NOS2_RAT
ID NOS2_RAT Reviewed; 1147 AA.
AC Q06518; O35765; O35766; O60591; O60604; P97774; Q63267; Q64005; Q64558;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 206.
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=NOS type II;
DE AltName: Full=Peptidyl-cysteine S-nitrosylase NOS2;
GN Name=Nos2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Vascular smooth muscle;
RX PubMed=7680561; DOI=10.1006/bbrc.1993.1188;
RA Nunokawa Y., Ishida N., Tanaka S.;
RT "Cloning of inducible nitric oxide synthase in rat vascular smooth muscle
RT cells.";
RL Biochem. Biophys. Res. Commun. 191:89-94(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Pancreatic islet;
RX PubMed=7540573; DOI=10.2337/diab.44.7.753;
RA Karlsen A.E., Andersen H.U., Vissing H., Larsen P.M., Fey S.J.,
RA Cuartero B.G., Madsen O.D., Petersen J.S., Mortensen S.B.,
RA Mandrup-Poulsen T., Boel E., Nerup J.;
RT "Cloning and expression of cytokine-inducible nitric oxide synthase cDNA
RT from rat islets of Langerhans.";
RL Diabetes 44:753-758(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Astrocyte;
RX PubMed=7513765; DOI=10.1002/jnr.490370313;
RA Galea E., Reis D.J., Feinstein D.L.;
RT "Cloning and expression of inducible nitric oxide synthase from rat
RT astrocytes.";
RL J. Neurosci. Res. 37:406-414(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Liver;
RX PubMed=7693462; DOI=10.1111/j.1432-1033.1993.tb18215.x;
RA Adachi H., Iida S., Oguchi S., Ohshima H., Suzuki H., Nagasaki K.,
RA Kawasaki H., Sugimura T., Esumi H.;
RT "Molecular cloning of a cDNA encoding an inducible calmodulin-dependent
RT nitric-oxide synthase from rat liver and its expression in COS 1 cells.";
RL Eur. J. Biochem. 217:37-43(1993).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Hepatocyte;
RX PubMed=7682072; DOI=10.1006/bbrc.1993.1283;
RA Wood E.R., Berger H. Jr., Sherman P.A., Lapetina E.G.;
RT "Hepatocytes and macrophages express an identical cytokine inducible nitric
RT oxide synthase gene.";
RL Biochem. Biophys. Res. Commun. 191:767-774(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Aorta;
RX PubMed=7519448; DOI=10.1016/0167-4781(94)90196-1;
RA Geng Y.J., Almquist M., Hansson G.K.;
RT "cDNA cloning and expression of inducible nitric oxide synthase from rat
RT vascular smooth muscle cells.";
RL Biochim. Biophys. Acta 1218:421-424(1994).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kosuga K., Yui Y., Hattori R., Sase K., Eizawa H., Aoyama T., Inoue R.,
RA Sasayama S.;
RT "Cloning of an inducible nitric oxide synthase from rat polymorphonuclear
RT neutrophils.";
RL Endothelium 2:217-221(1994).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8913516; DOI=10.1248/bpb.19.1374;
RA Tsutsumishita Y., Kawai Y., Takahara H., Onda T., Miyoshi J., Futaki S.,
RA Niwa M.;
RT "Sequence analysis of inducible nitric oxide synthase in rat kidney, lung,
RT and uterus.";
RL Biol. Pharm. Bull. 19:1374-1376(1996).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9851365; DOI=10.1006/niox.1998.0184;
RA Adams V., Krabbes S., Jiang H., Yu J., Rahmel A., Gielen S., Schuler G.,
RA Hambrecht R.;
RT "Complete coding sequence of inducible nitric oxide synthase from human
RT heart and skeletal muscle of patients with chronic heart failure.";
RL Nitric Oxide 2:242-249(1998).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 426-788.
RC STRAIN=Dahl/Rapp salt sensitive strain; TISSUE=Vascular smooth muscle;
RX PubMed=9535415; DOI=10.1161/01.hyp.31.4.918;
RA Chen P.Y., Gladish R.D., Sanders P.W.;
RT "Vascular smooth muscle nitric oxide synthase anomalies in Dahl/Rapp salt-
RT sensitive rats.";
RL Hypertension 31:918-924(1998).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 509-740.
