NOS2_PIG
ID NOS2_PIG Reviewed; 215 AA.
AC P79290;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 125.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RX PubMed=9613441; DOI=10.1016/s0165-2427(97)00139-6;
RA Pampusch M.S., Bennaars A.M., Harsch S., Murtaugh M.P.;
RT "Inducible nitric oxide synthase expression in porcine immune cells.";
RL Vet. Immunol. Immunopathol. 61:279-289(1998).
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; 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 {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 -!- TISSUE SPECIFICITY: Detected in both stimulated and unstimulated immune
CC cells and macrophages with little or no up-regulation following
CC cellular stimulation with lipopolysaccharides (LPS) or concanavalin A
CC (ConA).
CC -!- INDUCTION: Little by LPS or ConA in spleen cells.
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; U59390; AAB40614.1; -; mRNA.
DR AlphaFoldDB; P79290; -.
DR SMR; P79290; -.
DR STRING; 9823.ENSSSCP00000018812; -.
DR PaxDb; P79290; -.
DR PRIDE; P79290; -.
DR eggNOG; KOG1158; Eukaryota.
DR InParanoid; P79290; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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; 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 Gene3D; 3.90.1230.10; -; 1.
DR Gene3D; 3.90.340.10; -; 1.
DR Gene3D; 3.90.440.10; -; 1.
DR InterPro; IPR044943; NOS_dom_1.
DR InterPro; IPR044940; NOS_dom_2.
DR InterPro; IPR044944; NOS_dom_3.
DR InterPro; IPR004030; NOS_N.
DR InterPro; IPR036119; NOS_N_sf.
DR Pfam; PF02898; NO_synthase; 1.
DR SUPFAM; SSF56512; SSF56512; 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..>215
FT /note="Nitric oxide synthase, inducible"
FT /id="PRO_0000170935"
FT BINDING 51
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 160
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 161
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 165
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT NON_TER 1
FT NON_TER 215
SQ SEQUENCE 215 AA; 24716 MW; FECFF5BD85B65808 CRC64;
DARSCSTAQE MFEHICRHLR YATNNGNIRS AITVFPQRSD GKHDFRVWNA QLIRYAGYQM
PDGTIIGDPA SVEFTQLCID LGWKPKYGRF DVVPLVLHAD GRDPELFEIP PDLVLEVPME
HPKYEWFQEL ELKWYALPAV ANMLLEVGGL EFPGCPFNGW YMGTEIGVRD FCDVQRYNIL
EEVGRRMGLE THKLASLWKD RAVVEINVAV LHSFQ
