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Protein

Nitric oxide synthase, inducible

Gene

Nos2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7503239). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (PubMed:16373578). As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM (By similarity). Involved in inflammation, enhances the synthesis of proinflammatory mediators such as IL6 and IL8 (By similarity).By similarity2 Publications

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:

Activity regulationi

Not stimulated 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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi104Zinc1
Metal bindingi109Zinc1
Metal bindingi194Iron (heme axial ligand)1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi617 – 648FMNPROSITE-ProRule annotationAdd BLAST32
Nucleotide bindingi761 – 772FADBy similarityAdd BLAST12
Nucleotide bindingi897 – 907FADBy similarityAdd BLAST11
Nucleotide bindingi972 – 990NADPBy similarityAdd BLAST19
Nucleotide bindingi1070 – 1085NADPBy similarityAdd BLAST16

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCalmodulin-binding, Oxidoreductase
LigandFAD, Flavoprotein, FMN, Heme, Iron, Metal-binding, NADP, Zinc

Enzyme and pathway databases

BRENDAi1.14.13.39 3474
ReactomeiR-MMU-1222556 ROS, RNS production in phagocytes
R-MMU-392154 Nitric oxide stimulates guanylate cyclase
R-MMU-9033241 Peroxisomal protein import

Names & Taxonomyi

Protein namesi
Recommended name:
Nitric oxide synthase, inducible (EC:1.14.13.39)
Alternative name(s):
Inducible NO synthase
Short name:
Inducible NOS
Short name:
iNOS
Macrophage NOS
Short name:
MAC-NOS
NOS type II
Peptidyl-cysteine S-nitrosylase NOS2
Gene namesi
Name:Nos2
Synonyms:Inosl
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:97361 Nos2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3464

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001709341 – 1144Nitric oxide synthase, inducibleAdd BLAST1144

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei569PhosphotyrosineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiP29477
PaxDbiP29477
PRIDEiP29477

PTM databases

iPTMnetiP29477
PhosphoSitePlusiP29477
SwissPalmiP29477

Expressioni

Tissue specificityi

Macrophages.

Inductioni

By treatment with endotoxins or cytokines. By lipopolysaccharides (LPS) (in vitro). Expression in the liver oscillates in a circadian manner with peak levels occurring during the late night.1 Publication

Gene expression databases

BgeeiENSMUSG00000020826 Expressed in 33 organ(s), highest expression level in cerebral cortex subventricular zone
CleanExiMM_NOS2
ExpressionAtlasiP29477 baseline and differential
GenevisibleiP29477 MM

Interactioni

Subunit structurei

Homodimer. Binds SLC9A3R1 (By similarity). Interacts with GAPDH. Interacts with S100A8 and S100A9 to form the iNOS-S100A8/9 transnitrosylase complex (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
RelaQ042073EBI-298897,EBI-644400

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201806, 5 interactors
ComplexPortaliCPX-53 iNOS-S100A8/A9 complex
DIPiDIP-31080N
IntActiP29477, 2 interactors
MINTiP29477
STRINGi10090.ENSMUSP00000018610

Chemistry databases

BindingDBiP29477

Structurei

Secondary structure

11144
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP29477
SMRiP29477
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP29477

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini533 – 671Flavodoxin-likePROSITE-ProRule annotationAdd BLAST139
Domaini724 – 964FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST241

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni503 – 523Calmodulin-bindingSequence analysisAdd BLAST21

Sequence similaritiesi

Belongs to the NOS family.Curated

Phylogenomic databases

eggNOGiKOG1158 Eukaryota
COG0369 LUCA
COG4362 LUCA
GeneTreeiENSGT00840000129757
HOGENOMiHOG000220884
HOVERGENiHBG000159
InParanoidiP29477
KOiK13241
OrthoDBiEOG091G10Z0
PhylomeDBiP29477
TreeFamiTF324410

