[1]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Vascular smooth muscle; DOI=10.1006/bbrc.1993.1188; PubMed=7680561 [NCBI, ExPASy, EBI, Israel, Japan] Nunokawa Y., Ishida N., Tanaka S.; "Cloning of inducible nitric oxide synthase in rat vascular smooth muscle cells."; Biochem. Biophys. Res. Commun. 191:89-94(1993).
[2]	NUCLEOTIDE SEQUENCE [MRNA]. STRAIN=Wistar; TISSUE=Pancreatic islet; PubMed=7540573 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Cloning and expression of cytokine-inducible nitric oxide synthase cDNA from rat islets of Langerhans."; Diabetes 44:753-758(1995).
[3]	NUCLEOTIDE SEQUENCE [MRNA]. STRAIN=Sprague-Dawley; TISSUE=Astrocyte; PubMed=7513765 [NCBI, ExPASy, EBI, Israel, Japan] Galea E., Reis D.J., Feinstein D.L.; "Cloning and expression of inducible nitric oxide synthase from rat astrocytes."; J. Neurosci. Res. 37:406-414(1994).
[4]	NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE. TISSUE=Liver; PubMed=7693462 [NCBI, ExPASy, EBI, Israel, Japan] Adachi H., Iida S., Oguchi S., Ohshima H., Suzuki H., Nagasaki K., Kawasaki H., Sugimura T., Esumi H.; "Molecular cloning of a cDNA encoding an inducible calmodulin-dependent nitric-oxide synthase from rat liver and its expression in COS 1 cells."; Eur. J. Biochem. 217:37-43(1993).
[5]	NUCLEOTIDE SEQUENCE [MRNA]. STRAIN=Sprague-Dawley; TISSUE=Hepatocyte; DOI=10.1006/bbrc.1993.1283; PubMed=7682072 [NCBI, ExPASy, EBI, Israel, Japan] Wood E.R., Berger H. Jr., Sherman P.A., Lapetina E.G.; "Hepatocytes and macrophages express an identical cytokine inducible nitric oxide synthase gene."; Biochem. Biophys. Res. Commun. 191:767-774(1993).
[6]	NUCLEOTIDE SEQUENCE [MRNA]. STRAIN=Sprague-Dawley; TISSUE=Aorta; DOI=10.1016/0167-4781(94)90196-1; PubMed=7519448 [NCBI, ExPASy, EBI, Israel, Japan] Geng Y.J., Almquist M., Hansson G.K.; "cDNA cloning and expression of inducible nitric oxide synthase from rat vascular smooth muscle cells."; Biochim. Biophys. Acta 1218:421-424(1994).
[7]	NUCLEOTIDE SEQUENCE [MRNA]. Kosuga K., Yui Y., Hattori R., Sase K., Eizawa H., Aoyama T., Inoue R., Sasayama S.; "Cloning of an inducible nitric oxide synthase from rat polymorphonuclear neutrophils."; Endothelium 2:217-221(1994).
[8]	NUCLEOTIDE SEQUENCE [MRNA]. PubMed=8913516 [NCBI, ExPASy, EBI, Israel, Japan] Tsutsumishita Y., Kawai Y., Takahara H., Onda T., Miyoshi J., Futaki S., Niwa M.; "Sequence analysis of inducible nitric oxide synthase in rat kidney, lung, and uterus."; Biol. Pharm. Bull. 19:1374-1376(1996).
[9]	NUCLEOTIDE SEQUENCE [MRNA]. DOI=10.1006/niox.1998.0184; PubMed=9851365 [NCBI, ExPASy, EBI, Israel, Japan] Adams V., Krabbes S., Jiang H., Yu J., Rahmel A., Gielen S., Schuler G., Hambrecht R.; "Complete coding sequence of inducible nitric oxide synthase from human heart and skeletal muscle of patients with chronic heart failure."; Nitric Oxide 2:242-249(1998).
[10]	NUCLEOTIDE SEQUENCE [MRNA] OF 426-788. STRAIN=Dahl/Rapp salt sensitive strain; TISSUE=Vascular smooth muscle; PubMed=9535415 [NCBI, ExPASy, EBI, Israel, Japan] Chen P.Y., Gladish R.D., Sanders P.W.; "Vascular smooth muscle nitric oxide synthase anomalies in Dahl/Rapp salt-sensitive rats."; Hypertension 31:918-924(1998).
[11]	NUCLEOTIDE SEQUENCE [MRNA] OF 509-740. STRAIN=Wistar; TISSUE=Renal glomerulus; Saura M., Zaragoza C., Martinez-Dalmau R., Perez-Sala D., Lamas S.; "Advances in the studies of NO synthesis regulation in mesanglial cells."; Nefrologia 16:35-39(1996).
[12]	NUCLEOTIDE SEQUENCE [MRNA] OF 479-655. STRAIN=Sprague-Dawley; TISSUE=Renal glomerulus; PubMed=7516453 [NCBI, ExPASy, EBI, Israel, Japan] Morrissey J.J., McCracken R., Kaneto H., Vehaskari M., Montani D., Klahr S.; "Location of an inducible nitric oxide synthase mRNA in the normal kidney."; Kidney Int. 45:998-1005(1994).
[13]	NUCLEOTIDE SEQUENCE [MRNA] OF 420-479. TISSUE=Myocardium; Michel T., Balligand J.-L.; "Isolation and characterization of iNOS from rat cardiocytes."; Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.

