Nitric oxide synthase 2 (inducible)

Nitric oxide synthase, inducible is an enzyme which is encoded by the NOS2 gene in humans and mice.[5]

NOS2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1NSI, 2LL6, 2NSI, 3E7G, 3EJ8, 3HR4, 4CX7, 4NOS
Identifiers
Aliases	NOS2, HEP-NOS, INOS, NOS, NOS2A, Nitric oxide synthase 2
External IDs	OMIM: 163730 MGI: 97361 HomoloGene: 55473 GeneCards: NOS2
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q11.2 Start 27,756,766 bp[1] End 27,800,529 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 B5|11 46.74 cM Start 78,920,787 bp[2] End 78,960,254 bp[2]
RNA expression pattern 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 • GO:0001948 protein binding • heme binding • oxidoreductase activity • receptor binding • nitric-oxide synthase activity • NADPH-hemoprotein reductase activity • NADP binding Cellular component • cytoplasm • cytosol • cortical cytoskeleton • peroxisome • intracellular • perinuclear region of cytoplasm • cell nucleus • peroxisomal matrix • cell 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 • interleukin-6 secretion • response to lipopolysaccharide • cellular response to drug • innate immune response in mucosa • regulation of cell proliferation • peptidyl-cysteine S-nitrosylation • defense response to bacterium • circadian rhythm • defense response to Gram-negative bacterium • nitric oxide mediated signal transduction • interleukin-8 secretion • cellular response to interferon-gamma • regulation of cellular respiration • cellular response to lipopolysaccharide • oxidation-reduction process • superoxide metabolic process • positive regulation of blood vessel diameter • cytokine-mediated signaling pathway • protein targeting to peroxisome • response to hormone Sources:Amigo / QuickGO
Orthologs
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: 78.92 – 78.96 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[6]

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.

Function

Nitric oxide is a reactive free radical mediating in neurotransmission, antimicrobial and antitumoral activities. 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.[7] Nos2 is important for protective immunity against CMV.[8]

Caveolin 1 has been shown to interact with Nitric oxide synthase 2A.[9] and Rac2.[10]

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.[11]

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.[8]

References

1. GRCh38: Ensembl release 89: ENSG00000007171 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020826 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Geller DA, Lowenstein CJ, Shapiro RA, Nussler AK, Di Silvio M, Wang SC, Nakayama DK, Simmons RL, Snyder SH, Billiar TR (May 1993). "Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes". Proc Natl Acad Sci USA. 90 (8): 3491–5. doi:10.1073/pnas.90.8.3491. PMC 46326. PMID 7682706.
6. "Entrez Gene: NOS2A nitric oxide synthase 2A (inducible, hepatocytes)".
7. Nathan;, C. (2006-06-30). "Role of iNOS in Human Host Defense". Science. 312 (5782): 1874b–1875b. doi:10.1126/science.312.5782.1874b. ISSN 0036-8075.CS1 maint: extra punctuation (link)
8. Drutman, Scott B.; Mansouri, Davood; Mahdaviani, Seyed Alireza; Neehus, Anna-Lena; Hum, David; Bryk, Ruslana; Hernandez, Nicholas; Belkaya, Serkan; Rapaport, Franck; Bigio, Benedetta; Fisch, Robert (2020-01-30). "Fatal Cytomegalovirus Infection in an Adult with Inherited NOS2 Deficiency". New England Journal of Medicine. 382 (5): 437–445. doi:10.1056/NEJMoa1910640. ISSN 0028-4793.
9. Felley-Bosco E, Bender FC, Courjault-Gautier F, Bron C, Quest AF (December 2000). "Caveolin-1 down-regulates inducible nitric oxide synthase via the proteasome pathway in human colon carcinoma cells". Proc. Natl. Acad. Sci. U.S.A. 97 (26): 14334–9. doi:10.1073/pnas.250406797. PMC 18919. PMID 11114180.
10. Kuncewicz T, Balakrishnan P, Snuggs MB, Kone BC (August 2001). "Specific association of nitric oxide synthase-2 with Rac isoforms in activated murine macrophages". Am. J. Physiol. Renal Physiol. 281 (2): F326–36. PMID 11457725.
11. Noda, Satoshi; Tanaka, Kazuo; Sawamura, Sada-aki; Sasaki, Masafumi; Matsumoto, Takako; Mikami, Katsunaka; Aiba, Yuji; Hasegawa, Hideaki; Kawabe, Noboru; Koga, Yasuhiro (2001-03-01). "Role of Nitric Oxide Synthase Type 2 in Acute Infection with Murine Cytomegalovirus". The Journal of Immunology. 166 (5): 3533–3541. doi:10.4049/jimmunol.166.5.3533. ISSN 0022-1767.