RC STRAIN=Wistar; TISSUE=Renal glomerulus;
RA Saura M., Zaragoza C., Martinez-Dalmau R., Perez-Sala D., Lamas S.;
RT "Advances in the studies of NO synthesis regulation in mesanglial cells.";
RL Nefrologia 16:35-39(1996).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 479-655.
RC STRAIN=Sprague-Dawley; TISSUE=Renal glomerulus;
RX PubMed=7516453; DOI=10.1038/ki.1994.135;
RA Morrissey J.J., McCracken R., Kaneto H., Vehaskari M., Montani D.,
RA Klahr S.;
RT "Location of an inducible nitric oxide synthase mRNA in the normal
RT kidney.";
RL Kidney Int. 45:998-1005(1994).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 420-479.
RC TISSUE=Myocardium;
RA Michel T., Balligand J.-L.;
RT "Isolation and characterization of iNOS from rat cardiocytes.";
RL Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-564 AND TYR-572, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with
CC diverse functions throughout the body. 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. As component of the iNOS-S100A8/9 transnitrosylase complex
CC involved in the selective inflammatory stimulus-dependent S-
CC nitrosylation of GAPDH implicated in regulation of the GAIT complex
CC activity and probably multiple targets including ANXA5, EZR, MSN and
CC VIM. Involved in inflammation, enhances the synthesis of pro-
CC inflammatory mediators such as IL6 and IL8.
CC {ECO:0000250|UniProtKB:P29477, ECO:0000250|UniProtKB:P35228}.
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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Note=Binds 1 FAD.;
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Note=Binds 1 FMN.;
CC -!- COFACTOR:
CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin;
CC Xref=ChEBI:CHEBI:59560;
CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the
CC enzyme.;
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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer. Interacts with SLC9A3R1. Interacts with GAPDH;
CC induced by oxidatively-modified low-densitity lipoprotein (LDL(ox)).
CC Interacts with S100A8 and S100A9 to form the iNOS-S100A8/9
CC transnitrosylase complex. Interacts with SPSB1, SPSB2 and SPSB4.
CC Interacts with ELOC and CUL5 in the presence of SPSB1 or SPSB2 or
CC SPSB4. Forms a complex with ASL, ASS1 and HSP90AA1; the complex
CC regulates cell-autonomous L-arginine synthesis and citrulline recycling
CC while channeling extracellular L-arginine to nitric oxide synthesis
CC pathway. {ECO:0000250|UniProtKB:P29477}.
CC -!- INTERACTION:
CC Q06518; Q7TQN4: Rela; NbExp=3; IntAct=EBI-15919967, EBI-1187180;
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: In normal kidney, expressed primarily in the
CC medullary thick ascending limb, with minor amounts in the medullary
CC collecting duct and vasa recta bundle.
CC -!- INDUCTION: By interferon gamma and lipopolysaccharides (LPS).
CC -!- PTM: Polyubiquitinated; mediated by SPSB1, SPSB2 and SPSB4, leading to
CC proteasomal degradation. {ECO:0000250|UniProtKB:P35228}.
CC -!- SIMILARITY: Belongs to the NOS family. {ECO:0000305}.
CC -!- CAUTION: sequence Was originally thought to originate from human but
CC appears to be from rat. {ECO:0000305|PubMed:9851365}.
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DR EMBL; D14051; BAA03138.1; -; mRNA.
DR EMBL; U26686; AAA85861.1; -; mRNA.
DR EMBL; U03699; AAC13747.1; -; mRNA.
DR EMBL; D12520; BAA02090.1; -; mRNA.
DR EMBL; L12562; AAA41720.1; -; mRNA.
DR EMBL; X76881; CAA54208.1; -; mRNA.
DR EMBL; D44591; BAA07994.1; -; mRNA.
DR EMBL; D83661; BAA12035.1; -; mRNA.
DR EMBL; AF049656; AAC83553.1; -; mRNA.
DR EMBL; AF051164; AAC83554.1; -; mRNA.
DR EMBL; AF006619; AAC16401.1; -; mRNA.
DR EMBL; AF006620; AAC16402.1; -; mRNA.
