I23O2_MOUSE
ID I23O2_MOUSE Reviewed; 405 AA.
AC Q8R0V5; A4UHF3; E9QKA9;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2015, sequence version 3.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Indoleamine 2,3-dioxygenase 2;
DE Short=IDO-2;
DE EC=1.13.11.- {ECO:0000269|PubMed:17499941};
DE AltName: Full=Indoleamine 2,3-dioxygenase-like protein 1;
DE AltName: Full=Indoleamine-pyrrole 2,3-dioxygenase-like protein 1;
GN Name=Ido2; Synonyms=Indol1;
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], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, AND ACTIVITY REGULATION.
RX PubMed=17499941; DOI=10.1016/j.gene.2007.04.010;
RA Ball H.J., Sanchez-Perez A., Weiser S., Austin C.J.D., Astelbauer F.,
RA Miu J., McQuillan J.A., Stocker R., Jermiin L.S., Hunt N.H.;
RT "Characterization of an indoleamine 2,3-dioxygenase-like protein found in
RT humans and mice.";
RL Gene 396:203-213(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [5]
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=17671174; DOI=10.1158/0008-5472.can-07-1872;
RA Metz R., Duhadaway J.B., Kamasani U., Laury-Kleintop L., Muller A.J.,
RA Prendergast G.C.;
RT "Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target
RT of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-
RT methyl-tryptophan.";
RL Cancer Res. 67:7082-7087(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=24402311; DOI=10.1093/intimm/dxt073;
RA Metz R., Smith C., DuHadaway J.B., Chandler P., Baban B., Merlo L.M.,
RA Pigott E., Keough M.P., Rust S., Mellor A.L., Mandik-Nayak L., Muller A.J.,
RA Prendergast G.C.;
RT "IDO2 is critical for IDO1-mediated T-cell regulation and exerts a non-
RT redundant function in inflammation.";
RL Int. Immunol. 26:357-367(2014).
RN [9]
RP REVIEW, AND DISRUPTION PHENOTYPE.
RX PubMed=25477879; DOI=10.3389/fimmu.2014.00585;
RA Prendergast G.C., Metz R., Muller A.J., Merlo L.M., Mandik-Nayak L.;
RT "IDO2 in immunomodulation and autoimmune disease.";
RL Front. Immunol. 5:585-585(2014).
RN [10]
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 in the kynurenine
CC pathway of tryptophan catabolism (PubMed:17499941, PubMed:17499941).
CC Involved in immune regulation (PubMed:25477879).
CC {ECO:0000269|PubMed:17499941, ECO:0000303|PubMed:25477879}.
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; Evidence={ECO:0000269|PubMed:17499941};
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 D-1MT (1-methyl-D-
CC tryptophan) and MTH-trp (methylthiohydantoin-DL-tryptophan) but not L-
CC 1MT (1-methyl-L-tryptophan). {ECO:0000269|PubMed:17499941}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=38.85 mM for L-tryptophan {ECO:0000269|PubMed:18026683};
CC Note=Do not accept D-tryptophan as substrate.;
CC -!- PATHWAY: Amino-acid degradation; L-tryptophan degradation via
CC kynurenine pathway; L-kynurenine from L-tryptophan: step 1/2.
CC -!- TISSUE SPECIFICITY: Expressed mainly in antigen-presenting immune
CC cells, liver, kidney, brain, and placenta (PubMed:25691885,
CC PubMed:17671174). Highly expressed in kidney, followed by epididymis
CC and liver (at protein level) (PubMed:17499941). Detected in the tails
CC of the spermatozoa in the testis and in the kidney tubules (at protein
CC level) (PubMed:17499941). Constitutively expressed in brain.
CC {ECO:0000269|PubMed:17499941, ECO:0000269|PubMed:17671174,
CC ECO:0000303|PubMed:25691885}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice have no apparent defects in
CC embryonic development or hematopoietic differentiation and have wild-
CC type profiles for kynurenine in blood serum and for immune cells in
CC spleen, lymph nodes, peritoneum, thymus and bone marrow. Knockout mice
CC exhibit defects in IDO-mediated T-cell regulation and inflammatory
CC responses (PubMed:25691885). They exhibit defects in allergic or
CC autoimmune responses (PubMed:24402311). {ECO:0000269|PubMed:24402311,
CC ECO:0000303|PubMed:25691885}.
CC -!- MISCELLANEOUS: Ido1 and Ido2 are 2 distinct enzymes which catalyze the
CC same reaction. Ido2 Km for tryptophan is much higher than that of Ido1.
