Indoleamine 2,3-dioxygenase 1

Details

Name
Indoleamine 2,3-dioxygenase 1
Synonyms
  • 1.13.11.52
  • IDO
  • IDO-1
  • INDO
  • Indoleamine-pyrrole 2,3-dioxygenase
Gene Name
IDO1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0001382|Indoleamine 2,3-dioxygenase 1
MAHAMENSWTISKEYHIDEEVGFALPNPQENLPDFYNDWMFIAKHLPDLIESGQLRERVE
KLNMLSIDHLTDHKSQRLARLVLGCITMAYVWGKGHGDVRKVLPRNIAVPYCQLSKKLEL
PPILVYADCVLANWKKKDPNKPLTYENMDVLFSFRDGDCSKGFFLVSLLVEIAAASAIKV
IPTVFKAMQMQERDTLLKALLEIASCLEKALQVFHQIHDHVNPKAFFSVLRIYLSGWKGN
PQLSDGLVYEGFWEDPKEFAGGSAGQSSVFQCFDVLLGIQQTAGGGHAAQFLQDMRRYMP
PAHRNFLCSLESNPSVREFVLSKGDAGLREAYDACVKALVSLRSYHLQIVTKYILIPASQ
QPKENKTSEDPSKLEAKGTGGTDLMNFLKTVRSTTEKSLLKEG
Number of residues
403
Molecular Weight
45325.89
Theoretical pI
7.33
GO Classification
Functions
electron carrier activity / heme binding / indoleamine 2,3-dioxygenase activity / metal ion binding / tryptophan 2,3-dioxygenase activity
Processes
cellular nitrogen compound metabolic process / cytokine production involved in inflammatory response / female pregnancy / immune system process / kynurenic acid biosynthetic process / multicellular organismal response to stress / negative regulation of interleukin-10 production / negative regulation of T cell apoptotic process / negative regulation of T cell proliferation / positive regulation of chronic inflammatory response / positive regulation of interleukin-12 production / positive regulation of T cell apoptotic process / positive regulation of T cell tolerance induction / positive regulation of type 2 immune response / response to lipopolysaccharide / small molecule metabolic process / swimming behavior / tryptophan catabolic process / tryptophan catabolic process to kynurenine
Components
cytosol / smooth muscle contractile fiber / stereocilium bundle
General Function
Tryptophan 2,3-dioxygenase activity
Specific Function
Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway (PubMed:17671174). Involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses (PubMed:25691885). Tryptophan shortage inhibits T lymphocytes division and accumulation of tryptophan catabolites induces T-cell apoptosis and differentiation of regulatory T-cells (PubMed:25691885). Acts as a suppressor of anti-tumor immunity (PubMed:23103127, PubMed:25157255, PubMed:14502282, PubMed:25691885). Limits the growth of intracellular pathogens by depriving tryptophan (PubMed:25691885). Protects the fetus from maternal immune rejection (PubMed:25691885).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010485|Indoleamine 2,3-dioxygenase 1 (IDO1)
ATGGCACACGCTATGGAAAACTCCTGGACAATCAGTAAAGAGTACCATATTGATGAAGAA
GTGGGCTTTGCTCTGCCAAATCCACAGGAAAATCTACCTGATTTTTATAATGACTGGATG
TTCATTGCTAAACATCTGCCTGATCTCATAGAGTCTGGCCAGCTTCGAGAAAGAGTTGAG
AAGTTAAACATGCTCAGCATTGATCATCTCACAGACCACAAGTCACAGCGCCTTGCACGT
CTAGTTCTGGGATGCATCACCATGGCATATGTGTGGGGCAAAGGTCATGGAGATGTCCGT
