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Q06518 (NOS2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Nos2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1147 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2 By similarity.

Catalytic activity

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

Cofactor

Heme group.

Binds 1 FAD.

Binds 1 FMN.

Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.

Enzyme regulation

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 By similarity.

Subunit structure

Homodimer. Binds SLC9A3R1 By similarity.

Tissue specificity

In normal kidney, expressed primarily in the medullary thick ascending limb, with minor amounts in the medullary collecting duct and vasa recta bundle.

Induction

By interferon gamma and lipopolysaccharides (LPS).

Sequence similarities

Belongs to the NOS family.

Contains 1 FAD-binding FR-type domain.

Contains 1 flavodoxin-like domain.

Caution

sequence Was originally (Ref.9) thought to originate from human but appears to be from rat.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11471147Nitric oxide synthase, inducible
PRO_0000170937

Regions

Domain536 – 674139Flavodoxin-like
Domain727 – 967241FAD-binding FR-type
Nucleotide binding620 – 65132FMN By similarity
Nucleotide binding764 – 77512FAD By similarity
Nucleotide binding900 – 91011FAD By similarity
Nucleotide binding975 – 99319NADP By similarity
Nucleotide binding1073 – 108816NADP By similarity
Region506 – 52621Calmodulin-binding Potential

Sites

Metal binding1071Zinc By similarity
Metal binding1121Zinc By similarity
Metal binding1971Iron (heme axial ligand) By similarity

Experimental info

Sequence conflict101R → K in BAA07994. Ref.7
Sequence conflict721H → Y in BAA03138. Ref.1
Sequence conflict1071C → R in AAC13747. Ref.3
Sequence conflict1281D → V in BAA12035. Ref.8
Sequence conflict1301P → H in AAC13747. Ref.3
Sequence conflict1711E → G in BAA12035. Ref.8
Sequence conflict1951P → S in BAA12035. Ref.8
Sequence conflict2481S → N in AAC83553. Ref.9
Sequence conflict2481S → T Ref.3
Sequence conflict2481S → T Ref.5
Sequence conflict2641Y → I in AAC13747. Ref.3
Sequence conflict2711D → A in AAC83554. Ref.9
Sequence conflict2771D → E in AAC13747. Ref.3
Sequence conflict3481A → P in BAA03138. Ref.1
Sequence conflict3491V → A in CAA54208. Ref.6
Sequence conflict3801F → L Ref.2
Sequence conflict3801F → L Ref.7
Sequence conflict3801F → L Ref.8
Sequence conflict3801F → L in AAC83553. Ref.9
Sequence conflict3801F → L in AAC83554. Ref.9
Sequence conflict3951R → S in BAA02090. Ref.4
Sequence conflict3991E → G in AAC83553. Ref.9
Sequence conflict4121V → A in AAC13747. Ref.3
Sequence conflict4771M → I Ref.13
Sequence conflict5131T → R in AAB18620. Ref.11
Sequence conflict5151L → W in AAB31028. Ref.12
Sequence conflict5451G → R in AAB31028. Ref.12
Sequence conflict5511A → R in AAB18620. Ref.11
Sequence conflict5561A → S in AAB31028. Ref.12
Sequence conflict5591S → T in AAC83553. Ref.9
Sequence conflict5591S → T in AAC83554. Ref.9
Sequence conflict5641T → N in AAB31028. Ref.12
Sequence conflict5701E → D in AAB31028. Ref.12
Sequence conflict5831L → P Ref.5
Sequence conflict5831L → P Ref.10
Sequence conflict5911G → A in AAB31028. Ref.12
Sequence conflict5911G → V Ref.1
Sequence conflict5911G → V Ref.6
Sequence conflict6191A → R in AAA85861. Ref.2
Sequence conflict6401Q → P in AAC83553. Ref.9
Sequence conflict6641D → G in AAB18620. Ref.11
Sequence conflict679 – 6802ET → VP in BAA03138. Ref.1
Sequence conflict6901Q → P in AAB18620. Ref.11
Sequence conflict7111S → N in AAB18620. Ref.11
Sequence conflict714 – 7152SL → TR in AAB18620. Ref.11
Sequence conflict7141S → P Ref.2
Sequence conflict7141S → P Ref.7
Sequence conflict7141S → P Ref.8
Sequence conflict7141S → P in AAC83553. Ref.9
Sequence conflict7141S → P in AAC83554. Ref.9
Sequence conflict7141S → P in AAC16401. Ref.10
Sequence conflict7191K → R in AAB18620. Ref.11
Sequence conflict7211L → P Ref.6
Sequence conflict7221S → R Ref.1
Sequence conflict7221S → R Ref.6
Sequence conflict7221S → R Ref.11
Sequence conflict724 – 7263IHA → FLN Ref.11
Sequence conflict7301F → I in AAB18620. Ref.11
Sequence conflict7311T → A in AAC83553. Ref.9
Sequence conflict7401L → P in CAA54208. Ref.6
Sequence conflict7791A → G in AAC13747. Ref.3
Sequence conflict8341P → S in BAA12035. Ref.8
Sequence conflict8441A → G in BAA03138. Ref.1
Sequence conflict8951S → L in BAA02090. Ref.4
Sequence conflict9111Q → L in AAC13747. Ref.3
Sequence conflict9251V → D in BAA12035. Ref.8
Sequence conflict9371H → N in AAC83554. Ref.9
Sequence conflict9991H → R Ref.2
Sequence conflict9991H → R Ref.7
Sequence conflict9991H → R in AAC83553. Ref.9
Sequence conflict9991H → R in AAC83554. Ref.9
Sequence conflict1008 – 10092TL → NF in AAC83554. Ref.9
Sequence conflict10161P → R Ref.5
Sequence conflict10161P → S Ref.8
Sequence conflict10171E → R Ref.5
Sequence conflict10171E → R Ref.8
Sequence conflict10241E → K in AAC83554. Ref.9
Sequence conflict10761L → I in AAC83553. Ref.9
Sequence conflict10841M → I in CAA54208. Ref.6
Sequence conflict11291F → V in AAC83554. Ref.9
Sequence conflict11331A → V Ref.2
Sequence conflict11331A → V Ref.7
Sequence conflict11331A → V in AAC83553. Ref.9
Sequence conflict11331A → V in AAC83554. Ref.9
Sequence conflict11381T → A Ref.2
Sequence conflict11381T → A Ref.7
Sequence conflict11381T → A in AAC83553. Ref.9
Sequence conflict11381T → A in AAC83554. Ref.9

