NOS2_MACMU
ID NOS2_MACMU Reviewed; 162 AA.
AC O46660;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 105.
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 Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Microglia;
RX PubMed=8900532; DOI=10.1007/bf03402200;
RA Lane T.E., Buchmeier M.J., Watry D.D., Fox H.S.;
RT "Expression of inflammatory cytokines and inducible nitric oxide synthase
RT in brains of SIV-infected rhesus monkeys: applications to HIV-induced
RT central nervous system disease.";
RL Mol. Med. 2:27-37(1996).
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:P35228, ECO:0000250|UniProtKB:P79290}.
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: Regulated by calcium/calmodulin. {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 -!- 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 -!- INDUCTION: By lipopolysaccharide (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}.
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DR EMBL; U31907; AAC39525.1; -; mRNA.
DR AlphaFoldDB; O46660; -.
DR SMR; O46660; -.
DR InParanoid; O46660; -.
DR Proteomes; UP000006718; 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:0006809; P:nitric oxide biosynthetic process; IEA:InterPro.
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; 3.90.340.10; -; 1.
DR InterPro; IPR044943; NOS_dom_1.
DR InterPro; IPR036119; NOS_N_sf.
DR SUPFAM; SSF56512; SSF56512; 1.
PE 2: Evidence at transcript level;
KW Calcium; Calmodulin-binding; Cytoplasm; FAD; Flavoprotein; FMN; Heme; Iron;
KW Metal-binding; NADP; Oxidoreductase; Reference proteome; Ubl conjugation.
FT CHAIN <1..>162
FT /note="Nitric oxide synthase, inducible"
FT /id="PRO_0000170933"
FT REGION 24..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 24..43
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 98
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT NON_TER 1
FT NON_TER 162
SQ SEQUENCE 162 AA; 17813 MW; 0457464D32287065 CRC64;
GKDINNNMEK AACATSSLVT QDDLQYHSLS KQQNESPQPL VGTGKKSPES LVKPDATPLS
SPRHVRIKNW GSGMTFQDTL HHKAKGILTC RSKSCLGSIM TPKSLTRGPR DKPTPPDELL
PQAIEFVNLS LEISVQDQIP PVCNDCQYYG SFKEAKIEEH LA
