NOS2_CHICK
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 03-AUG-2022, entry version 153.
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). {ECO:0000250}.
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; Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC Note=Binds 1 FAD. {ECO:0000250};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210; Evidence={ECO:0000250};
CC Note=Binds 1 FMN. {ECO:0000250};
CC -!- COFACTOR:
CC Name=(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin;
CC Xref=ChEBI:CHEBI:59560; Evidence={ECO:0000250};
CC Note=Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the
CC enzyme. {ECO:0000250};
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}.
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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.ENSGALP00000034026; -.
DR PaxDb; Q90703; -.
DR PRIDE; Q90703; -.
DR GeneID; 395807; -.
DR KEGG; gga:395807; -.
DR CTD; 4843; -.
DR VEuPathDB; HostDB:geneid_395807; -.
DR eggNOG; KOG1158; Eukaryota.
DR InParanoid; Q90703; -.
DR OrthoDB; 90349at2759; -.
DR PhylomeDB; Q90703; -.
DR PRO; PR:Q90703; -.
DR Proteomes; UP000000539; Unplaced.
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:0012506; C:vesicle 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:0016491; F:oxidoreductase activity; IBA:GO_Central.
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: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: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 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 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 506..526
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
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 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 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