Sequences

Sequence LengthMass (Da)Tools
Q06518 [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: 77C77432DD8AB0A9

FASTA1,147130,628
        10         20         30         40         50         60 
MACPWKFLFR VKSYQGDLKE EKDINNNVEK TPGAIPSPTT QDDPKSHKHQ NGFPQFLTGT 

        70         80         90        100        110        120 
AQNVPESLDK LHVTPSTRPQ HVRIKNWGNG EIFHDTLHHK ATSDISCKSK LCMGSIMNSK 

       130        140        150        160        170        180 
SLTRGPRDKP TPVEELLPQA IEFINQYYGS FKEAKIEEHL ARLEAVTKEI ETTGTYQLTL 

       190        200        210        220        230        240 
DELIFATKMA WRNAPRCIGR IQWSNLQVFD ARSCSTASEM FQHICRHILY ATNSGNIRSA 

       250        260        270        280        290        300 
ITVFPQRSDG KHDFRIWNSQ LIRYAGYQMP DGTIRGDPAT LEFTQLCIDL GWKPRYGRFD 

       310        320        330        340        350        360 
VLPLVLQAHG QDPEVFEIPP DLVLEVTMEH PKYEWFQELG LKWYALPAVA NMLLEVGGLE 

       370        380        390        400        410        420 
FPACPFNGWY MGTEIGVRDF CDTQRYNILE EVGRRMGLET HTLASLWKDR AVTEINAAVL 

       430        440        450        460        470        480 
HSFQKQNVTI MDHHTASESF MKHMQNEYRA RGGCPADWIW LVPPVSGSIT PVFHQEMLNY 

       490        500        510        520        530        540 
VLSPFYYYQI EPWKTHIWQD EKLRPRRREI RFTVLVKAVF FASVLMRKVM ASRVRATVLF 

