ID NOS2_MOUSE Reviewed; 1144 AA. AC P29477; O70515; O70516; Q5SXT3; Q6P6A0; Q8R410; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1993, sequence version 1. DT 27-MAR-2024, entry version 230. DE RecName: Full=Nitric oxide synthase, inducible; DE EC=1.14.13.39 {ECO:0000250|UniProtKB:P35228}; DE AltName: Full=Inducible NO synthase; DE Short=Inducible NOS; DE Short=iNOS; DE AltName: Full=Macrophage NOS; DE Short=MAC-NOS; DE AltName: Full=NOS type II; DE AltName: Full=Peptidyl-cysteine S-nitrosylase NOS2; GN Name=Nos2; Synonyms=Inosl; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1373522; DOI=10.1126/science.1373522; RA Xie Q.-W., Cho H.J., Calaycay J., Mumford R.A., Swiderek K.M., Lee T.D., RA Ding A., Troso T., Nathan C.; RT "Cloning and characterization of inducible nitric oxide synthase from mouse RT macrophages."; RL Science 256:225-228(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1379716; DOI=10.1073/pnas.89.15.6711; RA Lowenstein C.J., Glatt C.S., Bredt D.S., Snyder S.H.; RT "Cloned and expressed macrophage nitric oxide synthase contrasts with the RT brain enzyme."; RL Proc. Natl. Acad. Sci. U.S.A. 89:6711-6715(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1372907; DOI=10.1016/s0021-9258(18)42704-4; RA Lyons C.R., Orloff G.J., Cunningham J.M.; RT "Molecular cloning and functional expression of an inducible nitric oxide RT synthase from a murine macrophage cell line."; RL J. Biol. Chem. 267:6370-6374(1992). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RX PubMed=7503239; DOI=10.1152/ajprenal.1995.269.5.f718; RA Kone B.C., Schwoebel J., Turner P., Mohaupt M.G., Cangro C.B.; RT "Role of NF-kappa B in the regulation of inducible nitric oxide synthase in RT an MTAL cell line."; RL Am. J. Physiol. 269:F718-F729(1995). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ARG-211; LEU-967 AND PHE-968. RC STRAIN=B10.S/J, BALB/cByJ, DBA/2J, NOD/LtJ, and SJL/J; TISSUE=Spleen; RX PubMed=10438970; RA Teuscher C., Butterfield R.J., Ma R.Z., Zachary J.F., Doerge R.W., RA Blankenhorn E.P.; RT "Sequence polymorphisms in the chemokines Scya1 (TCA-3), Scya2 (monocyte RT chemoattractant protein (MCP)-1), and Scya12 (MCP-5) are candidates for RT eae7, a locus controlling susceptibility to monophasic RT remitting/nonrelapsing experimental allergic encephalomyelitis."; RL J. Immunol. 163:2262-2266(1999). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=CD-1; RA Coge F., Levacher B., Rique H., Leopold O., Boutin J.A., Galizzi J.-P.; RT "Genomic structure of the murine inducible nitric oxide synthase (i-NOS) RT gene."; RL Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=ICR; RA Hagiwara K., Endo Y., Xin H., Takahashi M., Huqun X., Nukiwa T.; RT "Mouse inducible nitric oxide synthase mRNA."; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=NMRI; TISSUE=Mammary tumor; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP PROTEIN SEQUENCE OF 733-744, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=OF1; TISSUE=Hippocampus; RA Lubec G., Sunyer B., Chen W.-Q.; RL Submitted (JAN-2009) to UniProtKB. RN [11] RP EFFECT OF ASPIRIN. RC TISSUE=Macrophage; RX PubMed=7544010; DOI=10.1073/pnas.92.17.7926; RA Amin A.R., Vyas P., Attur M., Leszczynska-Piziak J., Patel I.R., RA Weissmann G., Abramson S.B.; RT "The mode of action of aspirin-like drugs: effect on inducible nitric oxide RT synthase."; RL Proc. Natl. Acad. Sci. U.S.A. 92:7926-7930(1995). RN [12] RP FUNCTION AS NITROSYLASE. RX PubMed=16373578; DOI=10.1126/science.1119407; RA Kim S.F., Huri D.A., Snyder S.H.; RT "Inducible nitric oxide synthase binds, S-nitrosylates, and activates RT cyclooxygenase-2."; RL Science 310:1966-1970(2005). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [14] RP POLYUBIQUITINATION, PROTEASOMAL DEGRADATION, INTERACTION WITH SPSB1; SPSB2 RP AND SPSB4, MOTIF DINNN, AND MUTAGENESIS OF LYS-22; ASP-23; ASN-25; ASN-27; RP VAL-28 AND LYS-30. RX PubMed=20603330; DOI=10.1083/jcb.200912087; RA Kuang Z., Lewis R.S., Curtis J.M., Zhan Y., Saunders B.M., Babon J.J., RA Kolesnik T.B., Low A., Masters S.L., Willson T.A., Kedzierski L., Yao S., RA Handman E., Norton R.S., Nicholson S.E.; RT "The SPRY domain-containing SOCS box protein SPSB2 targets iNOS for RT proteasomal degradation."; RL J. Cell Biol. 190:129-141(2010). RN [15] RP POLYUBIQUITINATION, AND PROTEASOMAL DEGRADATION. RX PubMed=21199876; DOI=10.1074/jbc.m110.190678; RA Nishiya T., Matsumoto K., Maekawa S., Kajita E., Horinouchi T., RA Fujimuro M., Ogasawara K., Uehara T., Miwa S.; RT "Regulation of inducible nitric-oxide synthase by the SPRY domain- and SOCS RT box-containing proteins."; RL J. Biol. Chem. 286:9009-9019(2011). RN [16] RP INTERACTION WITH ASL; ASS1 AND HSP90AA1. RX PubMed=22081021; DOI=10.1038/nm.2544; RA Erez