• Gene id: 4843

Gene Summary

• Gene Symbol: NOS2   Gene   UCSC   Ensembl
• Aliases: HEP-NOS, INOS, NOS, NOS2A
• Gene name: nitric oxide synthase 2
• Alternate names: nitric oxide synthase, inducible, 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,
• Gene location: 17q11.2 (31414776: 31334319)     Exons: 37     NC_000002.12
• Gene summary(Entrez): 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 inducibl
• OMIM: 163730

SNPs

rs10459953

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000017.11   g.27800492C>A
NC_000017.11   g.27800492C>G
NC_000017.11   g.27800492C>T
NC_000017.10   g.26127518C>A
NC_000017.10   g.26127518C>G
NC_000017.10   g.26127518C>T
NG_011470.1   g.5038G>T
NG_011470.1   g.5038G>C
NG_011470.1   g.5038G>A
NM_000625.4   c.-227G>T
  

rs2297518

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000017.11   g.27769571G>A
NC_000017.10   g.26096597G>A
NG_011470.1   g.35959C>T
NM_000625.4   c.1823C>T
NP_000616.3   p.Ser608Leu|SEQ=[G/A]|GENE=NOS2

Protein Summary

• Protein general information: P35228  
  • Name: Nitric oxide synthase, inducible (EC 1.14.13.39) (Hepatocyte NOS) (HEP NOS) (Inducible NO synthase) (Inducible NOS) (iNOS) (NOS type II) (Peptidyl cysteine S nitrosylase NOS2)
  • Length: 1153  
  • Mass: 131,117
• Sequence:

  MACPWKFLFKTKFHQYAMNGEKDINNNVEKAPCATSSPVTQDDLQYHNLSKQQNESPQPLVETGKKSPESLVKLD
  ATPLSSPRHVRIKNWGSGMTFQDTLHHKAKGILTCRSKSCLGSIMTPKSLTRGPRDKPTPPDELLPQAIEFVNQY
  YGSFKEAKIEEHLARVEAVTKEIETTGTYQLTGDELIFATKQAWRNAPRCIGRIQWSNLQVFDARSCSTAREMFE
  HICRHVRYSTNNGNIRSAITVFPQRSDGKHDFRVWNAQLIRYAGYQMPDGSIRGDPANVEFTQLCIDLGWKPKYG
  RFDVVPLVLQANGRDPELFEIPPDLVLEVAMEHPKYEWFRELELKWYALPAVANMLLEVGGLEFPGCPFNGWYMG
  TEIGVRDFCDVQRYNILEEVGRRMGLETHKLASLWKDQAVVEINIAVLHSFQKQNVTIMDHHSAAESFMKYMQNE
  YRSRGGCPADWIWLVPPMSGSITPVFHQEMLNYVLSPFYYYQVEAWKTHVWQDEKRRPKRREIPLKVLVKAVLFA
  CMLMRKTMASRVRVTILFATETGKSEALAWDLGALFSCAFNPKVVCMDKYRLSCLEEERLLLVVTSTFGNGDCPG
  NGEKLKKSLFMLKELNNKFRYAVFGLGSSMYPRFCAFAHDIDQKLSHLGASQLTPMGEGDELSGQEDAFRSWAVQ
  TFKAACETFDVRGKQHIQIPKLYTSNVTWDPHHYRLVQDSQPLDLSKALSSMHAKNVFTMRLKSRQNLQSPTSSR
  ATILVELSCEDGQGLNYLPGEHLGVCPGNQPALVQGILERVVDGPTPHQTVRLEALDESGSYWVSDKRLPPCSLS
  QALTYFLDITTPPTQLLLQKLAQVATEEPERQRLEALCQPSEYSKWKFTNSPTFLEVLEEFPSLRVSAGFLLSQL
  PILKPRFYSISSSRDHTPTEIHLTVAVVTYHTRDGQGPLHHGVCSTWLNSLKPQDPVPCFVRNASGFHLPEDPSH
  PCILIGPGTGIAPFRSFWQQRLHDSQHKGVRGGRMTLVFGCRRPDEDHIYQEEMLEMAQKGVLHAVHTAYSRLPG
  KPKVYVQDILRQQLASEVLRVLHKEPGHLYVCGDVRMARDVAHTLKQLVAAKLKLNEEQVEDYFFQLKSQKRYHE
  DIFGAVFPYEAKKDRVAVQPSSLEMSAL

