Indoleamine 2,3-dioxygenase 2 explained

Indoleamine 2,3-dioxygenase 2 (IDO2) is a protein that in humans is encoded by the IDO2 gene.^[1]

Function

IDO2 (indolamine-2,3-dioxygenase) is an enzyme with protein size of 420 amino acids (47 kDa) that is used for catabolism of tryptophan. In organisms, other enzymes participate in L-tryptophan cleavage, namely IDO1 and TDO. Despite IDO1 and IDO2 being closely related enzymes originating by gene duplication and sharing high level (43%) of sequence homology,^{[2] [3]} they differentiate by their kinetics, function and expression pattern. Genes encoding IDO1 and IDO2 have similar genomic structure and are situated closely to each other on chromosome 8.^[4] IDO2 is produced in a very limited type of tissues as kidney, liver or antigen presenting cells.^[5] IDO2 is less active on substrates of IDO1, better catabolizing other Trp derivates as 5-methoxytryptophan. There are several isoforms in population that comes from alternative splicing.^[6] As well as IDO1, IDO2 has been reported in Treg differentiation in vitro,^[7] suggesting a role in tolerance maintenance. Its expression has been found in several cancers, gastric, colon or renal tumors.^[8]

References

Further reading

• Ball HJ, Sanchez-Perez A, Weiser S, Austin CJ, Astelbauer F, Miu J, McQuillan JA, Stocker R, Jermiin LS, Hunt NH . Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice . Gene . 396 . 1 . 203–13 . July 2007 . 17499941 . 10.1016/j.gene.2007.04.010 .
• 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 Research . 67 . 15 . 7082–7 . August 2007 . 17671174 . 10.1158/0008-5472.CAN-07-1872 . free .
• Witkiewicz AK, Costantino CL, Metz R, Muller AJ, Prendergast GC, Yeo CJ, Brody JR . Genotyping and expression analysis of IDO2 in human pancreatic cancer: a novel, active target . Journal of the American College of Surgeons . 208 . 5 . 781–7; discussion 787–9 . May 2009 . 19476837 . 3176891 . 10.1016/j.jamcollsurg.2008.12.018 .
• Witkiewicz AK, Costantino CL, Metz R, Muller AJ, Prendergast GC, Yeo CJ, Brody JR . Genotyping and expression analysis of IDO2 in human pancreatic cancer: a novel, active target . Journal of the American College of Surgeons . 208 . 5 . 781–7; discussion 787–9 . May 2009 . 19476837 . 3176891 . 10.1016/j.jamcollsurg.2008.12.018 .
• Huttunen R, Syrjänen J, Aittoniemi J, Oja SS, Raitala A, Laine J, Pertovaara M, Vuento R, Huhtala H, Hurme M . High activity of indoleamine 2,3 dioxygenase enzyme predicts disease severity and case fatality in bacteremic patients . Shock . 33 . 2 . 149–54 . February 2010 . 19487973 . 10.1097/SHK.0b013e3181ad3195 . 24459411 . free .
• Cetindere T, Nambiar S, Santourlidis S, Essmann F, Hassan M . Induction of indoleamine 2, 3-dioxygenase by death receptor activation contributes to apoptosis of melanoma cells via mitochondrial damage-dependent ROS accumulation . Cellular Signalling . 22 . 2 . 197–211 . February 2010 . 19799997 . 10.1016/j.cellsig.2009.09.013 .
• Mao R, Zhang J, Jiang D, Cai D, Levy JM, Cuconati A, Block TM, Guo JT, Guo H . Indoleamine 2,3-dioxygenase mediates the antiviral effect of gamma interferon against hepatitis B virus in human hepatocyte-derived cells . Journal of Virology . 85 . 2 . 1048–57 . January 2011 . 21084489 . 3019998 . 10.1128/JVI.01998-10 .
• Sørensen RB, Køllgaard T, Andersen RS, van den Berg JH, Svane IM, Straten P, Andersen MH . Spontaneous cytotoxic T-Cell reactivity against indoleamine 2,3-dioxygenase-2 . Cancer Research . 71 . 6 . 2038–44 . March 2011 . 21406395 . 10.1158/0008-5472.CAN-10-3403 . free .
• Meininger D, Zalameda L, Liu Y, Stepan LP, Borges L, McCarter JD, Sutherland CL . Purification and kinetic characterization of human indoleamine 2,3-dioxygenases 1 and 2 (IDO1 and IDO2) and discovery of selective IDO1 inhibitors . Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics . 1814 . 12 . 1947–54 . December 2011 . 21835273 . 10.1016/j.bbapap.2011.07.023 .

Notes and References

1. Web site: Entrez Gene: Indoleamine 2,3-dioxygenase 2 .
2. Yuasa HJ, Mizuno K, Ball HJ . Low efficiency IDO2 enzymes are conserved in lower vertebrates, whereas higher efficiency IDO1 enzymes are dispensable . The FEBS Journal . 282 . 14 . 2735–45 . July 2015 . 25950090 . 10.1111/febs.13316 . 25834690 . free .
3. Ball HJ, Sanchez-Perez A, Weiser S, Austin CJ, Astelbauer F, Miu J, McQuillan JA, Stocker R, Jermiin LS, Hunt NH . Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice . Gene . 396 . 1 . 203–13 . July 2007 . 17499941 . 10.1016/j.gene.2007.04.010 .
4. Ball HJ, Sanchez-Perez A, Weiser S, Austin CJ, Astelbauer F, Miu J, McQuillan JA, Stocker R, Jermiin LS, Hunt NH . Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice . Gene . 396 . 1 . 203–13 . July 2007 . 17499941 . 10.1016/j.gene.2007.04.010 .
5. Merlo LM, Mandik-Nayak L . IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity . Clinical Medicine Insights. Pathology . 9 . Suppl 1 . 21–28 . 2016 . 27891058 . 5119657 . 10.4137/CPath.S39930 .
6. 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 Research . 67 . 15 . 7082–7 . August 2007 . 17671174 . 10.1158/0008-5472.CAN-07-1872 . free .
7. Metz R, Smith C, DuHadaway JB, Chandler P, Baban B, Merlo LM, Pigott E, Keough MP, Rust S, Mellor AL, Mandik-Nayak L, Muller AJ, Prendergast GC . IDO2 is critical for IDO1-mediated T-cell regulation and exerts a non-redundant function in inflammation . International Immunology . 26 . 7 . 357–67 . July 2014 . 24402311 . 4432394 . 10.1093/intimm/dxt073 .
8. Löb S, Königsrainer A, Zieker D, Brücher 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 Immunology, Immunotherapy . 58 . 1 . 153–7 . January 2009 . 18418598 . 10.1007/s00262-008-0513-6 . 6199515 . 11030193 .