       550        560        570        580        590        600 
ATETGKSEAL ARDLAALFSY AFNTKVVCME QYKANTLEEE QLLLVVTSTF GNGDCPSNGQ 

       610        620        630        640        650        660 
TLKKSLFMMK ELGHTFRYAV FGLGSSMYPQ FCAFAHDIDQ KLSHLGASQL APTGEGDELS 

       670        680        690        700        710        720 
GQEDAFRSWA VQTFRAACET FDVRSKHCIQ IPKRYTSNAT WEPEQYKLTQ SPESLDLNKA 

       730        740        750        760        770        780 
LSSIHAKNVF TMRLKSLQNL QSEKSSRTTL LVQLTFEGSR GPSYLPGEHL GIFPGNQTAL 

       790        800        810        820        830        840 
VQGILERVVD CSSPDQTVCL EVLDESGSYW VKDKRLPPCS LRQALTYFLD ITTPPTQLQL 

       850        860        870        880        890        900 
HKLARFATEE THRQRLEALC QPSEYNDWKF SNNPTFLEVL EEFPSLRVPA AFLLSQLPIL 

       910        920        930        940        950        960 
KPRYYSISSS QDHTPSEVHL TVAVVTYRTR DGQGPLHHGV CSTWINNLKP EDPVPCFVRS 

       970        980        990       1000       1010       1020 
VSGFQLPEDP SQPCILIGPG TGIAPFRSFW QQRLHDSQHR GLKGGRMTLV FGCRHPEEDH 

      1030       1040       1050       1060       1070       1080 
LYQEEMQEMV RKGVLFQVHT GYSRLPGKPK VYVQDILQKE LADEVFSVLH GEQGHLYVCG 

      1090       1100       1110       1120       1130       1140 
DVRMARDVAT TLKKLVAAKL NLSEEQVEDY FFQLKSQKRY HEDIFGAVFS YGAKKGNTLE 