Comments

FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body.
CATALYTIC ACTIVITY: L-arginine + n NADPH + m O₂ = citrulline + nitric oxide + n NADP⁺.
COFACTOR: Heme group.
COFACTOR: Binds 1 FAD.
COFACTOR: Binds 1 FMN.
COFACTOR: Metrahydrobiopterin (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: 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).
SIMILARITY: Belongs to the NOS family.
SIMILARITY: Contains 1 FAD-binding FR-type domain.
SIMILARITY: Contains 1 flavodoxin-like domain.
CAUTION: Ref.9 sequence was originally thought to originate from human but appears to be from rat.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

D14051; BAA03138.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U26686; AAA85861.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U03699; AAC13747.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
D12520; BAA02090.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L12562; AAA41720.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X76881; CAA54208.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
D44591; BAA07994.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
D83661; BAA12035.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF049656; AAC83553.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF051164; AAC83554.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF006619; AAC16401.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF006620; AAC16402.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
U48829; AAB18620.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
S71597; AAB31028.2; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
L36063; AAC02242.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

I53165; I53165.
I56575; I56575.
JC5027; JC5027.
S38253; S38253.
S47647; S47647.

RefSeq

NP_036743.3; -.

UniGene

Rn.10400

3D structure databases

HSSP

P29477; 1NOS. [HSSP ENTRY / PDB]

Q06518; 80-499.

PTM databases

Q06518; -.

Organism-specific databases

RGD

3185; Nos2.

Gene expression databases

ArrayExpress

Q06518; -.

GermOnline

ENSRNOG00000011023; Rattus norvegicus.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from direct assay from UniProtKB).
GO:0005634;	Cellular component: nucleus (inferred from direct assay from UniProtKB).
GO:0004517;	Molecular function: nitric-oxide synthase activity (traceable author statement from UniProtKB).
GO:0005515;	Molecular function: protein binding (inferred from sequence or structural similarity from UniProtKB).
GO:0042742;	Biological process: defense response to bacterium (inferred from sequence or structural similarity from UniProtKB).
GO:0006809;	Biological process: nitric oxide biosynthetic process (traceable author statement from UniProtKB).
GO:0006801;	Biological process: superoxide metabolic process (inferred from sequence or structural similarity from UniProtKB).
QuickGo view.

Family and domain databases

InterPro

IPR003097; FAD-binding_1.
IPR001094; Flavdoxin_like.
IPR008254; Flavodoxin/NO_synth.
IPR001709; FPN_cyt_redctse.
IPR004030; NO_synthase_oxygenase_reg.
IPR012144; NOS.
IPR001433; OxRdtase_FAD/NAD_bd.
Graphical view of domain structure.

Gene3D

G3DSA:3.90.340.10; NO_synthase_oxygenase_reg; 1.

