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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

NOS2 Gene

protein-coding GIFtS: 69
GCID: GC17M026083

nitric oxide synthase 2, inducible

(Previous names: nitric oxide synthase 2A (inducible, hepatocytes) )
(Previous symbol: NOS2A)

Explore 396 diseases affiliated with
NOS2 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Nitric Oxide Synthase 2, Inducible¹ ²		Inducible NOS² ³
NOS2A¹ ² ³ ⁵		Peptidyl-Cysteine S-Nitrosylase NOS2² ³
HEP-NOS¹ ² ³		NOS Type II² ³
NOS¹ ²		EC 1.14.13.39³ ⁸
Nitric Oxide Synthase 2A (Inducible, Hepatocytes)¹ ²		INOS²
INOS²		Nitric Oxide Synthase, Inducible²
Hepatocyte NOS² ³		Nitric Oxide Synthase, Macrophage²
Inducible NO Synthase² ³		NOS, Type II²

External Ids:	HGNC: 7873¹	Entrez Gene: 4843²	Ensembl: ENSG00000007171⁷	OMIM: 163730⁵	UniProtKB: P35228³

Export aliases for NOS2 gene to outside databases

Previous GC identifers: GC17M023108 GC17M022290

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for NOS2:

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)

UniProtKB/Swiss-Prot: NOS2_HUMAN, P35228

Function: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In

macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine

S-nitrosylation of cytoplasmic target proteins such COX2

Gene Wiki entry for NOS2 (Nitric oxide synthase 2)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000017.10 NC_018928.1 NT_010799.15

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the NOS2 gene promoter:
p300 MyoD IRF-1 HNF-3beta HNF-4alpha1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): NOS2 promoter sequence

Search SABiosciences Chromatin IP Primers for NOS2

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NOS2

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q11.2-q12 Ensembl cytogenetic band: 17q11.2 HGNC cytogenetic band: 17q11.2-q12

NOS2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NOS2 gene location

GeneLoc information about chromosome 17 GeneLoc Exon Structure

GeneLoc location for GC17M026083: view genomic region (about GC identifiers)

Start:	26,083,792 bp from pter	End:	26,127,555 bp from pter
Size:	43,764 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: NOS2_HUMAN, P35228 (See protein sequence)

Recommended Name: Nitric oxide synthase, inducible

Size: 1153 amino acids; 131117 Da

Cofactor: Heme group (By similarity)

Cofactor: Binds 1 FAD (By similarity)

Cofactor: Binds 1 FMN (By similarity)

Cofactor: Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme (By similarity)

Subunit: Homodimer. Binds SLC9A3R1

6/7 PDB 3D structures from and Proteopedia for NOS2 (see all 7):

1NSI (3D)

2LL6 (3D)

2NSI (3D)

3E7G (3D)

3EJ8 (3D)

3HR4 (3D)

Secondary accessions: A1L3U5 B7ZLY2 O60757 O94994 Q16263 Q16692 Q4TTS5 Q9UD42

Alternative splicing: 2 isoforms: P35228-1 P35228-2

Explore the universe of human proteins at neXtProt for NOS2: NX_P35228

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P35228

4/43 DME Specific Peptides for NOS2 (P35228) (see all 43)

VLEEFPS

GWYMGTE

LDITTPP

LQVFDAR

NOS2 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_000616.3

ENSEMBL proteins:

ENSP00000327251

Reactome Protein details: P35228
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Enzo Life Sciences proteins for NOS2
	OriGene Purified Protein: NOS2 OriGene Protein Over-expression Lysate: NOS2 OriGene Custom Protein Services for NOS2
	GenScript Custom Purified and Recombinant Proteins Services for NOS2
	Novus Biologicals NOS2 Protein Novus Biologicals NOS2 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for NOS2

Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005622	intracellular	IDA	7544003
GO:0005634	nucleus	ISS	--
GO:0005737	cytoplasm	IDA	9916929
GO:0005777	peroxisome	IDA	12085352
GO:0005829	cytosol	TAS	--

NOS2 for ontologies About GeneDecksing

NOS2 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of NOS2
	R&D Systems Antibodies for NOS2 (iNOS)
	Browse OriGene Antibodies OriGene Custom Antibody Services for NOS2
	GenScript Custom Superior Antibodies Services for NOS2
	Novus Biologicals NOS2 Antibodies
	Search for Antibodies for NOS2 at Abcam
	Uscn Antibodies for NOS2
	ThermoFisher Antibody for NOS2

