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Protein

Nitric oxide synthase, inducible

Gene

NOS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM.1 Publication

Catalytic activityi

2 L-arginine + 3 NADPH + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O.

Cofactori

Protein has several cofactor binding sites:
  • hemeBy similarity
  • FADBy similarityNote: Binds 1 FAD.By similarity
  • FMNBy similarityNote: Binds 1 FMN.By similarity
  • 5,6,7,8-tetrahydrobiopterinBy similarityNote: Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.By similarity

Enzyme regulationi

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi110 – 1101Zinc
Metal bindingi115 – 1151Zinc
Metal bindingi200 – 2001Iron (heme axial ligand)

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi623 – 65432FMNPROSITE-ProRule annotationAdd
BLAST
Nucleotide bindingi767 – 77812FADBy similarityAdd
BLAST
Nucleotide bindingi903 – 91311FADBy similarityAdd
BLAST
Nucleotide bindingi978 – 99619NADPBy similarityAdd
BLAST
Nucleotide bindingi1076 – 109116NADPBy similarityAdd
BLAST

GO - Molecular functioni

  • arginine binding Source: BHF-UCL
  • flavin adenine dinucleotide binding Source: BHF-UCL
  • FMN binding Source: BHF-UCL
  • heme binding Source: BHF-UCL
  • iron ion binding Source: InterPro
  • NADP binding Source: BHF-UCL
  • NADPH-hemoprotein reductase activity Source: GO_Central
  • nitric-oxide synthase activity Source: UniProtKB
  • protein homodimerization activity Source: BHF-UCL
  • receptor binding Source: UniProtKB
  • tetrahydrobiopterin binding Source: BHF-UCL

GO - Biological processi

  • arginine catabolic process Source: BHF-UCL
  • blood coagulation Source: Reactome
  • cellular response to interferon-gamma Source: Ensembl
  • cellular response to lipopolysaccharide Source: Ensembl
  • circadian rhythm Source: Ensembl
  • defense response to bacterium Source: UniProtKB
  • defense response to Gram-negative bacterium Source: BHF-UCL
  • inflammatory response Source: GO_Central
  • innate immune response in mucosa Source: BHF-UCL
  • interaction with host Source: Reactome
  • negative regulation of blood pressure Source: GO_Central
  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of protein catabolic process Source: Ensembl
  • nitric oxide biosynthetic process Source: UniProtKB
  • nitric oxide mediated signal transduction Source: GO_Central
  • peptidyl-cysteine S-nitrosylation Source: UniProtKB
  • phagosome maturation Source: Reactome
  • positive regulation of guanylate cyclase activity Source: GO_Central
  • positive regulation of killing of cells of other organism Source: BHF-UCL
  • positive regulation of leukocyte mediated cytotoxicity Source: BHF-UCL
  • positive regulation of vasodilation Source: GO_Central
  • regulation of cell proliferation Source: Ensembl
  • regulation of cellular respiration Source: BHF-UCL
  • regulation of insulin secretion Source: BHF-UCL
  • response to bacterium Source: UniProtKB
  • response to hypoxia Source: Ensembl
  • superoxide metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

Calcium, Calmodulin-binding, FAD, Flavoprotein, FMN, Heme, Iron, Metal-binding, NADP, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:HS00205-MONOMER.
BRENDAi1.14.13.39. 2681.
ReactomeiREACT_121256. Phagosomal maturation (early endosomal stage).
REACT_23862. Nitric oxide stimulates guanylate cyclase.
SignaLinkiP35228.

Names & Taxonomyi

Protein namesi
Recommended name:
Nitric oxide synthase, inducible (EC:1.14.13.39)
Alternative name(s):
Hepatocyte NOS
Short name:
HEP-NOS
Inducible NO synthase
Short name:
Inducible NOS
Short name:
iNOS
NOS type II
Peptidyl-cysteine S-nitrosylase NOS2
Gene namesi
Name:NOS2
Synonyms:NOS2A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:7873. NOS2.

