Go Annotations as Summary Text (Tabular View) (GO Graph)

GO curators for mouse genes have assigned the following annotations to the gene product of Nos2. (This text reflects annotations as of Wednesday, January 23, 2013.)

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Summary from NCBI RefSeq

[Summary is not available for the mouse gene. This summary is for the human ortholog.] Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

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Summary text based on GO annotations supported by experimental evidence in mouse

• Researchers have inferred from direct assay, that the gene product of Nos2
  • participates in the following biological processes:
    • arginine catabolic process ^[12]
    • cellular response to interferon-gamma ^[4]
    • cellular response to lipopolysaccharide ^{[2, 4]}
    • negative regulation of protein catabolic process ^[7]
    • nitric oxide biosynthetic process ^{[5, 12]}
    • oxidation-reduction process ^{[5, 12]}
    • peptidyl-cysteine S-nitrosylation ^[8]
    • response to hypoxia ^[3]
  • performs the following molecular functions:
    • arginine binding ^[5]
    • flavin adenine dinucleotide binding ^[12]
    • FMN binding ^[12]
    • heme binding ^{[5, 12]}
    • nitric-oxide synthase activity ^{[5, 12]}
    • protein homodimerization activity ^[5]
    • tetrahydrobiopterin binding ^[5]
  • is located in the following cellular components:
    • cortical cytoskeleton ^[3]
    • cytoplasm ^{[3, 9]}
    • perinuclear region of cytoplasm ^[3]
• The gene product of Nos2 has been shown to bind to the gene products of Actn4, Cd74. ^{[3, 7, 8, 13]}
• Researchers have inferred, based on phenotypic analysis of mouse mutants, that the gene product of Nos2
  • participates in the following biological processes:
    • defense response to bacterium ^[6]
    • superoxide metabolic process ^[6]
• Researchers have inferred, based on genetic interactions, that the gene product of Nos2
  • participates in the following biological processes:
    • negative regulation of gene expression based on interactions with ^[11]
    • regulation of cell proliferation based on interactions with Apc ^{[1, 10]}

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Summary text based on GO annotations supported by experimental evidence in other organisms

• From comparative sequence analysis (see table for details), MGI curators have determined that the gene product of Nos2:
  • participates in the following biological processes:
    • arginine catabolic process
    • blood vessel remodeling
    • cGMP-mediated signaling
    • defense response to bacterium
    • G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger
    • intracellular protein kinase cascade
    • negative regulation of blood pressure
    • negative regulation of gene expression
    • nitric oxide biosynthetic process
    • nitric oxide mediated signal transduction
    • oxidation-reduction process
    • positive regulation of apoptotic process
    • positive regulation of guanylate cyclase activity
    • positive regulation of killing of cells of other organism
    • positive regulation of vasodilation
    • regulation of blood pressure
    • regulation of heart contraction
    • regulation of insulin secretion
    • response to tumor necrosis factor
    • signal transduction
  • performs the following molecular functions:
    • cAMP-dependent protein kinase regulator activity
    • Hsp90 protein binding
    • NADPH-hemoprotein reductase activity
    • nitric-oxide synthase activity
    • protein homodimerization activity
    • receptor binding
  • is located in the following cellular components:
    • cytoplasm
    • cytosol
    • extracellular space
    • intracellular
    • nucleus
    • peroxisome
    • vesicle membrane

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Summary text based on GO annotations supported by structural data

• Nos2 encodes a protein or proteins that contain the following InterPro domains: FAD-binding, type 1, Ferredoxin reductase-type FAD-binding domain, Flavodoxin, Flavodoxin/nitric oxide synthase, Flavoprotein pyridine nucleotide cytochrome reductase, NADPH-cytochrome p450 reductase, FAD-binding, alpha-helical domain-3, Nitric oxide synthase, oxygenase domain, Nitric-oxide synthase, Nitric-oxide synthase, metazoa, Oxidoreductase FAD/NAD(P)-binding, Riboflavin synthase-like beta-barrel, indicating that the gene product:
  • performs the following molecular functions:
    • iron ion binding
    • NADP binding
    • oxidoreductase activity

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Summary text for additional MGI annotations

• Automated translation to GO terms of SwissProt keywords that describe Nos2 indicates that it:
  • performs the following molecular functions:
    • metal ion binding
    • oxidoreductase activity

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References

1. Ahn B et al. (2001) Suppression of intestinal polyposis in Apc(Min/+) mice by inhibiting nitric oxide production. Cancer Res, 61:8357-60. (PubMed:11731407)
2. Dai R et al. (2008) Suppression of LPS-induced Interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation. Blood, 112:4591-7. (PubMed:18791161)
3. Daniliuc S et al. (2003) Hypoxia inactivates inducible nitric oxide synthase in mouse macrophages by disrupting its interaction with alpha-actinin 4. J Immunol, 171:3225-32. (PubMed:12960352)
4. Degrandi D et al. (2007) Extensive characterization of IFN-induced GTPases mGBP1 to mGBP10 involved in host defense. J Immunol, 179:7729-40. (PubMed:18025219)
5. Ghosh DK et al. (1997) Characterization of the inducible nitric oxide synthase oxygenase domain identifies a 49 amino acid segment required for subunit dimerization and tetrahydrobiopterin interaction. Biochemistry, 36:10609-19. (PubMed:9271491)
6. Gyurko R et al. (2003) Mice lacking inducible nitric oxide synthase demonstrate impaired killing of Porphyromonas gingivalis. Infect Immun, 71:4917-24. (PubMed:12933833)
7. Huang D et al. (2008) Nitric-oxide synthase 2 interacts with CD74 and inhibits its cleavage by caspase during dendritic cell development. J Biol Chem, 283:1713-22. (PubMed:18003616)
8. Kim SF et al. (2005) Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2. Science, 310:1966-70. (PubMed:16373578)
9. Nishikimi A et al. (2001) Localization of nitric oxide synthase activity in unfertilized oocytes and fertilized embryos during preimplantation development in mice. Reproduction, 122:957-63. (PubMed:11732991)
10. Scott DJ et al. (2001) Lack of inducible nitric oxide synthase promotes intestinal tumorigenesis in the apc(min/+) mouse. Gastroenterology, 121:889-99. (PubMed:11606502)
11. Stolz DB et al. (2002) Peroxisomal localization of inducible nitric oxide synthase in hepatocytes. Hepatology, 36:81-93. (PubMed:12085352)
12. Stuehr DJ et al. (1992) Spectral characterization of brain and macrophage nitric oxide synthases. Cytochrome P-450-like hemeproteins that contain a flavin semiquinone radical. J Biol Chem, 267:20547-50. (PubMed:1383204)
13. Yoshida M et al. (2003) Heat shock protein 90 as an endogenous protein enhancer of inducible nitric-oxide synthase. J Biol Chem, 278:36953-8. (PubMed:12855682)

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Gene Ontology Evidence Code Abbreviations:

EXP Inferred from experiment

IC Inferred by curator

IDA Inferred from direct assay

IEA Inferred from electronic annotation

IGI Inferred from genetic interaction

IMP Inferred from mutant phenotype

IPI Inferred from physical interaction

ISS Inferred from sequence or structural similarity

ISO Inferred from sequence orthology

ISA Inferred from sequence alignment

ISM Inferred from sequence model

NAS Non-traceable author statement

ND No biological data available

RCA Reviewed computational analysis

TAS Traceable author statement

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