Assay Products for NOS2:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for NOS2 (iNOS)
	GenScript Custom Assay Services for NOS2
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for NOS2

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

NOS2 for domains About GeneDecksing

5/11 InterPro domains/families (see all 11):

IPR026009 NOS

IPR017927 Fd_Rdtase_FAD-bd

IPR001094 Flavdoxin

IPR008254 Flavodoxin/NO_synth

IPR012144 NOS_met

Graphical View of Domain Structure for InterPro Entry P35228

ProtoNet protein and cluster: P35228

5/6 Blocks protein families (see all 6):

IPB001094 Flavodoxin signature

IPB001433 Oxidoreductase FAD/NAD(P)-binding

IPB001709 Flavoprotein pyridine nucleotide cytochrome reductase signature

IPB003097 FAD-binding

IPB004030 Nitric oxide synthase

UniProtKB/Swiss-Prot: NOS2_HUMAN, P35228

Similarity: Belongs to the NOS family

Similarity: Contains 1 FAD-binding FR-type domain

Similarity: Contains 1 flavodoxin-like domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: NOS2_HUMAN, P35228

Function: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In

macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine

S-nitrosylation of cytoplasmic target proteins such COX2

Catalytic activity: 2 L-arginine + 3 NADPH + 4 O(2) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H(2)O

Enzyme regulation: Regulated by calcium/calmodulin. Aspirin inhibits expression and function of this enzyme and effects

may be exerted at the level of translational/post-translational modification and directly on the catalytic activity

(By similarity)

Induction: By endotoxins and cytokines. Induced by IFNG/IFN-gamma acting synergistically with bacterial

lipopolysaccharides (LPS), TNF or IL1B/interleukin-1 beta

Enzyme Number (IUBMB): EC 1.14.13.39¹ ²

miRNA Products:		OriGene 3'-UTR Clone: NOS2 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat NOS2
		2 QIAGEN miScript miRNA Assays for microRNAs that regulate NOS2:
		hsa-miR-485-3p hsa-miR-323-5p
		SwitchGear 3'UTR luciferase reporter plasmid: NOS2 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for NOS2 (see all 7) OriGene shRNA RFP: NOS2 OriGene siRNA: NOS2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat NOS2

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for NOS2

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for NOS2 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for NOS2 OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: NOS2 (NM_000625)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOS2
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOS2

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for NOS2
		Search LifeMap BioReagents cell lines for NOS2

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOS2

Gene Ontology (GO): 5/13 molecular function terms (GO ID links to tree view) (see all 13): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003958	NADPH-hemoprotein reductase activity	IBA	--
GO:0004517	nitric-oxide synthase activity	IDA	7504305
GO:0005102	receptor binding	IPI	--
GO:0005506	iron ion binding	IEA	--
GO:0005515	protein binding	IPI	12855682

NOS2 for ontologies About GeneDecksing

2 GenomeRNAi human phenotypes for NOS2:

Decreased viability after Chla

Increased gamma-H2AX phosphory

Animal Models:
Mouse knock-outs for NOS2: Nos2^tm1Mrl Nos2^tm1Lau Nos2^tm1Liew
15/23 MGI mutant phenotypes (inferred from 3 alleles) (MGI details for Nos2) (see all 23):

adipose tissue	behavior/neurological	cardiovascular system	cellular	craniofacial
digestive/alimentary	endocrine/exocrine gland	growth/size	hematopoietic system	homeostasis/metabolism
immune system	integument	liver/biliary system	mortality/aging	muscle

NOS2 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/35 super-pathways (see all 35) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Immune response IL-12-induced IFN-gamma production

	Immune response IL-12-induced IFN-gamma production	1.00			IL12-mediated signaling events	0.33
	Immune response_IL-12-induced IFN-gamma production	0.88

Immune response _CCR3 signaling in eosinophils

Immune response _CCR3 signaling in eosinophils

1.00

Immune response CCR3 signaling in eosinophils

1.00

Immune response_IL-1 signaling pathway

Immune response_IL-1 signaling pathway

1.00

Immune response IL-1 signaling pathway

0.98

Immune response_Bacterial infections in normal airways

Immune response_Bacterial infections in normal airways

1.00

Bacterial infections in CF airways

0.78

Nitric oxide stimulates guanylate cyclase

Nitric oxide stimulates guanylate cyclase

1.00

Platelet homeostasis

0.34

Pathway sources
See GeneCards unified pathways
Show all pathways

5/6 EMD Millipore Pathways for NOS2 (see all 6)

