I23O1_HUMAN
ID I23O1_HUMAN Reviewed; 403 AA.
AC P14902; E5RGR8; F6M9T7; Q540B4;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Indoleamine 2,3-dioxygenase 1;
DE Short=IDO-1;
DE EC=1.13.11.52 {ECO:0000269|PubMed:17671174};
DE AltName: Full=Indoleamine-pyrrole 2,3-dioxygenase;
GN Name=IDO1; Synonyms=IDO, INDO;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION BY IFNG.
RC TISSUE=Fibroblast;
RX PubMed=2109605; DOI=10.1016/0006-291x(90)91666-g;
RA Dai W., Gupta S.L.;
RT "Molecular cloning, sequencing and expression of human interferon-gamma-
RT inducible indoleamine 2,3-dioxygenase cDNA.";
RL Biochem. Biophys. Res. Commun. 168:1-8(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Lung;
RX PubMed=2326172; DOI=10.1093/nar/18.2.367;
RA Tone S., Takikawa O., Habara-Ohkubo A., Kadoya A., Yoshida R., Kido R.;
RT "Primary structure of human indoleamine 2,3-dioxygenase deduced from the
RT nucleotide sequence of its cDNA.";
RL Nucleic Acids Res. 18:367-367(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1449503; DOI=10.1016/0006-291x(92)91590-m;
RA Kadoya A., Tone S., Maeda H., Minatogawa Y., Kido R.;
RT "Gene structure of human indoleamine 2,3-dioxygenase.";
RL Biochem. Biophys. Res. Commun. 189:530-536(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Peripheral blood;
RA He X., Xu L., Liu Y., Zeng Y.;
RT "Human indoleamine 2,3-dioxygenase from peripheral blood.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RA Qureshi A.M., Asghar K., Ashiq T., Anwar A., Raza M.I., Noor F., Qadri I.;
RT "Cloning and expression of human indolamine 2,3 dioxygenase.";
RL Submitted (APR-2011) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [9]
RP REVIEW, AND INDUCTION BY IFNG.
RX PubMed=1907934; DOI=10.1096/fasebj.5.11.1907934;
RA Taylor M.W., Feng G.S.;
RT "Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and
RT tryptophan catabolism.";
RL FASEB J. 5:2516-2522(1991).
RN [10]
RP FUNCTION.
RX PubMed=14502282; DOI=10.1038/nm934;
RA Uyttenhove C., Pilotte L., Theate I., Stroobant V., Colau D.,
RA Parmentier N., Boon T., Van den Eynde B.J.;
RT "Evidence for a tumoral immune resistance mechanism based on tryptophan
RT degradation by indoleamine 2,3-dioxygenase.";
RL Nat. Med. 9:1269-1274(2003).
RN [11]
RP COFACTOR.
RX PubMed=16574111; DOI=10.1016/j.febslet.2006.03.034;
RA Vottero E., Mitchell D.A., Page M.J., MacGillivray R.T., Sadowski I.J.,
RA Roberge M., Mauk A.G.;
RT "Cytochrome b(5) is a major reductant in vivo of human indoleamine 2,3-
RT dioxygenase expressed in yeast.";
RL FEBS Lett. 580:2265-2268(2006).
RN [12]
RP FUNCTION, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
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 [13]
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 [14]
RP DIFFERENCE BETWEEN IDO1 AND IDO2.
RX PubMed=18418598; DOI=10.1007/s00262-008-0513-6;
RA Loeb S., Koenigsrainer A., Zieker D., Bruecher B.L., Rammensee H.G.,
RA Opelz G., Terness P.;
RT "IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl
RT tryptophan inhibits tryptophan catabolism.";
RL Cancer Immunol. Immunother. 58:153-157(2009).
RN [15]
RP DIFFERENCE BETWEEN IDO1 AND IDO2.
RX PubMed=25394548; DOI=10.1038/emm.2014.69;
RA Lee Y.K., Lee H.B., Shin D.M., Kang M.J., Yi E.C., Noh S., Lee J., Lee C.,
RA Min C.K., Choi E.Y.;
RT "Heme-binding-mediated negative regulation of the tryptophan metabolic
RT enzyme indoleamine 2,3-dioxygenase 1 (IDO1) by IDO2.";
RL Exp. Mol. Med. 46:E121-E121(2014).
