Nitric oxide synthase, inducible is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

which is encoded by the ''NOS2''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

in humans and mice.

Genetics

Three related pseudogenes are located within the Smith-Magenis syndrome region on

chromosome 17 Chromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 83 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total D ...

. Alternative splicing of this gene results in two transcript variants encoding different isoforms.

Location

Nitric oxide synthase 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 p ...

is expressed in epithelial cells of the

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

, lung and bone marrow. It is inducible by a combination of

lipopolysaccharide Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...

and certain

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

Function

Nitric oxide Nitric oxide (nitrogen oxide or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes denoted by a dot in its che ...

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. Nos2 is important for protective immunity against CMV.

Caveolin 1 Caveolin-1 is a protein that in humans is encoded by the ''CAV1'' gene. Function The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits ...

has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with Nitric oxide synthase 2A. and Rac2.

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. 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 Hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a ...

. 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.

References

EC 1.14.13 {{gene-17-stub