NOS2 nitric oxide synthase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NOS2provided by HGNC
Official Full Name: nitric oxide synthase 2provided by HGNC
Primary source: HGNC:HGNC:7873
See related: Ensembl:ENSG00000007171 MIM:163730; AllianceGenome:HGNC:7873
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NOS; INOS; NOS2A; HEP-NOS
Summary: 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]
Expression: Biased expression in small intestine (RPKM 10.3), appendix (RPKM 7.9) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q11.2

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (27756766..27800529, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (28698170..28741926, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (26083792..26127555, complement)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Analyzing the FMN-heme interdomain docking interactions in neuronal and inducible NOS isoforms by pulsed EPR experiments and conformational distribution modeling.
Title: Analyzing the FMN-heme interdomain docking interactions in neuronal and inducible NOS isoforms by pulsed EPR experiments and conformational distribution modeling.
Impact of Inducible Nitric Oxide Synthase Activation on Endothelial Behavior under Magnesium Deficiency.
Title: Impact of Inducible Nitric Oxide Synthase Activation on Endothelial Behavior under Magnesium Deficiency.
INOS ablation promotes corneal wound healing via activation of Akt signaling.
Title: INOS ablation promotes corneal wound healing via activation of Akt signaling.
Lysosomal trafficking regulator restricts intracellular growth of Coxiella burnetii by inhibiting the expansion of Coxiella-containing vacuole and upregulating nos2 expression.
Title: Lysosomal trafficking regulator restricts intracellular growth of Coxiella burnetii by inhibiting the expansion of Coxiella-containing vacuole and upregulating nos2 expression.
Influence of microRNAs on iNOS expression in postmortem human infarction hearts.
Title: Influence of microRNAs on iNOS expression in postmortem human infarction hearts.
High iNOS and IL-1beta immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival.
Title: High iNOS and IL-1β immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival.
NRF2 interacts with distal enhancer and inhibits nitric oxide synthase 2 expression in KRAS-driven pancreatic cancer cells.
Title: NRF2 interacts with distal enhancer and inhibits nitric oxide synthase 2 expression in KRAS-driven pancreatic cancer cells.
Role of NOS and Inflammatory Markers in the Early Restenosis After the Application of Femoral Arterial Stent.
Title: Role of NOS and Inflammatory Markers in the Early Restenosis After the Application of Femoral Arterial Stent.
The role of SOD2 and NOS2 genes in the molecular aspect of bladder cancer pathophysiology.
Title: The role of SOD2 and NOS2 genes in the molecular aspect of bladder cancer pathophysiology.
Inducible nitric oxide synthase activity mediates TNF-alpha-induced endothelial cell dysfunction.
Title: Inducible nitric oxide synthase activity mediates TNF-α-induced endothelial cell dysfunction.

Submit: New GeneRIF Correction See all GeneRIFs (659)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Malaria, susceptibility to MedGen: C1970028 OMIM: 611162 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis identifies three psoriasis susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Ascorbate supplementation prevents the deleterious upregulation of iNOS and associated neuronal (MAP2) and astrocytic (GFAP) protein expression and structural changes caused by gp120 in human brain cell cultures	PubMed
Envelope transmembrane glycoprotein gp41	env	The amino terminus of HIV-1 gp41 induces nitric oxide synthase in human glial and astrocyte cultures and that causes the dysregulation of nitric oxide production	PubMed
Tat	tat	HIV-1 Tat decreases expression of NOS2 (iNOS) in Leishmania-infected macrophages	PubMed
	tat	HIV-1 Tat potentiates NMDA-evoked (Ca2+)I responses involve LRP and a Src family kinase via the NOS/sGC/PKG pathway	PubMed
	tat	HIV-1 Tat induces iNOS in human astroglia and microglia through the activation of NF-kappaB and C/EBPbeta, an effect that may participate in the pathogenesis of HIV-associated dementia	PubMed
	tat	HIV-1 Tat induces iNOS in rat brain injected with Tat through upregulation of TNF-alpha, suggesting a mechanism for Tat-induced CNS damage	PubMed
	tat	HIV-1 Tat induces the expression of NOS-2 and NOS-3 which appears to be a mechanism for regulating Tat-mediated degradation of IkappaBalpha and activation of NFkappaB	PubMed
	tat	HIV-1 Tat inhibits interferon-induced iNOS activity in a murine macrophage cell line	PubMed
Vpr	vpr	Treatment of human primary astrocytes with HIV-1 Vpr upregulates expression of six genes, APOE, CCL5, DGKK, GPX5, NOS2, and PXDNL	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:374306 (e-PCR)
- UniSTS:156954

