NOS2_CAVPO
ID NOS2_CAVPO Reviewed; 1149 AA.
AC O54705;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 156.
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;
GN Name=NOS2; Synonyms=NOS;
OS Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Hartley; TISSUE=Lung;
RX PubMed=9677342; DOI=10.1042/bj3330795;
RA Shirato M., Sakamoto T., Uchida Y., Nomura A., Ishii Y., Iijima H.,
RA Goto Y., Hasegawa S.;
RT "Molecular cloning and characterization of Ca2+-dependent inducible nitric
RT oxide synthase from guinea-pig lung.";
RL Biochem. J. 333:795-799(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: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.
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: Expressed in the lung and colon. Not detected in
CC the heart, aorta, liver, kidney, and spleen.
CC -!- INDUCTION: By lipopolysaccharide (LPS); in kidney, spleen, and colon.
CC Expression is reduced in the presence of LPS in lung.
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; AF027180; AAC33177.1; -; mRNA.
DR RefSeq; NP_001166455.1; NM_001172984.1.
DR AlphaFoldDB; O54705; -.
DR SMR; O54705; -.
DR STRING; 10141.ENSCPOP00000017277; -.
DR PRIDE; O54705; -.
DR GeneID; 100135576; -.
DR KEGG; cpoc:100135576; -.
DR CTD; 4843; -.
DR eggNOG; KOG1158; Eukaryota.
DR InParanoid; O54705; -.
DR OrthoDB; 90349at2759; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
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:0042742; P:defense response to bacterium; 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 GO; GO:0006801; P:superoxide metabolic process; ISS:UniProtKB.
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 Calcium; Calmodulin-binding; Cytoplasm; FAD; Flavoprotein; FMN; Heme; Iron;
KW Metal-binding; NADP; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT CHAIN 1..1149
FT /note="Nitric oxide synthase, inducible"
FT /id="PRO_0000170929"
FT DOMAIN 538..676
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT DOMAIN 729..969
FT /note="FAD-binding FR-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00716"
FT REGION 22..83
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 508..528
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000255"
FT MOTIF 23..27
FT /note="DINNN-motif; mediates interaction with SPSB1, SPSB2
FT and SPSB4"
FT /evidence="ECO:0000250|UniProtKB:P35228"
FT COMPBIAS 49..83
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 117
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 199
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 262
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 371
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 372
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 376
FT /ligand="L-arginine"
FT /ligand_id="ChEBI:CHEBI:32682"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 462
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 475
FT /ligand="(6R)-L-erythro-5,6,7,8-tetrahydrobiopterin"
FT /ligand_id="ChEBI:CHEBI:59560"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 490
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /evidence="ECO:0000250|UniProtKB:P29474"
FT BINDING 622..653
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 766..777
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 902..912
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 977..995
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT BINDING 1075..1090
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT MOD_RES 574
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q06518"
SQ SEQUENCE 1149 AA; 130632 MW; 66D595A2486DB50E CRC64;
MACPWNFLWK LKSSRYDLTE EKDINNNVGK ASHLYSPEIQ DDPKYCSPGK HQNGSSQSLT
GTAKKVPESQ SKPHKPSPTC SQHMKIKNWG NGMILQDTLH TKAKTNFTCK PKSCLGSVMN
PRSMTRGPRD TPIPPDELLP QAIEFVNQYY DSFKEAKIEE YLARVETVTK EIETTGTYQL
TGDELIFATK LAWRNAPRCI GRIQWSNLQV FDARSCHTAQ EMFEHICRHV RYSTNNGNIR
SAITVFPQRT DGKHDFRVWN AQLIRYAGYQ MPDGTIQGDP ANLEFTQLCI DLGWKPRYGR
FDVLPLILQA DGRDPELFEI PPDLVLEVPM EHPKYEWFQD LGLKWYALPA VANMLLEVGG
LEFPACPFNG WYMGTEIGVR DFCDAQRYNI LEEVGRRMGL ETHTLASLWK DRAVTEINVA
VLHSFQKQNV TIMDHHSAAE SFMKHMQNEY RARGGCPADW IWLVPPISGS ITPVFHQEML
NYILSPFYYY QVEAWKTHVW QDETRRPKRR EIPFRVLAKA TLFASLLMRK MMASRVRATI
LFATETGKSE ALAQDLGALF SCAFNPKVLC MDQYQLSSLE EEKLLLVVTS TFGNGDCPGN
GETLKKSLFV LKKLTNTFRY AVFGLGSSMY PRFCAFAHDI DIKLSQLGAS QLTPVGEGDE
LSGQEDAFCT WAVQTFQAAC AAFDVRGRHH ITIPKRYTSS VTWEPYHYRL VQDSQPLDLN
KALSRMHATD VFTMRLKSQK NLQSPKSSRT TLLMELSCDD SRSLAYLPGE HLGVFPCNQP
ALVQGILECV VDNPGPHHTV CLEVLDDSGS YWAKDKRLPP CSLSQALTYF LDITTPPTQL
QLQKLARLAT EQAERLRLES LSQPSEYNKW KFTNSPTFLE VLEEFPSLRV PAAFLLSQLP
ILKPRYYSIS SSLDHTPAEV HLTVAVVTYR TRDGRGPLHH GVCSTWFSGL KPQDPVPCLV
RSVNSFQLPK DPSQPCILIG PGTGIAPFRS FWQQRLHNLK HTGLQGGRMT LLFGCRHPEE
DHIYKEEMQE MVQKGVLHEV HTAYSRLPGK PKAYVQDILR QQLAREVLRV LHEEPGHLYV
CGNVLMAQDV ACTLKQLLAA KLNLNEEQVE DYFFQLKSQK RYHEDIFGAV FPHGVKKDRA
ERPPGDDKL