Pfam

PF00667; FAD_binding_1; 1.
PF00258; Flavodoxin_1; 1.
PF00175; NAD_binding_1; 1.
PF02898; NO_synthase; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF000333; NOS; 1.

PRINTS

PR00369; FLAVODOXIN.
PR00371; FPNCR.

PROSITE

PS51384; FAD_FR; 1.
PS50902; FLAVODOXIN_LIKE; 1.
PS60001; NOS; 1.
PROSITE graphical view of domain structure (profiles).

BLOCKS

Q06518.

Genome annotation databases

Ensembl

ENSRNOG00000011023; Rattus norvegicus. [Contig view]

GeneID

24599; -.

KEGG

rno:24599; -.

Phylogenomic databases

HOVERGEN

Q06518; -.

Other

ProtoNet

Q06518.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Calmodulin-binding; Direct protein sequencing; FAD; FMN; Heme; Iron; Metal-binding; NADP; Oxidoreductase; Zinc.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 1147`	`1147`	`Nitric oxide synthase, inducible.`	`PRO_0000170937`
`DOMAIN`	`536 674`	`139`	`Flavodoxin-like.`
`DOMAIN`	`727 967`	`241`	`FAD-binding FR-type.`
`NP_BIND`	`620 651`	`32`	`FMN (By similarity).`
`NP_BIND`	`764 775`	`12`	`FAD (By similarity).`
`NP_BIND`	`900 910`	`11`	`FAD (By similarity).`
`NP_BIND`	`975 993`	`19`	`NADP (By similarity).`
`NP_BIND`	`1073 1088`	`16`	`NADP (By similarity).`
`REGION`	`506 526`	`21`	`Calmodulin-binding (Potential).`
`METAL`	`107 107`		`Zinc (By similarity).`
`METAL`	`112 112`		`Zinc (By similarity).`
`METAL`	`197 197`		`Iron (heme axial ligand) (By similarity).`
`CONFLICT`	`10 10`		`R -> K (in Ref. 7; BAA07994).`
`CONFLICT`	`72 72`		`H -> Y (in Ref. 1; BAA03138).`
`CONFLICT`	`107 107`		`C -> R (in Ref. 3; AAC13747).`
`CONFLICT`	`128 128`		`D -> V (in Ref. 8; BAA12035).`
`CONFLICT`	`130 130`		`P -> H (in Ref. 3; AAC13747).`
`CONFLICT`	`171 171`		`E -> G (in Ref. 8; BAA12035).`
`CONFLICT`	`195 195`		`P -> S (in Ref. 8; BAA12035).`
`CONFLICT`	`248 248`		`S -> N (in Ref. 9; AAC83553).`
`CONFLICT`	`248 248`		`S -> T (in Ref. 3 and 5).`
`CONFLICT`	`264 264`		`Y -> I (in Ref. 3; AAC13747).`
`CONFLICT`	`271 271`		`D -> A (in Ref. 9; AAC83554).`
`CONFLICT`	`277 277`		`D -> E (in Ref. 3; AAC13747).`
`CONFLICT`	`348 348`		`A -> P (in Ref. 1; BAA03138).`
`CONFLICT`	`349 349`		`V -> A (in Ref. 6; CAA54208).`
`CONFLICT`	`380 380`		`F -> L (in Ref. 2, 7, 8 and 9; AAC83553/AAC83554).`
`CONFLICT`	`395 395`		`R -> S (in Ref. 4; BAA02090).`
`CONFLICT`	`399 399`		`E -> G (in Ref. 9; AAC83553).`
`CONFLICT`	`412 412`		`V -> A (in Ref. 3; AAC13747).`
`CONFLICT`	`477 477`		`M -> I (in Ref. 13).`
`CONFLICT`	`513 513`		`T -> R (in Ref. 11; AAB18620).`
`CONFLICT`	`515 515`		`L -> W (in Ref. 12; AAB31028).`
`CONFLICT`	`545 545`		`G -> R (in Ref. 12; AAB31028).`
`CONFLICT`	`551 551`		`A -> R (in Ref. 11; AAB18620).`