	Immune response IL-12-induced IFN-gamma production
	G-protein signaling Rac2 regulation pathway
	Immune response MIF-mediated glucocorticoid regulation
	Immune response MIF in innate immunity response
	Immune response CCR3 signaling in eosinophils

5/11 GeneGo (Thomson Reuters) Pathways for NOS2 (see all 11)

	Immune response MIF-mediated glucocorticoid regulation
	Immune response Bacterial infections in normal airways
	Immune response MIF in innate immunity response
	Development VEGF signaling via VEGFR2 - generic cascades
	Mechanisms of CFTR activation by S-nitrosoglutathione (normal and CF)

5/10 BioSystems Pathways for NOS2 (see all 10)

	AGE/RAGE pathway
	Type II interferon signaling (IFNG)
	Prolactin Signaling Pathway
	citrulline-nitric oxide cycle
	IL23-mediated signaling events

5/6 Reactome Pathways for NOS2 (see all 6)

	Hemostasis
	Phagosomal maturation (early endosomal stage)
	Latent infection of Homo sapiens with Mycobacterium tuberculosis
	Platelet homeostasis
	Nitric oxide stimulates guanylate cyclase

2 PharmGKB Pathways for NOS2

	Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics
	Doxorubicin Pathway, Pharmacokinetics

5/12 Kegg Pathways (Kegg details for NOS2) (see all 12):

	Arginine and proline metabolism
	Metabolic pathways
	Calcium signaling pathway
	Peroxisome
	Pertussis

NOS2 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for NOS2

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/60 Interacting proteins for NOS2 (P35228³ ENSP00000327251⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 60)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
CALM2	P62158³, ENSP00000272298⁴	I2D: score=1 STRING: ENSP00000272298
CALM1	P62158³, ENSP00000349467⁴	I2D: score=1 STRING: ENSP00000349467
CALM3	P62158³	I2D: score=1
ACTN4	O43707³, ENSP00000252699⁴	I2D: score=4 STRING: ENSP00000252699
RAC2	P15153³, ENSP00000249071⁴	I2D: score=4 STRING: ENSP00000249071

About this table

Gene Ontology (GO): 26 biological process terms (GO ID links to tree view) (see first 5): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001666	response to hypoxia	IEA	--
GO:0001912	positive regulation of leukocyte mediated cytotoxicity	TAS	10450191
GO:0002227	innate immune response in mucosa	NAS	18390757
GO:0006527	arginine catabolic process	IDA	7504305
GO:0006801	superoxide metabolic process	ISS	--
GO:0006809	nitric oxide biosynthetic process	IDA	7504305
GO:0006954	inflammatory response	IBA	--
GO:0007263	nitric oxide mediated signal transduction	IBA	--
GO:0007596	blood coagulation	TAS	--
GO:0009617	response to bacterium	NAS	12085352
GO:0010629	negative regulation of gene expression	IGI	12085352
GO:0018119	peptidyl-cysteine S-nitrosylation	ISS	--
GO:0031284	positive regulation of guanylate cyclase activity	IBA	--
GO:0042127	regulation of cell proliferation	IEA	--
GO:0042177	negative regulation of protein catabolic process	IEA	--
GO:0042742	defense response to bacterium	ISS	--
GO:0043457	regulation of cellular respiration	TAS	10450191
GO:0045776	negative regulation of blood pressure	IBA	--
GO:0045909	positive regulation of vasodilation	IBA	--
GO:0050796	regulation of insulin secretion	IMP	8383325
GO:0050829	defense response to Gram-negative bacterium	NAS	18390757
GO:0051701	interaction with host	TAS	--
GO:0051712	positive regulation of killing of cells of other organism	IMP	7544003
GO:0071222	cellular response to lipopolysaccharide	IEA	--
GO:0071346	cellular response to interferon-gamma	IEA	--
GO:0090382	phagosome maturation	TAS	--