EPKGTRL 

« Hide

References

[1]"Cloning of inducible nitric oxide synthase in rat vascular smooth muscle cells."
Nunokawa Y., Ishida N., Tanaka S.
Biochem. Biophys. Res. Commun. 191:89-94(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Vascular smooth muscle.
[2]"Cloning and expression of cytokine-inducible nitric oxide synthase cDNA from rat islets of Langerhans."
Karlsen A.E., Andersen H.U., Vissing H., Larsen P.M., Fey S.J., Cuartero B.G., Madsen O.D., Petersen J.S., Mortensen S.B., Mandrup-Poulsen T., Boel E., Nerup J.
Diabetes 44:753-758(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Wistar.
Tissue: Pancreatic islet.
[3]"Cloning and expression of inducible nitric oxide synthase from rat astrocytes."
Galea E., Reis D.J., Feinstein D.L.
J. Neurosci. Res. 37:406-414(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Astrocyte.
[4]"Molecular cloning of a cDNA encoding an inducible calmodulin-dependent nitric-oxide synthase from rat liver and its expression in COS 1 cells."
Adachi H., Iida S., Oguchi S., Ohshima H., Suzuki H., Nagasaki K., Kawasaki H., Sugimura T., Esumi H.
Eur. J. Biochem. 217:37-43(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Liver.
[5]"Hepatocytes and macrophages express an identical cytokine inducible nitric oxide synthase gene."
Wood E.R., Berger H. Jr., Sherman P.A., Lapetina E.G.
Biochem. Biophys. Res. Commun. 191:767-774(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Hepatocyte.
[6]"cDNA cloning and expression of inducible nitric oxide synthase from rat vascular smooth muscle cells."
Geng Y.J., Almquist M., Hansson G.K.
Biochim. Biophys. Acta 1218:421-424(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Sprague-Dawley.
Tissue: Aorta.
[7]"Cloning of an inducible nitric oxide synthase from rat polymorphonuclear neutrophils."
Kosuga K., Yui Y., Hattori R., Sase K., Eizawa H., Aoyama T., Inoue R., Sasayama S.
Endothelium 2:217-221(1994)
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[8]"Sequence analysis of inducible nitric oxide synthase in rat kidney, lung, and uterus."
Tsutsumishita Y., Kawai Y., Takahara H., Onda T., Miyoshi J., Futaki S., Niwa M.
Biol. Pharm. Bull. 19:1374-1376(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[9]"Complete coding sequence of inducible nitric oxide synthase from human heart and skeletal muscle of patients with chronic heart failure."
Adams V., Krabbes S., Jiang H., Yu J., Rahmel A., Gielen S., Schuler G., Hambrecht R.
Nitric Oxide 2:242-249(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[10]"Vascular smooth muscle nitric oxide synthase anomalies in Dahl/Rapp salt-sensitive rats."
Chen P.Y., Gladish R.D., Sanders P.W.
Hypertension 31:918-924(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 426-788.
Strain: Dahl/Rapp salt sensitive strain.
Tissue: Vascular smooth muscle.
[11]"Advances in the studies of NO synthesis regulation in mesanglial cells."
Saura M., Zaragoza C., Martinez-Dalmau R., Perez-Sala D., Lamas S.
Nefrologia 16:35-39(1996)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 509-740.
Strain: Wistar.
Tissue: Renal glomerulus.
[12]"Location of an inducible nitric oxide synthase mRNA in the normal kidney."
Morrissey J.J., McCracken R., Kaneto H., Vehaskari M., Montani D., Klahr S.
Kidney Int. 45:998-1005(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 479-655.
Strain: Sprague-Dawley.
Tissue: Renal glomerulus.
[13]"Isolation and characterization of iNOS from rat cardiocytes."
Michel T., Balligand J.-L.
Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 420-479.
Tissue: Myocardium.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D14051 mRNA. Translation: BAA03138.1.
U26686 mRNA. Translation: AAA85861.1.
U03699 mRNA. Translation: AAC13747.1.
D12520 mRNA. Translation: BAA02090.1.
L12562 mRNA. Translation: AAA41720.1.
X76881 mRNA. Translation: CAA54208.1.
D44591 mRNA. Translation: BAA07994.1.
D83661 mRNA. Translation: BAA12035.1.
AF049656 mRNA. Translation: AAC83553.1.
AF051164 mRNA. Translation: AAC83554.1.
AF006619 mRNA. Translation: AAC16401.1.
AF006620 mRNA. Translation: AAC16402.1.
U48829 mRNA. Translation: AAB18620.1.
S71597 mRNA. Translation: AAB31028.2.
L36063 mRNA. Translation: AAC02242.1.
PIRI53165.
I56575.
JC5027.
S38253.
S47647.
RefSeqNP_036743.3. NM_012611.3.
UniGeneRn.10400.

3D structure databases

ProteinModelPortalQ06518.
SMRQ06518. Positions 80-499, 700-1127.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-59942N.

Chemistry

BindingDBQ06518.
ChEMBLCHEMBL3051.

PTM databases

PhosphoSiteQ06518.

Proteomic databases

PRIDEQ06518.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID24599.
KEGGrno:24599.

Organism-specific databases

CTD4843.
RGD3185. Nos2.

Phylogenomic databases

eggNOGCOG4362.
HOVERGENHBG000159.
InParanoidQ06518.
KOK13241.
PhylomeDBQ06518.

Gene expression databases

GenevestigatorQ06518.

Family and domain databases

Gene3D1.20.990.10. 1 hit.
3.40.50.360. 1 hit.
3.90.340.10. 1 hit.
InterProIPR003097. 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. NO_synthase_oxygenase_dom.
IPR012144. NOS_euk.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
PF02898. NO_synthase. 1 hit.
[Graphical view]
PIRSFPIRSF000333. NOS. 1 hit.
PRINTSPR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMSSF52218. SSF52218. 1 hit.
SSF56512. SSF56512. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
PS60001. NOS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio603804.

Entry information

Entry nameNOS2_RAT
AccessionPrimary (citable) accession number: Q06518
Secondary accession number(s): O35765 expand/collapse secondary AC list , O35766, O60591, O60604, P97774, Q63267, Q64005, Q64558
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: October 1, 1996
Last modified: June 11, 2014
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families