• Structural information:
  • Protein Domains: Flavodoxin-like. (539-677)
    FAD-binding (730-970)
  • Interpro: IPR003097  IPR017927  IPR001094  IPR008254  IPR001709   IPR029039  IPR023173  IPR012144  IPR004030  IPR036119  IPR001433  IPR017938  
  • Prosite: PS51384 PS50902 PS60001
  • PDB: 1NSI 2LL6 2NSI 3E7G 3EJ8 3HR4 4CX7 4NOS 5TP6 5XN3
  • PDBsum: 1NSI 2LL6 2NSI 3E7G 3EJ8 3HR4 4CX7 4NOS 5TP6 5XN3
  • DIP: 59359
  • STRING: ENSP00000327251
• Other Databases: GeneCards:  NOS2  Malacards:  NOS2

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0001666	response to hypoxia	IEA	biological process
GO:0001912	positive regulation of leukocyte mediated cytotoxicity	TAS	biological process
GO:0002227	innate immune response in mucosa	NAS	biological process
GO:0004517	nitric-oxide synthase activity	IDA	molecular function
GO:0004517	nitric-oxide synthase activity	IDA	molecular function
GO:0004517	nitric-oxide synthase activity	TAS	molecular function
GO:0005102	receptor binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005516	calmodulin binding	IEA	molecular function
GO:0005622	intracellular	IDA	cellular component
GO:0005634	nucleus	ISS	cellular component
GO:0005737	cytoplasm	IDA	cellular component
GO:0005737	cytoplasm	IDA	cellular component
GO:0005777	peroxisome	IDA	cellular component
GO:0005829	cytosol	IMP	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0006527	arginine catabolic process	IDA	biological process
GO:0006801	superoxide metabolic process	ISS	biological process
GO:0006809	nitric oxide biosynthetic process	IDA	biological process
GO:0006809	nitric oxide biosynthetic process	IDA	biological process
GO:0007263	nitric oxide mediated signal transduction	IBA	biological process
GO:0007623	circadian rhythm	IEA	biological process
GO:0009617	response to bacterium	NAS	biological process
GO:0010181	FMN binding	ISS	molecular function
GO:0010629	negative regulation of gene expression	IGI	biological process
GO:0018119	peptidyl-cysteine S-nitrosylation	ISS	biological process
GO:0020037	heme binding	ISS	molecular function
GO:0030863	cortical cytoskeleton	IEA	cellular component
GO:0031284	positive regulation of guanylate cyclase activity	IBA	biological process
GO:0032310	prostaglandin secretion	IDA	biological process
GO:0034617	tetrahydrobiopterin binding	ISS	molecular function
GO:0034618	arginine binding	ISS	molecular function
GO:0035690	cellular response to drug	IEA	biological process
GO:0042127	regulation of cell proliferation	IEA	biological process
GO:0042177	negative regulation of protein catabolic process	IEA	biological process
GO:0042742	defense response to bacterium	ISS	biological process
GO:0042742	defense response to bacterium	IMP	biological process
GO:0042803	protein homodimerization activity	ISS	molecular function
GO:0043457	regulation of cellular respiration	TAS	biological process
GO:0045454	cell redox homeostasis	TAS	biological process
GO:0045776	negative regulation of blood pressure	IBA	biological process
GO:0045909	positive regulation of vasodilation	IBA	biological process
GO:0046872	metal ion binding	IEA	molecular function
GO:0048471	perinuclear region of cytoplasm	IEA	cellular component
GO:0050660	flavin adenine dinucleotide binding	ISS	molecular function
GO:0050661	NADP binding	TAS	molecular function
GO:0050796	regulation of insulin secretion	IMP	biological process
GO:0050829	defense response to Gram-negative bacterium	NAS	biological process
GO:0051712	positive regulation of killing of cells of other organism	IMP	biological process
GO:0055114	oxidation-reduction process	IEA	biological process
GO:0071222	cellular response to lipopolysaccharide	IEA	biological process
GO:0071346	cellular response to interferon-gamma	IEA	biological process
GO:0072604	interleukin-6 secretion	IDA	biological process