A., Nagamani S.C., Shchelochkov O.A., Premkumar M.H., Campeau P.M., RA Chen Y., Garg H.K., Li L., Mian A., Bertin T.K., Black J.O., Zeng H., RA Tang Y., Reddy A.K., Summar M., O'Brien W.E., Harrison D.G., Mitch W.E., RA Marini J.C., Aschner J.L., Bryan N.S., Lee B.; RT "Requirement of argininosuccinate lyase for systemic nitric oxide RT production."; RL Nat. Med. 17:1619-1626(2011). RN [17] RP INDUCTION BY LIPOPOLYSACCHARIDES AND CIRCADIAN RHYTHM. RX PubMed=22073225; DOI=10.1371/journal.pone.0026954; RA Niu S., Shingle D.L., Garbarino-Pico E., Kojima S., Gilbert M., Green C.B.; RT "The circadian deadenylase Nocturnin is necessary for stabilization of the RT iNOS mRNA in mice."; RL PLoS ONE 6:E26954-E26954(2011). RN [18] RP INDUCTION BY LIPOPOLYSACCHARIDES. RX PubMed=24970700; DOI=10.1159/000362647; RA Ranjan R., Deng J., Chung S., Lee Y.G., Park G.Y., Xiao L., Joo M., RA Christman J.W., Karpurapu M.; RT "The transcription factor nuclear factor of activated T cells c3 modulates RT the function of macrophages in sepsis."; RL J. Innate Immun. 6:754-764(2014). RN [19] {ECO:0007744|PDB:1NOC, ECO:0007744|PDB:1NOS, ECO:0007744|PDB:2NOS} RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 116-496. RX PubMed=9334294; DOI=10.1126/science.278.5337.425; RA Crane B.R., Arvai A.S., Gachhui R., Wu C., Ghosh D.K., Getzoff E.D., RA Stuehr D.J., Tainer J.A.; RT "The structure of nitric oxide synthase oxygenase domain and inhibitor RT complexes."; RL Science 278:425-431(1997). RN [20] {ECO:0007744|PDB:1NOD, ECO:0007744|PDB:2NOD, ECO:0007744|PDB:3NOD} RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 77-496 IN COMPLEX WITH RP (6R)-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN AND HEME B. RX PubMed=9516116; DOI=10.1126/science.279.5359.2121; RA Crane B.R., Arvai A.S., Ghosh D.K., Wu C., Getzoff E.D., Stuehr D.J., RA Tainer J.A.; RT "Structure of nitric oxide synthase oxygenase dimer with pterin and RT substrate."; RL Science 279:2121-2126(1998). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 77-496. RX PubMed=10562538; DOI=10.1093/emboj/18.22.6260; RA Ghosh D.K., Crane B.R., Ghosh S., Wolan D., Gachhui R., Crooks C., RA Presta A., Tainer J.A., Getzoff E.D., Stuehr D.J.; RT "Inducible nitric oxide synthase: role of the N-terminal beta-hairpin hook RT and pterin-binding segment in dimerization and tetrahydrobiopterin RT interaction."; RL EMBO J. 18:6260-6270(1999). RN [22] {ECO:0007744|PDB:1DF1, ECO:0007744|PDB:1QOM} RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 77-499 IN COMPLEX WITH RP (6R)-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN; ZINC AND HEME B. RX PubMed=10562539; DOI=10.1093/emboj/18.22.6271; RA Crane B.R., Rosenfeld R.J., Arvai A.S., Ghosh D.K., Ghosh S., Tainer J.A., RA Stuehr D.J., Getzoff E.D.; RT "N-terminal domain swapping and metal ion binding in nitric oxide synthase RT dimerization."; RL EMBO J. 18:6271-6281(1999). RN [23] {ECO:0007744|PDB:1DWV, ECO:0007744|PDB:1DWW, ECO:0007744|PDB:1DWX} RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 77-496 IN COMPLEX WITH RP (6R)-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN; ZINC AND HEME B, AND SUBUNIT. RX PubMed=10769116; DOI=10.1021/bi992409a; RA Crane B.R., Arvai A.S., Ghosh S., Getzoff E.D., Stuehr D.J., Tainer J.A.; RT "Structures of the N(omega)-hydroxy-L-arginine complex of inducible nitric RT oxide synthase oxygenase dimer with active and inactive pterins."; RL Biochemistry 39:4608-4621(2000). RN [24] {ECO:0007744|PDB:1JWJ, ECO:0007744|PDB:1JWK} RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF TRP-457 MUTANT IN COMPLEX WITH RP (6R)-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN, AND SUBUNIT. RX PubMed=11669619; DOI=10.1021/bi011183k; RA Aoyagi M., Arvai A.S., Ghosh S., Stuehr D.J., Tainer J.A., Getzoff E.D.; RT "Structures of tetrahydrobiopterin binding-site mutants of inducible nitric RT oxide synthase oxygenase dimer and implicated roles of Trp457."; RL Biochemistry 40:12826-12832(2001). RN [25] {ECO:0007744|PDB:1M8D, ECO:0007744|PDB:1M8E, ECO:0007744|PDB:1M8H, ECO:0007744|PDB:1M8I, ECO:0007744|PDB:1M9T} RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 77-496 IN COMPLEX WITH RP (6R)-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN AND HEME B. RX PubMed=12437348; DOI=10.1021/bi026313j; RA Rosenfeld R.J., Garcin E.D., Panda K., Andersson G., Aberg A., RA Wallace A.V., Morris G.M., Olson A.J., Stuehr D.J., Tainer J.A., RA Getzoff E.D.; RT "Conformational changes in nitric oxide synthases induced by chlorzoxazone RT and nitroindazoles: crystallographic and computational analyses of RT inhibitor potency."; RL Biochemistry 41:13915-13925(2002). RN [26] {ECO:0007744|PDB:1N2N} RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 77-495 IN COMPLEX WITH RP (6R)-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN; ZINC AND HEME B. RX PubMed=12464241; DOI=10.1016/s0003-9861(02)00555-6; RA Fedorov R., Ghosh D.K., Schlichting I.; RT "Crystal structures of cyanide complexes of P450cam and the oxygenase RT domain of inducible nitric oxide synthase -- structural models of the RT short-lived oxygen complexes."; RL Arch. Biochem. Biophys. 