Nitric oxide synthase 2 (inducible)

Last updated
NOS2
PDB 1nsi EBI.jpg
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases NOS2 , HEP-NOS, INOS, NOS, NOS2A, Nitric oxide synthase 2
External IDs OMIM: 163730 MGI: 97361 HomoloGene: 55473 GeneCards: NOS2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 [3] [4]
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]

Contents

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]

Related Research Articles

<span class="mw-page-title-main">Nitric oxide synthase</span> Enzyme catalysing the formation of the gasotransmitter NO(nitric oxide)

Nitric oxide synthases (NOSs) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule. It helps modulate vascular tone, insulin secretion, airway tone, and peristalsis, and is involved in angiogenesis and neural development. It may function as a retrograde neurotransmitter. Nitric oxide is mediated in mammals by the calcium-calmodulin controlled isoenzymes eNOS and nNOS. The inducible isoform, iNOS, involved in immune response, binds calmodulin at physiologically relevant concentrations, and produces NO as an immune defense mechanism, as NO is a free radical with an unpaired electron. It is the proximate cause of septic shock and may function in autoimmune disease.

In molecular biology, caveolins are a family of integral membrane proteins that are the principal components of caveolae membranes and involved in receptor-independent endocytosis. Caveolins may act as scaffolding proteins within caveolar membranes by compartmentalizing and concentrating signaling molecules. They also induce positive (inward) membrane curvature by way of oligomerization, and hairpin insertion. Various classes of signaling molecules, including G-protein subunits, receptor and non-receptor tyrosine kinases, endothelial nitric oxide synthase (eNOS), and small GTPases, bind Cav-1 through its 'caveolin-scaffolding domain'.

Gasotransmitters is a class of neurotransmitters. The molecules are distinguished from other bioactive endogenous gaseous signaling molecules based on a need to meet distinct characterization criteria. Currently, only nitric oxide, carbon monoxide, and hydrogen sulfide are accepted as gasotransmitters.

<span class="mw-page-title-main">GTP cyclohydrolase I</span>

GTP cyclohydrolase I (GTPCH) (EC 3.5.4.16) is a member of the GTP cyclohydrolase family of enzymes. GTPCH is part of the folate and biopterin biosynthesis pathways. It is responsible for the hydrolysis of guanosine triphosphate (GTP) to form 7,8-dihydroneopterin triphosphate (7,8-DHNP-3'-TP, 7,8-NH2-3'-TP).

<span class="mw-page-title-main">Caveolin 3</span>

Caveolin-3 is a protein that in humans is encoded by the CAV3 gene. Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites.

<i>Human betaherpesvirus 5</i> Species of virus

Human betaherpesvirus 5, also called human cytomegalovirus (HCMV), is species of virus in the genus Cytomegalovirus, which in turn is a member of the viral family known as Herpesviridae or herpesviruses. It is also commonly called CMV. Within Herpesviridae, HCMV belongs to the Betaherpesvirinae subfamily, which also includes cytomegaloviruses from other mammals. CMV is a double-stranded DNA virus.

<span class="mw-page-title-main">STAT2</span> Protein-coding gene in Homo sapiens

Signal transducer and activator of transcription 2 is a protein that in humans is encoded by the STAT2 gene. It is a member of the STAT protein family. This protein is critical to the biological response of type I interferons (IFNs). STAT2 sequence identity between mouse and human is only 68%.

<span class="mw-page-title-main">Endothelial NOS</span> Mammalian protein found in Homo sapiens

Endothelial NOS (eNOS), also known as nitric oxide synthase 3 (NOS3) or constitutive NOS (cNOS), is an enzyme that in humans is encoded by the NOS3 gene located in the 7q35-7q36 region of chromosome 7. This enzyme is one of three isoforms that synthesize nitric oxide (NO), a small gaseous and lipophilic molecule that participates in several biological processes. The other isoforms include neuronal nitric oxide synthase (nNOS), which is constitutively expressed in specific neurons of the brain and inducible nitric oxide synthase (iNOS), whose expression is typically induced in inflammatory diseases. eNOS is primarily responsible for the generation of NO in the vascular endothelium, a monolayer of flat cells lining the interior surface of blood vessels, at the interface between circulating blood in the lumen and the remainder of the vessel wall. NO produced by eNOS in the vascular endothelium plays crucial roles in regulating vascular tone, cellular proliferation, leukocyte adhesion, and platelet aggregation. Therefore, a functional eNOS is essential for a healthy cardiovascular system.

<span class="mw-page-title-main">Caveolin 1</span> Protein-coding gene in the species Homo sapiens

Caveolin-1 is a protein that in humans is encoded by the CAV1 gene.

<span class="mw-page-title-main">NOS1</span> Protein-coding gene in the species Homo sapiens

Nitric oxide synthase 1 (neuronal), also known as NOS1, is an enzyme that in humans is encoded by the NOS1 gene.

<span class="mw-page-title-main">ATP5F1A</span>

ATP synthase F1 subunit alpha, mitochondrial is an enzyme that in humans is encoded by the ATP5F1A gene.

<span class="mw-page-title-main">HNRNPL</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein L is a protein that in humans is encoded by the HNRNPL gene.

<span class="mw-page-title-main">NOS1AP</span> Protein-coding gene in the species Homo sapiens

Nitric oxide synthase 1 adaptor protein (NOS1AP) also known as carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein (CAPON) is a protein that in humans is encoded by the NOS1AP gene.

<span class="mw-page-title-main">COQ2</span>

Para-hydroxybenzoate—polyprenyltransferase, mitochondrial is an enzyme that in humans is encoded by the COQ2 gene.

<span class="mw-page-title-main">SDPR</span>

Cavin-2 or Serum deprivation-response protein (SDPR) is a protein that in humans is encoded by the SDPR gene. Cavin-2 is highly expressed in a variety of human endothelial cells.

<span class="mw-page-title-main">NKRF (gene)</span> Protein-coding gene in the species Homo sapiens

NF-kappa-B-repressing factor is a protein that in humans is encoded by the NKRF gene.

<span class="mw-page-title-main">NOSIP</span> Protein-coding gene in the species Homo sapiens

Nitric oxide synthase-interacting protein is an enzyme that in humans is encoded by the NOSIP gene.

Nitric oxide is a molecule and chemical compound with chemical formula of NO. In mammals including humans, nitric oxide is a signaling molecule involved in several physiological and pathological processes. It is a powerful vasodilator with a half-life of a few seconds in the blood. Standard pharmaceuticals such as nitroglycerine and amyl nitrite are precursors to nitric oxide. Low levels of nitric oxide production are typically due to ischemic damage in the liver.

In molecular biology mir-939 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

<span class="mw-page-title-main">ARG2</span> Protein-coding gene in the species Homo sapiens

Arginase, type II is an arginase protein that in humans is encoded by the ARG2 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000007171 - Ensembl, May 2017
  2. 1 2 3 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. Bibcode:1993PNAS...90.3491G. 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.
  8. 1 2 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.
  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. Bibcode:2000PNAS...9714334F. 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. doi:10.1152/ajprenal.2001.281.2.F326. PMID   11457725. S2CID   15719851.
  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.