GO:0072606	interleukin-8 secretion	IDA	biological process
GO:1900015	regulation of cytokine production involved in inflammatory response	IDA	biological process
GO:0001666	response to hypoxia	IEA	biological process
GO:0001912	positive regulation of leukocyte mediated cytotoxicity	TAS	biological process
GO:0002227	innate immune response in mucosa	NAS	biological process
GO:0004517	nitric-oxide synthase activity	IEA	molecular function
GO:0004517	nitric-oxide synthase activity	IEA	molecular function
GO:0004517	nitric-oxide synthase activity	IEA	molecular function
GO:0004517	nitric-oxide synthase activity	IDA	molecular function
GO:0004517	nitric-oxide synthase activity	IDA	molecular function
GO:0004517	nitric-oxide synthase activity	TAS	molecular function
GO:0005102	receptor binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005516	calmodulin binding	IEA	molecular function
GO:0005622	intracellular	IDA	cellular component
GO:0005634	nucleus	ISS	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0005737	cytoplasm	IDA	cellular component
GO:0005737	cytoplasm	IDA	cellular component
GO:0005777	peroxisome	IDA	cellular component
GO:0005829	cytosol	IMP	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0006527	arginine catabolic process	IEA	biological process
GO:0006527	arginine catabolic process	IDA	biological process
GO:0006801	superoxide metabolic process	IEA	biological process
GO:0006801	superoxide metabolic process	ISS	biological process
GO:0006809	nitric oxide biosynthetic process	IEA	biological process
GO:0006809	nitric oxide biosynthetic process	IEA	biological process
GO:0006809	nitric oxide biosynthetic process	IDA	biological process
GO:0006809	nitric oxide biosynthetic process	IDA	biological process
GO:0007263	nitric oxide mediated signal transduction	IBA	biological process
GO:0007623	circadian rhythm	IEA	biological process
GO:0009617	response to bacterium	NAS	biological process
GO:0010181	FMN binding	IEA	molecular function
GO:0010181	FMN binding	IEA	molecular function
GO:0010181	FMN binding	ISS	molecular function
GO:0010629	negative regulation of gene expression	IEA	biological process
GO:0010629	negative regulation of gene expression	IGI	biological process
GO:0016491	oxidoreductase activity	IEA	molecular function
GO:0016491	oxidoreductase activity	IEA	molecular function
GO:0018119	peptidyl-cysteine S-nitrosylation	IEA	biological process
GO:0018119	peptidyl-cysteine S-nitrosylation	ISS	biological process
GO:0020037	heme binding	IEA	molecular function
GO:0020037	heme binding	ISS	molecular function
GO:0030863	cortical cytoskeleton	IEA	cellular component
GO:0031284	positive regulation of guanylate cyclase activity	IBA	biological process
GO:0032310	prostaglandin secretion	IDA	biological process
GO:0032496	response to lipopolysaccharide	IEA	biological process
GO:0034617	tetrahydrobiopterin binding	IEA	molecular function
GO:0034617	tetrahydrobiopterin binding	ISS	molecular function
GO:0034618	arginine binding	IEA	molecular function
GO:0034618	arginine binding	ISS	molecular function
GO:0035690	cellular response to drug	IEA	biological process
GO:0042127	regulation of cell proliferation	IEA	biological process
GO:0042177	negative regulation of protein catabolic process	IEA	biological process
GO:0042742	defense response to bacterium	IEA	biological process
GO:0042742	defense response to bacterium	ISS	biological process
GO:0042742	defense response to bacterium	IMP	biological process
GO:0042803	protein homodimerization activity	IEA	molecular function
GO:0042803	protein homodimerization activity	ISS	molecular function
GO:0043457	regulation of cellular respiration	TAS	biological process
GO:0045454	cell redox homeostasis	TAS	biological process
GO:0045776	negative regulation of blood pressure	IBA	biological process