Subcellular locationi

GO - Cellular componenti

  • cortical cytoskeleton Source: Ensembl
  • cytoplasm Source: UniProtKB
  • cytosol Source: BHF-UCL
  • intracellular Source: BHF-UCL
  • nucleus Source: BHF-UCL
  • perinuclear region of cytoplasm Source: Ensembl
  • peroxisome Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

MIMi611162. phenotype.
PharmGKBiPA164724093.

Chemistry

DrugBankiDB01234. Dexamethasone.
DB00997. Doxorubicin.
DB00125. L-Arginine.
DB00155. L-Citrulline.
DB01110. Miconazole.
DB08814. Triflusal.

Polymorphism and mutation databases

BioMutaiNOS2.
DMDMi1352513.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11531153Nitric oxide synthase, induciblePRO_0000170930Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei234 – 2341Phosphoserine; by PKASequence Analysis
Modified residuei578 – 5781Phosphoserine; by PKASequence Analysis
Modified residuei892 – 8921Phosphoserine; by PKASequence Analysis

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP35228.
PRIDEiP35228.

PTM databases

PhosphoSiteiP35228.

Expressioni

Tissue specificityi

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

Inductioni

By endotoxins and cytokines. Induced by IFNG/IFN-gamma acting synergistically with bacterial lipopolysaccharides (LPS), TNF or IL1B/interleukin-1 beta (PubMed:7528267). Down-regulated by zinc due to inhibition of NF-kappa-B transactivation activity (PubMed:25180171). By oxidatively-modified low-densitity lipoprotein (LDL(ox)) (PubMed:25417112).3 Publications

Gene expression databases

BgeeiP35228.
CleanExiHS_NOS2.
GenevisibleiP35228. HS.

Organism-specific databases

HPAiCAB002014.

Interactioni

Subunit structurei

Homodimer. Binds SLC9A3R1. Interacts with GAPDH; induced by oxidatively-modified low-densitity lipoprotein (LDL(ox)). Interacts with S100A8 and S100A9 to form the iNOS-S100A8/9 transnitrosylase complex.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
GAPDHP044068EBI-6662224,EBI-354056

Protein-protein interaction databases

BioGridi110906. 146 interactions.
DIPiDIP-59359N.
IntActiP35228. 4 interactions.
STRINGi9606.ENSP00000327251.

Structurei

Secondary structure

1
1153
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi85 – 895Combined sources
Turni90 – 923Combined sources
Beta strandi95 – 984Combined sources
Helixi100 – 1034Combined sources
Beta strandi104 – 1063Combined sources
Helixi123 – 1253Combined sources
Helixi136 – 15217Combined sources
Beta strandi154 – 1563Combined sources
Helixi159 – 17517Combined sources
Helixi183 – 19513Combined sources
Helixi203 – 2053Combined sources
Beta strandi210 – 2134Combined sources
Helixi220 – 23516Combined sources
Helixi236 – 2383Combined sources
Beta strandi243 – 2464Combined sources
Beta strandi251 – 2555Combined sources
Beta strandi261 – 2655Combined sources
Beta strandi269 – 2713Combined sources
Beta strandi277 – 2793Combined sources
Helixi281 – 2833Combined sources
Helixi284 – 2929Combined sources
Beta strandi307 – 3104Combined sources
Beta strandi317 – 3193Combined sources
Helixi323 – 3253Combined sources
Beta strandi328 – 3303Combined sources
Helixi337 – 3426Combined sources
Beta strandi345 – 3484Combined sources
Beta strandi356 – 3594Combined sources
Beta strandi362 – 3654Combined sources
Helixi375 – 3795Combined sources
Helixi381 – 3844Combined sources
Turni386 – 3894Combined sources
Helixi392 – 3998Combined sources
Helixi406 – 4083Combined sources
Helixi410 – 42819Combined sources
Helixi436 – 45419Combined sources
Helixi461 – 4644Combined sources
Beta strandi467 – 4693Combined sources
Helixi470 – 4723Combined sources
Helixi474 – 4774Combined sources
Beta strandi486 – 4916Combined sources
Helixi495 – 4984Combined sources
Helixi515 – 53420Combined sources
Beta strandi538 – 5447Combined sources
Beta strandi546 – 5483Combined sources
Helixi549 – 56113Combined sources
Turni562 – 5643Combined sources
Beta strandi565 – 5717Combined sources
Helixi572 – 5743Combined sources
Helixi577 – 5815Combined sources
Beta strandi584 – 5918Combined sources
Turni594 – 5963Combined sources
Helixi600 – 6023Combined sources
Helixi603 – 6119Combined sources
Beta strandi620 – 6278Combined sources
Beta strandi631 – 6333Combined sources
Helixi636 – 64813Combined sources
Beta strandi651 – 6544Combined sources
Beta strandi657 – 6604Combined sources
Helixi665 – 68319Combined sources
Helixi689 – 6913Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NSIX-ray2.55A/B/C/D74-504[»]
2LL6NMR-B515-531[»]
2NSIX-ray3.00A/B/C/D74-504[»]
3E7GX-ray2.20A/B/C/D82-505[»]
3EJ8X-ray2.55A/B/C/D82-505[»]
3HR4X-ray2.50A/C/E/G503-715[»]
4CX7X-ray3.16A/B/C/D74-504[»]
4NOSX-ray2.25A/B/C/D82-508[»]
ProteinModelPortaliP35228.
SMRiP35228. Positions 83-505, 511-699.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35228.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini539 – 677139Flavodoxin-likePROSITE-ProRule annotationAdd
BLAST
Domaini730 – 970241FAD-binding FR-typePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni509 – 52921Calmodulin-bindingSequence AnalysisAdd
BLAST