409:25-31(2003). CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with CC diverse functions throughout the body (PubMed:7503239). In macrophages, CC NO mediates tumoricidal and bactericidal actions. Also has nitrosylase CC activity and mediates cysteine S-nitrosylation of cytoplasmic target CC proteins such PTGS2/COX2 (PubMed:16373578). As component of the iNOS- CC S100A8/9 transnitrosylase complex involved in the selective CC inflammatory stimulus-dependent S-nitrosylation of GAPDH implicated in CC regulation of the GAIT complex activity and probably multiple targets CC including ANXA5, EZR, MSN and VIM (By similarity). Involved in CC inflammation, enhances the synthesis of pro-inflammatory mediators such CC as IL6 and IL8 (By similarity). {ECO:0000250|UniProtKB:P35228, CC ECO:0000250|UniProtKB:P79290, ECO:0000269|PubMed:16373578, CC ECO:0000269|PubMed:7503239}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + 2 L-arginine + 3 NADPH + 4 O2 = 4 H2O + 2 L-citrulline CC + 3 NADP(+) + 2 nitric oxide; Xref=Rhea:RHEA:19897, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16480, ChEBI:CHEBI:32682, ChEBI:CHEBI:57743, CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.14.13.39; CC Evidence={ECO:0000250|UniProtKB:P35228}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19898; CC Evidence={ECO:0000250|UniProtKB:P35228}; CC -!- COFACTOR: CC Name=heme b; Xref=ChEBI:CHEBI:60344; CC Evidence={ECO:0000269|PubMed:10562539, ECO:0000269|PubMed:10769116, CC ECO:0000269|PubMed:12437348, ECO:0000269|PubMed:12464241, CC ECO:0000269|PubMed:9516116}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000250|UniProtKB:P29476}; CC Note=Binds 1 FAD. {ECO:0000250|UniProtKB:P29476}; CC -!- COFACTOR: CC Name=FMN; Xref=ChEBI:CHEBI:58210; CC Evidence={ECO:0000250|UniProtKB:P35228}; CC Note=Binds 1 FMN. {ECO:0000250|UniProtKB:P35228}; CC -!- COFACTOR: CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin; CC Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000269|PubMed:10562539, CC ECO:0000269|PubMed:10769116, ECO:0000269|PubMed:11669619, CC ECO:0000269|PubMed:12437348, ECO:0000269|PubMed:12464241, CC ECO:0000269|PubMed:9516116}; CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the CC enzyme. {ECO:0000269|PubMed:10562539, ECO:0000269|PubMed:10769116, CC ECO:0000269|PubMed:11669619, ECO:0000269|PubMed:12437348, CC ECO:0000269|PubMed:12464241, ECO:0000269|PubMed:9516116}; CC -!- ACTIVITY REGULATION: Not stimulated by calcium/calmodulin. Aspirin CC inhibits expression and function of this enzyme and effects may be CC exerted at the level of translational/post-translational modification CC and directly on the catalytic activity. CC -!- SUBUNIT: Homodimer (PubMed:10769116, PubMed:11669619). Interacts with CC NHERF1 (By similarity). Interacts with GAPDH (By similarity). Interacts CC with S100A8 and S100A9 to form the iNOS-S100A8/9 transnitrosylase CC complex (By similarity). Interacts with SPSB1, SPSB2 and SPSB4 CC (PubMed:20603330). Interacts with ELOC and CUL5 in the presence of CC SPSB1 or SPSB2 or SPSB4 (By similarity). Forms a complex with ASL, ASS1 CC and HSP90AA1; the complex regulates cell-autonomous L-arginine CC synthesis and citrulline recycling while channeling extracellular L- CC arginine to nitric oxide synthesis pathway. CC {ECO:0000250|UniProtKB:P35228, ECO:0000269|PubMed:10769116, CC ECO:0000269|PubMed:11669619, ECO:0000269|PubMed:20603330, CC ECO:0000269|PubMed:22081021}. CC -!- INTERACTION: CC P29477; Q04207: Rela; NbExp=3; IntAct=EBI-298897, EBI-644400; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P35228}. Note=Localizes as discrete foci CC scattered throughout the cytosol and in the presence of SPSB1 and CC SPSB4, exhibits a more diffuse cytosolic localization. CC {ECO:0000250|UniProtKB:P35228}. CC -!- TISSUE SPECIFICITY: Macrophages. CC -!- INDUCTION: By treatment with endotoxins or cytokines. Induced by CC lipopolysaccharides (LPS) in macrophages (in vitro) (PubMed:22073225, CC PubMed:24970700). Expression in the liver oscillates in a circadian CC manner with peak levels occurring during the late night CC (PubMed:22073225). {ECO:0000269|PubMed:22073225, CC ECO:0000269|PubMed:24970700}. CC -!- PTM: Polyubiquitinated; mediated by SPSB1, SPSB2 and SPSB4, leading to CC proteasomal degradation. {ECO:0000269|PubMed:20603330, CC ECO:0000269|PubMed:21199876}. CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M87039; AAA39315.1; -; mRNA. DR EMBL; M92649; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; M84373; AAA39834.1; -; mRNA. DR EMBL; U43428; AAC52356.1; -; mRNA. DR EMBL; AF065919; AAC17914.1; -; mRNA. DR EMBL; AF065920; AAC17915.1; -; mRNA. DR EMBL; AF065921; AAC17916.2; -; mRNA. DR EMBL; AF065922; AAC17917.2; -; mRNA. DR EMBL; AF065923; AAC17918.2; -; mRNA. DR EMBL; AF427516; AAL24076.1; -; Genomic_DNA. DR EMBL; AY090567; AAM11887.1; -; mRNA. DR EMBL; AL592185; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC062378; AAH62378.1; -; mRNA. DR CCDS; CCDS25115.1; -. DR PIR; A43271; A43271. DR RefSeq; NP_001300850.1; NM_001313921.1. DR RefSeq; NP_001300851.1; NM_001313922.1. DR RefSeq; NP_035057.1; NM_010927.4. DR PDB; 1DD7; X-ray; 2.25 A; A=114-498. DR PDB; 1DF1; X-ray; 2.35 A; A/B=77-499. DR PDB; 1DWV; X-ray; 2.35 A; A/B=77-496. DR PDB; 1DWW; X-ray; 2.35 A; A/B=77-496. DR PDB; 1DWX; X-ray; 2.60 A; A/B=77-496. DR PDB; 1JWJ; X-ray; 2.60 A; A/B=66-498. DR PDB; 1JWK; X-ray; 2.30 A; A/B=66-498. DR PDB; 1M8D; X-ray; 2.35 A; A/B=65-498. DR PDB; 1M8E; X-ray; 2.90 A; A/B=65-498. DR PDB; 1M8H; X-ray; 2.85 A; A/B=65-498. DR PDB; 1M8I; X-ray; 2.70 A; A/B=65-498. DR PDB; 1M9T; X-ray; 2.40 A; A/B=65-498. DR PDB; 1N2N; X-ray; 2.40 A; A/B=77-495. DR PDB; 1NOC; X-ray; 2.60 A; A=115-498. DR PDB; 1NOD; X-ray; 2.60 A; A/B=77-499. DR PDB; 1NOS; X-ray; 2.10 A; A=115-498. DR PDB; 1QOM; X-ray; 2.70 A; A/B=65-498. DR PDB; 1QW4; X-ray; 2.40 A; A/B=77-495. DR PDB; 1QW5; X-ray; 2.70 A; A/B=77-495. DR PDB; 1R35; X-ray; 2.30 A; A/B=66-498. DR PDB; 1VAF; X-ray; 2.90 A; A/B=77-495. DR PDB; 2BHJ; X-ray; 3.20 A; A=77-498. DR PDB; 2NOD; X-ray; 2.60 A; A/B=77-499. DR PDB; 2NOS; X-ray; 2.30 A; A=115-498. DR PDB; 2ORO; X-ray; 2.00 A; A=114-498. DR PDB; 2ORP; X-ray; 1.97 A; A=114-498. DR PDB; 2ORQ; X-ray; 2.10 A; A=114-498. DR PDB; 2ORR; X-ray; 2.00 A; A=114-498. DR PDB; 2ORS; X-ray; 2.00 A; A=114-498. DR PDB; 2ORT; X-ray; 1.87 A; A=114-498. DR PDB; 2Y37; X-ray; 2.60 A; A/B=66-498. DR PDB; 3DWJ; X-ray; 2.75 A; A/B=66-496. DR PDB; 3E65; X-ray; 2.05 A; A/B=66-498. DR PDB; 3E67; X-ray; 2.60 A; A/B=66-498. DR PDB; 3E68; X-ray; 2.20 A; A/B=66-498. DR PDB; 3E6L; X-ray; 2.30 A; A/B=66-498. DR PDB; 3E6N; X-ray; 2.40 A; A/B=66-498. DR PDB; 3E6O; X-ray; 2.60 A; A/B=66-498. DR PDB; 3E6T; X-ray; 2.50 A; A/B=66-498. DR PDB; 3E7I; X-ray; 2.90 A; A/B=66-498. DR PDB; 3E7M; X-ray; 2.00 A; A/B=66-498. DR PDB; 3E7T; X-ray; 2.60 A; A/B=66-498. DR PDB; 3EAI; X-ray; 2.20 A; A/B=66-498. DR PDB; 3EBD; X-ray; 2.40 A; A/B=66-498. DR PDB; 3EBF; X-ray; 2.29 A; A/B=66-498. DR PDB; 3GOF; X-ray; 1.45 A; C/D=503-518. DR PDB; 3NOD; X-ray; 2.70 A; A/B=77-499. DR PDB; 3NQS; X-ray; 2.20 A; A/B=66-498. DR PDB; 3NW2; X-ray; 2.80 A; A/B=77-499. DR PDB; 4JS9; X-ray; 2.78 A; A/B=66-496. DR PDB; 4UX6; X-ray; 3.00 A; A=77-100, B=108-496. DR PDBsum; 1DD7; -. DR PDBsum; 1DF1; -. DR PDBsum; 1DWV; -. DR PDBsum; 1DWW; -. DR PDBsum; 1DWX; -. DR PDBsum; 1JWJ; -. DR PDBsum; 1JWK; -. DR PDBsum; 1M8D; -. DR PDBsum; 1M8E; -. DR PDBsum; 1M8H; -. DR PDBsum; 1M8I; -. DR PDBsum; 1M9T; -. DR PDBsum; 1N2N; -. DR PDBsum; 1NOC; -. DR PDBsum; 1NOD; -. DR PDBsum; 1NOS; -. DR PDBsum; 1QOM; -. DR PDBsum; 1QW4; -. DR PDBsum; 1QW5; -. DR PDBsum; 1R35; -. DR PDBsum; 1VAF; -. DR PDBsum; 2BHJ; -. DR PDBsum; 2NOD; -. DR PDBsum; 2NOS; -. DR PDBsum; 2ORO; -. DR PDBsum; 2ORP; -. DR PDBsum; 2ORQ; -. DR PDBsum; 2ORR; -. DR PDBsum; 2ORS; -. DR PDBsum; 2ORT; -. DR PDBsum; 2Y37; -. DR PDBsum; 3DWJ; -. DR PDBsum; 3E65; -. DR PDBsum; 3E67; -. DR PDBsum; 3E68; -. DR PDBsum; 3E6L; -. DR PDBsum; 3E6N; -. DR PDBsum; 3E6O; -. DR PDBsum; 3E6T; -. DR PDBsum; 3E7I; -. DR PDBsum; 3E7M; -. DR PDBsum; 3E7T; -. DR PDBsum; 3EAI; -. DR PDBsum; 3EBD; -. DR PDBsum; 3EBF; -. DR PDBsum; 3GOF; -. DR PDBsum; 3NOD; -. DR PDBsum; 3NQS; -. DR PDBsum; 3NW2; -. DR PDBsum; 4JS9; -. DR PDBsum; 4UX6; -. DR AlphaFoldDB; P29477; -. DR EMDB; EMD-2718; -. DR EMDB; EMD-2719; -. DR EMDB; EMD-2720; -. DR EMDB; EMD-2721; -. DR EMDB; EMD-2722; -. DR EMDB; EMD-2723; -. DR EMDB; EMD-2724; -. DR EMDB; EMD-2725; -. DR EMDB; EMD-2726; -. DR EMDB; EMD-2727; -. DR EMDB; EMD-2728; -. DR EMDB; EMD-2729; -. DR EMDB; EMD-2730; -. DR EMDB; EMD-2731; -. DR EMDB; EMD-2732; -. DR EMDB; EMD-2733; -. DR EMDB; EMD-2734; -. DR EMDB; EMD-2735; -. DR EMDB; EMD-2736; -. DR EMDB; EMD-2737; -. DR EMDB; EMD-2738; -. DR EMDB; EMD-2739; -. DR EMDB; EMD-2740; -. DR EMDB; EMD-2741; -. DR EMDB; EMD-2742; -. DR EMDB; EMD-2743; -. DR EMDB; EMD-2744; -. DR EMDB; EMD-2745; -. DR EMDB; EMD-2746; -. DR EMDB; EMD-2747; -. DR EMDB; EMD-2748; -. DR EMDB; EMD-2749; -. DR SMR; P29477; -. DR BioGRID; 201806; 9. DR ComplexPortal; CPX-53; iNOS-S100A8/A9 complex. DR DIP; DIP-31080N; -. DR IntAct; P29477; 2. DR