DR EMBL; U48829; AAB18620.1; -; mRNA.
DR EMBL; S71597; AAB31028.2; -; mRNA.
DR EMBL; L36063; AAC02242.1; -; mRNA.
DR PIR; I53165; I53165.
DR PIR; I56575; I56575.
DR PIR; JC5027; JC5027.
DR PIR; S38253; S38253.
DR PIR; S47647; S47647.
DR RefSeq; NP_036743.3; NM_012611.3.
DR AlphaFoldDB; Q06518; -.
DR SMR; Q06518; -.
DR CORUM; Q06518; -.
DR DIP; DIP-59942N; -.
DR IntAct; Q06518; 1.
DR STRING; 10116.ENSRNOP00000067662; -.
DR BindingDB; Q06518; -.
DR ChEMBL; CHEMBL3051; -.
DR iPTMnet; Q06518; -.
DR PhosphoSitePlus; Q06518; -.
DR PaxDb; Q06518; -.
DR PRIDE; Q06518; -.
DR GeneID; 24599; -.
DR KEGG; rno:24599; -.
DR CTD; 4843; -.
DR RGD; 3185; Nos2.
DR eggNOG; KOG1158; Eukaryota.
DR InParanoid; Q06518; -.
DR OrthoDB; 90349at2759; -.
DR PhylomeDB; Q06518; -.
DR BRENDA; 1.14.13.39; 5301.
DR Reactome; R-RNO-1222556; ROS and RNS production in phagocytes.
DR Reactome; R-RNO-392154; Nitric oxide stimulates guanylate cyclase.
DR Reactome; R-RNO-9033241; Peroxisomal protein import.
DR PRO; PR:Q06518; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030863; C:cortical cytoskeleton; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0012506; C:vesicle membrane; IDA:RGD.
DR GO; GO:0003779; F:actin binding; IDA:RGD.
DR GO; GO:0034618; F:arginine binding; ISO:RGD.
DR GO; GO:0008013; F:beta-catenin binding; IPI:RGD.
DR GO; GO:0045296; F:cadherin binding; IPI:RGD.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0008603; F:cAMP-dependent protein kinase regulator activity; IDA:RGD.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISO:RGD.
DR GO; GO:0010181; F:FMN binding; ISO:RGD.
DR GO; GO:0020037; F:heme binding; ISO:RGD.
DR GO; GO:0051879; F:Hsp90 protein binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
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:RGD.
DR GO; GO:0050998; F:nitric-oxide synthase binding; IPI:RGD.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0034617; F:tetrahydrobiopterin binding; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0006527; P:arginine catabolic process; ISO:RGD.
DR GO; GO:0001974; P:blood vessel remodeling; IMP:RGD.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IDA:MGI.
DR GO; GO:0071346; P:cellular response to interferon-gamma; ISO:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0071285; P:cellular response to lithium ion; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI.
DR GO; GO:0071461; P:cellular response to redox state; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0071305; P:cellular response to vitamin D; IEP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:RGD.
DR GO; GO:0019934; P:cGMP-mediated signaling; IDA:RGD.
DR GO; GO:0007623; P:circadian rhythm; ISO:RGD.
DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IEP:RGD.
DR GO; GO:0001935; P:endothelial cell proliferation; IEP:RGD.
DR GO; GO:0007199; P:G protein-coupled receptor signaling pathway coupled to cGMP nucleotide second messenger; IDA:RGD.
DR GO; GO:0016137; P:glycoside metabolic process; IEP:RGD.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:RGD.
DR GO; GO:0045776; P:negative regulation of blood pressure; IBA:GO_Central.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISO:RGD.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IDA:RGD.
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:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0031284; P:positive regulation of guanylate cyclase activity; IBA:GO_Central.
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:RGD.
DR GO; GO:0032310; P:prostaglandin secretion; ISS:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; IMP:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0008016; P:regulation of heart contraction; IMP:RGD.
DR GO; GO:0050796; P:regulation of insulin secretion; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:0071548; P:response to dexamethasone; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR GO; GO:0035902; P:response to immobilization stress; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0034612; P:response to tumor necrosis factor; IMP:RGD.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IEP:RGD.