NOS2 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

NOS2 for compounds About GeneDecksing

EMD Millipore small molecules for NOS2:
Small Molecule - inhibitor

Enzo Life Sciences drugs & compounds for NOS2

Compounds for NOS2 available from Tocris Bioscience About this table

Compound	Action	CAS #
BYK 191023 dihydrochloride	Potent and selective inhibitor of iNOS	[608880-48-4]
AR-C 102222	Selective iNOS inhibitor	[253771-21-0]
L-NIL hydrochloride	Selective iNOS inhibitor	[150403-89-7]
L-Canavanine sulfate	NOS inhibitor	[2219-31-0]
1400W dihydrochloride	Potent, highly selective iNOS inhibitor	[180001-34-7]

10 HMDB Compounds for NOS2 About this table

Compound	Synonyms	CAS #	PubMed Ids
Calcium	Ca (see all 2)	7440-70-2	--
Citrulline	(2S)-2-amino-5-(carbamoylamino)pentanoic acid (see all 55)	372-75-8	--
FAD	1H-Purin-6-amine flavin dinucleotide (see all 21)	146-14-5	--
Flavin Mononucleotide	FMN (see all 19)	146-17-8	--
Heme	(protoporphyrinato)iron (see all 19)	14875-96-8	--
L-Arginine	(S)-2-Amino-5-[(aminoiminomethyl)amino]pentanoate (see all 14)	74-79-3	--
NADP	Adenine-nicotinamide dinucleotide phosphate (see all 18)	53-59-8	--
NADPH	2'-(dihydrogen phosphate) 5'-(trihydrogen pyrophosphate) Adenosine 5'-ester with 1,4-dihydro-1-b-D-ribofuranosylnicotinamide (see all 23)	53-57-6	--
Nitric oxide	Mononitrogen monoxide (see all 9)	10102-43-9	--
Tetrahydrobiopterin	(1R,2S)-(2-Amino-3,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)-1,2-propandiol (see all 11)	17528-72-2	--

10/39 DrugBank Compounds for NOS2 (see all 39) About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
L-Arginine	(S)-2-Amino-5-guanidinovaleric acid (see all 4)	74-79-3	target	--	17513447 17340133 16778961 17362916 17363779
L-Citrulline	2-Amino-5-uredovaleric acid (see all 8)	372-75-8	target	--	12745988 10906994 11742852 10906995 10944418
Aminoguanidine	--	79-17-4	target	inhibitor	17139284 11752352 17016423 10592235
Dexamethasone	Desametasone (see all 9)	50-02-2	target	negative modulator	17494951 17503181 11752352 17379310
Miconazole	--	22916-47-8	target	inhibitor	7536941 7518297 7683652 9873034
Triflusal	--	--	target	agonist	9551715 19465361 16939630 10998082
3-Bromo-7-Nitroindazole	--	--	target	--	17139284 17016423 10592235
4r-Fluoro-N6-Ethanimidoyl-L-Lysine	--	--	target	--	17139284 17016423 10592235
5-Nitroindazole	--	--	target	--	17139284 17016423 10592235
6-Nitroindazole	--	--	target	--	17139284 17016423 10592235

10/124 Novoseek chemical compound relationships for NOS2 gene (see all 124) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
nitric oxide	97.5	18892	11680730 (10), 11342896 (8), 16957516 (8), 18554637 (8) (see all 99)
citrulline	87.5	279	20148434 (3), 20148433 (3), 8561501 (3), 7527657 (2) (see all 99)
l-nmma	87.3	488	9503327 (4), 12810424 (3), 17724209 (3), 18090547 (3) (see all 99)
arginine	86.4	1048	16245240 (5), 11275358 (5), 8639550 (5), 7664438 (4) (see all 99)
peroxynitrite	86.2	233	11788351 (4), 9180331 (3), 10383909 (3), 9122229 (3) (see all 99)
aminoguanidine	84.9	363	9538001 (5), 16553284 (4), 18790185 (4), 11062159 (3) (see all 99)
adma	83.5	234	8743168 (5), 15325021 (4), 19682580 (4), 10802528 (3) (see all 99)
tetrahydrobiopterin	79.4	94	15565652 (2), 14609340 (2), 16052472 (2), 16172396 (2) (see all 67)
cgmp	78.8	303	18606420 (5), 10802528 (4), 11181408 (4), 8633049 (4) (see all 99)
n(g)-nitro-l-arginine methyl ester	76.8	176	11891189 (2), 7684763 (1), 7673269 (1), 8991992 (1) (see all 99)