AAGGTCTTGCCAAGAAATATTGCTGTTCCTTACTGCCAACTCTCCAAGAAACTGGAACTG
CCTCCTATTTTGGTTTATGCAGACTGTGTCTTGGCAAACTGGAAGAAAAAGGATCCTAAT
AAGCCCCTGACTTATGAGAACATGGACGTTTTGTTCTCATTTCGTGATGGAGACTGCAGT
AAAGGATTCTTCCTGGTCTCTCTATTGGTGGAAATAGCAGCTGCTTCTGCAATCAAAGTA
ATTCCTACTGTATTCAAGGCAATGCAAATGCAAGAACGGGACACTTTGCTAAAGGCGCTG
TTGGAAATAGCTTCTTGCTTGGAGAAAGCCCTTCAAGTGTTTCACCAAATCCACGATCAT
GTGAACCCAAAAGCATTTTTCAGTGTTCTTCGCATATATTTGTCTGGCTGGAAAGGCAAC
CCCCAGCTATCAGACGGTCTGGTGTATGAAGGGTTCTGGGAAGACCCAAAGGAGTTTGCA
GGGGGCAGTGCAGGCCAAAGCAGCGTCTTTCAGTGCTTTGACGTCCTGCTGGGCATCCAG
CAGACTGCTGGTGGAGGACATGCTGCTCAGTTCCTCCAGGACATGAGAAGATATATGCCA
CCAGCTCACAGGAACTTCCTGTGCTCATTAGAGTCAAATCCCTCAGTCCGTGAGTTTGTC
CTTTCAAAAGGTGATGCTGGCCTGCGGGAAGCTTATGACGCCTGTGTGAAAGCTCTGGTC
TCCCTGAGGAGCTACCATCTGCAAATCGTGACTAAGTACATCCTGATTCCTGCAAGCCAG
CAGCCAAAGGAGAATAAGACCTCTGAAGACCCTTCAAAACTGGAAGCCAAAGGAACTGGA
GGCACTGATTTAATGAATTTCCTGAAGACTGTAAGAAGTACAACTGAGAAATCCCTTTTG
AAGGAAGGTTAA
Chromosome Location
8
Locus
8p12-p11
External Identifiers
ResourceLink
UniProtKB IDP14902
UniProtKB Entry NameI23O1_HUMAN
GenBank Protein ID306956
GenBank Gene IDM34455
GenAtlas IDINDO
HGNC IDHGNC:6059
General References
  1. Dai W, Gupta SL: Molecular cloning, sequencing and expression of human interferon-gamma-inducible indoleamine 2,3-dioxygenase cDNA. Biochem Biophys Res Commun. 1990 Apr 16;168(1):1-8. [PubMed:2109605]
  2. Tone S, Takikawa O, Habara-Ohkubo A, Kadoya A, Yoshida R, Kido R: Primary structure of human indoleamine 2,3-dioxygenase deduced from the nucleotide sequence of its cDNA. Nucleic Acids Res. 1990 Jan 25;18(2):367. [PubMed:2326172]
  3. Kadoya A, Tone S, Maeda H, Minatogawa Y, Kido R: Gene structure of human indoleamine 2,3-dioxygenase. Biochem Biophys Res Commun. 1992 Nov 30;189(1):530-6. [PubMed:1449503]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039]
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  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  7. Taylor MW, Feng GS: Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J. 1991 Aug;5(11):2516-22. [PubMed:1907934]
  8. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ: Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003 Oct;9(10):1269-74. Epub 2003 Sep 21. [PubMed:14502282]
  9. Vottero E, Mitchell DA, Page MJ, MacGillivray RT, Sadowski IJ, Roberge M, Mauk AG: Cytochrome b(5) is a major reductant in vivo of human indoleamine 2,3-dioxygenase expressed in yeast. FEBS Lett. 2006 Apr 17;580(9):2265-8. Epub 2006 Mar 20. [PubMed:16574111]
  10. Metz R, Duhadaway JB, Kamasani U, Laury-Kleintop L, Muller AJ, Prendergast GC: Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res. 2007 Aug 1;67(15):7082-7. [PubMed:17671174]
  11. Yuasa HJ, Takubo M, Takahashi A, Hasegawa T, Noma H, Suzuki T: Evolution of vertebrate indoleamine 2,3-dioxygenases. J Mol Evol. 2007 Dec;65(6):705-14. Epub 2007 Nov 17. [PubMed:18026683]