`CONFLICT`	`556 556`		`A -> S (in Ref. 12; AAB31028).`
`CONFLICT`	`559 559`		`S -> T (in Ref. 9; AAC83553/AAC83554).`
`CONFLICT`	`564 564`		`T -> N (in Ref. 12; AAB31028).`
`CONFLICT`	`570 570`		`E -> D (in Ref. 12; AAB31028).`
`CONFLICT`	`583 583`		`L -> P (in Ref. 5 and 10).`
`CONFLICT`	`591 591`		`G -> A (in Ref. 12; AAB31028).`
`CONFLICT`	`591 591`		`G -> V (in Ref. 1 and 6).`
`CONFLICT`	`619 619`		`A -> R (in Ref. 2; AAA85861).`
`CONFLICT`	`640 640`		`Q -> P (in Ref. 9; AAC83553).`
`CONFLICT`	`664 664`		`D -> G (in Ref. 11; AAB18620).`
`CONFLICT`	`679 680`		`ET -> VP (in Ref. 1; BAA03138).`
`CONFLICT`	`690 690`		`Q -> P (in Ref. 11; AAB18620).`
`CONFLICT`	`711 711`		`S -> N (in Ref. 11; AAB18620).`
`CONFLICT`	`714 715`		`SL -> TR (in Ref. 11; AAB18620).`
`CONFLICT`	`714 714`		`S -> P (in Ref. 2, 7, 8, 9; AAC83553/AAC83554 and 10; AAC16401).`
`CONFLICT`	`719 719`		`K -> R (in Ref. 11; AAB18620).`
`CONFLICT`	`721 721`		`L -> P (in Ref. 6).`
`CONFLICT`	`722 722`		`S -> R (in Ref. 1, 6 and 11).`
`CONFLICT`	`724 726`		`IHA -> FLN (in Ref. 11).`
`CONFLICT`	`730 730`		`F -> I (in Ref. 11; AAB18620).`
`CONFLICT`	`731 731`		`T -> A (in Ref. 9; AAC83553).`
`CONFLICT`	`740 740`		`L -> P (in Ref. 6; CAA54208).`
`CONFLICT`	`779 779`		`A -> G (in Ref. 3; AAC13747).`
`CONFLICT`	`834 834`		`P -> S (in Ref. 8; BAA12035).`
`CONFLICT`	`844 844`		`A -> G (in Ref. 1; BAA03138).`
`CONFLICT`	`895 895`		`S -> L (in Ref. 4; BAA02090).`
`CONFLICT`	`911 911`		`Q -> L (in Ref. 3; AAC13747).`
`CONFLICT`	`925 925`		`V -> D (in Ref. 8; BAA12035).`
`CONFLICT`	`937 937`		`H -> N (in Ref. 9; AAC83554).`
`CONFLICT`	`999 999`		`H -> R (in Ref. 2, 7 and 9; AAC83553/AAC83554).`
`CONFLICT`	`1008 1009`		`TL -> NF (in Ref. 9; AAC83554).`
`CONFLICT`	`1016 1016`		`P -> R (in Ref. 5).`
`CONFLICT`	`1016 1016`		`P -> S (in Ref. 8).`
`CONFLICT`	`1017 1017`		`E -> R (in Ref. 5 and 8).`
`CONFLICT`	`1024 1024`		`E -> K (in Ref. 9; AAC83554).`
`CONFLICT`	`1076 1076`		`L -> I (in Ref. 9; AAC83553).`
`CONFLICT`	`1084 1084`		`M -> I (in Ref. 6; CAA54208).`
`CONFLICT`	`1129 1129`		`F -> V (in Ref. 9; AAC83554).`
`CONFLICT`	`1133 1133`		`A -> V (in Ref. 2, 7 and 9; AAC83553/AAC83554).`
`CONFLICT`	`1138 1138`		`T -> A (in Ref. 2, 7 and 9; AAC83553/AAC83554).`

Sequence information

Length: 1147 AA [This is the length of the unprocessed precursor]

Molecular weight: 130628 Da [This is the MW of the unprocessed precursor]

CRC64: 77C77432DD8AB0A9 [This is a checksum on the sequence]

        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

Q06518 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools