ID NOS2_HUMAN Reviewed; 1153 AA. AC P35228; A1L3U5; B7ZLY2; O60757; O94994; Q16263; Q16692; Q4TTS5; Q9UD42; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 2. DT 27-MAR-2024, entry version 246. DE RecName: Full=Nitric oxide synthase, inducible {ECO:0000305}; DE EC=1.14.13.39 {ECO:0000269|PubMed:7504305, ECO:0000269|PubMed:7682706}; DE AltName: Full=Hepatocyte NOS; DE Short=HEP-NOS; DE AltName: Full=Inducible NO synthase; DE Short=Inducible NOS; DE Short=iNOS; DE AltName: Full=NOS type II; DE AltName: Full=Peptidyl-cysteine S-nitrosylase NOS2; GN Name=NOS2 {ECO:0000312|HGNC:HGNC:7873}; Synonyms=NOS2A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION. RC TISSUE=Colon adenocarcinoma; RX PubMed=7692964; DOI=10.1021/bi00094a017; RA Sherman P.A., Laubach V.E., Reep B.R., Wood E.R.; RT "Purification and cDNA sequence of an inducible nitric oxide synthase from RT a human tumor cell line."; RL Biochemistry 32:11600-11605(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND CATALYTIC ACTIVITY. RC TISSUE=Liver; RX PubMed=7682706; DOI=10.1073/pnas.90.8.3491; RA Geller D.A., Lowenstein C.J., Shapiro R.A., Nussler A.K., di Silvio M., RA Wang S.C., Nakayama D.K., Simmons R.L., Snyder S.H., Billiar T.R.; RT "Molecular cloning and expression of inducible nitric oxide synthase from RT human hepatocytes."; RL Proc. Natl. Acad. Sci. U.S.A. 90:3491-3495(1993). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, RP TISSUE SPECIFICITY, AND INDUCTION BY IL1B. RC TISSUE=Chondrocyte; RX PubMed=7504305; DOI=10.1073/pnas.90.23.11419; RA Charles I.G., Palmer R.M.J., Hickery M.S., Bayliss M.T., Chubb A.P., RA Hall V.S., Moss D.W., Moncada S.; RT "Cloning, characterization, and expression of a cDNA encoding an inducible RT nitric oxide synthase from the human chondrocyte."; RL Proc. Natl. Acad. Sci. U.S.A. 90:11419-11423(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Articular chondrocyte; RX PubMed=7522054; DOI=10.1016/0167-4838(94)90171-6; RA Maier R., Bilbe G., Rediske J., Lotz M.; RT "Inducible nitric oxide synthase from human articular chondrocytes: cDNA RT cloning and analysis of mRNA expression."; RL Biochim. Biophys. Acta 1208:145-150(1994). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-608, AND FUNCTION. RC TISSUE=Retina; RX PubMed=7528017; DOI=10.1006/bbrc.1994.2633; RA Park C.S., Pardhasaradhi K., Gianotti C., Villegas E., Krishna G.; RT "Human retina expresses both constitutive and inducible isoforms of nitric RT oxide synthase mRNA."; RL Biochem. Biophys. Res. Commun. 205:85-91(1994). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT LEU-608. RC TISSUE=Glioblastoma; RX PubMed=7531687; DOI=10.1093/oxfordjournals.jbchem.a124563; RA Hokari A., Zeniya M., Esumi H.; RT "Cloning and functional expression of human inducible nitric oxide synthase RT (NOS) cDNA from a glioblastoma cell line A-172."; RL J. Biochem. 116:575-581(1994). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Airway epithelium; RX PubMed=7544004; DOI=10.1073/pnas.92.17.7809; RA Guo F.H., de Raeve R.H., Rice T.W., Stuehr D.J., Thunnissen F.B.J.M., RA Erzurum S.C.; RT "Continuous nitric oxide synthesis by inducible nitric oxide synthase in RT normal human airway epithelium in vivo."; RL Proc. Natl. Acad. Sci. U.S.A. 92:7809-7813(1995). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Cardiac myocyte; RX PubMed=9160867; DOI=10.1006/jmcc.1996.0349; RA Luss H., Li R.-K., Shapiro R.A., Tzeng E., McGowan F.X., Yoneyama T., RA Hatakayama K., Geller D.A., Mickle D.A.G., Simmons R.L., Billiar T.R.; RT "Dedifferentiated human ventricular cardiac myocytes express inducible RT nitric oxide synthase mRNA but not protein in response to IL-1, TNF, RT IFNgamma, and LPS."; RL J. Mol. Cell. Cardiol. 29:1153-1165(1997). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Ogawa Y., Nishijima S., Goto M., Ida M.; RT "Cloning and characterization of a novel splice valiant of human inducible RT nitric oxide synthase."; RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS TRP-221; LEU-608; ALA-747 RP AND CYS-1009. RG NIEHS SNPs program; RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 380-473. RC TISSUE=Kidney; RX PubMed=7532248; DOI=10.1038/ki.1994.365; RA McLay J.S., Chatterjee P., Nicolson A.G., Jardine A.G., McKay N.G., RA Ralston S.H., Grabowski P., Haites N.E., Macleod A.M., Hawksworth G.M.; RT "Nitric oxide production by human proximal tubular cells: a novel RT immunomodulatory mechanism?"; RL Kidney Int. 46:1043-1049(1994). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 667-831, AND INDUCTION. RC TISSUE=Glioblastoma; RX PubMed=7528267; DOI=10.1046/j.1471-4159.1995.64010085.x; RA Fujisawa H., Ogura T., Hokari A., Weisz A., Yamashita J., Esumi H.; RT "Inducible nitric oxide synthase in a human glioblastoma cell line."; RL J. Neurochem. 64:85-91(1995). RN [15] RP CHARACTERIZATION. RX PubMed=7558036; DOI=10.1006/geno.1995.1086; RA Bloch K.D., Wolfram J.R., Brown D.M., Roberts J.D. Jr., Zapol D.G., RA Lepore J.J., Filippov G., Thomas J.E., Jacob H.J., Bloch D.B.; RT "Three members of the nitric oxide synthase II gene family (NOS2A, NOS2B, RT and NOS2C) colocalize to human chromosome 17."; RL Genomics 27:526-530(1995). RN [16] RP CHARACTERIZATION. RX PubMed=9721329; RA Taylor B.S., Alarcon L.H., Billiar T.R.; RT "Inducible nitric oxide synthase in the liver: regulation and function."; RL Biochemistry (Mosc.) 63:766-781(1998). RN [17] RP INTERACTION WITH NHERF1. RX PubMed=12080081; DOI=10.1074/jbc.m205764200; RA Glynne P.A., Darling K.E.A., Picot J., Evans T.J.; RT "Epithelial inducible nitric-oxide synthase is an apical EBP50-binding RT protein that directs vectorial nitric oxide output."; RL J. Biol. Chem. 277:33132-33138(2002). RN [18] RP POLYMORPHISM, AND INVOLVEMENT IN RESISTANCE TO MALARIA. RX PubMed=12433515; DOI=10.1016/s0140-6736(02)11474-7; RA Hobbs M.R., Udhayakumar V., Levesque M.C., Booth J., Roberts J.M., RA Tkachuk A.N., Pole A., Coon H., Kariuki S., Nahlen B.L., Mwaikambo E.D., RA Lal A.L., Granger D.L., Anstey N.M., Weinberg J.B.; RT "A new NOS2 promoter polymorphism associated with increased nitric oxide RT production and protection from severe malaria in Tanzanian and Kenyan RT children."; RL Lancet 360:1468-1475(2002). RN [19] RP FUNCTION. RX PubMed=19688109; DOI=10.1155/2009/345838; RA Vuolteenaho K., Koskinen A., Kukkonen M., Nieminen R., Paeivaerinta U., RA Moilanen T., Moilanen E.; RT "Leptin enhances synthesis of proinflammatory mediators in human RT osteoarthritic cartilage--mediator role of NO in leptin-induced PGE2, IL-6, RT and IL-8 production."; RL Mediators Inflamm. 2009:345838-345838(2009). RN [20] RP POLYUBIQUITINATION, PROTEASOMAL DEGRADATION, SUBCELLULAR LOCATION, RP INTERACTION WITH SPSB1; SPSB2; SPSB4; ELOC AND CUL5, MUTAGENESIS OF ASN-27, RP AND MOTIF DINNN. 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 [21] RP FUNCTION, INTERACTION WITH S100A8; S100A9 AND GAPDH, ASSEMBLY IN THE RP INOS-S100A8/A9 COMPLEX, AND INDUCTION BY LDL. RX PubMed=25417112; DOI=10.1016/j.cell.2014.09.032; RA Jia J., Arif A., Terenzi F., Willard B., Plow E.F., Hazen S.L., Fox P.L.; RT "Target-selective protein S-nitrosylation by sequence motif recognition."; RL Cell 159:623-634(2014). RN [22] RP INDUCTION. RX PubMed=25180171; DOI=10.1016/j.redox.2014.06.011; RA Cortese-Krott M.M., Kulakov L., Oplaender C., Kolb-Bachofen V., RA Kroencke K.D., Suschek C.V.; RT "Zinc regulates iNOS-derived nitric oxide formation in endothelial cells."; RL Redox Biol. 2:945-954(2014). RN [23] RP CATALYTIC ACTIVITY. RX PubMed=35772285; DOI=10.1016/j.bmc.2022.116878; RA Vasu D., Li H., Hardy C.D., Poulos T.L., Silverman R.B.; RT "2-Aminopyridines with a shortened amino sidechain as potent, selective, RT and highly permeable human neuronal nitric oxide synthase inhibitors."; RL Bioorg. Med. Chem. 69:116878-116878(2022). RN [24] {ECO:0007744|PDB:1NSI, ECO:0007744|PDB:2NSI} RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 74-504 IN COMPLEX WITH RP (6R)-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN; HEME B AND ZINC, COFACTOR, RP SUBUNIT, AND DISULFIDE BOND. RX PubMed=10409685; DOI=10.1074/jbc.274.30.21276; RA Li H., Raman C.S., Glaser C.B., Blasko E., Young T.A., Parkinson J.F., RA Whitlow M., Poulos T.L.; RT "Crystal structures of zinc-free and -bound heme domain of human inducible RT nitric-oxide synthase. Implications for dimer stability and comparison with RT endothelial nitric-oxide synthase."; RL J. Biol. Chem. 274:21276-21284(1999). RN [25] {ECO:0007744|PDB:4NOS} RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 82-528 IN COMPLEX WITH RP (6R)-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN; HEME B AND ZINC, COFACTOR, AND RP SUBUNIT. RX PubMed=10074942; DOI=10.1038/6675; RA Fischmann T.O., Hruza A., Niu X.D., Fossetta J.D., Lunn C.A., Dolphin E., RA Prongay A.J., Reichert P., Lundell D.J., Narula S.K., Weber P.C.; RT "Structural characterization of nitric oxide synthase isoforms reveals RT striking active-site conservation."; RL Nat. Struct. Biol. 6:233-242(1999). RN [26] {ECO:0007744|PDB:3HR4} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 503-715 IN COMPLEX WITH RP CALMODULIN AND FMN, AND COFACTOR. RX PubMed=19737939; DOI=10.1074/jbc.m109.031682; RA Xia C., Misra I., Iyanagi T., Kim J.J.; RT "Regulation of interdomain interactions by calmodulin in inducible nitric- RT oxide synthase."; RL J. Biol. Chem. 284:30708-30717(2009). RN [27] RP VARIANT [LARGE SCALE ANALYSIS] SER-679. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [28] RP VARIANT LEU-608, AND CHARACTERIZATION OF VARIANT LEU-608. RX PubMed=24430113; DOI=10.1038/ctg.2013.17; RA Dhillon S.S., Mastropaolo L.A., Murchie R., Griffiths C., Thoeni C., RA Elkadri A., Xu W., Mack A., Walters T., Guo C., Mack D., Huynh H., RA Baksh S., Silverberg M.S., Brumell J.H., Snapper S.B., Muise A.M.; RT "Higher activity of the inducible nitric oxide synthase contributes to very RT early onset inflammatory bowel disease."; RL Clin. Transl. Gastroenterol. 5:E46-E46(2014). CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with CC diverse functions throughout the body (PubMed:7531687, PubMed:7544004, CC PubMed:7682706, PubMed:7504305). In macrophages, NO mediates CC tumoricidal and bactericidal actions. Also has nitrosylase activity and CC mediates cysteine S-nitrosylation of cytoplasmic target proteins such CC PTGS2/COX2 (By similarity). As component of the iNOS-S100A8/9 CC transnitrosylase complex involved in the selective inflammatory CC stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in CC regulation of the GAIT complex activity and probably multiple targets CC including ANXA5, EZR, MSN and VIM (PubMed:25417112). Involved in CC inflammation, enhances the synthesis of pro-inflammatory mediators such CC as IL6 and IL8 (PubMed:19688109). {ECO:0000250|UniProtKB:P29477, CC ECO:0000269|PubMed:19688109, ECO:0000269|PubMed:25417112, CC ECO:0000269|PubMed:7504305, ECO:0000269|PubMed:7531687, CC ECO:0000269|PubMed:7544004, ECO:0000269|PubMed:7682706}. 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:0000269|PubMed:35772285, ECO:0000269|PubMed:7504305, CC ECO:0000269|PubMed:7682706}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19898; CC Evidence={ECO:0000305|PubMed:7504305, ECO:0000305|PubMed:7682706}; CC -!- COFACTOR: CC Name=heme b; Xref=ChEBI:CHEBI:60344; CC Evidence={ECO:0000269|PubMed:10074942, ECO:0000269|PubMed:10409685}; 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:0000269|PubMed:19737939}; CC Note=Binds 1 FMN. {ECO:0000269|PubMed:19737939}; CC -!- COFACTOR: CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin; CC Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000269|PubMed:10074942, CC ECO:0000269|PubMed:10409685}; CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the CC enzyme. {ECO:0000305|PubMed:10409685}; CC -!- ACTIVITY REGULATION: Regulated by calcium/calmodulin. Aspirin inhibits CC expression and function of this enzyme and effects may be exerted at CC the level of translational/post-translational modification and directly CC on the catalytic activity (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Homodimer (PubMed:10409685, PubMed:10074942). Interacts with CC NHERF1 (PubMed:12080081). Interacts with GAPDH; induced by oxidatively- CC modified low-densitity lipoprotein (LDL(ox)) (PubMed:25417112). CC Interacts with S100A8 and S100A9 to form the iNOS-S100A8/9 CC transnitrosylase complex (PubMed:25417112). Interacts with SPSB1, SPSB2 CC and SPSB4 (PubMed:21199876). Interacts with ELOC and CUL5 in the CC presence of SPSB1 or SPSB2 or SPSB4 (PubMed:21199876). Forms a complex CC with ASL, ASS1 and HSP90AA1; the complex regulates cell-autonomous L- CC arginine synthesis and citrulline recycling while channeling CC extracellular L-arginine to nitric oxide synthesis pathway. CC {ECO:0000250|UniProtKB:P29477, ECO:0000269|PubMed:10074942, CC ECO:0000269|PubMed:10409685, ECO:0000269|PubMed:12080081, CC ECO:0000269|PubMed:21199876, ECO:0000269|PubMed:25417112}. CC -!- INTERACTION: CC P35228; P04406: GAPDH; NbExp=8; IntAct=EBI-6662224, EBI-354056; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:21199876}. CC Note=Localizes as discrete foci scattered throughout the cytosol and in CC the presence of SPSB1 and SPSB4, exhibits a more diffuse cytosolic CC localization. {ECO:0000269|PubMed:21199876}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P35228-1; Sequence=Displayed; CC Name=2; CC IsoId=P35228-2; Sequence=VSP_003582, VSP_003583; CC -!- TISSUE SPECIFICITY: Expressed in the liver, retina, bone cells and CC airway epithelial cells of the lung. Not expressed in the platelets. CC Expressed in chondrocytes (PubMed:7504305). CC {ECO:0000269|PubMed:7504305}. CC -!