MINT; P29477; -. DR STRING; 10090.ENSMUSP00000018610; -. DR BindingDB; P29477; -. DR ChEMBL; CHEMBL3464; -. DR DrugCentral; P29477; -. DR GlyGen; P29477; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P29477; -. DR PhosphoSitePlus; P29477; -. DR SwissPalm; P29477; -. DR MaxQB; P29477; -. DR PaxDb; 10090-ENSMUSP00000018610; -. DR ProteomicsDB; 293704; -. DR Antibodypedia; 4550; 1293 antibodies from 47 providers. DR DNASU; 18126; -. DR Ensembl; ENSMUST00000018610.7; ENSMUSP00000018610.7; ENSMUSG00000020826.10. DR GeneID; 18126; -. DR KEGG; mmu:18126; -. DR UCSC; uc007kkc.1; mouse. DR AGR; MGI:97361; -. DR CTD; 4843; -. DR MGI; MGI:97361; Nos2. DR VEuPathDB; HostDB:ENSMUSG00000020826; -. DR eggNOG; KOG1158; Eukaryota. DR GeneTree; ENSGT00940000159752; -. DR HOGENOM; CLU_001570_16_0_1; -. DR InParanoid; P29477; -. DR OMA; CRHIRYA; -. DR OrthoDB; 276396at2759; -. DR PhylomeDB; P29477; -. DR TreeFam; TF324410; -. DR BRENDA; 1.14.13.39; 3474. DR Reactome; R-MMU-1222556; ROS and RNS production in phagocytes. DR Reactome; R-MMU-392154; Nitric oxide stimulates guanylate cyclase. DR Reactome; R-MMU-9033241; Peroxisomal protein import. DR BioGRID-ORCS; 18126; 4 hits in 81 CRISPR screens. DR EvolutionaryTrace; P29477; -. DR PRO; PR:P29477; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; P29477; Protein. DR Bgee; ENSMUSG00000020826; Expressed in ectoplacental cone and 40 other cell types or tissues. DR ExpressionAtlas; P29477; baseline and differential. DR GO; GO:0030863; C:cortical cytoskeleton; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005615; C:extracellular space; ISO:MGI. DR GO; GO:0005634; C:nucleus; ISO:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI. DR GO; GO:0005777; C:peroxisome; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0003779; F:actin binding; ISO:MGI. DR GO; GO:0034618; F:arginine binding; IDA:BHF-UCL. DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI. DR GO; GO:0045296; F:cadherin binding; ISO:MGI. DR GO; GO:0005516; F:calmodulin binding; TAS:UniProtKB. DR GO; GO:0008603; F:cAMP-dependent protein kinase regulator activity; ISO:MGI. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IDA:BHF-UCL. DR GO; GO:0010181; F:FMN binding; IDA:BHF-UCL. DR GO; GO:0020037; F:heme binding; IDA:BHF-UCL. DR GO; GO:0051879; F:Hsp90 protein binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; ISO:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0050661; F:NADP binding; IEA:InterPro. DR GO; GO:0004517; F:nitric-oxide synthase activity; IDA:BHF-UCL. DR GO; GO:0050998; F:nitric-oxide synthase binding; ISO:MGI. DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0034617; F:tetrahydrobiopterin binding; IDA:BHF-UCL. DR GO; GO:0006527; P:arginine catabolic process; IDA:BHF-UCL. DR GO; GO:0001974; P:blood vessel remodeling; ISO:MGI. DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISO:MGI. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:MGI. DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI. DR GO; GO:0071346; P:cellular response to type II interferon; IDA:MGI. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IDA:MGI. DR GO; GO:0019934; P:cGMP-mediated signaling; ISO:MGI. DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB. DR GO; GO:0042742; P:defense response to bacterium; IMP:MGI. DR GO; GO:0007199; P:G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger; ISO:MGI. DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central. DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI. DR GO; GO:0045776; P:negative regulation of blood pressure; IBA:GO_Central. DR GO; GO:0010629; P:negative regulation of gene expression; IGI:UniProtKB. DR GO; GO:0042177; P:negative regulation of protein catabolic process; IDA:BHF-UCL. DR GO; GO:0006809; P:nitric oxide biosynthetic process; IDA:BHF-UCL. DR GO; GO:0007263; P:nitric oxide mediated signal transduction; IBA:GO_Central. DR GO; GO:0018119; P:peptidyl-cysteine S-nitrosylation; IDA:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISS:UniProtKB. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB. DR GO; GO:0051712; P:positive regulation of killing of cells of another organism; ISO:MGI. DR GO; GO:0032310; P:prostaglandin secretion; ISS:UniProtKB. DR GO; GO:0008217; P:regulation of blood pressure; ISO:MGI. DR GO; GO:0042127; P:regulation of cell population proliferation; IGI:MGI. DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; ISS:UniProtKB. DR GO; GO:0050796; P:regulation of insulin secretion; ISO:MGI. DR GO; GO:0009617; P:response to bacterium; IEP:MGI. DR GO; GO:0009725; P:response to hormone; IBA:GO_Central. DR GO; GO:0001666; P:response to hypoxia; IDA:MGI. DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:UniProtKB. DR GO; GO:0034612; P:response to tumor