I23O1_MOUSE
ID I23O1_MOUSE Reviewed; 407 AA.
AC P28776;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Indoleamine 2,3-dioxygenase 1;
DE Short=IDO-1;
DE EC=1.13.11.52 {ECO:0000250|UniProtKB:P14902};
DE AltName: Full=Indoleamine-pyrrole 2,3-dioxygenase;
GN Name=Ido1; Synonyms=Ido, Indo;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=1937018; DOI=10.1016/0378-1119(91)90154-4;
RA Habara-Ohkubo A., Takikawa O., Yoshida R.;
RT "Cloning and expression of a cDNA encoding mouse indoleamine 2,3-
RT dioxygenase.";
RL Gene 105:221-227(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NMRI; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15063630; DOI=10.1016/j.jri.2003.11.003;
RA Baban B., Chandler P., McCool D., Marshall B., Munn D.H., Mellor A.L.;
RT "Indoleamine 2,3-dioxygenase expression is restricted to fetal trophoblast
RT giant cells during murine gestation and is maternal genome specific.";
RL J. Reprod. Immunol. 61:67-77(2004).
RN [4]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18026683; DOI=10.1007/s00239-007-9049-1;
RA Yuasa H.J., Takubo M., Takahashi A., Hasegawa T., Noma H., Suzuki T.;
RT "Evolution of vertebrate indoleamine 2,3-dioxygenases.";
RL J. Mol. Evol. 65:705-714(2007).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=18384884; DOI=10.1016/j.imlet.2008.02.006;
RA de Faudeur G., de Trez C., Muraille E., Leo O.;
RT "Normal development and function of dendritic cells in mice lacking IDO-1
RT expression.";
RL Immunol. Lett. 118:21-29(2008).
RN [6]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19741271; DOI=10.1369/jhc.2009.953604;
RA Dai X., Zhu B.T.;
RT "Indoleamine 2,3-dioxygenase tissue distribution and cellular localization
RT in mice: implications for its biological functions.";
RL J. Histochem. Cytochem. 58:17-28(2010).
RN [7]
RP DISRUPTION PHENOTYPE.
RX PubMed=22157149; DOI=10.4161/cbt.12.12.18142;
RA Chang M.Y., Smith C., DuHadaway J.B., Pyle J.R., Boulden J., Soler A.P.,
RA Muller A.J., Laury-Kleintop L.D., Prendergast G.C.;
RT "Cardiac and gastrointestinal liabilities caused by deficiency in the
RT immune modulatory enzyme indoleamine 2,3-dioxygenase.";
RL Cancer Biol. Ther. 12:1050-1058(2011).
RN [8]
RP REVIEW, AND TISSUE SPECIFICITY.
RX PubMed=25691885; DOI=10.3389/fimmu.2015.00034;
RA van Baren N., Van den Eynde B.J.;
RT "Tryptophan-degrading enzymes in tumoral immune resistance.";
RL Front. Immunol. 6:34-34(2015).
CC -!- FUNCTION: Catalyzes the first and rate limiting step of the catabolism
CC of the essential amino acid tryptophan along the kynurenine pathway.
CC Involved in the peripheral immune tolerance, contributing to maintain
CC homeostasis by preventing autoimmunity or immunopathology that would
CC result from uncontrolled and overreacting immune responses. Tryptophan
CC shortage inhibits T lymphocytes division and accumulation of tryptophan
CC catabolites induces T-cell apoptosis and differentiation of regulatory
CC T-cells. Acts as a suppressor of anti-tumor immunity (PubMed:25691885).
CC Limits the growth of intracellular pathogens by depriving tryptophan.
CC Protects the fetus from maternal immune rejection (Ref. 3).
CC {ECO:0000250|UniProtKB:P14902, ECO:0000269|PubMed:15063630,
CC ECO:0000303|PubMed:25691885}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-tryptophan + O2 = N-formyl-D-kynurenine;
CC Xref=Rhea:RHEA:14189, ChEBI:CHEBI:15379, ChEBI:CHEBI:57719,
CC ChEBI:CHEBI:60051; EC=1.13.11.52;
CC Evidence={ECO:0000250|UniProtKB:P14902};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tryptophan + O2 = N-formyl-L-kynurenine;
CC Xref=Rhea:RHEA:24536, ChEBI:CHEBI:15379, ChEBI:CHEBI:57912,
CC ChEBI:CHEBI:58629; EC=1.13.11.52;
CC Evidence={ECO:0000250|UniProtKB:P14902};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P14902};
CC Note=Binds 1 heme group per subunit. {ECO:0000250|UniProtKB:P14902};
CC -!- ACTIVITY REGULATION: Activity is inhibited by and MTH-trp
CC (methylthiohydantoin-DL-tryptophan), modestly inhibited by L-1MT (1-
CC methyl-L-tryptophan) but not D-1MT (1-methyl-D-tryptophan).
