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DIO2
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<h2 id="function">Function</h2> <p>The protein encoded by this gene belongs to the <a href="/facts/Iodothyronine_deiodinase/eqsE32xA">iodothyronine deiodinase</a> family. It activates <a href="/facts/Thyroid_hormone/9k4xJtCq">thyroid hormone</a> by converting the <a href="/facts/Prohormone/WFnBnINJ">prohormone</a> <a href="/facts/Thyroxine/9k4xJtCq">thyroxine</a> (T4) by outer ring deiodination (ORD) to bioactive <a href="/facts/Triiodothyronine/MPBz6ApV">3,3',5-triiodothyronine</a> (T3). It is highly expressed in the <a href="/facts/Thyroid_gland/bjovTJVu">thyroid</a>, and may contribute significantly to the relative increase in thyroidal T3 production in patients with <a href="/facts/Graves%27_disease/6CjnWNdE">Graves' disease</a> and thyroid <a href="/facts/Adenoma/HyTrLlpd">adenomas</a>. 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.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p> <h2 id="interactions">Interactions</h2> <p>DIO2 has been shown to <a href="/facts/Protein-protein_interaction/etvm9Wmg">interact</a> with <a href="/facts/USP33/wcBVUGNC">USP33</a>.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Deiodinase/HzyLgjXr">Deiodinase</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Gereben B, Salvatore D (2006). "Pretranslational regulation of type 2 deiodinase". <i>Thyroid</i>. 15 (8): 855–864. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1089%2Fthy.2005.15.855">10.1089/thy.2005.15.855</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16131328">16131328</a>.</li> <li>Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction". <i>Anal. Biochem</i>. 236 (1): 107–113. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1006%2Fabio.1996.0138">10.1006/abio.1996.0138</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8619474">8619474</a>.</li> <li>Salvatore D, Tu H, Harney JW, Larsen PR (1996). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507511">"Type 2 iodothyronine deiodinase is highly expressed in human thyroid"</a>. <i>J. Clin. Invest</i>. 98 (4): 962–968. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1172%2FJCI118880">10.1172/JCI118880</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507511">507511</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8770868">8770868</a>.</li> <li>Yu W, Andersson B, Worley KC, et al. (1997). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139146">"Large-scale concatenation cDNA sequencing"</a>. <i>Genome Res</i>. 7 (4): 353–8. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1101%2Fgr.7.4.353">10.1101/gr.7.4.353</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139146">139146</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9110174">9110174</a>.</li> <li>Buettner C, Harney JW, Larsen PR (1999). <a href="https://doi.org/10.1074%2Fjbc.273.50.33374">"The 3'-untranslated region of human type 2 iodothyronine deiodinase mRNA contains a functional selenocysteine insertion sequence element"</a>. <i>J. Biol. Chem</i>. 273 (50): 33374–33378. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.273.50.33374">10.1074/jbc.273.50.33374</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9837913">9837913</a>.</li> <li>Bartha T, Kim SW, Salvatore D, et al. (2000). <a href="https://doi.org/10.1210%2Fen.141.1.229">"Characterization of the 5'-flanking and 5'-untranslated regions of the cyclic adenosine 3',5'-monophosphate-responsive human type 2 iodothyronine deiodinase gene"</a>. <i>Endocrinology</i>. 141 (1): 229–237. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fen.141.1.229">10.1210/en.141.1.229</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10614643">10614643</a>.</li> <li>Baqui MM, Gereben B, Harney JW, et al. (2000). <a href="https://doi.org/10.1210%2Fendo.141.11.7872">"Distinct subcellular localization of transiently expressed types 1 and 2 iodothyronine deiodinases as determined by immunofluorescence confocal microscopy"</a>. <i>Endocrinology</i>. 141 (11): 4309–4312. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fendo.141.11.7872">10.1210/endo.141.11.7872</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11089566">11089566</a>.</li> <li>Ohba K, Yoshioka T, Muraki T (2001). "Identification of two novel splicing variants of human type II iodothyronine deiodinase mRNA". <i>Mol. Cell. Endocrinol</i>. 172 (1–2): 169–175. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0303-7207%2800%2900368-3">10.1016/S0303-7207(00)00368-3</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11165050">11165050</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:19110385">19110385</a>.</li> <li>Imai Y, Toyoda N, Maeda A, et al. (2002). "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". <i>Thyroid</i>. 11 (10): 899–907. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1089%2F105072501753210957">10.1089/105072501753210957</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11716036">11716036</a>.</li> <li>Molnár I, Balázs C, Szegedi G, Sipka S (2002). "Inhibition of type 2,5'-deiodinase by tumor necrosis factor alpha, interleukin-6 and interferon gamma in human thyroid tissue". <i>Immunol. Lett</i>. 80 (1): 3–7. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1016%2FS0165-2478%2801%2900301-7">10.1016/S0165-2478(01)00301-7</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11716958">11716958</a>.</li> <li>Kuiper GG, Klootwijk W, Visser TJ (2002). <a href="https://doi.org/10.1210%2Fen.143.4.1190">"Substitution of cysteine for a conserved alanine residue in the catalytic center of type II iodothyronine deiodinase alters interaction with reducing cofactor"</a>. <i>Endocrinology</i>. 143 (4): 1190–1198. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fen.143.4.1190">10.1210/en.143.4.1190</a>. <a href="/facts/Hdl_(identifier)/rdebSxmC">hdl</a>:<a href="https://hdl.handle.net/1765%2F9874">1765/9874</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11897672">11897672</a>.</li> <li>Gereben B, Kollár A, Harney JW, Larsen PR (2003). <a href="https://doi.org/10.1210%2Fmend.16.7.0879">"The mRNA structure has potent regulatory effects on type 2 iodothyronine deiodinase expression"</a>. <i>Mol. Endocrinol</i>. 16 (7): 1667–1679. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fmend.16.7.0879">10.1210/mend.16.7.0879</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12089359">12089359</a>.</li> <li>Baur A, Buchfelder M, Köhrle J (2002). <a href="https://doi.org/10.1530%2Feje.0.1470263">"Expression of 5'-deiodinase enzymes in normal pituitaries and in various human pituitary adenomas"</a>. <i>Eur. J. Endocrinol</i>. 147 (2): 263–268. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1530%2Feje.0.1470263">10.1530/eje.0.1470263</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12153750">12153750</a>.</li> <li>Botero D, Gereben B, Goncalves C, et al. (2003). <a href="https://doi.org/10.1210%2Fme.2002-0135">"Ubc6p and ubc7p are required for normal and substrate-induced endoplasmic reticulum-associated degradation of the human selenoprotein type 2 iodothyronine monodeiodinase"</a>. <i>Mol. Endocrinol</i>. 16 (9): 1999–2007. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fme.2002-0135">10.1210/me.2002-0135</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12198238">12198238</a>.</li> <li>Strausberg RL, Feingold EA, Grouse LH, et al. (2003). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139241">"Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences"</a>. <i>Proc. Natl. Acad. Sci. U.S.A</i>. 99 (26): 16899–16903. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/2002PNAS...9916899M">2002PNAS...9916899M</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.242603899">10.1073/pnas.242603899</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC139241">139241</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12477932">12477932</a>.</li> <li>Curcio-Morelli C, Gereben B, Zavacki AM, et al. (2003). <a href="https://doi.org/10.1210%2Fen.2002-220960">"In vivo dimerization of types 1, 2, and 3 iodothyronine selenodeiodinases"</a>. <i>Endocrinology</i>. 144 (3): 937–946. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fen.2002-220960">10.1210/en.2002-220960</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12586771">12586771</a>.</li> <li>Ambroziak M, Pachucki J, Chojnowski K, et al. (2003). "Pax-8 expression correlates with type II 5' deiodinase expression in thyroids from patients with Graves' disease". <i>Thyroid</i>. 13 (2): 141–148. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1089%2F105072503321319440">10.1089/105072503321319440</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12699588">12699588</a>.</li> <li>Dentice M, Morisco C, Vitale M, et al. (2004). <a href="https://doi.org/10.1210%2Fme.2002-0348">"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"</a>. <i>Mol. Endocrinol</i>. 17 (8): 1508–1521. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1210%2Fme.2002-0348">10.1210/me.2002-0348</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12775767">12775767</a>.</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Croteau W, Davey JC, Galton VA, St Germain DL (Sep 1996). "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. doi:10.1172/JCI118806. PMC 507444. PMID 8755651. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507444" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC507444</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Araki O, Murakami M, Morimura T, Kamiya Y, Hosoi Y, Kato Y, Mori M (Jun 1999). "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. doi:10.1159/000015218. PMID 10343107. S2CID 19715942. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"Entrez Gene: DIO2 deiodinase, iodothyronine, type II". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1734" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1734</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>"Entrez Gene: DIO2 deiodinase, iodothyronine, type II". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1734" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1734</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Curcio-Morelli C, Zavacki AM, Christofollete M, Gereben B, de Freitas BC, Harney JW, Li Z, Wu G, Bianco AC (July 2003). "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. doi:10.1172/JCI18348. PMC 164294. PMID 12865408. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC164294" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC164294</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> </ol>