- INDUCTION: By endotoxins and cytokines. Induced by IFNG/IFN-gamma CC acting synergistically with bacterial lipopolysaccharides (LPS), TNF or CC IL1B/interleukin-1 beta (PubMed:7528267, PubMed:7504305). Down- CC regulated by zinc due to inhibition of NF-kappa-B transactivation CC activity (PubMed:25180171). By oxidatively-modified low-densitity CC lipoprotein (LDL(ox)) (PubMed:25417112). {ECO:0000269|PubMed:25180171, CC ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:7504305, CC ECO:0000269|PubMed:7528267}. CC -!- PTM: Polyubiquitinated; mediated by SPSB1, SPSB2 and SPSB4, leading to CC proteasomal degradation. {ECO:0000269|PubMed:21199876}. CC -!- POLYMORPHISM: Genetic variations in NOS2 are involved in resistance to CC malaria [MIM:611162]. {ECO:0000269|PubMed:12433515}. CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/nos2a/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Nitric oxide synthase entry; CC URL="https://en.wikipedia.org/wiki/Nitric_oxide_synthase"; 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; L24553; AAA36375.1; -; mRNA. DR EMBL; L09210; AAA59171.1; -; mRNA. DR EMBL; X73029; CAA51512.1; -; mRNA. DR EMBL; U05810; AAA56666.1; -; mRNA. DR EMBL; U31511; AAB49041.1; -; mRNA. DR EMBL; D26525; BAA05531.1; -; mRNA. DR EMBL; U20141; AAB60366.1; -; mRNA. DR EMBL; AF068236; AAC19133.1; -; mRNA. DR EMBL; AB022318; BAA37123.1; -; mRNA. DR EMBL; DQ060518; AAY43131.1; -; Genomic_DNA. DR EMBL; EU332854; ABY87543.1; -; Genomic_DNA. DR EMBL; BC130283; AAI30284.1; -; mRNA. DR EMBL; BC144126; AAI44127.1; -; mRNA. DR EMBL; S75615; AAD14179.1; -; mRNA. DR CCDS; CCDS11223.1; -. [P35228-1] DR PIR; A49676; A49676. DR RefSeq; NP_000616.3; NM_000625.4. [P35228-1] DR RefSeq; XP_011523161.1; XM_011524859.2. DR PDB; 1NSI; X-ray; 2.55 A; A/B/C/D=74-504. DR PDB; 2LL6; NMR; -; B=515-531. DR PDB; 2NSI; X-ray; 3.00 A; A/B/C/D=74-504. DR PDB; 3E7G; X-ray; 2.20 A; A/B/C/D=82-505. DR PDB; 3EJ8; X-ray; 2.55 A; A/B/C/D=82-505. DR PDB; 3HR4; X-ray; 2.50 A; A/C/E/G=503-715. DR PDB; 4CX7; X-ray; 3.16 A; A/B/C/D=74-504. DR PDB; 4NOS; X-ray; 2.25 A; A/B/C/D=82-508. DR PDB; 5TP6; NMR; -; B=507-531. DR PDB; 5XN3; X-ray; 1.34 A; B=23-28. DR PDB; 6JWM; X-ray; 1.23 A; B=21-27. DR PDB; 6JWN; X-ray; 1.61 A; B/D=21-29. DR PDB; 6KEY; X-ray; 1.24 A; B=22-30. DR PDBsum; 1NSI; -. DR PDBsum; 2LL6; -. DR PDBsum; 2NSI; -. DR PDBsum; 3E7G; -. DR PDBsum; 3EJ8; -. DR PDBsum; 3HR4; -. DR PDBsum; 4CX7; -. DR PDBsum; 4NOS; -. DR PDBsum; 5TP6; -. DR PDBsum; 5XN3; -. DR PDBsum; 6JWM; -. DR PDBsum; 6JWN; -. DR PDBsum; 6KEY; -. DR AlphaFoldDB; P35228; -. DR BMRB; P35228; -. DR SMR; P35228; -. DR BioGRID; 110906; 177. DR ComplexPortal; CPX-52; iNOS-S100A8/A9 complex. DR CORUM; P35228; -. DR DIP; DIP-59359N; -. DR IntAct; P35228; 7. DR MINT; P35228; -. DR STRING; 9606.ENSP00000327251; -. DR BindingDB; P35228; -. DR ChEMBL; CHEMBL4481; -. DR DrugBank; DB07003; (2S)-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepin-5-amine. DR DrugBank; DB07007; (3R)-3-[(1,2,3,4-tetrahydroisoquinolin-7-yloxy)methyl]-2,3-dihydrothieno[2,3-f][1,4]oxazepin-5-amine. DR DrugBank; DB07011; (3S)-1-(1,3-BENZODIOXOL-5-YLMETHYL)-3-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PIPERIDINE. DR DrugBank; DB07405; 1-(6-CYANO-3-PYRIDYLCARBONYL)-5',8'-DIFLUOROSPIRO[PIPERIDINE-4,2'(1'H)-QUINAZOLINE]-4'-AMINE. DR DrugBank; DB08750; 1-[4-(AMINOMETHYL)BENZOYL]-5'-FLUORO-1'H-SPIRO[PIPERIDINE-4,2'-QUINAZOLIN]-4'-AMINE. DR DrugBank; DB01997; 3-Bromo-7-Nitroindazole. DR DrugBank; DB07029; 4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMIDAZOL-1-YL)PHENOXY]-6-METHYLPYRIMIDINE. DR DrugBank; DB07008; 4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PYRIMIDINE. DR DrugBank; DB08214; 4-(1H-IMIDAZOL-1-YL)PHENOL. DR DrugBank; DB07002; 4-({4-[(4-methoxypyridin-2-yl)amino]piperidin-1-yl}carbonyl)benzonitrile. DR DrugBank; DB01835; 4R-Fluoro-N6-ethanimidoyl-L-lysine. DR DrugBank; DB06879; 5-(4'-AMINO-1'-ETHYL-5',8'-DIFLUORO-1'H-SPIRO[PIPERIDINE-4,2'-QUINAZOLINE]-1-YLCARBONYL)PICOLINONITRILE. DR DrugBank; DB04534; 5-Nitroindazole. DR DrugBank; DB03100; 6-Nitroindazole. DR DrugBank; DB02207; 7-Nitroindazole. DR DrugBank; DB00125; Arginine. DR DrugBank; DB00155; Citrulline. DR DrugBank; DB01234; Dexamethasone. DR DrugBank; DB14649; Dexamethasone acetate. DR DrugBank; DB11327; Dipyrithione. DR DrugBank; DB00997; Doxorubicin. DR DrugBank; DB07306; ETHYL 4-[(4-CHLOROPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE. DR DrugBank; DB07388; ETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE. DR DrugBank; DB05252; Fenoxaprop-ethyl. DR DrugBank; DB01381; Ginkgo biloba. DR DrugBank; DB03366; Imidazole. DR DrugBank; DB05214; KD7040. DR DrugBank; DB04400; L-erythro-7,8-dihydrobiopterin. DR DrugBank; DB09237; Levamlodipine. DR DrugBank; DB00244; Mesalazine. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB01017; Minocycline. DR DrugBank; DB03144; N(5)-[(hydroxyamino)(imino)methyl]-L-ornithine. DR DrugBank; DB01686; N,N-dimethylarginine. DR DrugBank; DB03449; N-(4-{2-[(3-chlorobenzyl)amino]ethyl}phenyl)thiophene-2-carboximidamide. DR DrugBank; DB06916; N-[2-(1,3-BENZODIOXOL-5-YL)ETHYL]-1-[2-(1H-IMIDAZOL-1-YL)-6-METHYLPYRIMIDIN-4-YL]-D-PROLINAMIDE. DR DrugBank; DB07318; N-[2-(4-AMINO-5,8-DIFLUORO-1,2-DIHYDROQUINAZOLIN-2-YL)ETHYL]-3-FURAMIDE. DR DrugBank; DB07389; N-[2-(6-AMINO-4-METHYLPYRIDIN-2-YL)ETHYL]-4-CYANOBENZAMIDE. DR DrugBank; DB02044; N-[3-(aminomethyl)benzyl]acetamidine. DR DrugBank; DB02644; N-omega-propyl-L-arginine. DR DrugBank; DB05383; Pimagedine. DR DrugBank; DB02234; S-Ethylisothiourea. DR DrugBank; DB03953; Thiocitrulline. DR DrugBank; DB02462; Thiocoumarin. DR DrugBank; DB08814; Triflusal. DR DrugCentral; P35228; -. DR GuidetoPHARMACOLOGY; 1250; -. DR GlyGen; P35228; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P35228; -. DR PhosphoSitePlus; P35228; -. DR SwissPalm; P35228; -. DR BioMuta; NOS2; -. DR DMDM; 1352513; -. DR jPOST; P35228; -. DR MassIVE; P35228; -. DR PaxDb; 9606-ENSP00000327251; -. DR PeptideAtlas; P35228; -. DR ProteomicsDB; 54993; -. [P35228-1] DR ProteomicsDB; 54994; -. [P35228-2] DR Antibodypedia; 4550; 1293 antibodies from 47 providers. DR DNASU; 4843; -. DR Ensembl; ENST00000313735.11; ENSP00000327251.6; ENSG00000007171.19. [P35228-1] DR GeneID; 4843; -. DR KEGG; hsa:4843; -. DR MANE-Select; ENST00000313735.11; ENSP00000327251.6; NM_000625.4; NP_000616.3. DR UCSC; uc002gzu.4; human. [P35228-1] DR AGR; HGNC:7873; -. DR CTD; 4843; -. DR DisGeNET; 4843; -. DR GeneCards; NOS2; -. DR HGNC; HGNC:7873; NOS2. DR HPA; ENSG00000007171; Group enriched (intestine, lymphoid tissue). DR MalaCards; NOS2; -. DR MIM; 163730; gene. DR MIM; 611162; phenotype. DR neXtProt; NX_P35228; -. DR OpenTargets; ENSG00000007171; -. DR PharmGKB; PA164724093; -. DR VEuPathDB; HostDB:ENSG00000007171; -. DR eggNOG; KOG1158; Eukaryota. DR GeneTree; ENSGT00940000159752; -. DR HOGENOM; CLU_001570_16_0_1; -. DR InParanoid; P35228; -. DR OMA; CRHIRYA; -. DR OrthoDB; 276396at2759; -. DR PhylomeDB; P35228; -. DR TreeFam; TF324410; -. DR BioCyc; MetaCyc:HS00205-MONOMER; -. DR BRENDA; 1.14.13.39; 2681. DR PathwayCommons; P35228; -. DR Reactome; R-HSA-1222556; ROS and RNS production in phagocytes. DR Reactome; R-HSA-392154; Nitric oxide stimulates guanylate cyclase. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-9033241; Peroxisomal protein import. DR Reactome; R-HSA-9636249; Inhibition of nitric oxide production. DR SignaLink; P35228; -. DR SIGNOR; P35228; -. DR BioGRID-ORCS; 4843; 11 hits in 1163 CRISPR screens. DR ChiTaRS; NOS2; human. DR EvolutionaryTrace; P35228; -. DR GeneWiki; Nitric_oxide_synthase_2_(inducible); -. DR GenomeRNAi; 4843; -. DR Pharos; P35228; Tchem. DR PRO; PR:P35228; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P35228; Protein. DR Bgee; ENSG00000007171; Expressed in cartilage tissue and 98 other cell types or tissues. DR ExpressionAtlas; P35228; baseline and differential. DR GO; GO:0030863; C:cortical cytoskeleton; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IMP:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; ISS:BHF-UCL. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0005782; C:peroxisomal matrix; TAS:Reactome. DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0034618; F:arginine binding; ISS:BHF-UCL. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:BHF-UCL. DR GO; GO:0010181; F:FMN binding; ISS:BHF-UCL. DR GO; GO:0020037; F:heme binding; ISS:BHF-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0050661; F:NADP binding; TAS:BHF-UCL. DR GO; GO:0004517; F:nitric-oxide synthase activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:BHF-UCL. DR GO; GO:0034617; F:tetrahydrobiopterin binding; ISS:BHF-UCL. DR GO; GO:0006527; P:arginine catabolic process; IDA:BHF-UCL. DR GO; GO:0045454; P:cell redox homeostasis; TAS:Reactome. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0071346; P:cellular response to type II interferon; IEA:Ensembl. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl. DR GO; GO:0042742; P:defense response to bacterium; IMP:BHF-UCL. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; NAS:BHF-UCL. DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central. DR GO; GO:0002227; P:innate immune response in mucosa; NAS:BHF-UCL. 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; IEA:Ensembl. DR GO; GO:0006809; P:nitric oxide biosynthetic process; IDA:UniProtKB. DR GO; GO:0007263; P:nitric oxide mediated signal transduction; IBA:GO_Central. DR GO; GO:0018119; P:peptidyl-cysteine S-nitrosylation; ISS:UniProtKB. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:UniProtKB. DR GO; GO:0051712; P:positive regulation of killing of cells of another organism; IMP:BHF-UCL. DR GO; GO:0001912; P:positive regulation of leukocyte mediated cytotoxicity; TAS:BHF-UCL. DR GO; GO:0032310; P:prostaglandin secretion; IDA:UniProtKB. DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0043457; P:regulation of cellular respiration; TAS:BHF-UCL. DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; IDA:UniProtKB. DR GO; GO:0050796; P:regulation of insulin secretion; IMP:BHF-UCL. DR GO; GO:0009617; P:response to bacterium; NAS:UniProtKB. DR GO; GO:0009725; P:response to hormone; IBA:GO_Central. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IBA:GO_Central. DR GO; GO:0006801; P:superoxide metabolic process; ISS:UniProtKB. 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; P35228; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Calmodulin-binding; Cytoplasm; KW FAD; Flavoprotein; FMN; Heme; Iron; Metal-binding; NADP; Oxidoreductase; KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc. FT CHAIN 1..1153 FT /note="Nitric oxide synthase, inducible" FT /id="PRO_0000170930" FT DOMAIN 539..677 FT /note="Flavodoxin-like" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088" FT DOMAIN 730..970 FT /note="FAD-binding FR-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716" FT REGION 515..535 FT /note="Calmodulin-binding" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT MOTIF 23..27 FT /note="DINNN-motif; mediates interaction with SPSB1, SPSB2 FT and SPSB4" FT /evidence="ECO:0000269|PubMed:21199876" FT BINDING 110 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="ligand shared between homodimeric partners" FT /evidence="ECO:0000269|PubMed:10074942, FT ECO:0000269|PubMed:10409685, ECO:0007744|PDB:1NSI, FT ECO:0007744|PDB:4NOS" FT BINDING 115 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="ligand shared between homodimeric partners" FT /evidence="ECO:0000269|PubMed:10074942, FT ECO:0000269|PubMed:10409685, ECO:0007744|PDB:1NSI, FT ECO:0007744|PDB:4NOS" FT BINDING 118 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:10074942, FT ECO:0000269|PubMed:10409685, ECO:0007744|PDB:1NSI, FT ECO:0007744|PDB:2NSI, ECO:0007744|PDB:4NOS" FT BINDING 200 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:10074942, FT ECO:0000269|PubMed:10409685, ECO:0007744|PDB:1NSI, FT ECO:0007744|PDB:2NSI, ECO:0007744|PDB:4NOS" FT BINDING 263 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 372 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 373 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 377 FT /ligand="L-arginine" FT /ligand_id="ChEBI:CHEBI:32682" FT /evidence="ECO:0000250|UniProtKB:P29474" FT BINDING 381 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:10074942, FT ECO:0000269|PubMed:10409685, ECO:0007744|PDB:1NSI, FT ECO:0007744|PDB:2NSI, ECO:0007744|PDB:4NOS" FT BINDING 462 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:10074942, FT ECO:0000269|PubMed:10409685, ECO:0007744|PDB:1NSI, FT ECO:0007744|PDB:2NSI, ECO:0007744|PDB:4NOS" FT BINDING 463 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:10074942, FT ECO:0000269|PubMed:10409685, ECO:0007744|PDB:1NSI, FT ECO:0007744|PDB:2NSI, ECO:0007744|PDB:4NOS" FT BINDING 476 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000269|PubMed:10074942, FT ECO:0000269|PubMed:10409685, ECO:0007744|PDB:1NSI, FT ECO:0007744|PDB:2NSI, ECO:0007744|PDB:4NOS" FT BINDING 491 FT /ligand="heme b" FT /ligand_id="ChEBI:CHEBI:60344" FT /evidence="ECO:0000269|PubMed:10074942, FT ECO:0000269|PubMed:10409685, ECO:0007744|PDB:1NSI, FT ECO:0007744|PDB:2NSI, ECO:0007744|PDB:4NOS" FT BINDING 545 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT BINDING 546 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT BINDING 547 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT BINDING 549 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT BINDING 550 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT BINDING 591 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT BINDING 592 