DIO3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesDIO3, 5DIII, D3, DIOIII, TXDI3, deiodinase, iodothyronine, type III, iodothyronine deiodinase 3, Dio3 Gene
External IDsOMIM: 601038 MGI: 1306782 HomoloGene: 1044 GeneCards: DIO3
Orthologs
SpeciesHumanMouse
Entrez

1735

107585

Ensembl

ENSG00000197406

ENSMUSG00000075707

UniProt

P55073

Q91ZI8

RefSeq (mRNA)

NM_001362

NM_172119

RefSeq (protein)

NP_001353

NP_742117

Location (UCSC)Chr 14: 101.56 – 101.56 MbChr 12: 110.25 – 110.25 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Thyroxine 5-deiodinase also known as type III iodothyronine deiodinase (EC number 1.21.99.3) is an enzyme that in humans is encoded by the DIO3 gene.[5][6] This enzyme catalyses the following chemical reaction

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.[7]

Discovery

The gene was mapped to chromosome 14q32 using fluorescence in situ hybridization (FISH) in 1998.[8]

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.[7]

Function

Thyroxine 5-deiodinase
Identifiers
EC no.1.21.99.3
CAS no.74506-30-2
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Search
PMCarticles
PubMedarticles
NCBIproteins

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 .[9] 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.[10] 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.[11] 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.[12] Many factors modify genetic imprinting of Dio3, making it a potential aid in understanding prenatal insults and their production of spectrum disorders.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000197406 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000075707 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Chopra IJ, Chua Teco GN (Jan 1982). "Characteristics of inner ring (3 or 5) monodeiodination of 3,5-diiodothyronine in rat liver: evidence suggesting marked similarities of inner and outer ring deiodinases for iodothyronines". Endocrinology. 110 (1): 89–97. doi:10.1210/endo-110-1-89. PMID 7053997.
  6. ↑ Köhrle J (2002). "Iodothyronine deiodinases". Protein Sensors and Reactive Oxygen Species - Part A: Selenoproteins and Thioredoxin. Methods in Enzymology. Vol. 347. pp. 125–167. doi:10.1016/s0076-6879(02)47014-0. ISBN 9780121822484. PMID 11898402.
  7. 1 2 "Entrez Gene: Deiodinase, iodothyronine, type III".
  8. ↑ Hernandez A, Park JP, Lyon GJ, Mohandas TK, St Germain DL (Oct 1998). "Localization of the type 3 iodothyronine deiodinase (DIO3) gene to human chromosome 14q32 and mouse chromosome 12F1". Genomics. 53 (1): 119–121. doi:10.1006/geno.1998.5505. PMID 9787088.
  9. ↑ Lin SP, Coan P, da Rocha ST, Seitz H, Cavaille J, Teng PW, Takada S, Ferguson-Smith AC (Jan 2007). "Differential regulation of imprinting in the murine embryo and placenta by the Dlk1-Dio3 imprinting control region". Development. 134 (2): 417–426. doi:10.1242/dev.02726. PMID 17166925.
  10. ↑ Hernandez A, Fiering S, Martinez E, Galton VA, St Germain D (Nov 2002). "The gene locus encoding iodothyronine deiodinase type 3 (Dio3) is imprinted in the fetus and expresses antisense transcripts". Endocrinology. 143 (11): 4483–4486. doi:10.1210/en.2002-220800. PMID 12399446.
  11. ↑ Medina MC, Molina J, Gadea Y, Fachado A, Murillo M, Simovic G, Pileggi A, Hernández A, Edlund H, Bianco AC (Oct 2011). "The thyroid hormone-inactivating type III deiodinase is expressed in mouse and human beta-cells and its targeted inactivation impairs insulin secretion". Endocrinology. 152 (10): 3717–3727. doi:10.1210/en.2011-1210. PMC 3176649. PMID 21828183.
  12. ↑ Sittig LJ, Shukla PK, Herzing LB, Redei EE (Jul 2011). "Strain-specific vulnerability to alcohol exposure in utero via hippocampal parent-of-origin expression of deiodinase-III". FASEB Journal. 25 (7): 2313–2324. doi:10.1096/fj.10-179234. PMC 3114527. PMID 21429942.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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