DR GO; GO:0007165; P:signal transduction; IDA:RGD.
DR GO; GO:0006801; P:superoxide metabolic process; ISS:UniProtKB.
DR GO; GO:0042060; P:wound healing; IEP:RGD.
DR Gene3D; 1.20.990.10; -; 1.
DR Gene3D; 3.40.50.360; -; 2.
DR Gene3D; 3.40.50.80; -; 1.
DR Gene3D; 3.90.1230.10; -; 1.
DR Gene3D; 3.90.340.10; -; 1.
DR Gene3D; 3.90.440.10; -; 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 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; SSF52218; SSF52218; 1.
DR SUPFAM; SSF52343; SSF52343; 1.
DR SUPFAM; SSF56512; SSF56512; 1.
DR SUPFAM; SSF63380; SSF63380; 1.
DR PROSITE; PS51384; FAD_FR; 1.
DR PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
DR PROSITE; PS60001; NOS; 1.
PE 1: Evidence at protein level;
KW Calmodulin-binding; Cytoplasm; Direct protein sequencing; FAD;
KW Flavoprotein; FMN; Heme; Iron; Metal-binding; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc.
FT CHAIN 1..1147
FT /note="Nitric oxide synthase, inducible"
FT /id="PRO_0000170937"
FT DOMAIN 536..674
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT DOMAIN 727..967
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 22..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 506..526
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
FT MOTIF 23..27
FT /note="DINNN-motif; mediates interaction with SPSB1, SPSB2
FT and SPSB4"
FT /evidence="ECO:0000250|UniProtKB:P35228"
FT BINDING 107
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 115
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 197
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:0000250|UniProtKB:P29474"
FT BINDING 260
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 369
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 370
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 374
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 460
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 473
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 488
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 620..651
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 764..775
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 900..910
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 975..993
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 1073..1088
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 564
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT MOD_RES 572
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT CONFLICT 10
FT /note="R -> K (in Ref. 7; BAA07994)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="H -> Y (in Ref. 1; BAA03138)"
FT /evidence="ECO:0000305"
FT CONFLICT 107
FT /note="C -> R (in Ref. 3; AAC13747)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="D -> V (in Ref. 8; BAA12035)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="P -> H (in Ref. 3; AAC13747)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="E -> G (in Ref. 8; BAA12035)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="P -> S (in Ref. 8; BAA12035)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="S -> N (in Ref. 9; AAC83553)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="S -> T (in Ref. 3 and 5)"