GO:0045909	positive regulation of vasodilation	IBA	biological process
GO:0046872	metal ion binding	IEA	molecular function
GO:0048471	perinuclear region of cytoplasm	IEA	cellular component
GO:0050660	flavin adenine dinucleotide binding	IEA	molecular function
GO:0050660	flavin adenine dinucleotide binding	ISS	molecular function
GO:0050661	NADP binding	TAS	molecular function
GO:0050796	regulation of insulin secretion	IMP	biological process
GO:0050829	defense response to Gram-negative bacterium	NAS	biological process
GO:0051712	positive regulation of killing of cells of other organism	IMP	biological process
GO:0055114	oxidation-reduction process	IEA	biological process
GO:0055114	oxidation-reduction process	IEA	biological process
GO:0071222	cellular response to lipopolysaccharide	IEA	biological process
GO:0071346	cellular response to interferon-gamma	IEA	biological process
GO:0072604	interleukin-6 secretion	IDA	biological process
GO:0072606	interleukin-8 secretion	IDA	biological process
GO:1900015	regulation of cytokine production involved in inflammatory response	IDA	biological process
GO:0001912	positive regulation of leukocyte mediated cytotoxicity	TAS	biological process
GO:0002227	innate immune response in mucosa	NAS	biological process
GO:0004517	nitric-oxide synthase activity	IDA	molecular function
GO:0004517	nitric-oxide synthase activity	IDA	molecular function
GO:0004517	nitric-oxide synthase activity	TAS	molecular function
GO:0005102	receptor binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005622	intracellular	IDA	cellular component
GO:0005634	nucleus	ISS	cellular component
GO:0005737	cytoplasm	IDA	cellular component
GO:0005737	cytoplasm	IDA	cellular component
GO:0005777	peroxisome	IDA	cellular component
GO:0005829	cytosol	IMP	cellular component
GO:0005829	cytosol	TAS	cellular component
GO:0006527	arginine catabolic process	IDA	biological process
GO:0006801	superoxide metabolic process	ISS	biological process
GO:0006809	nitric oxide biosynthetic process	IDA	biological process
GO:0006809	nitric oxide biosynthetic process	IDA	biological process
GO:0007263	nitric oxide mediated signal transduction	IBA	biological process
GO:0009617	response to bacterium	NAS	biological process
GO:0010181	FMN binding	ISS	molecular function
GO:0010629	negative regulation of gene expression	IGI	biological process
GO:0018119	peptidyl-cysteine S-nitrosylation	ISS	biological process
GO:0020037	heme binding	ISS	molecular function
GO:0031284	positive regulation of guanylate cyclase activity	IBA	biological process
GO:0032310	prostaglandin secretion	IDA	biological process
GO:0034617	tetrahydrobiopterin binding	ISS	molecular function
GO:0034618	arginine binding	ISS	molecular function
GO:0042742	defense response to bacterium	ISS	biological process
GO:0042742	defense response to bacterium	IMP	biological process
GO:0042803	protein homodimerization activity	ISS	molecular function
GO:0043457	regulation of cellular respiration	TAS	biological process
GO:0045454	cell redox homeostasis	TAS	biological process
GO:0045776	negative regulation of blood pressure	IBA	biological process
GO:0045909	positive regulation of vasodilation	IBA	biological process
GO:0050660	flavin adenine dinucleotide binding	ISS	molecular function
GO:0050661	NADP binding	TAS	molecular function
GO:0050796	regulation of insulin secretion	IMP	biological process
GO:0050829	defense response to Gram-negative bacterium	NAS	biological process
GO:0051712	positive regulation of killing of cells of other organism	IMP	biological process
GO:0072604	interleukin-6 secretion	IDA	biological process
GO:0072606	interleukin-8 secretion	IDA	biological process
GO:1900015	regulation of cytokine production involved in inflammatory response	IDA	biological process

