Nitric oxide synthase 2 (inducible)

NOS2
Available structures
PDB	Ortholog search: PDBe RCSB
showList 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
showGene location (Human)
Chr.	Chromosome 17 (human)
End	27,800,529 bp
showGene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	78,960,254 bp
showRNA expression pattern
	More reference expression data
showGene 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; • 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; • cellular response to drug; • innate immune response in mucosa; • regulation of cell population proliferation; • peptidyl-cysteine S-nitrosylation; • defense response to bacterium; • circadian rhythm; • GO:0051636 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
	4843
	18126
	ENSG00000007171
	ENSMUSG00000020826
	P35228
	P29477
	NM_000625; NM_153292
	NM_010927; NM_001313921; NM_001313922
	NP_000616
	NP_001300850; NP_001300851; NP_035057
	Wikidata
View/Edit Human	View/Edit Mouse

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

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.^{[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.^[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[]

^ Jump up to: ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000007171 - Ensembl, May 2017
^ Jump up to: ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020826 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ "Entrez Gene: NOS2A nitric oxide synthase 2A (inducible, hepatocytes)".
^ 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. PMID 16809512. S2CID 37395425.
^ Jump up to: ^a ^b 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. PMC 7063989. PMID 31995689.
^ 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.
^ 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. doi:10.1152/ajprenal.2001.281.2.F326. PMID 11457725.
^ 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. PMID 11207313.

This article on a gene on human chromosome 17 is a stub. You can help Wikipedia by .

[refGRCh38Ensembl-1] Jump up to: ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000007171 - Ensembl, May 2017

[refGRCm38Ensembl-2] Jump up to: ^a ^b ^c 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.

[pmid7682706-5] 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. PMID 16809512. S2CID 37395425.

[nejm-8] Jump up to: ^a ^b 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. PMC 7063989. PMID 31995689.

[pmid11114180-9] 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.

[pmid11457725-10] 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. doi:10.1152/ajprenal.2001.281.2.F326. 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. PMID 11207313.

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show v t Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)
1.14.11: 2-oxoglutarate	Prolyl hydroxylase HIF prolyl-hydroxylase EGLN1 EGLN2 EGLN3 P4HTM Lysyl hydroxylase
1.14.13: NADH or NADPH	Flavin-containing monooxygenase FMO1 FMO2 FMO3 FMO4 FMO5 Nitric oxide synthase NOS1 NOS2 NOS3 Cholesterol 7 alpha-hydroxylase Methane monooxygenase 3A4 14α-demethylase 24-hydroxycholesterol 7α-hydroxylase
1.14.14: reduced flavin or flavoprotein	19A1 2D6 2E1
1.14.15: reduced iron-sulfur protein	11B1 11B2 11A1
1.14.16: reduced pteridine (BH4 dependent)	Phenylalanine hydroxylase Tyrosine hydroxylase Tryptophan hydroxylase
1.14.17: reduced ascorbate	Dopamine beta-hydroxylase
1.14.18-19: other	Tyrosinase Stearoyl-CoA desaturase-1
1.14.99 - miscellaneous	Cyclooxygenase Heme oxygenase (HMOX1) Squalene monooxygenase 17A1 21A2 Ecdysone 20-monooxygenase Deoxyhypusine monooxygenase

show v t Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)