FT /evidence="ECO:0000305"
FT CONFLICT 264
FT /note="Y -> I (in Ref. 3; AAC13747)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="D -> A (in Ref. 9; AAC83554)"
FT /evidence="ECO:0000305"
FT CONFLICT 277
FT /note="D -> E (in Ref. 3; AAC13747)"
FT /evidence="ECO:0000305"
FT CONFLICT 348
FT /note="A -> P (in Ref. 1; BAA03138)"
FT /evidence="ECO:0000305"
FT CONFLICT 349
FT /note="V -> A (in Ref. 6; CAA54208)"
FT /evidence="ECO:0000305"
FT CONFLICT 380
FT /note="F -> L (in Ref. 2, 7, 8 and 9; AAC83553/AAC83554)"
FT /evidence="ECO:0000305"
FT CONFLICT 395
FT /note="R -> S (in Ref. 4; BAA02090)"
FT /evidence="ECO:0000305"
FT CONFLICT 399
FT /note="E -> G (in Ref. 9; AAC83553)"
FT /evidence="ECO:0000305"
FT CONFLICT 412
FT /note="V -> A (in Ref. 3; AAC13747)"
FT /evidence="ECO:0000305"
FT CONFLICT 477
FT /note="M -> I (in Ref. 13)"
FT /evidence="ECO:0000305"
FT CONFLICT 513
FT /note="T -> R (in Ref. 11; AAB18620)"
FT /evidence="ECO:0000305"
FT CONFLICT 515
FT /note="L -> W (in Ref. 12; AAB31028)"
FT /evidence="ECO:0000305"
FT CONFLICT 545
FT /note="G -> R (in Ref. 12; AAB31028)"
FT /evidence="ECO:0000305"
FT CONFLICT 551
FT /note="A -> R (in Ref. 11; AAB18620)"
FT /evidence="ECO:0000305"
FT CONFLICT 556
FT /note="A -> S (in Ref. 12; AAB31028)"
FT /evidence="ECO:0000305"
FT CONFLICT 559
FT /note="S -> T (in Ref. 9; AAC83553/AAC83554)"
FT /evidence="ECO:0000305"
FT CONFLICT 564
FT /note="T -> N (in Ref. 12; AAB31028)"
FT /evidence="ECO:0000305"
FT CONFLICT 570
FT /note="E -> D (in Ref. 12; AAB31028)"
FT /evidence="ECO:0000305"
FT CONFLICT 583
FT /note="L -> P (in Ref. 5 and 10)"
FT /evidence="ECO:0000305"
FT CONFLICT 591
FT /note="G -> A (in Ref. 12; AAB31028)"
FT /evidence="ECO:0000305"
FT CONFLICT 591
FT /note="G -> V (in Ref. 1 and 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 619
FT /note="A -> R (in Ref. 2; AAA85861)"
FT /evidence="ECO:0000305"
FT CONFLICT 640
FT /note="Q -> P (in Ref. 9; AAC83553)"
FT /evidence="ECO:0000305"
FT CONFLICT 664
FT /note="D -> G (in Ref. 11; AAB18620)"
FT /evidence="ECO:0000305"
FT CONFLICT 679..680
FT /note="ET -> VP (in Ref. 1; BAA03138)"
FT /evidence="ECO:0000305"
FT CONFLICT 690
FT /note="Q -> P (in Ref. 11; AAB18620)"
FT /evidence="ECO:0000305"
FT CONFLICT 711
FT /note="S -> N (in Ref. 11; AAB18620)"
FT /evidence="ECO:0000305"
FT CONFLICT 714..715
FT /note="SL -> TR (in Ref. 11; AAB18620)"
FT /evidence="ECO:0000305"
FT CONFLICT 714
FT /note="S -> P (in Ref. 2, 7, 8, 9; AAC83553/AAC83554 and
FT 10; AAC16401)"
FT /evidence="ECO:0000305"
FT CONFLICT 719
FT /note="K -> R (in Ref. 11; AAB18620)"
FT /evidence="ECO:0000305"
FT CONFLICT 721
FT /note="L -> P (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 722
FT /note="S -> R (in Ref. 1, 6 and 11)"
FT /evidence="ECO:0000305"
FT CONFLICT 724..726
FT /note="IHA -> FLN (in Ref. 11)"
FT /evidence="ECO:0000305"
FT CONFLICT 730
FT /note="F -> I (in Ref. 11; AAB18620)"
FT /evidence="ECO:0000305"
