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Protein

Nitric oxide synthase, inducible

Gene

NOS2

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 PTGS2/COX2. 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. Involved in inflammation, enhances the synthesis of proinflammatory mediators such as IL6 and IL8.By similarity

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.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi197Iron (heme axial ligand)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi620 – 651FMNPROSITE-ProRule annotationAdd BLAST32
Nucleotide bindingi764 – 775FADBy similarityAdd BLAST12
Nucleotide bindingi900 – 910FADBy similarityAdd BLAST11
Nucleotide bindingi975 – 993NADPBy similarityAdd BLAST19
Nucleotide bindingi1073 – 1088NADPBy similarityAdd BLAST16

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Ligandi

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

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
NOS type II
Peptidyl-cysteine S-nitrosylase NOS2
Gene namesi
Name:NOS2
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001709271 – 1154Nitric oxide synthase, inducibleAdd BLAST1154

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei572PhosphotyrosineBy similarity1

Keywords - PTMi

Phosphoprotein

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

Structurei

3D structure databases

ProteinModelPortaliO62699.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini536 – 674Flavodoxin-likePROSITE-ProRule annotationAdd BLAST139
Domaini727 – 967FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST241

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni506 – 526Calmodulin-bindingSequence analysisAdd BLAST21

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

HOGENOMiHOG000220884.
HOVERGENiHBG000159.
InParanoidiO62699.
KOiK13241.

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-like.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like_dom.
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]

Sequencei

Sequence statusi: Complete.

O62699-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MACPWKFLFR AKFHQYGMKE EKDINNNVEK PPGATPSPST QDDLKNHKHH
60 70 80 90 100
NDSPQPLTET VQKLPESLDK LHATPLSRPQ HVRIKNWGNG MTFQDTLHHK
110 120 130 140 150
AKGDLACKSK SCLGAIMNPK SLTREPRDKP TPPDELLPQA IEFVNQYYSS
160 170 180 190 200
FKEAKIEEHL ARVEAVTKEI ETTGTYQLTG DELIFATKQA WRNAPRCIGR
210 220 230 240 250
IQWSNLQVFD ARSCSTAKEM FEHICRHLRY ASNNGNIRSA ITVFPQRTDG
260 270 280 290 300
KHDFRVWNAQ LIRYAGYQMP DGTILGDPAS VEFTQLCIDL GWKPKYGRFD
310 320 330 340 350
VVPLVLQADG QDPEFFEIPP DLVLEVPMEH PKYEWFRELE LKWYALPAVA
360 370 380 390 400
NMLLEVGGLE FPGCPFNGWY MGTEIGVRDF CDVQRYNILE EVGRRMGLET
410 420 430 440 450
HKLASLWKDR AVIEINVAVL HSFQKQNVTI MDHHSAAESF MKYMQSEYRS
460 470 480 490 500
RGGCPADWIW LVPPISGSIT PVFHQEMLNY VLSPFYYYQV EAWKTHVWQD
510 520 530 540 550
EKRRPQRRKI QLKVLVKAVL FASMLMRKTM ASRVRVTILF ATETGKSETL
560 570 580 590 600
ARDLGALFSC AFHPKVLCMD EYKLSHLEEE QLLLVVTSTF GNGDSPGNGE
610 620 630 640 650
KLKKSLFMLK ELTNKFRYAV FGLGSSMYPQ FCAFAHDIDH KLSHLGASQL
660 670 680 690 700
TPGGEGDELN GKEEAFRCWA VQTFKAACDT SDVRGKHCIQ IPRLYTSNVT
710 720 730 740 750
WDPHHYRLLQ DSQPLDLNKA LSKMHAKNVF TLRLKSQRNL QSPISNRTTL
760 770 780 790 800
QVELSCEDSQ ELSYLPGEHL GVFPGNQLAL VQGILERVVY SPAPLQPVHL
810 820 830 840 850
ETLSERGSYW VRNNRLPPCS LSQALTYFLD ITTPPTHLLL RKLAQLAHQY
860 870 880 890 900
AERHRLEILC HPSEYNKWKL TNSPTFLEVL EEFPSLRVSA GFLLSQLPIL
910 920 930 940 950
KPRYYSISSS RDCTPMEVHL TVAVLVYPTR DGQGPLHHGV CSTWLSNLKP
960 970 980 990 1000
QDPVPCFVRS AGNFKLPEDP SRPCILIGPG TGIAPFRSFW QQRLHDIKHK
1010 1020 1030 1040 1050
GLRGSRMTLV FGCRRPDEDH LYREEMLEMA QSGVLHEVHT AYSRLPGQPK
1060 1070 1080 1090 1100
VYVQDILRQQ LASQVLRMLH EEQGHLYVCG DVRMARDVAH TLKHLVAAKL
1110 1120 1130 1140 1150
SLSEEQVEDY FFQLKSQKRY HEDIFGAVFP YEVKKDGAAK QPSDPRVPAA