Sequence similaritiesi

Belongs to the NOS family.Curated
Contains 1 FAD-binding FR-type domain.PROSITE-ProRule annotation
Contains 1 flavodoxin-like domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG4362.
GeneTreeiENSGT00620000087711.
HOVERGENiHBG000159.
InParanoidiP35228.
KOiK13241.
OMAiKFTNSPT.
OrthoDBiEOG79SDW7.
PhylomeDBiP35228.
TreeFamiTF324410.

Family and domain databases

Gene3Di1.20.990.10. 1 hit.
3.40.50.360. 1 hit.
3.90.340.10. 1 hit.
InterProiIPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR004030. NOS_N.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamiPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
PF02898. NO_synthase. 1 hit.
[Graphical view]
PRINTSiPR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMiSSF52218. SSF52218. 1 hit.
SSF56512. SSF56512. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
PS60001. NOS. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P35228-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MACPWKFLFK TKFHQYAMNG EKDINNNVEK APCATSSPVT QDDLQYHNLS
60 70 80 90 100
KQQNESPQPL VETGKKSPES LVKLDATPLS SPRHVRIKNW GSGMTFQDTL
110 120 130 140 150
HHKAKGILTC RSKSCLGSIM TPKSLTRGPR DKPTPPDELL PQAIEFVNQY
160 170 180 190 200
YGSFKEAKIE EHLARVEAVT KEIETTGTYQ LTGDELIFAT KQAWRNAPRC
210 220 230 240 250
IGRIQWSNLQ VFDARSCSTA REMFEHICRH VRYSTNNGNI RSAITVFPQR
260 270 280 290 300
SDGKHDFRVW NAQLIRYAGY QMPDGSIRGD PANVEFTQLC IDLGWKPKYG
310 320 330 340 350
RFDVVPLVLQ ANGRDPELFE IPPDLVLEVA MEHPKYEWFR ELELKWYALP
360 370 380 390 400
AVANMLLEVG GLEFPGCPFN GWYMGTEIGV RDFCDVQRYN ILEEVGRRMG
410 420 430 440 450
LETHKLASLW KDQAVVEINI AVLHSFQKQN VTIMDHHSAA ESFMKYMQNE
460 470 480 490 500
YRSRGGCPAD WIWLVPPMSG SITPVFHQEM LNYVLSPFYY YQVEAWKTHV
510 520 530 540 550
WQDEKRRPKR REIPLKVLVK AVLFACMLMR KTMASRVRVT ILFATETGKS
560 570 580 590 600
EALAWDLGAL FSCAFNPKVV CMDKYRLSCL EEERLLLVVT STFGNGDCPG
610 620 630 640 650
NGEKLKKSLF MLKELNNKFR YAVFGLGSSM YPRFCAFAHD IDQKLSHLGA
660 670 680 690 700
SQLTPMGEGD ELSGQEDAFR SWAVQTFKAA CETFDVRGKQ HIQIPKLYTS
710 720 730 740 750
NVTWDPHHYR LVQDSQPLDL SKALSSMHAK NVFTMRLKSR QNLQSPTSSR
760 770 780 790 800
ATILVELSCE DGQGLNYLPG EHLGVCPGNQ PALVQGILER VVDGPTPHQT
810 820 830 840 850
VRLEALDESG SYWVSDKRLP PCSLSQALTY FLDITTPPTQ LLLQKLAQVA
860 870 880 890 900
TEEPERQRLE ALCQPSEYSK WKFTNSPTFL EVLEEFPSLR VSAGFLLSQL
910 920 930 940 950
PILKPRFYSI SSSRDHTPTE IHLTVAVVTY HTRDGQGPLH HGVCSTWLNS
960 970 980 990 1000
LKPQDPVPCF VRNASGFHLP EDPSHPCILI GPGTGIAPFR SFWQQRLHDS
1010 1020 1030 1040 1050
QHKGVRGGRM TLVFGCRRPD EDHIYQEEML EMAQKGVLHA VHTAYSRLPG
1060 1070 1080 1090 1100
KPKVYVQDIL RQQLASEVLR VLHKEPGHLY VCGDVRMARD VAHTLKQLVA
1110 1120 1130 1140 1150
AKLKLNEEQV EDYFFQLKSQ KRYHEDIFGA VFPYEAKKDR VAVQPSSLEM

