DIO2

Deiodinase, iodothyronine, type II
Identifiers
Symbols	DIO2 ; 5DII; D2; DIOII; SelY; TXDI2
External IDs	OMIM: 601413 MGI: 1338833 HomoloGene: 621 ChEMBL: 2054 GeneCards: DIO2 Gene
EC number	1.97.1.10
Gene ontology Molecular function • thyroxine 5'-deiodinase activity • selenium binding • ubiquitin protein ligase binding Cellular component • plasma membrane • membrane • integral component of membrane Biological process • selenocysteine incorporation • thyroid hormone generation • cellular nitrogen compound metabolic process • thyroid hormone metabolic process • hormone biosynthetic process • small molecule metabolic process • oxidation-reduction process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1734	13371
Ensembl	ENSG00000211448	ENSMUSG00000007682
UniProt	Q92813	Q9Z1Y9
RefSeq (mRNA)	NM_000793	NM_010050
RefSeq (protein)	NP_000784	NP_034180
Location (UCSC)	Chr 14: 80.2 – 80.39 Mb	Chr 12: 90.72 – 90.74 Mb
PubMed search

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

References

1. 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.
2. 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.
3. "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 (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.

Further reading

• Gereben B, Salvatore D (2006). "Pretranslational regulation of type 2 deiodinase". Thyroid 15 (8): 855–864. doi:10.1089/thy.2005.15.855. PMID 16131328.
• Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–113. doi:10.1006/abio.1996.0138. PMID 8619474.
• Salvatore D, Tu H, Harney JW, Larsen PR (1996). "Type 2 iodothyronine deiodinase is highly expressed in human thyroid". J. Clin. Invest. 98 (4): 962–968. doi:10.1172/JCI118880. PMC 507511. PMID 8770868.
• Yu W, Andersson B, Worley KC, et al. (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146. PMID 9110174.
• Buettner C, Harney JW, Larsen PR (1999). "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. doi:10.1074/jbc.273.50.33374. PMID 9837913.
• Bartha T, Kim SW, Salvatore D, et al. (2000). "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. doi:10.1210/en.141.1.229. PMID 10614643.
• Baqui MM, Gereben B, Harney JW, et al. (2000). "Distinct subcellular localization of transiently expressed types 1 and 2 iodothyronine deiodinases as determined by immunofluorescence confocal microscopy". Endocrinology 141 (11): 4309–4312. doi:10.1210/en.141.11.4309. PMID 11089566.
• Ohba K, Yoshioka T, Muraki T (2001). "Identification of two novel splicing variants of human type II iodothyronine deiodinase mRNA". Mol. Cell. Endocrinol. 172 (1–2): 169–175. doi:10.1016/S0303-7207(00)00368-3. PMID 11165050.
• 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". Thyroid 11 (10): 899–907. doi:10.1089/105072501753210957. PMID 11716036.
• 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". Immunol. Lett. 80 (1): 3–7. doi:10.1016/S0165-2478(01)00301-7. PMID 11716958.
• Kuiper GG, Klootwijk W, Visser TJ (2002). "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. doi:10.1210/en.143.4.1190. PMID 11897672.
• Gereben B, Kollár A, Harney JW, Larsen PR (2003). "The mRNA structure has potent regulatory effects on type 2 iodothyronine deiodinase expression". Mol. Endocrinol. 16 (7): 1667–1679. doi:10.1210/me.16.7.1667. PMID 12089359.
• Baur A, Buchfelder M, Köhrle J (2002). "Expression of 5'-deiodinase enzymes in normal pituitaries and in various human pituitary adenomas". Eur. J. Endocrinol. 147 (2): 263–268. doi:10.1530/eje.0.1470263. PMID 12153750.
• Botero D, Gereben B, Goncalves C, et al. (2003). "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. doi:10.1210/me.2002-0135. PMID 12198238.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Curcio-Morelli C, Gereben B, Zavacki AM, et al. (2003). "In vivo dimerization of types 1, 2, and 3 iodothyronine selenodeiodinases". Endocrinology 144 (3): 937–946. doi:10.1210/en.2002-220960. PMID 12586771.
• 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". Thyroid 13 (2): 141–148. doi:10.1089/105072503321319440. PMID 12699588.
• Dentice M, Morisco C, Vitale M, et al. (2004). "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. doi:10.1210/me.2002-0348. PMID 12775767.