Search CenterWatch for drugs/clinical trials and news about NOS2

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for NOS2 gene (2 alternative transcripts):

NM_000625.4 NM_153292.1

Unigene Cluster for NOS2:

Nitric oxide synthase 2, inducible

Hs.709191 [show with all ESTs]

Unigene Representative Sequence: NM_000625

1 Ensembl transcript including schematic representation, and UCSC links where relevant:

ENST00000313735(uc002gzu.3 uc010wab.1 uc010crh.1)

miRNA Products:		OriGene 3'-UTR Clone: NOS2 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat NOS2
		2 QIAGEN miScript miRNA Assays for microRNAs that regulate NOS2:
		hsa-miR-485-3p hsa-miR-323-5p
		SwitchGear 3'UTR luciferase reporter plasmid: NOS2 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for NOS2 (see all 7) OriGene shRNA RFP: NOS2 OriGene siRNA: NOS2
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat NOS2

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for NOS2 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for NOS2 OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: NOS2 (NM_000625)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for NOS2
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat NOS2

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for NOS2 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat NOS2
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat NOS2
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Additional cDNA sequence:

AB022318.1 AF068236.1 AK304252.1 BC130283.1 BC144126.1 D26525.1 L09210.1 L24553.1

S75615.1 S76479.1 U05810.1 U20141.1 U31511.1 X73029.1

2 DOTS entries:

DT.412801 DT.95333286

24/75 AceView cDNA sequences (see all 75):

S75615 L24553 NM_153292 NM_000625 S76479 AW445097 BM834810 U31511

AW297448 AI738789 AI797675 CD609259 BE073638 AI953734 AW449618 X73029

BE073577 AI991263 U05810 AF068236 CD609257 CD609216 U20141 CD609212

GeneLoc Exon Structure

3 Alternative Splicing Database (ASD) splice patterns (SP) for NOS2 About this scheme

ExUns:	1	^	2a	·	2b	^	3	^	4	^	5	^	6	^	7	^	8	^	9	^	10	^	11	^	12	^	13	^	14	^	15	^	16	^	17	^	18	^	19	^	20	^	21	^	22	^	23	^	24	^	25	^
SP1:							-
SP2:							-
SP3:													-

ExUns:	26	^	27	^	28
SP1:
SP2:
SP3:

ECgene alternative splicing isoforms for NOS2

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

NOS2 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: AATTGCATTT

About this image

NOS2 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

Stem Cell Differentiation: 1 LifeMap Cell

Name

Category

N2/LSB induced-cells (Generation of midbra...)

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See NOS2 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for NOS2

SOURCE GeneReport for Unigene cluster: Hs.709191

UniProtKB/Swiss-Prot: NOS2_HUMAN, P35228

Tissue specificity: Expressed in the liver, retina, bone cells and airway epithelial cells of the lung. Not expressed

in the platelets

SABiosciences Expression via Pathway-Focused PCR Arrays including NOS2 (see all 14):

Insulin Signaling Pathway in human mouse rat

G-Protein-Coupled Receptor Signaling PathwayFinder in human mouse rat

Oxidative Stress in human mouse rat

Nitric Oxide Signaling Pathway in human mouse rat

Skeletal Muscle: Myogenesis & Myopathy in human mouse rat

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for NOS2 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat NOS2
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat NOS2
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat NOS2

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NOS2

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the last universal common ancestor (LUCA).