RN [16]
RP DIFFERENCE BETWEEN IDO1 AND IDO2.
RX PubMed=25950090; DOI=10.1111/febs.13316;
RA Yuasa H.J., Mizuno K., Ball H.J.;
RT "Low efficiency IDO2 enzymes are conserved in lower vertebrates, whereas
RT higher efficiency IDO1 enzymes are dispensable.";
RL FEBS J. 282:2735-2745(2015).
RN [17]
RP TISSUE SPECIFICITY.
RX PubMed=26155395; DOI=10.1080/2162402x.2014.1003012;
RA Vigneron N., van Baren N., Van den Eynde B.J.;
RT "Expression profile of the human IDO1 protein, a cancer drug target
RT involved in tumoral immune resistance.";
RL OncoImmunology 4:E1003012-E1003012(2015).
RN [18]
RP REVIEW.
RX PubMed=23103127; DOI=10.1016/j.it.2012.10.001;
RA Munn D.H., Mellor A.L.;
RT "Indoleamine 2,3 dioxygenase and metabolic control of immune responses.";
RL Trends Immunol. 34:137-143(2013).
RN [19]
RP REVIEW.
RX PubMed=25157255; DOI=10.3389/fimmu.2014.00384;
RA Schmidt S.V., Schultze J.L.;
RT "New insights into IDO biology in bacterial and viral infections.";
RL Front. Immunol. 5:384-384(2014).
RN [20]
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).
RN [21]
RP REVIEW.
RX PubMed=25970480; DOI=10.1021/acs.jmedchem.5b00326;
RA Roehrig U.F., Majjigapu S.R., Vogel P., Zoete V., Michielin O.;
RT "Challenges in the discovery of indoleamine 2,3-dioxygenase 1 (IDO1)
RT inhibitors.";
RL J. Med. Chem. 58:9421-9437(2015).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH HEME, AND COFACTOR.
RX PubMed=16477023; DOI=10.1073/pnas.0508996103;
RA Sugimoto H., Oda S., Otsuki T., Hino T., Yoshida T., Shiro Y.;
RT "Crystal structure of human indoleamine 2,3-dioxygenase: catalytic
RT mechanism of O2 incorporation by a heme-containing dioxygenase.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:2611-2616(2006).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) IN COMPLEX WITH HEME, AND COFACTOR.
RX PubMed=25313323; DOI=10.1021/ml500247w;
RA Tojo S., Kohno T., Tanaka T., Kamioka S., Ota Y., Ishii T., Kamimoto K.,
RA Asano S., Isobe Y.;
RT "Crystal structures and structure-activity relationships of imidazothiazole
RT derivatives as IDO1 inhibitors.";
RL ACS Med. Chem. Lett. 5:1119-1123(2014).
CC -!- FUNCTION: Catalyzes the first and rate limiting step of the catabolism
CC of the essential amino acid tryptophan along the kynurenine pathway
CC (PubMed:17671174). Involved in the peripheral immune tolerance,
CC contributing to maintain homeostasis by preventing autoimmunity or
CC immunopathology that would result from uncontrolled and overreacting
CC immune responses (PubMed:25691885). Tryptophan shortage inhibits T
CC lymphocytes division and accumulation of tryptophan catabolites induces
CC T-cell apoptosis and differentiation of regulatory T-cells
CC (PubMed:25691885). Acts as a suppressor of anti-tumor immunity
CC (PubMed:23103127, PubMed:25157255, PubMed:14502282, PubMed:25691885).
CC Limits the growth of intracellular pathogens by depriving tryptophan
CC (PubMed:25691885). Protects the fetus from maternal immune rejection
CC (PubMed:25691885). {ECO:0000269|PubMed:14502282,
CC ECO:0000269|PubMed:17671174, ECO:0000303|PubMed:23103127,
CC ECO:0000303|PubMed:25157255, 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:0000269|PubMed:17671174};
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:0000269|PubMed:17671174};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:16477023, ECO:0000269|PubMed:25313323};
CC Note=Binds 1 heme group per subunit (PubMed:16477023, PubMed:25313323).
CC In the active form, the heme iron is in its ferrous state Fe(+2). The
CC catalytic cycle does not alter the oxidation state of the heme, but
CC IDO1 is prone to autoxidation (PubMed:16574111).
