducible is an enzyme which is encoded by the NOS2 gene in humans and mice.

Genetics

Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. Alternative splicing of this gene results in two transcript variants encoding different isoforms.

Location

Nitric oxide synthase is expressed in epithelial cells of the liver, lung and bone marrow. It is inducible by a combination of lipopolysaccharide and certain cytokines.^{[citation needed]}

Function

Nitric oxide is a reactive free radical mediating in neurotransmission, antimicrobial and antitumoral activities.^{[citation needed]} In mice, the function of Nos2 in immunity against a number of viruses, bacteria, fungi, and parasites has been well characterized, whereas in humans the role of NOS2 has remained elusive and controversial. Nos2 is important for protective immunity against CMV.

Caveolin 1 has been shown to interact with Nitric oxide synthase 2A. and Rac2.

Deficiency

Autosomal recessive NOS2 deficiency has been described in mice. They lack the gene encoding nitric oxide synthase 2 (Nos2) and are susceptible to murine CMV infection.

In February 2020, the same autosomal recessive, complete NOS2 deficiency was described in a human. A 51-year-old previously healthy person died after 29 months of progressive CMV infection due to respiratory failure secondary to CMV pneumonitis, CMV encephalitis, and hemophagocytic lymphohistiocytosis. Whole-exome sequencing on genomic DNA from his blood showed he had homozygous variants in five genes. The only loss-of-function variant was a homozygous frameshift mutation in nitric oxide synthase 2. This condition is extremely rare, occurring in fewer than 1 per million persons.