Orthologs for NOS2 gene from 8/29 species (see all 29) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	NOS2¹	nitric oxide synthase 2, inducible	68.43(n) 70.46(a)		395807 NM_204961.1 NP_990292.1
lizard (Anolis carolinensis)	Reptilia	NOS2⁶ NDOR1⁶	--	64(a) 25(a)	1 ↔ 1 possible ortholog	GL343729.1(144450-178005) GL344097.1(1892-21914)
zebrafish (Danio rerio)	Actinopterygii	nos2b¹	nitric oxide synthase 2b, inducible	61.56(n) 60.63(a)		563654 NM_001113501.1 NP_001106973.1
fruit fly (Drosophila melanogaster)	Insecta	Nos⁶ CG13667⁶	--	37(a) 23(a)	1 ↔ 1 possible ortholog	2L(10804269-10838448) 3L(8398554-8400454)
worm (Caenorhabditis elegans)	Secernentea	fre-1⁶	Flavin REductase family member (fre-1)	21(a)	possible ortholog	V(20075890-20087702)
thale cress (Arabidopsis thaliana)	eudicotyledons	AT3G02280⁶ ATLFNR1⁶ (see all 5)	ferredoxin--NADP+ reductase (see all 5)	23(a) 19(a) (see all 5)	possible ortholog possible ortholog (see all 5)	3(453421-457841) 5(26450964-26453199)
rice (Oryza sativa)	Liliopsida	-- -- (see all 5)	NADPH reductase, putative, expressed ferredoxin--NADP reductase, chloroplast precursor,... (see all 5)	24(a) 19(a) (see all 5)	possible ortholog possible ortholog (see all 5)	1(30592390-30597478) 3(32559330-32562489)
E. coli (Escherichia coli)	Gamma proteobacteria	cysJ⁶	sulfite reductase, alpha subunit, flavoprotein	24(a)	possible ortholog	Chromosome(2888121-2889920)

ENSEMBL Gene Tree for NOS2 (if available)
TreeFam Gene Tree for NOS2 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for NOS2 gene

NOS3² POR² MTRR² NOS1²

2 SIMAP similar genes for NOS2 using alignment to 1 protein entry: NOS2_HUMAN:

NOS1 NOS3

NOS2 for paralogs About GeneDecksing

5/15 Pseudogenes.org Pseudogenes for NOS2 (see all 15)
PGOHUM00000247699 PGOHUM00000248028 PGOHUM00000250807 PGOHUM00000237000 PGOHUM00000237005

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

UniProtKB/Swiss-Prot: NOS2_HUMAN, P35228

Polymorphism: Note=Genetic variations in NOS2 are involved in resistance to malaria [MIM:611162]

SNP ID	Valid	Clinical significance	Chr 17 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs28944222^1,2	C,F,	--	22290292(-)	`CTTGGG/ATTTGG`	1	--	ds500¹		5		NS WA	244
rs28944221^1,2	C,F,	--	22290346(-)	`CGTGTC/TGAGGC`	1	--	ds500¹		6		NS WA	246
rs28944220^1,2	C,F,	--	22290469(-)	`TGTTTC/TGAGGA`	1	--	ds500¹		5		NS WA	244
rs28944219^1,2	C	--	22290474(-)	`GCCAGT/CGTTTC`	1	--	ds500¹		4		NS	126
rs28944218^1,2	C,F,	--	22290650(-)	`CGACAG/AAGGGA`	1	--	ds500¹		6		NS WA	256
rs28944217^1,2	C,	--	22290803(-)	`GCCACT/CTGGGT`	1	--	ut3¹ ese³		4		NS	138
rs144004051^1,2	C,	--	22290865(+)	`TGTACA/GCAAGG`	1	--	ut3¹		0	--	--	--	--
rs28944216^1,2	C,	--	22290891(-)	`CTATCG/ACACCA`	1	--	ut3¹ ese³		7		NS NA	572
rs28944215^1,2	C,	--	22290894(-)	`GTGCTA/GTCGCA`	1	--	ut3¹		5		NS	568
rs28944214^1,2	C,F,H,	--	22290942(-)	`AAGATG/AGAACT`	1	--	ut3¹		18		NS EA NA	2162

HapMap Linkage Disequilibrium report for NOS2 (26083792 - 26127555 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 3 variations for NOS2
3 CNVs: 4029 30820 72853
Human Gene Mutation Database (HGMD): NOS2

Locus Specific Mutation Databases (LSDB): NOS2

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing NOS2

DNA2.0 Custom Variant and Variant Library Synthesis for NOS2

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

NOS2 for disorders           About GeneDecksing

OMIM gene information: 163730
OMIM disorders: 145500  611162
20/396 diseases for NOS2 (see all 396):    About MalaCards

smith-magenis syndrome spinal cord injury internal hemorrhoid relapsing-remitting multiple sclerosis

periapical granuloma malignant fibrous histiocytoma toxic epidermal necrolysis cytokine receptor deficiency

stevens-johnson syndrome fibrous histiocytoma middle ear cholesteatoma pityriasis lichenoides

aids dementia complex guillain-barre syndrome resting heart rate sudden infant death syndrome

end stage renal failure migraine without aura focal segmental glomerulosclerosis age related macular degeneration