CC {ECO:0000269|PubMed:16477023, ECO:0000269|PubMed:16574111,
CC ECO:0000269|PubMed:25313323};
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:0000269|PubMed:17671174}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=21.23 uM for L-tryptophan {ECO:0000269|PubMed:18026683};
CC KM=4.6 mM for D-tryptophan {ECO:0000269|PubMed:18026683};
CC Note=Catalytic efficiency for L-tryptophan is 150 times higher than
CC for D-tryptophan.;
CC -!- PATHWAY: Amino-acid degradation; L-tryptophan degradation via
CC kynurenine pathway; L-kynurenine from L-tryptophan: step 1/2.
CC -!- SUBUNIT: Monomer. {ECO:0000303|PubMed:25691885}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P28776,
CC ECO:0000303|PubMed:25691885}.
CC -!- TISSUE SPECIFICITY: Expressed in mature dendritic cells located in
CC lymphoid organs (including lymph nodes, spleen, tonsils, Peyers's
CC patches, the gut lamina propria, and the thymic medulla), in some
CC epithelial cells of the female genital tract, as well as in endothelial
CC cells of term placenta and in lung parenchyma (PubMed:25691885). Weakly
CC or not expressed in most normal tissues, but mostly inducible in most
CC tissues (PubMed:25691885). Expressed in more than 50% of tumors, either
CC by tumoral, stromal, or endothelial cells (expression in tumor is
CC associated with a worse clinical outcome) (PubMed:18418598). Not
CC overexpressed in tumor-draining lymph nodes (PubMed:26155395,
CC PubMed:25691885). {ECO:0000269|PubMed:18418598,
CC ECO:0000269|PubMed:25691885, ECO:0000269|PubMed:26155395}.
CC -!- INDUCTION: By IFNG/IFN-gamma in most cells (PubMed:2109605,
CC PubMed:1907934). Exogenous inflammatory stimuli induce the expression
CC of IDO1 in antigen-presenting cells such as dendritic cells,
CC macrophages and B-cells (PubMed:25157255). {ECO:0000269|PubMed:2109605,
CC ECO:0000303|PubMed:1907934, ECO:0000303|PubMed:25157255}.
CC -!- MISCELLANEOUS: IDO1 is the target for therapy in a range of clinical
CC settings, including cancer, chronic infections, autoimmune and allergic
CC syndromes, and transplantation. {ECO:0000303|PubMed:25970480}.
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. 50% of Caucasians harbor polymorphisms which abolish IDO2
CC enzymatic activity. IDO2 is expressed in human tumors in an inactive
CC form: tryptophan degradation is entirely provided by IDO1 in these
CC cells (PubMed:18418598). IDO2 may play a role as a negative regulator
CC of IDO1 by competing for heme-binding with IDO1 (PubMed:25394548). Low
CC efficiency IDO2 enzymes have been conserved throughout vertebrate
CC evolution, whereas higher efficiency IDO1 enzymes are dispensable in
CC many lower vertebrate lineages (PubMed:25950090). 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:0000269|PubMed:18418598, ECO:0000269|PubMed:25394548,
CC ECO:0000269|PubMed:25950090}.
CC -!- MISCELLANEOUS: Elevated IDO1 expression is a hallmark of major viral
CC infections including HIV, HBV, HCV or influenza and also of major
CC bacteria infections, such as Tb, CAP, listeriosis and sepsis. Depletion
CC of tryptophan and production of tryptophan metabolites with
CC bactericidal activity are important as direct anti-pathogen mechanisms.
CC Pathogens are able to highjack the immunosuppressive effects of IDO1
CC and make use of them to facilitate their own life cycle.
CC {ECO:0000303|PubMed:25157255}.
CC -!- SIMILARITY: Belongs to the indoleamine 2,3-dioxygenase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AC007991; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/IDO1ID40973ch8p11.html";
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DR EMBL; M34455; AAA36081.1; -; mRNA.
DR EMBL; X17668; CAA35663.1; -; mRNA.
DR EMBL; M86472; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M86473; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M86474; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M86475; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M86476; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M86477; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M86478; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M86479; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M86480; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M86481; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; JF772862; AEF30540.1; -; mRNA.
DR EMBL; AY221100; AAO34405.1; -; mRNA.
DR EMBL; AK313259; BAG36069.1; -; mRNA.
DR EMBL; AC007991; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027882; AAH27882.1; -; mRNA.
