ID NOS2_RABIT Reviewed; 496 AA. AC O19114; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 27-MAR-2024, entry version 126. 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; DE Flags: Fragment; GN Name=NOS2; OS Oryctolagus cuniculus (Rabbit). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus. OX NCBI_TaxID=9986; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=New Zealand white; TISSUE=Heart; RA Broner C.W., Eledath F.M.; RT "Rabbit iducible nitric oxide synthase gene-NOS II."; RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases. 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 Evidence={ECO:0000250|UniProtKB:P35228}; 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:0000250|UniProtKB:P35228}; CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the CC enzyme. {ECO:0000250|UniProtKB:P35228}; CC -!- ACTIVITY REGULATION: Not stimulated by calcium/calmodulin. CC {ECO:0000250}. CC -!- SUBUNIT: Homodimer. Interacts with NHERF1. 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 -!- 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 -!- 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 --------------------------------------------------------------------------- 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; U85094; AAB65618.1; -; mRNA. DR AlphaFoldDB; O19114; -. DR SMR; O19114; -. DR STRING; 9986.ENSOCUP00000001643; -. DR InParanoid; O19114; -. DR Proteomes; UP000001811; Unplaced. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004517; F:nitric-oxide synthase activity; ISS:UniProtKB. DR GO; GO:0018119; P:peptidyl-cysteine S-nitrosylation; ISS:UniProtKB. 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:0032310; P:prostaglandin secretion; ISS:UniProtKB. DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; ISS:UniProtKB. DR Gene3D; 3.40.50.360; -; 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; 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; 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; PF00175; NAD_binding_1; 1. DR PRINTS; PR00371; FPNCR. DR SUPFAM; SSF52343; Ferredoxin reductase-like, C-terminal NADP-linked domain; 1. DR SUPFAM; SSF52218; Flavoproteins; 1. DR SUPFAM; SSF63380; Riboflavin synthase domain-like; 1. DR PROSITE; PS51384; FAD_FR; 1. PE 2: Evidence at transcript level; KW Calmodulin-binding; Cytoplasm; FAD; Flavoprotein; FMN; Heme; Iron; KW Metal-binding; NADP; Oxidoreductase; Reference proteome; Ubl conjugation. FT CHAIN <1..>496 FT /note="Nitric oxide synthase, inducible" FT /id="PRO_0000170936" FT DOMAIN 101..341 FT /note="FAD-binding FR-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716" FT BINDING 6 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 32 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 36 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 121 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 143 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 277 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 279 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 280 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 295 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 297 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 300 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 301 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 314 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 315 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 316 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 355 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 388 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 417 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 418 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 424 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 426 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 428 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 461 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT NON_TER 1 FT NON_TER 496 SQ SEQUENCE 496 AA; 56397 MW; A0A1D303C57F0EEC CRC64; MYPHFCAFVM TSTRNCLTWA ASQLAPTGEG DELSGQEDAF RSWAVQTFRA ACETFDVRSK HCIQIPKRYT SNATWEPEQY KLTQSPEPLD LNKALSSIHA KNLFTMRLRS LQNLHSEKSS RTTLLVQLTF EGSRGPSYLP GEHLGIFPGN QTGLVQGILE RVVDCSSPDQ TVCLEVHDES GSYWVKDKRL PPCSLRQALT YFLDITTPPT QLQLHKLARF ATEETHRQRL EALCQPSEYN DWKFSNNPTF LEVLEEFPSL RVPAAFLLSQ LPILKPRYYS ISSSQDHTPS EVHLTVAVVT YRTRDGQGPL HHGVCSTWIN NLKPEDPVPC FVRSVSGFQL PEDPSQPCIL IGPGTGIAPF RSFWQQRLHD SQHRGLKGGR MTLVFGCRHP EEDHLYQEEM QEMVRKGVLF QVHTGYSRLP GKPKVYVQDI LQKELADEVF SVLHGEQGHL YVCGDVRMAR DVATTLKKLV AAKLNLSEEQ VEDYFFQLKY HEDIFG //