1. Discovery

2. Structure

3. Function

4. References

5. Further reading

6. External links

3,3',5'-triiodo-L-thyronine + iodide + A + H⁺ L-thyroxine + AH₂

The protein encoded by this intronless gene belongs to the iodothyronine deiodinase family. It catalyzes the inactivation of thyroid hormone by inner ring deiodination of the prohormone thyroxine (T₄) and the bioactive hormone 3,3',5-triiodothyronine (T₃) to inactive metabolites, 3,3',5'-triiodothyronine (RT₃) and 3,3'-diiodothyronine (T₂), respectively. This enzyme is highly expressed in the pregnant uterus, placenta, fetal and neonatal tissues, suggesting that it plays an essential role in the regulation of thyroid hormone inactivation during embryological development.^[3]

Discovery

The gene was mapped to chromosome 14q32 using fluorescence in situ hybridization (FISH) in 1998.^[4]

Structure

This protein contains a selenocysteine (Sec) residue, which is essential for efficient enzyme activity. The selenocysteine is 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.^[3]

Function

The DIO3 gene codes for type 3 iodothyronine deiodinase (D3), an enzyme that inactivates thyroid hormones and is highly expressed throughout fetal development, peaking early and decreasing towards the end of gestation. Part of the Dlk1-Dio3 imprinting control region, this gene is one involved in the epigenetic process that causes a subset of genes to be regulated based on their parental origin (see Genomic Imprinting).^[6] Such imprinted genes are required for the formation of the placenta as well as the development of cellular lineages such as those derived from the mesoderm and ectoderm. D3 is found in the pregnant uterus, placenta, and mammalian fetal tissues where it is thought to be involved in the transfer of thyroid hormone between the mother and fetus.^[8] Expression of D3 contributes to the development of the brain, skin, liver, bone, ovary, testis, intestine, and brown adipose tissue. Introductory observations of D3-deficient mice indicate growth retardation and even some neonatal death. Due to its ability to activate or inactivate thyroid hormone, Dio3 coding of D3 could be a target for therapeutic intervention in insulin-related illness such as diabetes. In addition, an abnormal amount of Dio3 related to insufficient thyroid hormone levels could be responsible for the disruption of brain development in conjunction with alcohol exposure.^[9] Many factors modify genetic imprinting of Dio3, making it a potential aid in understanding prenatal insults and their production of spectrum disorders.

References

Further reading

• {{cite journal | vauthors = Kuiper GG, Klootwijk W, Visser TJ | title = Substitution of cysteine for selenocysteine in the catalytic center of type III iodothyronine deiodinase reduces catalytic efficiency and alters substrate preference | journal = Endocrinology | volume = 144 | issue = 6 | date = Jun 2003 | pmid = 12746313 | doi = 10.1210/en.2003-0084 | pages=2505–13}}
• {{cite journal | vauthors = Bessho K, Etani Y, Ichimori H, Miyoshi Y, Namba N, Yoneda A, Ooue T, Chihara T, Morii E, Aoki T, Murakami M, Mushiake S, Ozono K | title = Increased type 3 iodothyronine deiodinase activity in a regrown hepatic hemangioma with consumptive hypothyroidism | journal = European Journal of Pediatrics | volume = 169 | issue = 2 | date = Feb 2010 | pmid = 19548001 | doi = 10.1007/s00431-009-1009-x | pages=215–21}}
• {{cite journal | vauthors = Sagar GD, Gereben B, Callebaut I, Mornon JP, Zeöld A, Curcio-Morelli C, Harney JW, Luongo C, Mulcahey MA, Larsen PR, Huang SA, Bianco AC | title = The thyroid hormone-inactivating deiodinase functions as a homodimer | journal = Molecular Endocrinology | volume = 22 | issue = 6 | date = Jun 2008 | pmid = 18356288 | doi = 10.1210/me.2007-0490 | pmc=2422829 | pages=1382–1393}}
• {{cite journal | vauthors = Dentice M, Salvatore D | title = Deiodinases: the balance of thyroid hormone: local impact of thyroid hormone inactivation | journal = The Journal of Endocrinology | volume = 209 | issue = 3 | date = Jun 2011 | pmid = 21398344 | doi = 10.1530/JOE-11-0002 | pages=273–82}}
• {{cite journal | vauthors = Medina MC, Molina J, Gadea Y, Fachado A, Murillo M, Simovic G, Pileggi A, Hernández A, Edlund H, Bianco AC | title = The thyroid hormone-inactivating type III deiodinase is expressed in mouse and human beta-cells and its targeted inactivation impairs insulin secretion | journal = Endocrinology | volume = 152 | issue = 10 | date = Oct 2011 | pmid = 21828183 | doi = 10.1210/en.2011-1210 | pmc=3176649 | pages=3717–3727}}
• {{cite journal | vauthors = Luk JM, Burchard J, Zhang C, Liu AM, Wong KF, Shek FH, Lee NP, Fan ST, Poon RT, Ivanovska I, Philippar U, Cleary MA, Buser CA, Shaw PM, Lee CN, Tenen DG, Dai H, Mao M | title = DLK1-DIO3 genomic imprinted microRNA cluster at 14q32.2 defines a stemlike subtype of hepatocellular carcinoma associated with poor survival | journal = The Journal of Biological Chemistry | volume = 286 | issue = 35 | date = Sep 2011 | pmid = 21737452 | doi = 10.1074/jbc.M111.229831 | pmc=3162431 | pages=30706–30713}}
• {{cite journal | vauthors = Benetatos L, Hatzimichael E, Londin E, Vartholomatos G, Loher P, Rigoutsos I, Briasoulis E | title = The microRNAs within the DLK1-DIO3 genomic region: involvement in disease pathogenesis | journal = Cellular and Molecular Life Sciences | volume = 70 | issue = 5 | date = Mar 2013 | pmid = 22825660 | doi = 10.1007/s00018-012-1080-8 | pages=795–814}}
• {{cite journal | vauthors = Romitti M, Wajner SM, Zennig N, Goemann IM, Bueno AL, Meyer EL, Maia AL | title = Increased type 3 deiodinase expression in papillary thyroid carcinoma | journal = Thyroid | volume = 22 | issue = 9 | date = Sep 2012 | pmid = 22823995 | doi = 10.1089/thy.2012.0031 | pages=897–904}}
• {{cite journal | vauthors = Hernandez A, Park JP, Lyon GJ, Mohandas TK, St Germain DL | title = Localization of the type 3 iodothyronine deiodinase (DIO3) gene to human chromosome 14q32 and mouse chromosome 12F1 | journal = Genomics | volume = 53 | issue = 1 | date = Oct 1998 | pmid = 9787088 | doi = 10.1006/geno.1998.5505 | pages=119–21}}

External links

• {{MeshName|Thyroxine+5-deiodinase}}

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