DIO2

DIO2
Identifiers
Aliases	DIO2, 5DII, D2, DIOII, SelY, TXDI2, deiodinase, iodothyronine, type II, iodothyronine deiodinase 2, SELENOY
External IDs	OMIM: 601413; MGI: 1338833; HomoloGene: 621; GeneCards: DIO2; OMA:DIO2 - orthologs
Gene location (Human) Chr. Chromosome 14 (human) Band 14q31.1 Start 80,197,526 bp End 80,387,757 bp
Gene location (Mouse) Chr. Chromosome 12 (mouse) Band 12|12 D3 Start 90,691,326 bp End 90,705,212 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in mucosa of pharynx tendon of biceps brachii body of tongue superior surface of tongue oral cavity thyroid gland right lobe of thyroid gland nipple human penis left lobe of thyroid gland Top expressed in median eminence cervix ascending aorta ligament Region I of hippocampus proper arcuate nucleus lumbar subsegment of spinal cord aortic valve spiral ligament perirhinal cortex More reference expression data BioGPS n/a
Gene ontology Molecular function oxidoreductase activity selenium binding thyroxine 5'-deiodinase activity ubiquitin protein ligase binding Cellular component integral component of membrane plasma membrane membrane Biological process thyroid hormone metabolic process thyroid hormone generation selenocysteine incorporation hormone biosynthetic process positive regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1734 13371 Ensembl ENSG00000211448 ENSMUSG00000007682 UniProt Q92813 Q9Z1Y9 RefSeq (mRNA) NM_013989 NM_000793 NM_001007023 NM_001242503 NM_001324462 NM_001366496 NM_010050 RefSeq (protein) NP_000784 NP_001311391 NP_054644 NP_001353425 NP_034180 Location (UCSC) Chr 14: 80.2 – 80.39 Mb Chr 12: 90.69 – 90.71 Mb PubMed search
Wikidata
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Type II iodothyronine deiodinase (iodothyronine 5'-deiodinase, iodothyronine 5'-monodeiodinase) is an enzyme that in humans is encoded by the DIO2 gene.

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.

Interactions

DIO2 has been shown to interact with USP33.

See also

• Deiodinase

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/endo.141.11.7872. 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. S2CID 19110385.
• 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. hdl:1765/9874. 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/mend.16.7.0879. 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. Bibcode:2002PNAS...9916899M. 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.