CC {ECO:0000250|UniProtKB:P14902}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=28.1 uM for L-tryptophan {ECO:0000269|PubMed:18026683};
CC KM=2.87 mM for D-tryptophan {ECO:0000269|PubMed:18026683};
CC Note=Catalytic efficiency for L-tryptophan is 90 times higher than
CC for D-tryptophan.;
CC -!- SUBUNIT: Monomer. {ECO:0000303|PubMed:25691885}.
CC -!- INTERACTION:
CC P28776; P35235: Ptpn11; NbExp=5; IntAct=EBI-4410822, EBI-397236;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:19741271}.
CC -!- TISSUE SPECIFICITY: Highly expressed in epididymis, duodemum, jejunum,
CC ileum, colon and spleen (PubMed:19741271). Highly expressed in
CC epididymis, prostate, duodemum, jejunum, ileum, colon and spleen, not
CC detected in the liver (at protein level) (PubMed:19741271). Expressed
CC in tumors only upon exposure to IFN gamma (PubMed:25691885).
CC Constitutively expressed in placenta in trophoblast cells
CC (PubMed:15063630). Expression is restricted to perinuclear regions of
CC primary trophoblast giant cells (TGCs) of fetal origin at mid-gestation
CC (10.5 dpc). After placentation (14 dpc), no IDO expression was detected
CC at the maternal-fetal interface (PubMed:15063630).
CC {ECO:0000269|PubMed:15063630, ECO:0000269|PubMed:19741271,
CC ECO:0000303|PubMed:25691885}.
CC -!- INDUCTION: By IFNG/IFN-gamma in most cells.
CC {ECO:0000250|UniProtKB:P14902}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice display normal development and
CC function of dendritic cells, on T- or B-cells development
CC (PubMed:18384884). They display increased sensitivity to the induction
CC of inflammatory and autoimmune reactions (PubMed:22157149). They
CC produce litters of normal sizes at normal rates, implying that
CC compensatory or redundant immunosuppressive mechanisms protected
CC allogeneic fetuses during gestation in knockout mice. Knockout mice
CC display cardiac and gastrointestinal liabilities (PubMed:22157149).
CC {ECO:0000269|PubMed:18384884, ECO:0000269|PubMed:22157149}.
CC -!- MISCELLANEOUS: Ido1 and Ido2 are 2 distinct enzymes which catalyze the
CC same reaction. Ido2 affinity for tryptophan is much lower than that of
CC Ido1. Ido2 may play a role as a negative regulator of Ido1 by competing
CC for heme-binding with Ido1. Low efficiency Ido2 enzymes have been
CC conserved throughout vertebrate evolution, whereas higher efficiency
CC Ido1 enzymes are dispensable in many lower vertebrate lineages. Ido1
CC may have arisen by gene duplication of a more ancient proto-IDO gene
CC before the divergence of marsupial and eutherian (placental) mammals.
CC {ECO:0000250|UniProtKB:P14902}.
CC -!- SIMILARITY: Belongs to the indoleamine 2,3-dioxygenase family.
CC {ECO:0000305}.
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DR EMBL; M69109; AAA37872.1; -; mRNA.
DR EMBL; BC049931; AAH49931.1; -; mRNA.
DR CCDS; CCDS40299.1; -.
DR PIR; JH0492; JH0492.
DR RefSeq; NP_001280619.1; NM_001293690.1.
DR RefSeq; NP_032350.1; NM_008324.2.
DR AlphaFoldDB; P28776; -.
DR SMR; P28776; -.
DR BioGRID; 200512; 2.
DR DIP; DIP-48663N; -.
DR IntAct; P28776; 4.
DR STRING; 10090.ENSMUSP00000033956; -.
DR BindingDB; P28776; -.
DR ChEMBL; CHEMBL1075294; -.
DR DrugCentral; P28776; -.
DR iPTMnet; P28776; -.
DR PhosphoSitePlus; P28776; -.
DR MaxQB; P28776; -.
DR PaxDb; P28776; -.
DR PRIDE; P28776; -.
DR ProteomicsDB; 269517; -.
DR Antibodypedia; 5705; 1008 antibodies from 45 providers.
DR DNASU; 15930; -.
DR Ensembl; ENSMUST00000033956; ENSMUSP00000033956; ENSMUSG00000031551.
DR GeneID; 15930; -.
DR KEGG; mmu:15930; -.
DR UCSC; uc009lfa.2; mouse.