DR CCDS; CCDS47847.1; -.
DR PIR; PC1161; PC1161.
DR RefSeq; NP_002155.1; NM_002164.5.
DR PDB; 2D0T; X-ray; 2.30 A; A/B=1-403.
DR PDB; 2D0U; X-ray; 3.40 A; A/B=1-403.
DR PDB; 4PK5; X-ray; 2.79 A; A/B=1-403.
DR PDB; 4PK6; X-ray; 3.45 A; A/B=1-403.
DR PDB; 4U72; X-ray; 2.00 A; A/B=1-403.
DR PDB; 4U74; X-ray; 2.31 A; A/B=1-403.
DR PDB; 5EK2; X-ray; 2.68 A; A/B=1-403.
DR PDB; 5EK3; X-ray; 2.21 A; A/B=1-403.
DR PDB; 5EK4; X-ray; 2.64 A; A/B=1-403.
DR PDB; 5ETW; X-ray; 2.70 A; A/B=1-403.
DR PDB; 5WHR; X-ray; 2.28 A; A/B=12-403.
DR PDB; 5WMU; X-ray; 2.40 A; A/B=11-403.
DR PDB; 5WMV; X-ray; 2.60 A; A/B=11-403.
DR PDB; 5WMW; X-ray; 3.03 A; A/B=11-403.
DR PDB; 5WMX; X-ray; 2.69 A; A/B=11-403.
DR PDB; 5WN8; X-ray; 2.50 A; A/B=12-403.
DR PDB; 5XE1; X-ray; 3.20 A; A/B=1-403.
DR PDB; 6AZU; X-ray; 2.82 A; A/B/C/D=5-403.
DR PDB; 6AZV; X-ray; 2.75 A; A/B/C/D=5-403.
DR PDB; 6AZW; X-ray; 2.78 A; A/B=11-403.
DR PDB; 6CXU; X-ray; 2.49 A; A/B=11-403.
DR PDB; 6CXV; X-ray; 2.60 A; A/B=11-403.
DR PDB; 6DPQ; X-ray; 2.94 A; A/B=11-403.
DR PDB; 6DPR; X-ray; 3.20 A; A/B=13-403.
DR PDB; 6E35; X-ray; 2.41 A; A/B=11-403.
DR PDB; 6E40; X-ray; 2.31 A; A/B/C/D=15-403.
DR PDB; 6E41; X-ray; 2.29 A; A/B/C/D=15-403.
DR PDB; 6E42; X-ray; 2.10 A; A/B/C/D=15-403.
DR PDB; 6E43; X-ray; 1.71 A; A/B/C/D=15-403.
DR PDB; 6E44; X-ray; 1.90 A; A/B/C/D=15-403.
DR PDB; 6E45; X-ray; 2.00 A; A/B/C/D=15-403.
DR PDB; 6E46; X-ray; 2.09 A; A/B/C/D=15-403.
DR PDB; 6F0A; X-ray; 2.26 A; A/C=11-403.
DR PDB; 6KOF; X-ray; 2.26 A; A/B=1-403.
DR PDB; 6KPS; X-ray; 2.25 A; A/B=1-403.
DR PDB; 6KW7; X-ray; 3.02 A; A/B=1-403.
DR PDB; 6MQ6; X-ray; 3.05 A; A/B=11-403.
DR PDB; 6O3I; X-ray; 2.69 A; A/B=2-403.
DR PDB; 6PU7; X-ray; 2.43 A; A/B=11-402.
DR PDB; 6PZ1; X-ray; 2.65 A; A/B=11-403.
DR PDB; 6R63; X-ray; 2.89 A; A/B=1-403.
DR PDB; 6UBP; X-ray; 2.95 A; A/B=11-403.
DR PDB; 6V52; X-ray; 1.78 A; A/B=11-403.
DR PDB; 6WJY; X-ray; 1.91 A; A/B=11-403.
DR PDB; 6WPE; X-ray; 2.43 A; A/B=11-403.
DR PDB; 6X5Y; X-ray; 2.65 A; A/B=11-403.
DR PDB; 7A62; X-ray; 2.44 A; A/B/C/D=15-403.
DR PDB; 7AH4; X-ray; 2.40 A; A/B=1-403.
DR PDB; 7AH5; X-ray; 2.90 A; A/B=1-403.