  12. Lob S, Konigsrainer A, Zieker D, Brucher BL, Rammensee HG, Opelz G, Terness P: IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl tryptophan inhibits tryptophan catabolism. Cancer Immunol Immunother. 2009 Jan;58(1):153-7. doi: 10.1007/s00262-008-0513-6. Epub 2008 Apr 17. [PubMed:18418598]
  13. Lee YK, Lee HB, Shin DM, Kang MJ, Yi EC, Noh S, Lee J, Lee C, Min CK, Choi EY: Heme-binding-mediated negative regulation of the tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) by IDO2. Exp Mol Med. 2014 Nov 14;46:e121. doi: 10.1038/emm.2014.69. [PubMed:25394548]
  14. Yuasa HJ, Mizuno K, Ball HJ: Low efficiency IDO2 enzymes are conserved in lower vertebrates, whereas higher efficiency IDO1 enzymes are dispensable. FEBS J. 2015 Jul;282(14):2735-45. doi: 10.1111/febs.13316. Epub 2015 May 20. [PubMed:25950090]
  15. Vigneron N, van Baren N, Van den Eynde BJ: Expression profile of the human IDO1 protein, a cancer drug target involved in tumoral immune resistance. Oncoimmunology. 2015 Feb 3;4(5):e1003012. eCollection 2015 May. [PubMed:26155395]
  16. Munn DH, Mellor AL: Indoleamine 2,3 dioxygenase and metabolic control of immune responses. Trends Immunol. 2013 Mar;34(3):137-43. doi: 10.1016/j.it.2012.10.001. Epub 2012 Oct 25. [PubMed:23103127]
  17. Schmidt SV, Schultze JL: New Insights into IDO Biology in Bacterial and Viral Infections. Front Immunol. 2014 Aug 11;5:384. doi: 10.3389/fimmu.2014.00384. eCollection 2014. [PubMed:25157255]
  18. van Baren N, Van den Eynde BJ: Tryptophan-degrading enzymes in tumoral immune resistance. Front Immunol. 2015 Feb 3;6:34. doi: 10.3389/fimmu.2015.00034. eCollection 2015. [PubMed:25691885]
  19. Rohrig UF, Majjigapu SR, Vogel P, Zoete V, Michielin O: Challenges in the Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors. J Med Chem. 2015 Dec 24;58(24):9421-37. doi: 10.1021/acs.jmedchem.5b00326. Epub 2015 May 26. [PubMed:25970480]
  20. Sugimoto H, Oda S, Otsuki T, Hino T, Yoshida T, Shiro Y: Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2611-6. Epub 2006 Feb 13. [PubMed:16477023]
  21. Tojo S, Kohno T, Tanaka T, Kamioka S, Ota Y, Ishii T, Kamimoto K, Asano S, Isobe Y: Crystal Structures and Structure-Activity Relationships of Imidazothiazole Derivatives as IDO1 Inhibitors. ACS Med Chem Lett. 2014 Aug 21;5(10):1119-23. doi: 10.1021/ml500247w. eCollection 2014 Oct 9. [PubMed:25313323]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01065Melatoninapproved, nutraceutical, vet_approvedunknownsubstrateDetails
DB00150Tryptophanapproved, nutraceutical, withdrawnunknownsubstrateDetails
DB00435Nitric OxideapprovedunknownDetails
DB09061Cannabidiolapproved, investigationalunknowninhibitorDetails
DB14011NabiximolsinvestigationalunknowninhibitorDetails
DB14009Medical Cannabisexperimental, investigationalunknowninhibitorDetails