DIO2 explained

Type II iodothyronine deiodinase (iodothyronine 5'-deiodinase, iodothyronine 5'-monodeiodinase) is an enzyme that in humans is encoded by the DIO2 gene.^{[1] [2] [3]}

Function

The protein encoded by this gene belongs to the iodothyronine deiodinase family. It activates thyroid hormone by converting the prohormone thyroxine (T₄) by outer ring deiodination (ORD) to bioactive 3,3',5-triiodothyronine (T₃). It is highly expressed in the thyroid, and may contribute significantly to the relative increase in thyroidal T₃ production in patients with Graves' disease and thyroid adenomas. This protein contains selenocysteine (Sec) residues encoded by the UGA codon, which normally signals translation termination. The 3' UTR of Sec-containing genes have a common stem-loop structure, the Sec insertion sequence (SECIS), which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. Alternative splicing results in multiple transcript variants encoding different isoforms.^[3]

Interactions

DIO2 has been shown to interact with USP33.^[4]

See also

• Deiodinase

Further reading

• Gereben B, Salvatore D . Pretranslational regulation of type 2 deiodinase . Thyroid . 15 . 8 . 855–864 . 2006 . 16131328 . 10.1089/thy.2005.15.855 .
• Andersson B . A "double adaptor" method for improved shotgun library construction . Anal. Biochem. . 236 . 1 . 107–113 . 1996 . 8619474 . 10.1006/abio.1996.0138 . vanc. Wentland MA . Ricafrente JY . 3 . Liu . W . Gibbs . RA .
• Salvatore D, Tu H, Harney JW, Larsen PR . Type 2 iodothyronine deiodinase is highly expressed in human thyroid . J. Clin. Invest. . 98 . 4 . 962–968 . 1996 . 8770868 . 10.1172/JCI118880 . 507511 .
• Yu W . Large-scale concatenation cDNA sequencing . Genome Res. . 7 . 4 . 353–8 . 1997 . 9110174 . 10.1101/gr.7.4.353. 139146 . vanc. Andersson B . Worley KC . 3 . Muzny . DM . Ding . Y . Liu . W . Ricafrente . JY . Wentland . MA . Lennon . G .
• Buettner C, Harney JW, Larsen PR . The 3'-untranslated region of human type 2 iodothyronine deiodinase mRNA contains a functional selenocysteine insertion sequence element . J. Biol. Chem. . 273 . 50 . 33374–33378 . 1999 . 9837913 . 10.1074/jbc.273.50.33374 . free .
• Bartha T . Characterization of the 5'-flanking and 5'-untranslated regions of the cyclic adenosine 3',5'-monophosphate-responsive human type 2 iodothyronine deiodinase gene . Endocrinology . 141 . 1 . 229–237 . 2000 . 10614643 . 10.1210/en.141.1.229 . vanc. Kim SW . Salvatore D . 3 . Gereben . B . Tu . HM . Harney . JW . Rudas . P . Larsen . PR . free .
• Baqui MM . Distinct subcellular localization of transiently expressed types 1 and 2 iodothyronine deiodinases as determined by immunofluorescence confocal microscopy . Endocrinology . 141 . 11 . 4309–4312 . 2000 . 11089566 . 10.1210/endo.141.11.7872 . vanc. Gereben B . Harney JW . 3 . Larsen . PR . Bianco . AC . free.
• Ohba K, Yoshioka T, Muraki T . Identification of two novel splicing variants of human type II iodothyronine deiodinase mRNA . Mol. Cell. Endocrinol. . 172 . 1–2 . 169–175 . 2001 . 11165050 . 10.1016/S0303-7207(00)00368-3 . 19110385 .
• Imai Y . Type 2 iodothyronine deiodinase expression is upregulated by the protein kinase A-dependent pathway and is downregulated by the protein kinase C-dependent pathway in cultured human thyroid cells . Thyroid . 11 . 10 . 899–907 . 2002 . 11716036 . 10.1089/105072501753210957 . vanc. Toyoda N . Maeda A . 3 . Kadobayashi . Tamayo . Wang . Fangzheng . Kuma . Kanji . Nishikawa . Mitsushige . Iwasaka . Toshiji .