necrosis factor; ISO:MGI. DR GO; GO:0006801; P:superoxide metabolic process; IMP:MGI. DR CDD; cd00795; NOS_oxygenase_euk; 1. DR Gene3D; 3.40.50.360; -; 2. DR Gene3D; 6.10.250.410; -; 1. DR Gene3D; 3.90.440.10; Nitric Oxide Synthase;Heme Domain;Chain A domain 2; 1. DR Gene3D; 3.40.50.80; Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module; 1. DR Gene3D; 2.40.30.10; Translation factors; 1. DR InterPro; IPR003097; CysJ-like_FAD-binding. DR InterPro; IPR017927; FAD-bd_FR_type. DR InterPro; IPR001094; Flavdoxin-like. DR InterPro; IPR008254; Flavodoxin/NO_synth. DR InterPro; IPR001709; Flavoprot_Pyr_Nucl_cyt_Rdtase. DR InterPro; IPR029039; Flavoprotein-like_sf. DR InterPro; IPR039261; FNR_nucleotide-bd. DR InterPro; IPR023173; NADPH_Cyt_P450_Rdtase_alpha. DR InterPro; IPR044943; NOS_dom_1. DR InterPro; IPR044940; NOS_dom_2. DR InterPro; IPR044944; NOS_dom_3. DR InterPro; IPR012144; NOS_euk. DR InterPro; IPR004030; NOS_N. DR InterPro; IPR036119; NOS_N_sf. DR InterPro; IPR001433; OxRdtase_FAD/NAD-bd. DR InterPro; IPR017938; Riboflavin_synthase-like_b-brl. DR PANTHER; PTHR43410; NITRIC OXIDE SYNTHASE OXYGENASE; 1. DR PANTHER; PTHR43410:SF1; NITRIC OXIDE SYNTHASE OXYGENASE; 1. DR Pfam; PF00667; FAD_binding_1; 1. DR Pfam; PF00258; Flavodoxin_1; 1. DR Pfam; PF00175; NAD_binding_1; 1. DR Pfam; PF02898; NO_synthase; 1. DR PIRSF; PIRSF000333; NOS; 1. DR PRINTS; PR00369; FLAVODOXIN. DR PRINTS; PR00371; FPNCR. DR SUPFAM; SSF52343; Ferredoxin reductase-like, C-terminal NADP-linked domain; 1. DR SUPFAM; SSF52218; Flavoproteins; 1. DR SUPFAM; SSF56512; Nitric oxide (NO) synthase oxygenase domain; 1. DR SUPFAM; SSF63380; Riboflavin synthase domain-like; 1. DR PROSITE; PS51384; FAD_FR; 1. DR PROSITE; PS50902; FLAVODOXIN_LIKE; 1. DR PROSITE; PS60001; NOS; 1. DR Genevisible; P29477; MM. PE 1: Evidence at protein level; KW 3D-structure; Calmodulin-binding; Cytoplasm; Direct protein sequencing; KW FAD; Flavoprotein; FMN; Heme; Iron; Metal-binding; NADP; Oxidoreductase; KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc. FT CHAIN 1..1144 FT /note="Nitric oxide synthase, inducible" FT /id="PRO_0000170934" FT DOMAIN 533..671 FT /note="Flavodoxin-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088" FT DOMAIN 724..964 FT /note="FAD-binding FR-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716" FT REGION 37..59 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 509..529 FT /note="Calmodulin-binding" FT /evidence="ECO:0000250|UniProtKB:P35228" FT MOTIF 23..27 FT /note="DINNN-motif; mediates interaction with SPSB1, SPSB2 FT and SPSB4" FT /evidence="ECO:0000269|PubMed:20603330" FT COMPBIAS 41..59 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 104 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="ligand shared between homodimeric partners" FT /evidence="ECO:0000269|PubMed:10562539, FT ECO:0000269|PubMed:10769116, ECO:0000269|PubMed:12464241, FT ECO:0007744|PDB:1DF1, ECO:0007744|PDB:1DWV, FT ECO:0007744|PDB:1DWW, ECO:0007744|PDB:1N2N" FT BINDING 109 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="ligand shared between homodimeric partners" FT /evidence="ECO:0000269|PubMed:10562539, FT ECO:0000269|PubMed:10769116, ECO:0000269|PubMed:12464241, FT ECO:0007744|PDB:1DF1, ECO:0007744|PDB:1DWV, FT ECO:0007744|PDB:1DWW, ECO:0007744|PDB:1N2N" FT BINDING 112 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:10562539, FT ECO:0000269|PubMed:10769116, ECO:0000269|PubMed:11669619, FT ECO:0000269|PubMed:12437348, ECO:0000269|PubMed:12464241, FT ECO:0000269|PubMed:9516116, ECO:0007744|PDB:1DF1, FT ECO:0007744|PDB:1DWX, ECO:0007744|PDB:1JWJ, FT ECO:0007744|PDB:1M8D, ECO:0007744|PDB:1M8E, FT ECO:0007744|PDB:1M8H, ECO:0007744|PDB:1M8I, FT ECO:0007744|PDB:1M9T, ECO:0007744|PDB:1N2N, FT ECO:0007744|PDB:1NOD, ECO:0007744|PDB:1QOM, FT ECO:0007744|PDB:2NOD, ECO:0007744|PDB:3NOD" FT BINDING 194 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /ligand_part="Fe" FT /ligand_part_id="ChEBI:CHEBI:18248" FT /note="axial binding residue" FT /evidence="ECO:0000269|PubMed:10562539, FT ECO:0000269|PubMed:10769116, ECO:0000269|PubMed:11669619, FT ECO:0000269|PubMed:12437348, ECO:0000269|PubMed:12464241, FT ECO:0000269|PubMed:9334294, ECO:0000269|PubMed:9516116, FT ECO:0007744|PDB:1DF1, ECO:0007744|PDB:1DWV, FT ECO:0007744|PDB:1DWW, ECO:0007744|PDB:1DWX, FT ECO:0007744|PDB:1JWJ, ECO:0007744|PDB:1JWK, FT ECO:0007744|PDB:1M8D, ECO:0007744|PDB:1M8E, FT ECO:0007744|PDB:1M8H, ECO:0007744|PDB:1M8I, FT ECO:0007744|PDB:1M9T, ECO:0007744|PDB:1N2N, FT ECO:0007744|PDB:1NOC, ECO:0007744|PDB:1NOD, FT ECO:0007744|PDB:1NOS, ECO:0007744|PDB:1QOM, FT ECO:0007744|PDB:2NOD, ECO:0007744|PDB:2NOS, FT ECO:0007744|PDB:3NOD" FT BINDING 257 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 366 