ID NOS2_CHICK Reviewed; 1136 AA. AC Q90703; Q90677; Q90934; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 24-JAN-2024, entry version 160. 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 AltName: Full=NOS type II; DE AltName: Full=Peptidyl-cysteine S-nitrosylase NOS2; GN Name=NOS2; OS Gallus gallus (Chicken). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; OC Phasianinae; Gallus. OX NCBI_TaxID=9031; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8662618; DOI=10.1074/jbc.271.20.11911; RA Lin A.W., Chang C.C., McCormick C.C.; RT "Molecular cloning and expression of an avian macrophage nitric-oxide RT synthase cDNA and the analysis of the genomic 5'-flanking region."; RL J. Biol. Chem. 271:11911-11919(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 171-472. RC TISSUE=Osteoclast; RX PubMed=8707887; RX DOI=10.1002/(sici)1097-4644(19960315)60:4<469::aid-jcb4>3.0.co;2-q; RA Sunyer T., Rothe L., Jiang X., Osdoby P., Collin-Osdoby P.; RT "Proinflammatory agents, IL-8 and IL-10, upregulate inducible nitric oxide RT synthase expression and nitric oxide production in avian osteoclast-like RT cells."; RL J. Cell. Biochem. 60:469-483(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 646-986. RC TISSUE=Heart; RX PubMed=9709401; DOI=10.1016/s0008-6363(98)00005-4; RA Shimizu T., Kinugawa K., Sugishita Y., Sugishita K., Harada K., Matsui H., RA Kohmoto O., Serizawa T., Takahashi T.; RT "Molecular cloning and expression of inducible nitric oxide synthase in RT chick embryonic ventricular myocytes."; RL Cardiovasc. Res. 38:405-413(1998). CC -!- FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with CC diverse functions throughout the body. NO may serve as both a paracrine CC and autocrine signal for modulating osteoclast bone resorption. Also CC has nitrosylase activity and mediates cysteine S-nitrosylation of CC cytoplasmic target proteins such COX2 (By similarity). CC {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 -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P35228}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P35228}. CC -!- INDUCTION: By treatment with lipopolysaccharides (LPS) or cytokines, CC but not in osteoclasts where they are induced by calcium and PMA CC (phorbol 12-myristate 13-acetate). 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; U46504; AAC59886.1; -; mRNA. DR EMBL; U34045; AAB17499.1; -; mRNA. DR EMBL; D85422; BAA12817.1; -; mRNA. DR RefSeq; NP_990292.1; NM_204961.1. DR AlphaFoldDB; Q90703; -. DR SMR; Q90703; -. DR STRING; 9031.ENSGALP00000058328; -. DR PaxDb; 9031-ENSGALP00000034026; -. DR GeneID; 395807; -. DR KEGG; gga:395807; -. DR CTD; 4843; -. DR VEuPathDB; HostDB:geneid_395807; -. DR eggNOG; KOG1158; Eukaryota. DR InParanoid; Q90703; -. DR PhylomeDB; Q90703; -. DR PRO; PR:Q90703; -. DR Proteomes; UP000000539; Unassembled WGS sequence. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central. DR GO; GO:0010181; F:FMN binding; IBA:GO_Central. DR GO; GO:0020037; F:heme binding; IEA:InterPro. 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; ISS:UniProtKB. DR GO; GO:0006527; P:arginine catabolic process; IBA:GO_Central. DR GO; GO:0042742; P:defense response to bacterium; IBA:GO_Central. DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central. DR GO; GO:0045776; P:negative regulation of blood pressure; IBA:GO_Central. DR GO; GO:0006809; P:nitric oxide biosynthetic process; IBA:GO_Central. 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; 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 GO; GO:0009725; P:response to hormone; IBA:GO_Central. DR GO; GO:0032496; P:response to lipopolysaccharide; IBA:GO_Central. DR CDD; cd06202; Nitric_oxide_synthase; 1. 