• Molnár I, Balázs C, Szegedi G, Sipka S . Inhibition of type 2,5'-deiodinase by tumor necrosis factor alpha, interleukin-6 and interferon gamma in human thyroid tissue . Immunol. Lett. . 80 . 1 . 3–7 . 2002 . 11716958 . 10.1016/S0165-2478(01)00301-7 .
• Kuiper GG, Klootwijk W, Visser TJ . Substitution of cysteine for a conserved alanine residue in the catalytic center of type II iodothyronine deiodinase alters interaction with reducing cofactor . Endocrinology . 143 . 4 . 1190–1198 . 2002 . 11897672 . 10.1210/en.143.4.1190 . free . 1765/9874 . free .
• Gereben B, Kollár A, Harney JW, Larsen PR . The mRNA structure has potent regulatory effects on type 2 iodothyronine deiodinase expression . Mol. Endocrinol. . 16 . 7 . 1667–1679 . 2003 . 12089359 . 10.1210/mend.16.7.0879 . free .
• Baur A, Buchfelder M, Köhrle J . Expression of 5'-deiodinase enzymes in normal pituitaries and in various human pituitary adenomas . Eur. J. Endocrinol. . 147 . 2 . 263–268 . 2002 . 12153750 . 10.1530/eje.0.1470263 . free .
• Botero D . Ubc6p and ubc7p are required for normal and substrate-induced endoplasmic reticulum-associated degradation of the human selenoprotein type 2 iodothyronine monodeiodinase . Mol. Endocrinol. . 16 . 9 . 1999–2007 . 2003 . 12198238 . 10.1210/me.2002-0135 . vanc. Gereben B . Goncalves C . 3 . De Jesus . LA . Harney . JW . Bianco . AC . free .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–16903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . vanc. Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Curcio-Morelli C . In vivo dimerization of types 1, 2, and 3 iodothyronine selenodeiodinases . Endocrinology . 144 . 3 . 937–946 . 2003 . 12586771 . 10.1210/en.2002-220960 . vanc. Gereben B . Zavacki AM . 3 . Kim . BW . Huang . S . Harney . JW . Larsen . PR . Bianco . AC . free .
• Ambroziak M . Pax-8 expression correlates with type II 5' deiodinase expression in thyroids from patients with Graves' disease . Thyroid . 13 . 2 . 141–148 . 2003 . 12699588 . 10.1089/105072503321319440 . vanc. Pachucki J . Chojnowski K . 3 . Wiechno . Wiesław . Nauman . Janusz . Nauman . Alicja .
• Dentice M . The different cardiac expression of the type 2 iodothyronine deiodinase gene between human and rat is related to the differential response of the Dio2 genes to Nkx-2.5 and GATA-4 transcription factors . Mol. Endocrinol. . 17 . 8 . 1508–1521 . 2004 . 12775767 . 10.1210/me.2002-0348 . vanc. Morisco C . Vitale M . 3 . Rossi . G . Fenzi . G . Salvatore . D . free.

Notes and References

1. Croteau W, Davey JC, Galton VA, St Germain DL . Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues . J Clin Invest . 98 . 2 . 405–417 . Sep 1996 . 8755651 . 507444 . 10.1172/JCI118806 .
2. Araki O, Murakami M, Morimura T, Kamiya Y, Hosoi Y, Kato Y, Mori M . Assignment of type II iodothyronine deiodinase gene (DIO2) to human chromosome band 14q24.2→q24.3 by in situ hybridization . Cytogenet Cell Genet . 84 . 1–2 . 73–74 . Jun 1999 . 10343107 . 10.1159/000015218 . 19715942 .
3. Web site: Entrez Gene: DIO2 deiodinase, iodothyronine, type II.
4. Curcio-Morelli C, Zavacki AM, Christofollete M, Gereben B, de Freitas BC, Harney JW, Li Z, Wu G, Bianco AC . Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation . J. Clin. Invest. . 112 . 2 . 189–96 . July 2003 . 12865408 . 164294 . 10.1172/JCI18348 .