CC Ido2 may play a role as a negative regulator of Ido1 by competing for
CC heme-binding with Ido1. Low efficiency Ido2 enzymes have been conserved
CC throughout vertebrate evolution, whereas higher efficiency Ido1 enzymes
CC are dispensable in many lower vertebrate lineages. Ido1 may have arisen
CC by gene duplication of a more ancient proto-IDO gene before the
CC 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH26393.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; EF137182; ABO33433.1; -; mRNA.
DR EMBL; AC114602; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466580; EDL32857.1; -; Genomic_DNA.
DR EMBL; BC026393; AAH26393.1; ALT_INIT; mRNA.
DR CCDS; CCDS40298.2; -.
DR RefSeq; NP_666061.3; NM_145949.2.
DR AlphaFoldDB; Q8R0V5; -.
DR SMR; Q8R0V5; -.
DR STRING; 10090.ENSMUSP00000113979; -.
DR BindingDB; Q8R0V5; -.
DR ChEMBL; CHEMBL2189159; -.
DR DrugCentral; Q8R0V5; -.
DR iPTMnet; Q8R0V5; -.
DR PhosphoSitePlus; Q8R0V5; -.
DR jPOST; Q8R0V5; -.
DR MaxQB; Q8R0V5; -.
DR PaxDb; Q8R0V5; -.
DR PRIDE; Q8R0V5; -.
DR ProteomicsDB; 269518; -.
DR Antibodypedia; 42276; 469 antibodies from 34 providers.
DR Ensembl; ENSMUST00000121992; ENSMUSP00000113979; ENSMUSG00000031549.
DR GeneID; 209176; -.
DR KEGG; mmu:209176; -.
DR UCSC; uc009ley.2; mouse.
DR UCSC; uc009lez.2; mouse.
DR CTD; 169355; -.
DR MGI; MGI:2142489; Ido2.
DR VEuPathDB; HostDB:ENSMUSG00000031549; -.
DR eggNOG; ENOG502QT99; Eukaryota.
DR GeneTree; ENSGT00940000161813; -.
DR InParanoid; Q8R0V5; -.
DR OMA; CMPKGLV; -.
DR OrthoDB; 1206249at2759; -.
DR PhylomeDB; Q8R0V5; -.
DR TreeFam; TF330978; -.
DR BRENDA; 1.13.11.52; 3474.
DR Reactome; R-MMU-71240; Tryptophan catabolism.
DR SABIO-RK; Q8R0V5; -.
DR UniPathway; UPA00333; UER00453.
DR BioGRID-ORCS; 209176; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Ido2; mouse.
DR PRO; PR:Q8R0V5; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8R0V5; protein.
DR Bgee; ENSMUSG00000031549; Expressed in right kidney and 30 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0033754; F:indoleamine 2,3-dioxygenase activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004833; F:tryptophan 2,3-dioxygenase activity; IBA:GO_Central.
DR GO; GO:0034354; P:'de novo' NAD biosynthetic process from tryptophan; IBA:GO_Central.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
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.
PE 1: Evidence at protein level;
KW Dioxygenase; Heme; Immunity; Iron; Metal-binding; Oxidoreductase;
KW Reference proteome; Tryptophan catabolism.
FT CHAIN 1..405
FT /note="Indoleamine 2,3-dioxygenase 2"
FT /id="PRO_0000285263"
FT BINDING 347
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"
FT CONFLICT 256
FT /note="V -> A (in Ref. 4; AAH26393)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 405 AA; 45255 MW; DCDFD1A09842E96B CRC64;
MEPQSQSMTL EVPLSLGRYH ISEEYGFLLP NPLEALPDHY KPWMEIALRL PHLIENRQLR
AHVYRMPLLD CRFLKSYREQ RLAHMALAAI TMGFVWQEGE GQPQKVLPRS LAIPFVEVSR
NLGLPPILVH SDLVLTNWTK RNPEGPLEIS NLETIISFPG GESLRGFILV TVLVEKAAVP
GLKALVQGME AIRQHSQDTL LEALQQLRLS IQDITRALAQ MHDYVDPDIF YSVIRIFLSG
WKDNPAMPVG LVYEGVATEP LKYSGGSAAQ SSVLHAFDEF LGIEHCKESV GFLHRMRDYM
PPSHKAFLED LHVAPSLRDY ILASGPGDCL MAYNQCVEAL GELRSYHINV VARYIISAAT
RARSRGLTNP SPHALEDRGT GGTAMLSFLK SVREKTMEAL LCPGA