DR CTD; 3620; -.
DR MGI; MGI:96416; Ido1.
DR VEuPathDB; HostDB:ENSMUSG00000031551; -.
DR eggNOG; ENOG502RZ6X; Eukaryota.
DR GeneTree; ENSGT00940000161410; -.
DR InParanoid; P28776; -.
DR OMA; TMAYVWN; -.
DR OrthoDB; 1206249at2759; -.
DR PhylomeDB; P28776; -.
DR TreeFam; TF330978; -.
DR BRENDA; 1.13.11.11; 3474.
DR BRENDA; 1.13.11.52; 3474.
DR Reactome; R-MMU-71240; Tryptophan catabolism.
DR SABIO-RK; P28776; -.
DR BioGRID-ORCS; 15930; 2 hits in 77 CRISPR screens.
DR PRO; PR:P28776; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P28776; protein.
DR Bgee; ENSMUSG00000031551; Expressed in dorsal striatum and 48 other tissues.
DR ExpressionAtlas; P28776; baseline and differential.
DR Genevisible; P28776; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030485; C:smooth muscle contractile fiber; IDA:MGI.
DR GO; GO:0032421; C:stereocilium bundle; IDA:MGI.
DR GO; GO:0016597; F:amino acid binding; ISO:MGI.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0033754; F:indoleamine 2,3-dioxygenase activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019825; F:oxygen binding; ISO:MGI.
DR GO; GO:0004833; F:tryptophan 2,3-dioxygenase activity; IDA:MGI.
DR GO; GO:0034354; P:'de novo' NAD biosynthetic process from tryptophan; IBA:GO_Central.
DR GO; GO:0006952; P:defense response; TAS:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0034276; P:kynurenic acid biosynthetic process; IMP:MGI.
DR GO; GO:0033555; P:multicellular organismal response to stress; IMP:MGI.
DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; IMP:MGI.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IMP:MGI.
DR GO; GO:0070233; P:negative regulation of T cell apoptotic process; IMP:MGI.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI.
DR GO; GO:0002678; P:positive regulation of chronic inflammatory response; IMP:MGI.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IMP:MGI.
DR GO; GO:0070234; P:positive regulation of T cell apoptotic process; ISO:MGI.
DR GO; GO:0002666; P:positive regulation of T cell tolerance induction; IMP:MGI.
DR GO; GO:0002830; P:positive regulation of type 2 immune response; IMP:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:MGI.
DR GO; GO:0036269; P:swimming behavior; IMP:MGI.
DR GO; GO:0042098; P:T cell proliferation; IMP:MGI.
DR GO; GO:0019441; P:tryptophan catabolic process to kynurenine; IDA:MGI.
DR InterPro; IPR000898; Indolamine_dOase.
DR InterPro; IPR037217; Trp/Indoleamine_2_3_dOase-like.
DR PANTHER; PTHR28657; PTHR28657; 1.
DR Pfam; PF01231; IDO; 1.
DR SUPFAM; SSF140959; SSF140959; 1.
DR PROSITE; PS00876; IDO_1; 1.
DR PROSITE; PS00877; IDO_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Dioxygenase; Direct protein sequencing; Heme; Immunity; Iron;
KW Metal-binding; Oxidoreductase; Reference proteome; Tryptophan catabolism.
FT CHAIN 1..407
FT /note="Indoleamine 2,3-dioxygenase 1"
FT /id="PRO_0000215205"
FT REGION 362..407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 362..377
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..394
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 350
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="proximal binding residue"
FT /evidence="ECO:0000250|UniProtKB:P14902"
SQ SEQUENCE 407 AA; 45641 MW; 317681EABF96A727 CRC64;
MALSKISPTE GSRRILEDHH IDEDVGFALP HPLVELPDAY SPWVLVARNL PVLIENGQLR
EEVEKLPTLS TDGLRGHRLQ RLAHLALGYI TMAYVWNRGD DDVRKVLPRN IAVPYCELSE
KLGLPPILSY ADCVLANWKK KDPNGPMTYE NMDILFSFPG GDCDKGFFLV SLLVEIAASP
AIKAIPTVSS AVERQDLKAL EKALHDIATS LEKAKEIFKR MRDFVDPDTF FHVLRIYLSG
WKCSSKLPEG LLYEGVWDTP KMFSGGSAGQ SSIFQSLDVL LGIKHEAGKE SPAEFLQEMR
EYMPPAHRNF LFFLESAPPV REFVISRHNE DLTKAYNECV NGLVSVRKFH LAIVDTYIMK
PSKKKPTDGD KSEEPSNVES RGTGGTNPMT FLRSVKDTTE KALLSWP