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT BINDING 628 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT BINDING 633 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT BINDING 635 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT BINDING 661 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT BINDING 665 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000269|PubMed:19737939, FT ECO:0007744|PDB:3HR4" FT BINDING 750 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 772 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 906 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 908 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 909 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" 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 926 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 929 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 930 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 943 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 944 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 945 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 984 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1017 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1046 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 1053 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1055 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1057 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1090 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT MOD_RES 234 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT MOD_RES 575 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q06518" FT MOD_RES 578 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT MOD_RES 892 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT VAR_SEQ 264..288 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.9" FT /id="VSP_003582" FT VAR_SEQ 298..311 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.9" FT /id="VSP_003583" FT VARIANT 221 FT /note="R -> W (in dbSNP:rs3730017)" FT /evidence="ECO:0000269|Ref.10" FT /id="VAR_024548" FT VARIANT 608 FT /note="S -> L (found in patients with very early onset FT inflammatory bowel disease; increases NOS2 activity; FT dbSNP:rs2297518)" FT /evidence="ECO:0000269|PubMed:24430113, FT ECO:0000269|PubMed:7528017, ECO:0000269|PubMed:7531687, FT ECO:0000269|Ref.10" FT /id="VAR_022127" FT VARIANT 679 FT /note="A -> S (in a breast cancer sample; somatic mutation; FT dbSNP:rs769900089)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036302" FT VARIANT 747 FT /note="T -> A (in dbSNP:rs28944173)" FT /evidence="ECO:0000269|Ref.10" FT /id="VAR_025020" FT VARIANT 1009 FT /note="R -> C (in dbSNP:rs28944201)" FT /evidence="ECO:0000269|Ref.10" FT /id="VAR_025021" FT MUTAGEN 27 FT /note="N->A: Loss of interaction with SPSB1 and SPSB4." FT /evidence="ECO:0000269|PubMed:21199876" FT CONFLICT 23 FT /note="D -> G (in Ref. 4; AAA56666)" FT /evidence="ECO:0000305" FT CONFLICT 154 FT /note="F -> L (in Ref. 4; AAA56666)" FT /evidence="ECO:0000305" FT CONFLICT 177 FT /note="G -> V (in Ref. 4; AAA56666)" FT /evidence="ECO:0000305" FT CONFLICT 266 FT /note="R -> H (in Ref. 8; AAC19133)" FT /evidence="ECO:0000305" FT CONFLICT 423 FT /note="L -> I (in Ref. 2; AAA59171)" FT /evidence="ECO:0000305" FT CONFLICT 439 FT /note="A -> T (in Ref. 8; AAC19133)" FT /evidence="ECO:0000305" FT CONFLICT 552 FT /note="A -> G (in Ref. 12; AAI44127)" FT /evidence="ECO:0000305" FT CONFLICT 676 FT /note="T -> I (in Ref. 7; AAB60366)" FT /evidence="ECO:0000305" FT CONFLICT 800 FT /note="T -> A (in Ref. 4; AAA56666)" FT /evidence="ECO:0000305" FT CONFLICT 805 FT /note="A -> D (in Ref. 2; AAA59171)" FT /evidence="ECO:0000305" FT CONFLICT 831..832 FT /note="FL -> SP (in Ref. 2; AAA59171)" FT /evidence="ECO:0000305" FT CONFLICT 913 FT /note="S -> P (in Ref. 4; AAA56666)" FT /evidence="ECO:0000305" FT CONFLICT 933 FT /note="R -> G (in Ref. 2; AAA59171 and 7; AAB60366)" FT /evidence="ECO:0000305" FT CONFLICT 966 FT /note="G -> A (in Ref. 2; AAA59171 and 7; AAB60366)" FT /evidence="ECO:0000305" FT CONFLICT 987 FT /note="A -> V (in Ref. 2; AAA59171)" FT /evidence="ECO:0000305" FT STRAND 85..89 FT /evidence="ECO:0007829|PDB:3E7G" FT TURN 90..92 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 95..98 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 100..103 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 104..106 FT /evidence="ECO:0007829|PDB:4NOS" FT HELIX 123..125 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 136..152 