Family and domain databases

Gene3Di1.20.990.10, 1 hit
3.40.50.360, 1 hit
3.40.50.80, 1 hit
InterProiView protein in InterPro
IPR003097 CysJ-like_FAD-binding
IPR017927 FAD-bd_FR_type
IPR001094 Flavdoxin-like
IPR008254 Flavodoxin/NO_synth
IPR001709 Flavoprot_Pyr_Nucl_cyt_Rdtase
IPR029039 Flavoprotein-like_sf
IPR039261 FNR_nucleotide-bd
IPR023173 NADPH_Cyt_P450_Rdtase_alpha
IPR012144 NOS_euk
IPR004030 NOS_N
IPR036119 NOS_N_sf
IPR001433 OxRdtase_FAD/NAD-bd
IPR017938 Riboflavin_synthase-like_b-brl
PfamiView protein in Pfam
PF00667 FAD_binding_1, 1 hit
PF00258 Flavodoxin_1, 1 hit
PF00175 NAD_binding_1, 1 hit
PF02898 NO_synthase, 1 hit
PIRSFiPIRSF000333 NOS, 1 hit
PRINTSiPR00369 FLAVODOXIN
PR00371 FPNCR
SUPFAMiSSF52218 SSF52218, 1 hit
SSF52343 SSF52343, 1 hit
SSF56512 SSF56512, 1 hit
SSF63380 SSF63380, 1 hit
PROSITEiView protein in PROSITE
PS51384 FAD_FR, 1 hit
PS50902 FLAVODOXIN_LIKE, 1 hit
PS60001 NOS, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P29477-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MACPWKFLFK VKSYQSDLKE EKDINNNVKK TPCAVLSPTI QDDPKSHQNG
60 70 80 90 100
SPQLLTGTAQ NVPESLDKLH VTSTRPQYVR IKNWGSGEIL HDTLHHKATS
110 120 130 140 150
DFTCKSKSCL GSIMNPKSLT RGPRDKPTPL EELLPHAIEF INQYYGSFKE
160 170 180 190 200
AKIEEHLARL EAVTKEIETT GTYQLTLDEL IFATKMAWRN APRCIGRIQW
210 220 230 240 250
SNLQVFDARN CSTAQEMFQH ICRHILYATN NGNIRSAITV FPQRSDGKHD
260 270 280 290 300
FRLWNSQLIR YAGYQMPDGT IRGDAATLEF TQLCIDLGWK PRYGRFDVLP
310 320 330 340 350
LVLQADGQDP EVFEIPPDLV LEVTMEHPKY EWFQELGLKW YALPAVANML
360 370 380 390 400
LEVGGLEFPA CPFNGWYMGT EIGVRDFCDT QRYNILEEVG RRMGLETHTL
410 420 430 440 450
ASLWKDRAVT EINVAVLHSF QKQNVTIMDH HTASESFMKH MQNEYRARGG
460 470 480 490 500
CPADWIWLVP PVSGSITPVF HQEMLNYVLS PFYYYQIEPW KTHIWQNEKL
510 520 530 540 550
RPRRREIRFR VLVKVVFFAS MLMRKVMASR VRATVLFATE TGKSEALARD
560 570 580 590 600
LATLFSYAFN TKVVCMDQYK ASTLEEEQLL LVVTSTFGNG DCPSNGQTLK
610 620 630 640 650
KSLFMLRELN HTFRYAVFGL GSSMYPQFCA FAHDIDQKLS HLGASQLAPT
660 670 680 690 700
GEGDELSGQE DAFRSWAVQT FRAACETFDV RSKHHIQIPK RFTSNATWEP
710 720 730 740 750
QQYRLIQSPE PLDLNRALSS IHAKNVFTMR LKSQQNLQSE KSSRTTLLVQ
760 770 780 790 800
LTFEGSRGPS YLPGEHLGIF PGNQTALVQG ILERVVDCPT PHQTVCLEVL
810 820 830 840 850
DESGSYWVKD KRLPPCSLSQ ALTYFLDITT PPTQLQLHKL ARFATDETDR
860 870 880 890 900
QRLEALCQPS EYNDWKFSNN PTFLEVLEEF PSLHVPAAFL LSQLPILKPR
910 920 930 940 950
YYSISSSQDH TPSEVHLTVA VVTYRTRDGQ GPLHHGVCST WIRNLKPQDP
960 970 980 990 1000
VPCFVRSVSG FQLPEDPSQP CILIGPGTGI APFRSFWQQR LHDSQHKGLK
1010 1020 1030 1040 1050
GGRMSLVFGC RHPEEDHLYQ EEMQEMVRKR VLFQVHTGYS RLPGKPKVYV
1060 1070 1080 1090 1100
QDILQKQLAN EVLSVLHGEQ GHLYICGDVR MARDVATTLK KLVATKLNLS
1110 1120 1130 1140
EEQVEDYFFQ LKSQKRYHED IFGAVFSYGA KKGSALEEPK ATRL
Length:1,144
Mass (Da):130,575
Last modified:April 1, 1993 - v1
Checksum:i0735BE676113457F
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1L1STZ4A0A1L1STZ4_MOUSE
Nitric oxide synthase,-inducible
Nos2
1,031Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti19K → T in AAC52356 (PubMed:7503239).Curated1
Sequence conflicti72T → TP in AAM11887 (Ref. 7) Curated1
Sequence conflicti72T → TP in AAH62378 (PubMed:15489334).Curated1
Sequence conflicti191A → V in M92649 (PubMed:1379716).Curated1
Sequence conflicti245S → T in AAM11887 (Ref. 7) Curated1
Sequence conflicti245S → T in AAH62378 (PubMed:15489334).Curated1
Sequence conflicti844A → G in M92649 (PubMed:1379716).Curated1
Sequence conflicti1075I → V in AAH62378 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti211C → R in strain: NOD/LtJ. 1 Publication1
Natural varianti967P → L in strain: SJL/J. 1 Publication1
Natural varianti968S → F in strain: BALB/CBYJ. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M87039 mRNA Translation: AAA39315.1
M92649 mRNA No translation available.
M84373 mRNA Translation: AAA39834.1
U43428 mRNA Translation: AAC52356.1
AF065919 mRNA Translation: AAC17914.1
AF065920 mRNA Translation: AAC17915.1
AF065921 mRNA Translation: AAC17916.2
AF065922 mRNA Translation: AAC17917.2
AF065923 mRNA Translation: AAC17918.2
AF427516 Genomic DNA Translation: AAL24076.1
AY090567 mRNA Translation: AAM11887.1
AL592185 Genomic DNA Translation: CAI25275.1
BC062378 mRNA Translation: AAH62378.1
CCDSiCCDS25115.1
PIRiA43271
RefSeqiNP_001300850.1, NM_001313921.1
NP_001300851.1, NM_001313922.1
NP_035057.1, NM_010927.4
UniGeneiMm.2893

