ID   I23O2_RAT               Reviewed;         405 AA.
AC   F1LV46;
DT   14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT   14-OCT-2015, sequence version 4.
DT   03-AUG-2022, entry version 61.
DE   RecName: Full=Indoleamine 2,3-dioxygenase 2;
DE            Short=IDO-2;
DE            EC=1.13.11.- {ECO:0000250|UniProtKB:Q8R0V5};
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Liver;
RA   Katinka M., Da Silva C., Cruaud C., Pravenec M., Poulain J., Wincker P.,
RA   Weissenbach J.;
RL   Submitted (JUN-2010) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
CC   -!- FUNCTION: Catalyzes the first and rate-limiting step in the kynurenine
CC       pathway of tryptophan catabolism. Involved in immune regulation.
CC       {ECO:0000250|UniProtKB:Q8R0V5}.
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:0000250|UniProtKB:Q8R0V5};
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:0000250|UniProtKB:Q8R0V5}.
CC   -!- PATHWAY: Amino-acid degradation; L-tryptophan degradation via
CC       kynurenine pathway; L-kynurenine from L-tryptophan: step 1/2.
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; FQ109047; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AABR07026331; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR07026332; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   RefSeq; XP_003752968.1; XM_003752920.3.
DR   AlphaFoldDB; F1LV46; -.
DR   SMR; F1LV46; -.
DR   STRING; 10116.ENSRNOP00000036799; -.
DR   PaxDb; F1LV46; -.
DR   PeptideAtlas; F1LV46; -.
DR   Ensembl; ENSRNOT00000032116; ENSRNOP00000036799; ENSRNOG00000025365.
DR   GeneID; 681319; -.
DR   CTD; 169355; -.
DR   RGD; 1596771; Ido2.
DR   eggNOG; ENOG502QT99; Eukaryota.
DR   GeneTree; ENSGT00940000161813; -.
DR   HOGENOM; CLU_010089_1_0_1; -.
DR   InParanoid; F1LV46; -.
DR   OrthoDB; 1206249at2759; -.
DR   TreeFam; TF330978; -.
DR   Reactome; R-RNO-71240; Tryptophan catabolism.
DR   UniPathway; UPA00333; UER00453.
DR   PRO; PR:F1LV46; -.
DR   Proteomes; UP000002494; Chromosome 16.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0033754; F:indoleamine 2,3-dioxygenase activity; ISO:RGD.
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; ISO:RGD.
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   2: Evidence at transcript 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_0000434002"
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"
SQ   SEQUENCE   405 AA;  45236 MW;  5CAE75E87ECAD42F CRC64;
     MEAQRQDGKL ASSLSLGKYH ISEEYGFLLP NPLEELPDHY KPWMEIAHRL PHLIESHQLQ
     AHVYEMPLLD CRFLTSYREQ RLAHLVLAAI TMGFVWQEGE AQPQKVLPRT LAIPFVEVSR
     SLGLPPILVH SDLVLTNWTK RNPEGPLEIG NLETIISFPG GESLQGFILV TVLVEKAAVP
     GIKALVLGVE AIRQHSQDTL LEALQQLRLS IQDITRALAQ MHDYVDPEIF YLVIRIFLSG
     WKDNPVMPVG LVYEGVSTEP LKYSGGSAAQ SSVLHAFDEF LGIQHCKESV DFLHRMRDYM
     PPSHKAFLED LHSAPSLRDY ILDSGPGGCL MAYNQCVEAL GELRSYHINM VARYIISAAS
     KARSRMLTRL SPHALEDRGT GGTAVLSFLK SVREKTMEAI LCPGA