DR PDB; 7AH6; X-ray; 3.00 A; A/B=1-403.
DR PDB; 7B1O; X-ray; 2.58 A; A/B=11-403.
DR PDB; 7E0O; X-ray; 3.34 A; A/B=12-403.
DR PDB; 7E0P; X-ray; 2.63 A; A/B=12-403.
DR PDB; 7E0Q; X-ray; 2.46 A; A/B=12-403.
DR PDB; 7E0S; X-ray; 2.71 A; A/B=12-403.
DR PDB; 7E0T; X-ray; 2.14 A; A/B=12-403.
DR PDB; 7E0U; X-ray; 2.28 A; A/B=12-403.
DR PDB; 7M63; X-ray; 3.10 A; A/B=11-403.
DR PDB; 7M7D; X-ray; 2.60 A; A/B=11-403.
DR PDB; 7NGE; X-ray; 2.30 A; A/B/C/D=15-403.
DR PDB; 7P0N; X-ray; 2.50 A; A/B/C/D=15-403.
DR PDB; 7P0R; X-ray; 2.50 A; A/B/C/D=15-403.
DR PDB; 7RRB; X-ray; 2.69 A; A/B=11-403.
DR PDB; 7RRC; X-ray; 2.18 A; A/B=11-403.
DR PDBsum; 2D0T; -.
DR PDBsum; 2D0U; -.
DR PDBsum; 4PK5; -.
DR PDBsum; 4PK6; -.
DR PDBsum; 4U72; -.
DR PDBsum; 4U74; -.
DR PDBsum; 5EK2; -.
DR PDBsum; 5EK3; -.
DR PDBsum; 5EK4; -.
DR PDBsum; 5ETW; -.
DR PDBsum; 5WHR; -.
DR PDBsum; 5WMU; -.
DR PDBsum; 5WMV; -.
DR PDBsum; 5WMW; -.
DR PDBsum; 5WMX; -.
DR PDBsum; 5WN8; -.
DR PDBsum; 5XE1; -.
DR PDBsum; 6AZU; -.
DR PDBsum; 6AZV; -.
DR PDBsum; 6AZW; -.
DR PDBsum; 6CXU; -.
DR PDBsum; 6CXV; -.
DR PDBsum; 6DPQ; -.
DR PDBsum; 6DPR; -.
DR PDBsum; 6E35; -.
DR PDBsum; 6E40; -.
DR PDBsum; 6E41; -.
DR PDBsum; 6E42; -.
DR PDBsum; 6E43; -.
DR PDBsum; 6E44; -.
DR PDBsum; 6E45; -.
DR PDBsum; 6E46; -.
DR PDBsum; 6F0A; -.
DR PDBsum; 6KOF; -.
DR PDBsum; 6KPS; -.
DR PDBsum; 6KW7; -.
DR PDBsum; 6MQ6; -.
DR PDBsum; 6O3I; -.
DR PDBsum; 6PU7; -.
DR PDBsum; 6PZ1; -.
DR PDBsum; 6R63; -.
DR PDBsum; 6UBP; -.
DR PDBsum; 6V52; -.
DR PDBsum; 6WJY; -.
DR PDBsum; 6WPE; -.
DR PDBsum; 6X5Y; -.
DR PDBsum; 7A62; -.
DR PDBsum; 7AH4; -.
DR PDBsum; 7AH5; -.
DR PDBsum; 7AH6; -.
DR PDBsum; 7B1O; -.
DR PDBsum; 7E0O; -.
DR PDBsum; 7E0P; -.
DR PDBsum; 7E0Q; -.
DR PDBsum; 7E0S; -.
DR PDBsum; 7E0T; -.
DR PDBsum; 7E0U; -.
DR PDBsum; 7M63; -.
DR PDBsum; 7M7D; -.
DR PDBsum; 7NGE; -.
DR PDBsum; 7P0N; -.
DR PDBsum; 7P0R; -.
DR PDBsum; 7RRB; -.
DR PDBsum; 7RRC; -.
DR AlphaFoldDB; P14902; -.
DR SMR; P14902; -.
DR BioGRID; 109832; 7.
DR IntAct; P14902; 6.
DR MINT; P14902; -.
DR STRING; 9606.ENSP00000430950; -.
DR BindingDB; P14902; -.