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. PE 2: Evidence at transcript level; KW Calmodulin-binding; Cytoplasm; FAD; Flavoprotein; FMN; Heme; Iron; KW Metal-binding; NADP; Oxidoreductase; Reference proteome; Zinc. FT CHAIN 1..1136 FT /note="Nitric oxide synthase, inducible" FT /id="PRO_0000170938" 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 512..532 FT /note="Calmodulin-binding" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 107 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="ligand shared between homodimeric partners" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 112 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="ligand shared between homodimeric partners" FT /evidence="ECO:0000250|UniProtKB:P35228" 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 378 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 459 FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin" FT /ligand_id="ChEBI:CHEBI:59560" FT /evidence="ECO:0000250|UniProtKB:P35228" 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 542 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 546 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 547 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 588 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 589 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 625 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 632 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 658 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 662 FT /ligand="FMN" FT /ligand_id="ChEBI:CHEBI:58210" FT /evidence="ECO:0000250|UniProtKB:P35228" FT BINDING 747 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 769 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 905 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 921 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 923 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 927 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 940 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 941 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 942 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 981 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1014 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1043 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1044 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1050 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1052 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1054 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT BINDING 1087 FT /ligand="NADP(+)" FT /ligand_id="ChEBI:CHEBI:58349" FT /evidence="ECO:0000250|UniProtKB:P29476" FT CONFLICT 400 FT /note="S -> T (in Ref. 2; AAB17499)" FT /evidence="ECO:0000305" FT CONFLICT 873 FT /note="R -> S (in Ref. 3; BAA12817)" FT /evidence="ECO:0000305" SQ SEQUENCE 1136 AA; 129649 MW; D5CB73AC7BA94B9D CRC64; MLCPWQFAFK PHAVKNQSSE EKDINNNVEK DVKVHSFVKD DAKLHSLSKK QMKMSPIITS AEKHPQNGIK ASNQISRCPR HVKVRNMENG SSLLDTLHLT AKEVINCRTR ACQGALMTPK GLVRSTRDGP VPPAELLPQA VDFVKQYYSS FKELKIEEHL ARLETVTKEI ETTGTYHLTK DELIFAAKQA WRNAPRCIGR IQWSNLQVFD ARDCKTAKEM FEYICRHIQY ATNNGNIRSA ITIFPQRTDG KHDFRVWNSQ LIRYAGYQMP DGSVIGDPAS VEFTKLCIEL GWKPKYGRFD VVPLILQANG QDPEIFEYPP EIILEVPMEH PKYEWFKELD LKWYALPAVA NMLLEVGGLE FTACPFNGWY MGTEIGVRDF CDVQRYNILK EVGRRMGLES NKLASLWKDR AVVEINVAVL HSFQKQNVTI MDHHSAAESF MKYMQNEYRV RGGCPADWVW IVPPMSGSIT PVFHQEMLNY VLTPFFYYQV DAWKTHIWHD ETRRPKKREI KLSILAKAVL LASLLLQKTM AARPKVTVIY ATETGKSETL ANSLCSLFSC AFNTKILCMD EYNISDLEKE TLLLVVTSTF GNGDSPNNGK TLKNSLLTLK LLRKNIRYAV FGLGSTMYPE FCAFAHAIDQ KLSQLGALQL TPVGEGDELN GQEEAFRTWA VTAFKTACDI FDIRGKNSIQ LPEIYTSDDS WNPKKHRIVY DSQTMDLTKA LSDIHGKNVI PMKLKFRQNL QSLKSSRVTI LVKLSCETNQ EVHYLPGEHI GISPGNQPEL VHGLIARVKD APPADQTIRL ETCTEGGYWA SEKKIPACTL SQALTYLLDI TTPPTQQLLK KLSQLVTAEG DKQRLEVLCH STEEYNKWKF YNRPNILEVL EEFPSAEVST AFLLTQLPLL KPRYYSVSSS CDMTPREIHL TVAVVNYRTR DGQGPLHHGV CSTWLNKIAL NETVPCFVRS ADGFRLPKEP AKPCILIGPG TGIAPFRSFW QQRLYDLEKK GIKGGDMILL FGCRHPDMDH IYKEEVEEMK RKGVLKEVFT AYSRQPGQPK VYVQDILQNE LETKVCNILH KEEGHLYVCG DVRMARDVAQ TLKRMLVKKL NHTEQQAEEY FFQLKSQKRY HEDIFGAVFP HEVKRI //