Genome annotation databases

EnsembliENSMUST00000018610; ENSMUSP00000018610; ENSMUSG00000020826
GeneIDi18126
KEGGimmu:18126
UCSCiuc007kkc.1 mouse

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M87039 mRNA Translation: AAA39315.1
M92649 mRNA No translation available.
M84373 mRNA Translation: AAA39834.1
U43428 mRNA Translation: AAC52356.1
AF065919 mRNA Translation: AAC17914.1
AF065920 mRNA Translation: AAC17915.1
AF065921 mRNA Translation: AAC17916.2
AF065922 mRNA Translation: AAC17917.2
AF065923 mRNA Translation: AAC17918.2
AF427516 Genomic DNA Translation: AAL24076.1
AY090567 mRNA Translation: AAM11887.1
AL592185 Genomic DNA Translation: CAI25275.1
BC062378 mRNA Translation: AAH62378.1
CCDSiCCDS25115.1
PIRiA43271
RefSeqiNP_001300850.1, NM_001313921.1
NP_001300851.1, NM_001313922.1
NP_035057.1, NM_010927.4
UniGeneiMm.2893

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DD7X-ray2.25A114-498[»]
1DF1X-ray2.35A/B77-499[»]
1DWVX-ray2.35A/B77-496[»]
1DWWX-ray2.35A/B77-496[»]
1DWXX-ray2.60A/B77-496[»]
1JWJX-ray2.60A/B66-498[»]
1JWKX-ray2.30A/B66-498[»]
1M8DX-ray2.35A/B65-498[»]
1M8EX-ray2.90A/B65-498[»]
1M8HX-ray2.85A/B65-498[»]
1M8IX-ray2.70A/B65-498[»]
1M9TX-ray2.40A/B65-498[»]
1N2NX-ray2.40A/B77-495[»]
1NOCX-ray2.60A115-498[»]
1NODX-ray2.60A/B77-499[»]
1NOSX-ray2.10A115-498[»]
1QOMX-ray2.70A/B65-498[»]
1QW4X-ray2.40A/B77-495[»]
1QW5X-ray2.70A/B77-495[»]
1R35X-ray2.30A/B66-498[»]
1VAFX-ray2.90A/B77-495[»]
2BHJX-ray3.20A77-498[»]
2NODX-ray2.60A/B77-499[»]
2NOSX-ray2.30A115-498[»]
2OROX-ray2.00A114-498[»]
2ORPX-ray1.97A114-498[»]
2ORQX-ray2.10A114-498[»]
2ORRX-ray2.00A114-498[»]
2ORSX-ray2.00A114-498[»]
2ORTX-ray1.87A114-498[»]
2Y37X-ray2.60A/B66-498[»]
3DWJX-ray2.75A/B66-496[»]
3E65X-ray2.05A/B66-498[»]
3E67X-ray2.60A/B66-498[»]
3E68X-ray2.20A/B66-498[»]
3E6LX-ray2.30A/B66-498[»]
3E6NX-ray2.40A/B66-498[»]
3E6OX-ray2.60A/B66-498[»]
3E6TX-ray2.50A/B66-498[»]
3E7IX-ray2.90A/B66-498[»]
3E7MX-ray2.00A/B66-498[»]
3E7TX-ray2.60A/B66-498[»]
3EAIX-ray2.20A/B66-498[»]
3EBDX-ray2.40A/B66-498[»]
3EBFX-ray2.29A/B66-498[»]
3GOFX-ray1.45C/D503-518[»]
3NODX-ray2.70A/B77-499[»]
3NQSX-ray2.20A/B66-498[»]
3NW2X-ray2.80A/B77-499[»]
4JS9X-ray2.78A/B66-496[»]
4UX6X-ray3.00A77-100[»]
B108-496[»]
ProteinModelPortaliP29477
SMRiP29477
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201806, 5 interactors
ComplexPortaliCPX-53 iNOS-S100A8/A9 complex
DIPiDIP-31080N
IntActiP29477, 2 interactors
MINTiP29477
STRINGi10090.ENSMUSP00000018610