HGRS
Length:1,154
Mass (Da):131,847
Last modified:September 13, 2005 - v2
Checksum:iD6AD3A88AE89E995
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti42 – 52DDLKNHKHHND → KCHSLSKHRDE (Ref. 2) CuratedAdd BLAST11
Sequence conflicti56P → S in AAC15587 (Ref. 2) Curated1
Sequence conflicti59 – 64ETVQKL → GTVKTS in AAC15587 (Ref. 2) Curated6
Sequence conflicti68 – 80LDKLH…LSRPQ → TIKPAAPPLACPR (Ref. 2) CuratedAdd BLAST13
Sequence conflicti91 – 92MT → RS in AAC78630 (PubMed:9746458).Curated2
Sequence conflicti102 – 104KGD → MGV in AAC78630 (PubMed:9746458).Curated3
Sequence conflicti108K → T in AAC78630 (PubMed:9746458).Curated1
Sequence conflicti111 – 115SCLGA → LCMGS in AAC78630 (PubMed:9746458).Curated5
Sequence conflicti119P → T in AAC78630 (PubMed:9746458).Curated1
Sequence conflicti125 – 127EPR → GPS in AAC78630 (PubMed:9746458).Curated3
Sequence conflicti133 – 134PD → TE in AAC78630 (PubMed:9746458).Curated2
Sequence conflicti149S → G in AAC78630 (PubMed:9746458).Curated1
Sequence conflicti169E → D in AAC78630 (PubMed:9746458).Curated1
Sequence conflicti394 – 395RR → SK in AAC78630 (PubMed:9746458).Curated2
Sequence conflicti497 – 499VWQ → LWL in AAC78630 (PubMed:9746458).Curated3
Sequence conflicti506 – 508QRR → HRK in AAC78630 (PubMed:9746458).Curated3
Sequence conflicti615K → N in AAC78630 (PubMed:9746458).Curated1
Sequence conflicti624 – 626GSS → RSN in AAC78630 (PubMed:9746458).Curated3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077821 mRNA. Translation: AAC78630.1.
AF032909 mRNA. Translation: AAC15587.1.
RefSeqiNP_001300777.1. NM_001313848.1.
UniGeneiCfa.45041.

Genome annotation databases

GeneIDi403822.
KEGGicfa:403822.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077821 mRNA. Translation: AAC78630.1.
AF032909 mRNA. Translation: AAC15587.1.
RefSeqiNP_001300777.1. NM_001313848.1.
UniGeneiCfa.45041.

3D structure databases

ProteinModelPortaliO62699.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi403822.
KEGGicfa:403822.

Organism-specific databases

CTDi4843.

Phylogenomic databases

HOGENOMiHOG000220884.
HOVERGENiHBG000159.
InParanoidiO62699.
KOiK13241.

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-like.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like_dom.
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...

Entry informationi

Entry nameiNOS2_CANLF
AccessioniPrimary (citable) accession number: O62699
Secondary accession number(s): O97604
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: September 13, 2005
Last modified: October 5, 2016
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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 one 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.