SAL
Length:1,153
Mass (Da):131,117
Last modified:February 1, 1996 - v2
Checksum:i47671E5385CB3A52
GO
Isoform 2 (identifier: P35228-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     264-288: Missing.
     298-311: Missing.

Show »
Length:1,114
Mass (Da):126,749
Checksum:iC1F9624774435571
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti23 – 231D → G in AAA56666 (PubMed:7522054).Curated
Sequence conflicti154 – 1541F → L in AAA56666 (PubMed:7522054).Curated
Sequence conflicti177 – 1771G → V in AAA56666 (PubMed:7522054).Curated
Sequence conflicti266 – 2661R → H in AAC19133 (PubMed:9160867).Curated
Sequence conflicti423 – 4231L → I in AAA59171 (PubMed:7682706).Curated
Sequence conflicti439 – 4391A → T in AAC19133 (PubMed:9160867).Curated
Sequence conflicti552 – 5521A → G in AAI44127 (PubMed:15489334).Curated
Sequence conflicti676 – 6761T → I in AAB60366 (PubMed:7544004).Curated
Sequence conflicti800 – 8001T → A in AAA56666 (PubMed:7522054).Curated
Sequence conflicti805 – 8051A → D in AAA59171 (PubMed:7682706).Curated
Sequence conflicti831 – 8322FL → SP in AAA59171 (PubMed:7682706).Curated
Sequence conflicti913 – 9131S → P in AAA56666 (PubMed:7522054).Curated
Sequence conflicti933 – 9331R → G in AAA59171 (PubMed:7682706).Curated
Sequence conflicti933 – 9331R → G in AAB60366 (PubMed:7544004).Curated
Sequence conflicti966 – 9661G → A in AAA59171 (PubMed:7682706).Curated
Sequence conflicti966 – 9661G → A in AAB60366 (PubMed:7544004).Curated
Sequence conflicti987 – 9871A → V in AAA59171 (PubMed:7682706).Curated

Polymorphismi

Note: Genetic variations in NOS2 are involved in resistance to malaria [MIMi:611162].

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti221 – 2211R → W.1 Publication
Corresponds to variant rs3730017 [ dbSNP | Ensembl ].
VAR_024548
Natural varianti608 – 6081S → L Polymorphism; found in patients with very early onset inflammatory bowel disease; increases NOS2 activity. 4 Publications
Corresponds to variant rs2297518 [ dbSNP | Ensembl ].
VAR_022127
Natural varianti679 – 6791A → S in a breast cancer sample; somatic mutation. 1 Publication
VAR_036302
Natural varianti747 – 7471T → A.1 Publication
Corresponds to variant rs28944173 [ dbSNP | Ensembl ].
VAR_025020
Natural varianti1009 – 10091R → C.1 Publication
Corresponds to variant rs28944201 [ dbSNP | Ensembl ].
VAR_025021

