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]
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]
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]
Referencesedit
^ 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, 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. Bibcode:1993PNAS...90.3491G. doi:10.1073/pnas.90.8.3491. PMC46326. PMID 7682706.
^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.
^ abDrutman, 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. PMC7063989. 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. Bibcode:2000PNAS...9714334F. doi:10.1073/pnas.250406797. PMC18919. 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. S2CID 15719851.
^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.
nitric, oxide, synthase, inducible, nitric, oxide, synthase, inducible, enzyme, which, encoded, nos2, gene, humans, mice, nos2available, structurespdbortholog, search, pdbe, rcsblist, codes1nsi, 2ll6, 2nsi, 3e7g, 3ej8, 3hr4, 4cx7, 4nosidentifiersaliasesnos2, i. Nitric oxide synthase inducible is an enzyme which is encoded by the NOS2 gene in humans and mice 5 NOS2Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1NSI 2LL6 2NSI 3E7G 3EJ8 3HR4 4CX7 4NOSIdentifiersAliasesNOS2 HEP NOS INOS NOS NOS2A Nitric oxide synthase 2External IDsOMIM 163730 MGI 97361 HomoloGene 55473 GeneCards NOS2Gene location Human Chr Chromosome 17 human 1 Band17q11 2Start27 756 766 bp 1 End27 800 529 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 B5 11 46 74 cMStart78 811 613 bp 2 End78 851 080 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inrectumappendixprefrontal cortexduodenumBrodmann area 9cingulate gyrusupper lobe of left lungright lungganglionic eminencesmooth muscle tissueTop expressed injejunumplacentathymusentorhinal cortexskeletal muscle tissueesophagusneural tubeadrenal glandlensstomachMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionFMN 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 bindingCellular componentcytoplasm cytosol cortical cytoskeleton peroxisome intracellular anatomical structure perinuclear region of cytoplasm nucleus peroxisomal matrix plasma membrane vesicle membraneBiological processpositive 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 hormoneSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez484318126EnsemblENSG00000007171ENSMUSG00000020826UniProtP35228P29477RefSeq mRNA NM 000625NM 153292NM 010927NM 001313921NM 001313922RefSeq protein NP 000616NP 001300850NP 001300851NP 035057Location UCSC Chr 17 27 76 27 8 MbChr 11 78 81 78 85 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Genetics 2 Location 3 Function 4 Deficiency 5 ReferencesGenetics editThree 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 editNitric 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 editNitric 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 editAutosomal 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 edit a b c GRCh38 Ensembl release 89 ENSG00000007171 Ensembl May 2017 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 Bibcode 1993PNAS 90 3491G 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 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 Bibcode 2000PNAS 9714334F 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 S2CID 15719851 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 Portal nbsp Biology nbsp This article on a gene on human chromosome 17 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Nitric oxide synthase 2 inducible amp oldid 1115514763, wikipedia, wiki, book, books, library,