DR ChEMBL; CHEMBL4685; -.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB01065; Melatonin.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB00435; Nitric Oxide.
DR DrugBank; DB00150; Tryptophan.
DR DrugCentral; P14902; -.
DR GuidetoPHARMACOLOGY; 2829; -.
DR iPTMnet; P14902; -.
DR PhosphoSitePlus; P14902; -.
DR BioMuta; IDO1; -.
DR DMDM; 123948; -.
DR EPD; P14902; -.
DR MassIVE; P14902; -.
DR PaxDb; P14902; -.
DR PeptideAtlas; P14902; -.
DR PRIDE; P14902; -.
DR ProteomicsDB; 15758; -.
DR ProteomicsDB; 53093; -.
DR Antibodypedia; 5705; 1008 antibodies from 45 providers.
DR CPTC; P14902; 3 antibodies.
DR DNASU; 3620; -.
DR Ensembl; ENST00000518237.6; ENSP00000430950.1; ENSG00000131203.13.
DR Ensembl; ENST00000522495.5; ENSP00000430505.1; ENSG00000131203.13.
DR GeneID; 3620; -.
DR KEGG; hsa:3620; -.
DR MANE-Select; ENST00000518237.6; ENSP00000430950.1; NM_002164.6; NP_002155.1.
DR UCSC; uc003xnm.5; human.
DR UCSC; uc064mfy.1; human.
DR CTD; 3620; -.
DR DisGeNET; 3620; -.
DR GeneCards; IDO1; -.
DR HGNC; HGNC:6059; IDO1.
DR HPA; ENSG00000131203; Tissue enhanced (lymphoid tissue, placenta).
DR MIM; 147435; gene.
DR neXtProt; NX_P14902; -.
DR OpenTargets; ENSG00000131203; -.
DR PharmGKB; PA29869; -.
DR VEuPathDB; HostDB:ENSG00000131203; -.
DR eggNOG; ENOG502RZ6X; Eukaryota.
DR GeneTree; ENSGT00940000161410; -.
DR HOGENOM; CLU_010089_1_0_1; -.
DR InParanoid; P14902; -.
DR OMA; TMAYVWN; -.
DR OrthoDB; 1206249at2759; -.
DR PhylomeDB; P14902; -.
DR TreeFam; TF330978; -.
DR BioCyc; MetaCyc:HS05502-MON; -.
DR BRENDA; 1.13.11.11; 2681.
DR BRENDA; 1.13.11.52; 2681.
DR PathwayCommons; P14902; -.
DR Reactome; R-HSA-71240; Tryptophan catabolism.
DR SABIO-RK; P14902; -.
DR SignaLink; P14902; -.
DR UniPathway; UPA00333; UER00453.
DR BioGRID-ORCS; 3620; 10 hits in 1079 CRISPR screens.
DR ChiTaRS; IDO1; human.
DR EvolutionaryTrace; P14902; -.
DR GeneWiki; Indoleamine_2,3-dioxygenase; -.
DR GenomeRNAi; 3620; -.
DR Pharos; P14902; Tchem.
DR PRO; PR:P14902; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P14902; protein.
DR Bgee; ENSG00000131203; Expressed in palpebral conjunctiva and 120 other tissues.
DR ExpressionAtlas; P14902; baseline and differential.
DR Genevisible; P14902; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030485; C:smooth muscle contractile fiber; IEA:Ensembl.
DR GO; GO:0032421; C:stereocilium bundle; IEA:Ensembl.
DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0033754; F:indoleamine 2,3-dioxygenase activity; IMP:UniProtKB.
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:0007565; P:female pregnancy; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0034276; P:kynurenic acid biosynthetic process; IEA:Ensembl.
DR GO; GO:0033555; P:multicellular organismal response to stress; IEA:Ensembl.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IEA:Ensembl.
DR GO; GO:0070233; P:negative regulation of T cell apoptotic process; IEA:Ensembl.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IEA:Ensembl.
DR GO; GO:0002678; P:positive regulation of chronic inflammatory response; IEA:Ensembl.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IEA:Ensembl.
DR GO; GO:0070234; P:positive regulation of T cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0002666; P:positive regulation of T cell tolerance induction; IEA:Ensembl.
DR GO; GO:0002830; P:positive regulation of type 2 immune response; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0036269; P:swimming behavior; IEA:Ensembl.
DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl.