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 367 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 371 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 375 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:10562539, FT ECO:0000269|PubMed:10769116, ECO:0000269|PubMed:11669619, FT ECO:0000269|PubMed:12437348, ECO:0000269|PubMed:12464241, FT ECO:0000269|PubMed:9516116, ECO:0007744|PDB:1DF1, FT ECO:0007744|PDB:1DWX, ECO:0007744|PDB:1JWJ, FT ECO:0007744|PDB:1JWK, ECO:0007744|PDB:1M8D, FT ECO:0007744|PDB:1M8E, ECO:0007744|PDB:1M8H, FT ECO:0007744|PDB:1M8I, ECO:0007744|PDB:1M9T, FT ECO:0007744|PDB:1N2N, ECO:0007744|PDB:1NOD, FT ECO:0007744|PDB:1QOM, ECO:0007744|PDB:3NOD" FT BINDING 456 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:10562539, FT ECO:0000269|PubMed:12437348, ECO:0000269|PubMed:12464241, FT ECO:0007744|PDB:1DF1, ECO:0007744|PDB:1M9T, FT ECO:0007744|PDB:1N2N" FT BINDING 457 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:10562539, FT ECO:0000269|PubMed:10769116, ECO:0000269|PubMed:12437348, FT ECO:0000269|PubMed:12464241, ECO:0000269|PubMed:9516116, FT ECO:0007744|PDB:1DF1, ECO:0007744|PDB:1DWX, FT ECO:0007744|PDB:1M8D, ECO:0007744|PDB:1M8E, FT ECO:0007744|PDB:1M8I, ECO:0007744|PDB:1M9T, FT ECO:0007744|PDB:1N2N, ECO:0007744|PDB:1NOD, FT ECO:0007744|PDB:1QOM, ECO:0007744|PDB:2NOD, FT ECO:0007744|PDB:3NOD" FT BINDING 470 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:10562539, FT ECO:0000269|PubMed:10769116, ECO:0000269|PubMed:11669619, FT ECO:0000269|PubMed:12437348, ECO:0000269|PubMed:12464241, FT ECO:0000269|PubMed:9516116, ECO:0007744|PDB:1DF1, FT ECO:0007744|PDB:1DWX, ECO:0007744|PDB:1JWJ, FT ECO:0007744|PDB:1JWK, ECO:0007744|PDB:1M8D, FT ECO:0007744|PDB:1M8E, ECO:0007744|PDB:1M8H, FT ECO:0007744|PDB:1M8I, ECO:0007744|PDB:1N2N, FT ECO:0007744|PDB:1NOD, ECO:0007744|PDB:1QOM, FT ECO:0007744|PDB:2NOD, ECO:0007744|PDB:3NOD" FT BINDING 485 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000269|PubMed:10562539, FT ECO:0000269|PubMed:10769116, ECO:0000269|PubMed:9516116, FT ECO:0007744|PDB:1DF1, ECO:0007744|PDB:1DWX, FT ECO:0007744|PDB:1NOD, ECO:0007744|PDB:1QOM, FT ECO:0007744|PDB:2NOD, ECO:0007744|PDB:3NOD" FT BINDING 539 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 540 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 541 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 543 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 544 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 585 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 586 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 622 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 629 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 655 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 659 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 744 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 766 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 900 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 902 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 903 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 918 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 920 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 923 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 924 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 937 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 938 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 939 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 978 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1011 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1040 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1041 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1047 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1049 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1051 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1084 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT MOD_RES 569 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q06518" FT VARIANT 211 FT /note="C -> R (in strain: NOD/LtJ)" FT /evidence="ECO:0000269|PubMed:10438970" FT VARIANT 967 FT /note="P -> L (in strain: SJL/J)" FT /evidence="ECO:0000269|PubMed:10438970" FT VARIANT 968 FT /note="S -> F (in strain: BALB/CBYJ)" FT /evidence="ECO:0000269|PubMed:10438970" FT MUTAGEN 22 FT /note="K->A: Reduced interaction with SPSB2." FT /evidence="ECO:0000269|PubMed:20603330" FT MUTAGEN 23 FT /note="D->A: Significant loss of interaction with SPSB2." FT /evidence="ECO:0000269|PubMed:20603330" FT MUTAGEN 25 FT /note="N->A,Q: Significant loss of interaction with SPSB2." FT /evidence="ECO:0000269|PubMed:20603330" FT MUTAGEN 27 FT /note="N->A,Q: Loss of interaction with