KEGG pathways

Pathway id	Pathway name
hsa01100	Metabolic pathways
hsa04066	HIF-1 signaling pathway
hsa04020	Calcium signaling pathway
hsa04146	Peroxisome
hsa04926	Relaxin signaling pathway
hsa05200	Pathways in cancer
hsa05222	Small cell lung cancer
hsa05132	Salmonella infection
hsa05133	Pertussis
hsa05152	Tuberculosis
hsa05146	Amoebiasis
hsa05145	Toxoplasmosis
hsa05140	Leishmaniasis
hsa05142	Chagas disease

Diseases

Associated diseases	References
Cancer (adenocarcinoma)	GAD: 18349295
Cancer (bladder)	GAD: 17482959
Cancer (brain)	GAD: 19505917
Cancer (cervical)	GAD: 17404026
Cancer (colorectal)	GAD: 15922861
Cancer (epithelial ovarian)	GAD: 19064572
Cancer (esophageal)	GAD: 20453000
Cancer (glaucoma)	GAD: 16288199
Cancer (leukemia)	GAD: 19074885
Cancer (lung)	GAD: 19773451
Cancer (lymphoma)	GAD: 17149600
Cancer (melanoma)	GAD: 17328085
Cancer (meningeal)	GAD: 20406964
Cancer (non-Hodgkin lymphoma)	GAD: 16543247
Cancer (prostate)	GAD: 18398039
Cancer (stomach)	GAD: 15617837
Cancer (esophageal)	KEGG: H00017
Cancer (breast)	GAD: 20711808
Atherosclerosis	GAD: 14636285
Brain ischemia	GAD: 19131662
Cardiovascular disease	GAD: 11294696
Hypertension	GAD: 11702222
Brain infarction	GAD: 20886685
Spinal dysraphism	GAD: 19161160
Cystic fibrosis	GAD: 20028935
Achalasia	GAD: 16848803
Esophageal achalasia	GAD: 19337240
Macular degeneration	GAD: 20374233
Beta-thalassemia	GAD: 19103526
Henoch-Schonlein purpura	GAD: 15940772
Kawasaki disease	GAD: 12709136
Asthma	GAD: 19996333
Atopy	GAD: 11692109
Behcet's disease	GAD: 17296902
Chronic ulcerative colitis	GAD: 17955236
Crohn's disease	GAD: 16634870
Rheumatoid arthritis	GAD: 12140750
Rheumatoid arthritis	GAD: 15226517
Multiple sclerosis	GAD: 11525805
Psoriasis	GAD: 20953189
Systemic lupus erythematosus (SLE)	GAD: 12509623
Systemic lupus erythematosus (SLE)	GAD: 12509623
Albuminuria	GAD: 21054877
Diabetes	GAD: 19479237
Osteomyelitis	GAD: 16889995
Migraine disorder	GAD: 19559392
Giant cell arteritis	GAD: 16265698
Guillain-Barre syndrome	GAD: 17761309
Alzheimer's disease	GAD: 19141999
Parkinson disease	GAD: 12490535
Cerebral palsy	GAD: 18977990
Cirrhosis	GAD: 15583989
Autism	GAD: 18563708
Psychological disorders	GAD: 19086053
Several psychiatric disorders	GAD: 19086053
Chronic renal failure	GAD: 21085059
Chorioamnionitis	GAD: 20452482
Preeclampsia	GAD: 17991113
Premature ovarian insufficiency (POI)	INFBASE: 23176758
Adenomyosis	INFBASE: 11451019
Ectopic endometriosis	INFBASE: 11451019
Ectopic endometriosis	INFBASE: 11268729
Adenomyosis	INFBASE: 11268729
Endometriosis-associated infertility	INFBASE: 16580392
Female infertility	INFBASE: 23935397
Oocyte competence	INFBASE: 24607880
Polycystic ovary syndrome (PCOS)	INFBASE: 23900753
Unexplained infertility	INFBASE: 16139338
Varicocele	MIK: 17346270
Varicocele	MIK: 18572859
Azoospermia	MIK: 22050043
Congenital bilateral absence of the vas deferens (CBAVD)	MIK: 11445485
Maturation arrest	MIK: 15804870
Oligoasthenoteratozoospermia	MIK: 25744373
Male factor infertility	MIK: 16683572
Oligoasthenozoospermia	MIK: 24522616
Sperm function	MIK: 20684956
Spermatogenesis defects	MIK: 17346270
Hypospermatogenesis	MIK: 15804870
Sertoli cell only syndrome (SCOS)	MIK: 15804870
Chronic obstructive pulmonary disease (COPD)	GAD: 19625176
Erythema	GAD: 19225544
Azoospermia	MIK: 22050043
Congenital bilateral absence of the vas deferens (CBAVD)	MIK: 11445485
Cryptorchidism	MIK: 28606200
Hypospermatogenesis	MIK: 15804870
Maturation arrest	MIK: 15804870
Sertoli cell only syndrome	MIK: 15804870
Oligoasthenozoospermia	MIK: 24522616
Male infertility	MIK: 17511668
Spermatogenic defects	MIK: 20684956
Oligoasthenoteratozoospermia	MIK: 25744373
Varicocele	MIK: 17346270
Unexplained infertility	MIK: 25753583

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
20684956	Male infertility, sperm function				Male infertility
22050043	Azoospermia			20 diopathic infertile men presenting nonobstructive azoospermia	Male infertility
17346270	Spermatogenesis, varicocele, Male infertility			32 (27 men who had a left varicocelectomy, 5 with 'normal' spermatogenesis (controls) who had scrotal surgery)	Male infertility
15804870	Hypospermatogenesis, maturation arrest, Sertoli cell only syndrome			80 patients with infertility	Male infertility
11445485	Congenital bilateral absence of the vas deferens (CBAVD)				Male infertility
17511668	Male infertility				Male infertility
25744373	Oligoasthenoteratozoospermic (OAT)	eNOS G894T and T786C genotypes		300 (80 healthy fertile males, 220 infertile OAT men)	Male infertility	NOS
24522616	Idiopathic oligoasthenozoospermia	AR (CAG repeat length), NOS (Glu298Asp variant)			Male infertility
16683572	Male infertility			80 (40 infertile patients with positive AsAb in seminal plasma as experimental group, 40 fertile men as control group)	Male infertility	NOS SOD
28606200	Cryptorchidism			Monozgotic twins (1 control, I cwith cryptorchidism)	Male infertility	MeDIP-Seq
25753583	Unexplained infertility			46 (17 fertile men, 29 male patients)	Male infertility	Microarray