Nitric oxide synthase, inducibleis anenzymewhich is encoded by theNOS2genein humans and mice.[5]
Genetics
editThree relatedpseudogenesare located within the Smith-Magenis syndrome region onchromosome 17.Alternative splicing of this gene results in two transcript variants encoding different isoforms.[6]
Location
editNitric oxide synthaseis expressed in epithelial cells of theliver,lung and bone marrow. It is inducible by a combination oflipopolysaccharideand certaincytokines.[citation needed]
Function
editNitric oxideis 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 againstCMV.[8]
Caveolin 1has been shown tointeractwith Nitric oxide synthase 2A.[9]andRac2.[10]
Deficiency
editAutosomal recessive NOS2 deficiency has been described in mice. They lack the gene encoding nitric oxide synthase 2 (Nos2) and are susceptible to murineCMVinfection.[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, andhemophagocytic 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 homozygousframeshift mutationin nitric oxide synthase 2. This condition is extremely rare, occurring in fewer than 1 per million persons.[8]
References
edit- ^abcGRCh38: Ensembl release 89: ENSG00000007171–Ensembl,May 2017
- ^abcGRCm38: 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, et al. (April 1993)."Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes".Proceedings of the National Academy of Sciences of the United States of America.90(8): 3491–3495.Bibcode:1993PNAS...90.3491G.doi:10.1073/pnas.90.8.3491.PMC46326.PMID7682706.
- ^"Entrez Gene: NOS2A nitric oxide synthase 2A (inducible, hepatocytes)".
- ^Nathan C (June 2006). "Role of iNOS in human host defense".Science.312(5782): 1874b–1875b.doi:10.1126/science.312.5782.1874b.PMID16809512.S2CID37395425.
- ^abDrutman SB, Mansouri D, Mahdaviani SA, Neehus AL, Hum D, Bryk R, et al. (January 2020)."Fatal Cytomegalovirus Infection in an Adult with Inherited NOS2 Deficiency".The New England Journal of Medicine.382(5): 437–445.doi:10.1056/NEJMoa1910640.PMC7063989.PMID31995689.
- ^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".Proceedings of the National Academy of Sciences of the United States of America.97(26): 14334–14339.Bibcode:2000PNAS...9714334F.doi:10.1073/pnas.250406797.PMC18919.PMID11114180.
- ^Kuncewicz T, Balakrishnan P, Snuggs MB, Kone BC (August 2001). "Specific association of nitric oxide synthase-2 with Rac isoforms in activated murine macrophages".American Journal of Physiology. Renal Physiology.281(2): F326–F336.doi:10.1152/ajprenal.2001.281.2.F326.PMID11457725.S2CID15719851.
- ^Noda S, Tanaka K, Sawamura S, Sasaki M, Matsumoto T, Mikami K, et al. (March 2001)."Role of nitric oxide synthase type 2 in acute infection with murine cytomegalovirus".Journal of Immunology.166(5): 3533–3541.doi:10.4049/jimmunol.166.5.3533.PMID11207313.
 | This article on ageneon humanchromosome 17is astub.You can help Wikipedia byexpanding it. |