PMC151125P1 (e-PCR)
- UniSTS:271136

RH79885 (e-PCR)
- UniSTS:84524

D17S1878 (e-PCR), detects polymorphism
- UniSTS:9795

GDB:437694 (e-PCR)
- UniSTS:157251

D17S582 (e-PCR)
- UniSTS:147022

D17S33 (e-PCR)
- UniSTS:146841

RH119978 (e-PCR)
- UniSTS:133301

AFM311ZB1 (e-PCR)
- UniSTS:56820

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables FMN binding	IBA Inferred from Biological aspect of Ancestor more info
enables FMN binding	ISS Inferred from Sequence or Structural Similarity more info
enables NADP binding	TAS Traceable Author Statement more info	PubMed
enables arginine binding	ISS Inferred from Sequence or Structural Similarity more info
enables calmodulin binding	IEA Inferred from Electronic Annotation more info
enables flavin adenine dinucleotide binding	IBA Inferred from Biological aspect of Ancestor more info
enables flavin adenine dinucleotide binding	ISS Inferred from Sequence or Structural Similarity more info
enables heme binding	ISS Inferred from Sequence or Structural Similarity more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nitric-oxide synthase activity	IBA Inferred from Biological aspect of Ancestor more info
enables nitric-oxide synthase activity	IDA Inferred from Direct Assay more info	PubMed
enables nitric-oxide synthase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISS Inferred from Sequence or Structural Similarity more info
enables tetrahydrobiopterin binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in Fc-gamma receptor signaling pathway involved in phagocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in arginine catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in arginine catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in cell redox homeostasis	TAS Traceable Author Statement more info
involved_in cellular response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in cellular response to type II interferon	IEA Inferred from Electronic Annotation more info
involved_in cellular response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in circadian rhythm	IEA Inferred from Electronic Annotation more info
involved_in defense response to Gram-negative bacterium	NAS Non-traceable Author Statement more info	PubMed
involved_in defense response to bacterium	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to bacterium	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to bacterium	ISS Inferred from Sequence or Structural Similarity more info
involved_in inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in innate immune response in mucosa	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of blood pressure	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of protein catabolic process	IEA Inferred from Electronic Annotation more info
involved_in nitric oxide biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in nitric oxide biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in nitric oxide mediated signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in peptidyl-cysteine S-nitrosylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-6 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of leukocyte mediated cytotoxicity	TAS Traceable Author Statement more info	PubMed
involved_in prostaglandin secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in regulation of cellular respiration	TAS Traceable Author Statement more info	PubMed
involved_in regulation of cytokine production involved in inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of insulin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to bacterium	NAS Non-traceable Author Statement more info	PubMed
involved_in response to hormone	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in response to lipopolysaccharide	IBA Inferred from Biological aspect of Ancestor more info
involved_in superoxide metabolic process	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cortical cytoskeleton	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IMP Inferred from Mutant Phenotype more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in peroxisomal matrix	TAS Traceable Author Statement more info
located_in peroxisome	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: nitric oxide synthase, inducible

Names: NOS, type II; hepatocyte NOS; inducible NO synthase; inducible NOS; nitric oxide synthase 2, inducible; nitric oxide synthase 2A (inducible, hepatocytes); nitric oxide synthase, macrophage; peptidyl-cysteine S-nitrosylase NOS2

NP_000616.3

EC 1.14.13.39

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011470.1 RefSeqGene

Range

5001..48764

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000625.4 → NP_000616.3 nitric oxide synthase, inducible

See identical proteins and their annotated locations for NP_000616.3

Status: REVIEWED

Source sequence(s)

AC130289

Consensus CDS

CCDS11223.1

UniProtKB/Swiss-Prot

A1L3U5, B7ZLY2, O60757, O94994, P35228, Q16263, Q16692, Q4TTS5, Q9UD42

UniProtKB/TrEMBL

A0A2R8YDS4

Related

ENSP00000327251.6, ENST00000313735.11

Conserved Domains (4) summary

COG0369
Location:538 → 1127

CysJ; Sulfite reductase, alpha subunit (flavoprotein) [Inorganic ion transport and metabolism]

cd00795
Location:84 → 496

NOS_oxygenase_euk; Nitric oxide synthase (NOS) eukaryotic oxygenase domain. NOS produces nitric oxide (NO) by catalyzing a five-electron heme-based oxidation of a guanidine nitrogen of L-arginine to L-citrulline via two successive monooxygenation reactions producing N ...

pfam00258
Location:541 → 672

Flavodoxin_1; Flavodoxin

cl06868
Location:736 → 1132

FNR_like; Ferredoxin reductase (FNR), an FAD and NAD(P) binding protein, was intially identified as a chloroplast reductase activity, catalyzing the electron transfer from reduced iron-sulfur protein ferredoxin to NADP+ as the final step in the electron transport ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

27756766..27800529 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060941.1 Alternate T2T-CHM13v2.0

Range

28698170..28741926 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_153292.1: Suppressed sequence

Description

NM_153292.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.