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 154..156 FT /evidence="ECO:0007829|PDB:1NSI" FT HELIX 159..175 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 183..195 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 203..205 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 210..213 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 220..235 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 236..238 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 243..246 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 251..255 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 261..265 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 269..271 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 277..279 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 281..283 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 284..292 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 307..310 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 317..319 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 323..325 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 328..330 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 337..342 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 345..348 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 356..359 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 362..365 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 375..379 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 381..384 FT /evidence="ECO:0007829|PDB:3E7G" FT TURN 386..389 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 392..399 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 406..408 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 410..428 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 436..454 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 461..464 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 467..469 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 470..472 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 474..477 FT /evidence="ECO:0007829|PDB:3E7G" FT STRAND 486..491 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 495..498 FT /evidence="ECO:0007829|PDB:3E7G" FT HELIX 515..534 FT /evidence="ECO:0007829|PDB:3HR4" FT STRAND 538..544 FT /evidence="ECO:0007829|PDB:3HR4" FT STRAND 546..548 FT /evidence="ECO:0007829|PDB:3HR4" FT HELIX 549..561 FT /evidence="ECO:0007829|PDB:3HR4" FT TURN 562..564 FT /evidence="ECO:0007829|PDB:3HR4" FT STRAND 565..571 FT /evidence="ECO:0007829|PDB:3HR4" FT HELIX 572..574 FT /evidence="ECO:0007829|PDB:3HR4" FT HELIX 577..581 FT /evidence="ECO:0007829|PDB:3HR4" FT STRAND 584..591 FT /evidence="ECO:0007829|PDB:3HR4" FT TURN 594..596 FT /evidence="ECO:0007829|PDB:3HR4" FT HELIX 600..602 FT /evidence="ECO:0007829|PDB:3HR4" FT HELIX 603..611 FT /evidence="ECO:0007829|PDB:3HR4" FT STRAND 620..627 FT /evidence="ECO:0007829|PDB:3HR4" FT STRAND 631..633 FT /evidence="ECO:0007829|PDB:3HR4" FT HELIX 636..648 FT /evidence="ECO:0007829|PDB:3HR4" FT STRAND 651..654 FT /evidence="ECO:0007829|PDB:3HR4" FT STRAND 657..660 FT /evidence="ECO:0007829|PDB:3HR4" FT HELIX 665..683 FT /evidence="ECO:0007829|PDB:3HR4" FT HELIX 689..691 FT /evidence="ECO:0007829|PDB:3HR4" SQ SEQUENCE 1153 AA; 131117 MW; 47671E5385CB3A52 CRC64; MACPWKFLFK TKFHQYAMNG EKDINNNVEK APCATSSPVT QDDLQYHNLS KQQNESPQPL VETGKKSPES LVKLDATPLS SPRHVRIKNW GSGMTFQDTL HHKAKGILTC RSKSCLGSIM TPKSLTRGPR DKPTPPDELL PQAIEFVNQY YGSFKEAKIE EHLARVEAVT KEIETTGTYQ LTGDELIFAT KQAWRNAPRC IGRIQWSNLQ VFDARSCSTA REMFEHICRH VRYSTNNGNI RSAITVFPQR SDGKHDFRVW NAQLIRYAGY QMPDGSIRGD PANVEFTQLC IDLGWKPKYG RFDVVPLVLQ ANGRDPELFE IPPDLVLEVA MEHPKYEWFR ELELKWYALP AVANMLLEVG GLEFPGCPFN GWYMGTEIGV RDFCDVQRYN ILEEVGRRMG LETHKLASLW KDQAVVEINI AVLHSFQKQN VTIMDHHSAA ESFMKYMQNE YRSRGGCPAD WIWLVPPMSG SITPVFHQEM LNYVLSPFYY YQVEAWKTHV WQDEKRRPKR REIPLKVLVK AVLFACMLMR KTMASRVRVT ILFATETGKS EALAWDLGAL FSCAFNPKVV CMDKYRLSCL EEERLLLVVT STFGNGDCPG NGEKLKKSLF MLKELNNKFR YAVFGLGSSM YPRFCAFAHD IDQKLSHLGA SQLTPMGEGD ELSGQEDAFR SWAVQTFKAA CETFDVRGKQ HIQIPKLYTS NVTWDPHHYR LVQDSQPLDL SKALSSMHAK NVFTMRLKSR QNLQSPTSSR ATILVELSCE DGQGLNYLPG EHLGVCPGNQ PALVQGILER VVDGPTPHQT VRLEALDESG SYWVSDKRLP PCSLSQALTY FLDITTPPTQ LLLQKLAQVA TEEPERQRLE ALCQPSEYSK WKFTNSPTFL EVLEEFPSLR VSAGFLLSQL PILKPRFYSI SSSRDHTPTE IHLTVAVVTY HTRDGQGPLH HGVCSTWLNS LKPQDPVPCF VRNASGFHLP EDPSHPCILI GPGTGIAPFR SFWQQRLHDS QHKGVRGGRM TLVFGCRRPD EDHIYQEEML EMAQKGVLHA VHTAYSRLPG KPKVYVQDIL RQQLASEVLR VLHKEPGHLY VCGDVRMARD VAHTLKQLVA AKLKLNEEQV EDYFFQLKSQ KRYHEDIFGA VFPYEAKKDR VAVQPSSLEM SAL //