3 diseases from the University of Copenhagen DISEASES database for NOS2:

Vascular disease Gastrointestinal system disease Arthritis

10/96 Novoseek disease relationships for NOS2 gene (see all 96) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
inflammation	76.7	531	14657339 (3), 17449036 (3), 16537027 (3), 12613978 (3) (see all 99)
necrosis	75.9	590	16827641 (4), 17452936 (3), 9856818 (3), 10713108 (3) (see all 99)
tumors	64.1	1265	11156233 (6), 17980097 (6), 16557582 (5), 20338478 (5) (see all 99)
shock septic	63.8	96	7536056 (4), 12594864 (3), 14654318 (3), 10791377 (3) (see all 58)
sepsis	54.4	152	12016107 (5), 17997414 (4), 12594864 (3), 10669117 (3) (see all 72)
atherosclerosis	51.8	77	8683942 (3), 10073969 (3), 10334927 (2), 11139364 (2) (see all 47)
neurodegenerative diseases	50.5	18	16144552 (1), 7523410 (1), 11246231 (1), 16807879 (1) (see all 11)
inflammatory bowel diseases	46.6	44	17955236 (2), 12792224 (2), 10102942 (1), 10630438 (1) (see all 28)
cell damage	46.4	28	11218753 (2), 9377819 (1), 11139364 (1), 11488434 (1) (see all 22)
ischemia	46.1	102	15327760 (4), 16154689 (4), 11708836 (3), 8787213 (3) (see all 61)

Genetic Association Database (GAD): NOS2
Human Genome Epidemiology (HuGE) Navigator: NOS2 (192 documents)

Export disorders for NOS2 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for NOS2 gene, integrated from 9 sources (see all 4058):
(articles sorted by number of sources associating them with NOS2)

Utopia: connect your pdf to the dynamic
world of online information

Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. (PubMed id 7682706)^{1, 2, 3, 9} Geller D.A....Billiar T.R. (1993)
A new NOS2 promoter polymorphism associated with increased nitric oxide production and protection from severe malaria in Tanzanian and Kenyan children. (PubMed id 12433515)^{1, 2, 4, 9} Hobbs M.R....Weinberg J.B. (2002)
Dedifferentiated human ventricular cardiac myocytes express inducible nitric oxide synthase mRNA but not protein in response to IL-1, TNF, IFNgamma, and LPS. (PubMed id 9160867)^{1, 2, 9} Luss H.... Billiar T.R. (1997)
Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase. (PubMed id 10409685)^{1, 2, 9} Li H.... Poulos T.L. (1999)
Cloning and functional expression of human inducible nitric oxide synthase (NOS) cDNA from a glioblastoma cell line A-172. (PubMed id 7531687)^{1, 2, 9} Hokari A.... Esumi H. (1994)
Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumor cell line. (PubMed id 7692964)^{1, 2, 9} Sherman P.A.... Wood E.R. (1993)
Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output. (PubMed id 12080081)^{1, 2} Glynne P.A.... Evans T.J. (2002)
Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation. (PubMed id 10074942)^{1, 2} Fischmann T.O....Weber P.C. (1999)
Continuous nitric oxide synthesis by inducible nitric oxide synthase in normal human airway epithelium in vivo. (PubMed id 7544004)^{1, 2} Guo F.H....Erzurum S.C. (1995)
Three members of the nitric oxide synthase II gene family (NOS2A, NOS2B, and NOS2C) colocalize to human chromosome 17. (PubMed id 7558036)^{1, 2} Bloch K.D.... Bloch D.B. (1995)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 4843	HGNC: 7873	AceView: NOS2A	Ensembl:ENSG00000007171	euGenes: HUgn4843
ECgene: NOS2	Kegg: 4843	H-InvDB: NOS2

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for NOS2	Pharmacogenomics, SNPs, Pathways
NIEHS-SNPs	http://egp.gs.washington.edu/data/nos2a/
Wikipedia	http://en.wikipedia.org/wiki/Nitric_oxide_synthase

Intellectual Property for NOS2 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for NOS2 gene:
Search GeneIP for patents involving NOS2

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
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nitric oxide synthase 2, inducible

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NOS2 Gene

nitric oxide synthase 2, inducible

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