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei264 – 28825Missing in isoform 2. 1 PublicationVSP_003582Add
BLAST
Alternative sequencei298 – 31114Missing in isoform 2. 1 PublicationVSP_003583Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L24553 mRNA. Translation: AAA36375.1.
L09210 mRNA. Translation: AAA59171.1.
X73029 mRNA. Translation: CAA51512.1.
U05810 mRNA. Translation: AAA56666.1.
U31511 mRNA. Translation: AAB49041.1.
D26525 mRNA. Translation: BAA05531.1.
U20141 mRNA. Translation: AAB60366.1.
AF068236 mRNA. Translation: AAC19133.1.
AB022318 mRNA. Translation: BAA37123.1.
DQ060518 Genomic DNA. Translation: AAY43131.1.
EU332854 Genomic DNA. Translation: ABY87543.1.
BC130283 mRNA. Translation: AAI30284.1.
BC144126 mRNA. Translation: AAI44127.1.
S75615 mRNA. Translation: AAD14179.1.
CCDSiCCDS11223.1. [P35228-1]
PIRiA49676.
RefSeqiNP_000616.3. NM_000625.4. [P35228-1]
XP_011523161.1. XM_011524859.1. [P35228-1]
UniGeneiHs.709191.

Genome annotation databases

EnsembliENST00000313735; ENSP00000327251; ENSG00000007171.
ENST00000621962; ENSP00000482291; ENSG00000007171. [P35228-2]
GeneIDi4843.
KEGGihsa:4843.
UCSCiuc002gzu.3. human. [P35228-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

Nitric oxide synthase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L24553 mRNA. Translation: AAA36375.1.
L09210 mRNA. Translation: AAA59171.1.
X73029 mRNA. Translation: CAA51512.1.
U05810 mRNA. Translation: AAA56666.1.
U31511 mRNA. Translation: AAB49041.1.
D26525 mRNA. Translation: BAA05531.1.
U20141 mRNA. Translation: AAB60366.1.
AF068236 mRNA. Translation: AAC19133.1.
AB022318 mRNA. Translation: BAA37123.1.
DQ060518 Genomic DNA. Translation: AAY43131.1.
EU332854 Genomic DNA. Translation: ABY87543.1.
BC130283 mRNA. Translation: AAI30284.1.
BC144126 mRNA. Translation: AAI44127.1.
S75615 mRNA. Translation: AAD14179.1.
CCDSiCCDS11223.1. [P35228-1]
PIRiA49676.
RefSeqiNP_000616.3. NM_000625.4. [P35228-1]
XP_011523161.1. XM_011524859.1. [P35228-1]
UniGeneiHs.709191.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NSIX-ray2.55A/B/C/D74-504[»]
2LL6NMR-B515-531[»]
2NSIX-ray3.00A/B/C/D74-504[»]
3E7GX-ray2.20A/B/C/D82-505[»]
3EJ8X-ray2.55A/B/C/D82-505[»]
3HR4X-ray2.50A/C/E/G503-715[»]
4CX7X-ray3.16A/B/C/D74-504[»]
4NOSX-ray2.25A/B/C/D82-508[»]
ProteinModelPortaliP35228.
SMRiP35228. Positions 83-505, 511-699.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110906. 146 interactions.
DIPiDIP-59359N.
IntActiP35228. 4 interactions.
STRINGi9606.ENSP00000327251.

Chemistry

BindingDBiP35228.
ChEMBLiCHEMBL2096621.
DrugBankiDB01234. Dexamethasone.
DB00997. Doxorubicin.
DB00125. L-Arginine.
DB00155. L-Citrulline.
DB01110. Miconazole.
DB08814. Triflusal.
GuidetoPHARMACOLOGYi1250.

PTM databases

PhosphoSiteiP35228.

Polymorphism and mutation databases

BioMutaiNOS2.
DMDMi1352513.