FT CONFLICT 731
FT /note="T -> A (in Ref. 9; AAC83553)"
FT /evidence="ECO:0000305"
FT CONFLICT 740
FT /note="L -> P (in Ref. 6; CAA54208)"
FT /evidence="ECO:0000305"
FT CONFLICT 779
FT /note="A -> G (in Ref. 3; AAC13747)"
FT /evidence="ECO:0000305"
FT CONFLICT 834
FT /note="P -> S (in Ref. 8; BAA12035)"
FT /evidence="ECO:0000305"
FT CONFLICT 844
FT /note="A -> G (in Ref. 1; BAA03138)"
FT /evidence="ECO:0000305"
FT CONFLICT 895
FT /note="S -> L (in Ref. 4; BAA02090)"
FT /evidence="ECO:0000305"
FT CONFLICT 911
FT /note="Q -> L (in Ref. 3; AAC13747)"
FT /evidence="ECO:0000305"
FT CONFLICT 925
FT /note="V -> D (in Ref. 8; BAA12035)"
FT /evidence="ECO:0000305"
FT CONFLICT 937
FT /note="H -> N (in Ref. 9; AAC83554)"
FT /evidence="ECO:0000305"
FT CONFLICT 999
FT /note="H -> R (in Ref. 2, 7 and 9; AAC83553/AAC83554)"
FT /evidence="ECO:0000305"
FT CONFLICT 1008..1009
FT /note="TL -> NF (in Ref. 9; AAC83554)"
FT /evidence="ECO:0000305"
FT CONFLICT 1016
FT /note="P -> R (in Ref. 5)"
FT /evidence="ECO:0000305"
FT CONFLICT 1016
FT /note="P -> S (in Ref. 8)"
FT /evidence="ECO:0000305"
FT CONFLICT 1017
FT /note="E -> R (in Ref. 5 and 8)"
FT /evidence="ECO:0000305"
FT CONFLICT 1024
FT /note="E -> K (in Ref. 9; AAC83554)"
FT /evidence="ECO:0000305"
FT CONFLICT 1076
FT /note="L -> I (in Ref. 9; AAC83553)"
FT /evidence="ECO:0000305"
FT CONFLICT 1084
FT /note="M -> I (in Ref. 6; CAA54208)"
FT /evidence="ECO:0000305"
FT CONFLICT 1129
FT /note="F -> V (in Ref. 9; AAC83554)"
FT /evidence="ECO:0000305"
FT CONFLICT 1133
FT /note="A -> V (in Ref. 2, 7 and 9; AAC83553/AAC83554)"
FT /evidence="ECO:0000305"
FT CONFLICT 1138
FT /note="T -> A (in Ref. 2, 7 and 9; AAC83553/AAC83554)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1147 AA; 130628 MW; 77C77432DD8AB0A9 CRC64;
MACPWKFLFR VKSYQGDLKE EKDINNNVEK TPGAIPSPTT QDDPKSHKHQ NGFPQFLTGT
AQNVPESLDK LHVTPSTRPQ HVRIKNWGNG EIFHDTLHHK ATSDISCKSK LCMGSIMNSK
SLTRGPRDKP TPVEELLPQA IEFINQYYGS FKEAKIEEHL ARLEAVTKEI ETTGTYQLTL
DELIFATKMA WRNAPRCIGR IQWSNLQVFD ARSCSTASEM FQHICRHILY ATNSGNIRSA
ITVFPQRSDG KHDFRIWNSQ LIRYAGYQMP DGTIRGDPAT LEFTQLCIDL GWKPRYGRFD
VLPLVLQAHG QDPEVFEIPP DLVLEVTMEH PKYEWFQELG LKWYALPAVA NMLLEVGGLE
FPACPFNGWY MGTEIGVRDF CDTQRYNILE EVGRRMGLET HTLASLWKDR AVTEINAAVL
HSFQKQNVTI MDHHTASESF MKHMQNEYRA RGGCPADWIW LVPPVSGSIT PVFHQEMLNY
VLSPFYYYQI EPWKTHIWQD EKLRPRRREI RFTVLVKAVF FASVLMRKVM ASRVRATVLF
ATETGKSEAL ARDLAALFSY AFNTKVVCME QYKANTLEEE QLLLVVTSTF GNGDCPSNGQ
TLKKSLFMMK ELGHTFRYAV FGLGSSMYPQ FCAFAHDIDQ KLSHLGASQL APTGEGDELS
GQEDAFRSWA VQTFRAACET FDVRSKHCIQ IPKRYTSNAT WEPEQYKLTQ SPESLDLNKA
LSSIHAKNVF TMRLKSLQNL QSEKSSRTTL LVQLTFEGSR GPSYLPGEHL GIFPGNQTAL
VQGILERVVD CSSPDQTVCL EVLDESGSYW VKDKRLPPCS LRQALTYFLD ITTPPTQLQL
HKLARFATEE THRQRLEALC QPSEYNDWKF SNNPTFLEVL EEFPSLRVPA AFLLSQLPIL
KPRYYSISSS QDHTPSEVHL TVAVVTYRTR DGQGPLHHGV CSTWINNLKP EDPVPCFVRS
VSGFQLPEDP SQPCILIGPG TGIAPFRSFW QQRLHDSQHR GLKGGRMTLV FGCRHPEEDH
LYQEEMQEMV RKGVLFQVHT GYSRLPGKPK VYVQDILQKE LADEVFSVLH GEQGHLYVCG
DVRMARDVAT TLKKLVAAKL NLSEEQVEDY FFQLKSQKRY HEDIFGAVFS YGAKKGNTLE
EPKGTRL