Chemistry databases

BindingDBiP29477
ChEMBLiCHEMBL3464

PTM databases

iPTMnetiP29477
PhosphoSitePlusiP29477
SwissPalmiP29477

Proteomic databases

MaxQBiP29477
PaxDbiP29477
PRIDEiP29477

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000018610; ENSMUSP00000018610; ENSMUSG00000020826
GeneIDi18126
KEGGimmu:18126
UCSCiuc007kkc.1 mouse

Organism-specific databases

CTDi4843
MGIiMGI:97361 Nos2

Phylogenomic databases

eggNOGiKOG1158 Eukaryota
COG0369 LUCA
COG4362 LUCA
GeneTreeiENSGT00840000129757
HOGENOMiHOG000220884
HOVERGENiHBG000159
InParanoidiP29477
KOiK13241
OrthoDBiEOG091G10Z0
PhylomeDBiP29477
TreeFamiTF324410

Enzyme and pathway databases

BRENDAi1.14.13.39 3474
ReactomeiR-MMU-1222556 ROS, RNS production in phagocytes
R-MMU-392154 Nitric oxide stimulates guanylate cyclase
R-MMU-9033241 Peroxisomal protein import

Miscellaneous databases

EvolutionaryTraceiP29477
PROiPR:P29477
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000020826 Expressed in 33 organ(s), highest expression level in cerebral cortex subventricular zone
CleanExiMM_NOS2
ExpressionAtlasiP29477 baseline and differential
GenevisibleiP29477 MM

Family and domain databases

Gene3Di1.20.990.10, 1 hit
3.40.50.360, 1 hit
3.40.50.80, 1 hit
InterProiView protein in InterPro
IPR003097 CysJ-like_FAD-binding
IPR017927 FAD-bd_FR_type
IPR001094 Flavdoxin-like
IPR008254 Flavodoxin/NO_synth
IPR001709 Flavoprot_Pyr_Nucl_cyt_Rdtase
IPR029039 Flavoprotein-like_sf
IPR039261 FNR_nucleotide-bd
IPR023173 NADPH_Cyt_P450_Rdtase_alpha
IPR012144 NOS_euk
IPR004030 NOS_N
IPR036119 NOS_N_sf
IPR001433 OxRdtase_FAD/NAD-bd
IPR017938 Riboflavin_synthase-like_b-brl
PfamiView protein in Pfam
PF00667 FAD_binding_1, 1 hit
PF00258 Flavodoxin_1, 1 hit
PF00175 NAD_binding_1, 1 hit
PF02898 NO_synthase, 1 hit
PIRSFiPIRSF000333 NOS, 1 hit
PRINTSiPR00369 FLAVODOXIN
PR00371 FPNCR
SUPFAMiSSF52218 SSF52218, 1 hit
SSF52343 SSF52343, 1 hit
SSF56512 SSF56512, 1 hit
SSF63380 SSF63380, 1 hit
PROSITEiView protein in PROSITE
PS51384 FAD_FR, 1 hit
PS50902 FLAVODOXIN_LIKE, 1 hit
PS60001 NOS, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNOS2_MOUSE
AccessioniPrimary (citable) accession number: P29477
Secondary accession number(s): O70515
, O70516, Q5SXT3, Q6P6A0, Q8R410
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: November 7, 2018
This is version 202 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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