Proteomic databases

PaxDbiP35228.
PRIDEiP35228.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000313735; ENSP00000327251; ENSG00000007171.
ENST00000621962; ENSP00000482291; ENSG00000007171. [P35228-2]
GeneIDi4843.
KEGGihsa:4843.
UCSCiuc002gzu.3. human. [P35228-1]

Organism-specific databases

CTDi4843.
GeneCardsiGC17M026083.
H-InvDBHIX0027239.
HGNCiHGNC:7873. NOS2.
HPAiCAB002014.
MIMi163730. gene.
611162. phenotype.
neXtProtiNX_P35228.
PharmGKBiPA164724093.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG4362.
GeneTreeiENSGT00620000087711.
HOVERGENiHBG000159.
InParanoidiP35228.
KOiK13241.
OMAiKFTNSPT.
OrthoDBiEOG79SDW7.
PhylomeDBiP35228.
TreeFamiTF324410.

Enzyme and pathway databases

BioCyciMetaCyc:HS00205-MONOMER.
BRENDAi1.14.13.39. 2681.
ReactomeiREACT_121256. Phagosomal maturation (early endosomal stage).
REACT_23862. Nitric oxide stimulates guanylate cyclase.
SignaLinkiP35228.

Miscellaneous databases

ChiTaRSiNOS2. human.
EvolutionaryTraceiP35228.
GeneWikiiNitric_oxide_synthase_2_(inducible).
GenomeRNAii4843.
NextBioi18662.
PROiP35228.
SOURCEiSearch...

Gene expression databases

BgeeiP35228.
CleanExiHS_NOS2.
GenevisibleiP35228. HS.

Family and domain databases

Gene3Di1.20.990.10. 1 hit.
3.40.50.360. 1 hit.
3.90.340.10. 1 hit.
InterProiIPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR004030. NOS_N.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamiPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
PF02898. NO_synthase. 1 hit.
[Graphical view]
PRINTSiPR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMiSSF52218. SSF52218. 1 hit.
SSF56512. SSF56512. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEiPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
PS60001. NOS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Purification and cDNA sequence of an inducible nitric oxide synthase from a human tumor cell line."
    Sherman P.A., Laubach V.E., Reep B.R., Wood E.R.
    Biochemistry 32:11600-11605(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Colon adenocarcinoma.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Liver.
  3. "Cloning, characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte."
    Charles I.G., Palmer R.M.J., Hickery M.S., Bayliss M.T., Chubb A.P., Hall V.S., Moss D.W., Moncada S.
    Proc. Natl. Acad. Sci. U.S.A. 90:11419-11423(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Chondrocyte.
  4. "Inducible nitric oxide synthase from human articular chondrocytes: cDNA cloning and analysis of mRNA expression."
    Maier R., Bilbe G., Rediske J., Lotz M.
    Biochim. Biophys. Acta 1208:145-150(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Articular chondrocyte.
  5. "Human retina expresses both constitutive and inducible isoforms of nitric oxide synthase mRNA."
    Park C.S., Pardhasaradhi K., Gianotti C., Villegas E., Krishna G.
    Biochem. Biophys. Res. Commun. 205:85-91(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-608.
    Tissue: Retina.
  6. "Cloning and functional expression of human inducible nitric oxide synthase (NOS) cDNA from a glioblastoma cell line A-172."
    Hokari A., Zeniya M., Esumi H.
    J. Biochem. 116:575-581(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-608.
    Tissue: Glioblastoma.
  7. "Continuous nitric oxide synthesis by inducible nitric oxide synthase in normal human airway epithelium in vivo."
    Guo F.H., de Raeve R.H., Rice T.W., Stuehr D.J., Thunnissen F.B.J.M., Erzurum S.C.
    Proc. Natl. Acad. Sci. U.S.A. 92:7809-7813(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Airway epithelium.
  8. "Dedifferentiated human ventricular cardiac myocytes express inducible nitric oxide synthase mRNA but not protein in response to IL-1, TNF, IFNgamma, and LPS."
    Luss H., Li R.-K., Shapiro R.A., Tzeng E., McGowan F.X., Yoneyama T., Hatakayama K., Geller D.A., Mickle D.A.G., Simmons R.L., Billiar T.R.
    J. Mol. Cell. Cardiol. 29:1153-1165(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Cardiac myocyte.
  9. "Cloning and characterization of a novel splice valiant of human inducible nitric oxide synthase."
    Ogawa Y., Nishijima S., Goto M., Ida M.
    Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
  10. NIEHS SNPs program
    Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TRP-221; LEU-608; ALA-747 AND CYS-1009.
  11. NHLBI resequencing and genotyping service (RS&G)
    Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  12. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  13. "Nitric oxide production by human proximal tubular cells: a novel immunomodulatory mechanism?"
    McLay J.S., Chatterjee P., Nicolson A.G., Jardine A.G., McKay N.G., Ralston S.H., Grabowski P., Haites N.E., Macleod A.M., Hawksworth G.M.
    Kidney Int. 46:1043-1049(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 380-473.
    Tissue: Kidney.
  14. "Inducible nitric oxide synthase in a human glioblastoma cell line."
    Fujisawa H., Ogura T., Hokari A., Weisz A., Yamashita J., Esumi H.
    J. Neurochem. 64:85-91(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 667-831, INDUCTION.
    Tissue: Glioblastoma.
  15. "Three members of the nitric oxide synthase II gene family (NOS2A, NOS2B, and NOS2C) colocalize to human chromosome 17."
    Bloch K.D., Wolfram J.R., Brown D.M., Roberts J.D. Jr., Zapol D.G., Lepore J.J., Filippov G., Thomas J.E., Jacob H.J., Bloch D.B.
    Genomics 27:526-530(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.
  16. "Inducible nitric oxide synthase in the liver: regulation and function."
    Taylor B.S., Alarcon L.H., Billiar T.R.
    Biochemistry (Mosc.) 63:766-781(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.
  17. "Epithelial inducible nitric-oxide synthase is an apical EBP50-binding protein that directs vectorial nitric oxide output."
    Glynne P.A., Darling K.E.A., Picot J., Evans T.J.
    J. Biol. Chem. 277:33132-33138(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SLC9A3R1.
  18. "A new NOS2 promoter polymorphism associated with increased nitric oxide production and protection from severe malaria in Tanzanian and Kenyan children."
    Hobbs M.R., Udhayakumar V., Levesque M.C., Booth J., Roberts J.M., Tkachuk A.N., Pole A., Coon H., Kariuki S., Nahlen B.L., Mwaikambo E.D., Lal A.L., Granger D.L., Anstey N.M., Weinberg J.B.
    Lancet 360:1468-1475(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: POLYMORPHISM, INVOLVEMENT IN RESISTANCE TO MALARIA.
  19. "Target-selective protein S-nitrosylation by sequence motif recognition."
    Jia J., Arif A., Terenzi F., Willard B., Plow E.F., Hazen S.L., Fox P.L.
    Cell 159:623-634(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH S100A8 AND S100A9, ASSEMBLY IN THE INOS-S100A8/A9 COMPLEX, INDUCTION BY LDL.
  20. "Zinc regulates iNOS-derived nitric oxide formation in endothelial cells."
    Cortese-Krott M.M., Kulakov L., Oplaender C., Kolb-Bachofen V., Kroencke K.D., Suschek C.V.
    Redox Biol. 2:945-954(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.
  21. "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."
    Li H., Raman C.S., Glaser C.B., Blasko E., Young T.A., Parkinson J.F., Whitlow M., Poulos T.L.
    J. Biol. Chem. 274:21276-21284(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 74-504.
  22. "Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation."
    Fischmann T.O., Hruza A., Niu X.D., Fossetta J.D., Lunn C.A., Dolphin E., Prongay A.J., Reichert P., Lundell D.J., Narula S.K., Weber P.C.
    Nat. Struct. Biol. 6:233-242(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 82-528.
  23. Cited for: VARIANT [LARGE SCALE ANALYSIS] SER-679.
  24. Cited for: VARIANT LEU-608, CHARACTERIZATION OF VARIANT LEU-608.

Entry informationi

Entry nameiNOS2_HUMAN
AccessioniPrimary (citable) accession number: P35228
Secondary accession number(s): A1L3U5
, B7ZLY2, O60757, O94994, Q16263, Q16692, Q4TTS5, Q9UD42
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1996
Last modified: July 22, 2015
This is version 184 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.