DR GO; GO:0006569; P:tryptophan catabolic process; TAS:ProtInc.
DR GO; GO:0019441; P:tryptophan catabolic process to kynurenine; IBA:GO_Central.
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 3D-structure; Cytoplasm; Dioxygenase; Direct protein sequencing; Heme;
KW Immunity; Iron; Metal-binding; Oxidoreductase; Reference proteome;
KW Tryptophan catabolism.
FT CHAIN 1..403
FT /note="Indoleamine 2,3-dioxygenase 1"
FT /id="PRO_0000215204"
FT REGION 360..381
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 346
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:0000269|PubMed:16477023,
FT ECO:0000269|PubMed:25313323, ECO:0007744|PDB:2D0T,
FT ECO:0007744|PDB:2D0U, ECO:0007744|PDB:4PK5,
FT ECO:0007744|PDB:4PK6"
FT VARIANT 4
FT /note="A -> T (in dbSNP:rs35059413)"
FT /id="VAR_053368"
FT CONFLICT 251
FT /note="G -> R (in Ref. 5; AEF30540)"
FT /evidence="ECO:0000305"
FT STRAND 6..8
FT /evidence="ECO:0007829|PDB:6AZV"
FT HELIX 13..15
FT /evidence="ECO:0007829|PDB:6V52"
FT TURN 19..21
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 34..36
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 37..44
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 46..51
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 55..60
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 67..69
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 73..92
FT /evidence="ECO:0007829|PDB:6E43"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:6E43"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 105..118
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 126..129
FT /evidence="ECO:0007829|PDB:6E43"
FT TURN 130..132
FT /evidence="ECO:0007829|PDB:6E43"
FT STRAND 135..138
FT /evidence="ECO:0007829|PDB:6E43"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:5WMV"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:6E43"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:6E46"
FT STRAND 154..158
FT /evidence="ECO:0007829|PDB:6PZ1"
FT HELIX 160..178
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 181..189
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 193..214
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 216..220
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 223..228
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 230..234
FT /evidence="ECO:0007829|PDB:6E43"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 241..243
FT /evidence="ECO:0007829|PDB:6E43"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:6E43"
FT TURN 250..252
FT /evidence="ECO:0007829|PDB:6E43"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:7E0T"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 269..277
FT /evidence="ECO:0007829|PDB:6E43"
FT STRAND 281..284
FT /evidence="ECO:0007829|PDB:6V52"
FT HELIX 287..296
FT /evidence="ECO:0007829|PDB:6E43"
FT STRAND 297..299
FT /evidence="ECO:0007829|PDB:5WMW"
FT HELIX 301..312
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 316..321
FT /evidence="ECO:0007829|PDB:6E43"
FT TURN 322..324
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 326..353
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 355..358
FT /evidence="ECO:0007829|PDB:6E43"
FT STRAND 360..363
FT /evidence="ECO:0007829|PDB:7NGE"
FT TURN 367..369
FT /evidence="ECO:0007829|PDB:7NGE"
FT HELIX 372..374
FT /evidence="ECO:0007829|PDB:6E42"
FT TURN 377..379
FT /evidence="ECO:0007829|PDB:6E43"
FT HELIX 381..397
FT /evidence="ECO:0007829|PDB:6E43"
SQ SEQUENCE 403 AA; 45326 MW; E92CF57AD0D0BA8D CRC64;
MAHAMENSWT ISKEYHIDEE VGFALPNPQE NLPDFYNDWM FIAKHLPDLI ESGQLRERVE
KLNMLSIDHL TDHKSQRLAR LVLGCITMAY VWGKGHGDVR KVLPRNIAVP YCQLSKKLEL
PPILVYADCV LANWKKKDPN KPLTYENMDV LFSFRDGDCS KGFFLVSLLV EIAAASAIKV
IPTVFKAMQM QERDTLLKAL LEIASCLEKA LQVFHQIHDH VNPKAFFSVL RIYLSGWKGN
PQLSDGLVYE GFWEDPKEFA GGSAGQSSVF QCFDVLLGIQ QTAGGGHAAQ FLQDMRRYMP
PAHRNFLCSL ESNPSVREFV LSKGDAGLRE AYDACVKALV SLRSYHLQIV TKYILIPASQ
QPKENKTSED PSKLEAKGTG GTDLMNFLKT VRSTTEKSLL KEG