SPSB2." FT /evidence="ECO:0000269|PubMed:20603330" FT MUTAGEN 28 FT /note="V->A: Reduced interaction with SPSB2." FT /evidence="ECO:0000269|PubMed:20603330" FT MUTAGEN 30 FT /note="K->A: Reduced interaction with SPSB2." FT /evidence="ECO:0000269|PubMed:20603330" FT CONFLICT 19 FT /note="K -> T (in Ref. 4; AAC52356)" FT /evidence="ECO:0000305" FT CONFLICT 72 FT /note="T -> TP (in Ref. 7; AAM11887 and 9; AAH62378)" FT /evidence="ECO:0000305" FT CONFLICT 191 FT /note="A -> V (in Ref. 2; M92649)" FT /evidence="ECO:0000305" FT CONFLICT 245 FT /note="S -> T (in Ref. 7; AAM11887 and 9; AAH62378)" FT /evidence="ECO:0000305" FT CONFLICT 844 FT /note="A -> G (in Ref. 2; M92649)" FT /evidence="ECO:0000305" FT CONFLICT 1075 FT /note="I -> V (in Ref. 9; AAH62378)" FT /evidence="ECO:0000305" FT STRAND 79..83 FT /evidence="ECO:0007829|PDB:3E7M" FT TURN 84..86 FT /evidence="ECO:0007829|PDB:3E7M" FT STRAND 89..92 FT /evidence="ECO:0007829|PDB:3E7M" FT HELIX 94..97 FT /evidence="ECO:0007829|PDB:3E7M" FT STRAND 103..107 FT /evidence="ECO:0007829|PDB:1QOM" FT HELIX 117..119 FT /evidence="ECO:0007829|PDB:3E7M" FT HELIX 130..146 FT /evidence="ECO:0007829|PDB:2ORT" FT TURN 147..150 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 153..170 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 177..189 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 195..199 FT /evidence="ECO:0007829|PDB:2ORT" FT STRAND 204..207 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 208..210 FT /evidence="ECO:0007829|PDB:2BHJ" FT HELIX 214..229 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 230..232 FT /evidence="ECO:0007829|PDB:2ORT" FT STRAND 237..240 FT /evidence="ECO:0007829|PDB:2ORT" FT STRAND 245..249 FT /evidence="ECO:0007829|PDB:2ORT" FT STRAND 255..259 FT /evidence="ECO:0007829|PDB:2ORT" FT STRAND 263..265 FT /evidence="ECO:0007829|PDB:2ORP" FT STRAND 267..269 FT /evidence="ECO:0007829|PDB:2BHJ" FT STRAND 271..273 FT /evidence="ECO:0007829|PDB:2ORP" FT HELIX 275..277 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 278..286 FT /evidence="ECO:0007829|PDB:2ORT" FT STRAND 294..296 FT /evidence="ECO:0007829|PDB:1DF1" FT STRAND 301..304 FT /evidence="ECO:0007829|PDB:2ORT" FT STRAND 311..313 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 317..319 FT /evidence="ECO:0007829|PDB:2ORT" FT STRAND 322..324 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 332..334 FT /evidence="ECO:0007829|PDB:2ORO" FT TURN 335..337 FT /evidence="ECO:0007829|PDB:2ORO" FT STRAND 339..342 FT /evidence="ECO:0007829|PDB:2ORT" FT STRAND 350..353 FT /evidence="ECO:0007829|PDB:2ORT" FT STRAND 356..359 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 369..373 FT /evidence="ECO:0007829|PDB:3E7M" FT HELIX 375..378 FT /evidence="ECO:0007829|PDB:3E7M" FT TURN 380..383 FT /evidence="ECO:0007829|PDB:3E7M" FT HELIX 386..392 FT /evidence="ECO:0007829|PDB:3E7M" FT HELIX 400..402 FT /evidence="ECO:0007829|PDB:3E7M" FT HELIX 415..422 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 430..442 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 455..458 FT /evidence="ECO:0007829|PDB:3E7M" FT STRAND 461..463 FT /evidence="ECO:0007829|PDB:3E7M" FT HELIX 464..466 FT /evidence="ECO:0007829|PDB:3E7M" FT HELIX 468..471 FT /evidence="ECO:0007829|PDB:3E7M" FT STRAND 480..485 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 489..492 FT /evidence="ECO:0007829|PDB:2ORT" FT HELIX 509..517 FT /evidence="ECO:0007829|PDB:3GOF" SQ SEQUENCE 1144 AA; 130575 MW; 0735BE676113457F CRC64; MACPWKFLFK VKSYQSDLKE EKDINNNVKK TPCAVLSPTI QDDPKSHQNG SPQLLTGTAQ NVPESLDKLH VTSTRPQYVR IKNWGSGEIL HDTLHHKATS DFTCKSKSCL GSIMNPKSLT RGPRDKPTPL EELLPHAIEF INQYYGSFKE AKIEEHLARL EAVTKEIETT GTYQLTLDEL IFATKMAWRN APRCIGRIQW SNLQVFDARN CSTAQEMFQH ICRHILYATN NGNIRSAITV FPQRSDGKHD FRLWNSQLIR YAGYQMPDGT IRGDAATLEF TQLCIDLGWK PRYGRFDVLP LVLQADGQDP EVFEIPPDLV LEVTMEHPKY EWFQELGLKW YALPAVANML LEVGGLEFPA CPFNGWYMGT EIGVRDFCDT QRYNILEEVG RRMGLETHTL ASLWKDRAVT EINVAVLHSF QKQNVTIMDH HTASESFMKH MQNEYRARGG CPADWIWLVP PVSGSITPVF HQEMLNYVLS PFYYYQIEPW KTHIWQNEKL RPRRREIRFR VLVKVVFFAS MLMRKVMASR VRATVLFATE TGKSEALARD LATLFSYAFN TKVVCMDQYK ASTLEEEQLL LVVTSTFGNG DCPSNGQTLK KSLFMLRELN HTFRYAVFGL GSSMYPQFCA FAHDIDQKLS HLGASQLAPT GEGDELSGQE DAFRSWAVQT FRAACETFDV RSKHHIQIPK RFTSNATWEP QQYRLIQSPE PLDLNRALSS IHAKNVFTMR LKSQQNLQSE KSSRTTLLVQ LTFEGSRGPS YLPGEHLGIF PGNQTALVQG ILERVVDCPT PHQTVCLEVL DESGSYWVKD KRLPPCSLSQ ALTYFLDITT PPTQLQLHKL ARFATDETDR QRLEALCQPS EYNDWKFSNN PTFLEVLEEF PSLHVPAAFL LSQLPILKPR YYSISSSQDH TPSEVHLTVA VVTYRTRDGQ GPLHHGVCST WIRNLKPQDP VPCFVRSVSG FQLPEDPSQP CILIGPGTGI APFRSFWQQR LHDSQHKGLK GGRMSLVFGC RHPEEDHLYQ EEMQEMVRKR VLFQVHTGYS RLPGKPKVYV QDILQKQLAN EVLSVLHGEQ GHLYICGDVR MARDVATTLK KLVATKLNLS EEQVEDYFFQ LKSQKRYHED IFGAVFSYGA KKGSALEEPK ATRL //