Dio3 iodothyronine deiodinase 3 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Dio3provided by RGD
Official Full Name: iodothyronine deiodinase 3provided by RGD
Primary source: RGD:68420
See related: Ensembl:ENSRNOG00000052017 AllianceGenome:RGD:68420
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: 5DIII; DIOIII
Summary: This is an intronless, imprinted gene that is preferentially expressed from the paternal allele. The encoded protein belongs to the iodothyronine deiodinase family, and 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. It is highly expressed in placenta, fetal and neonatal tissues, and thought to prevent premature exposure of developing fetal tissues to adult levels of thyroid hormones. It thus plays a critical role in mammalian development by regulating circulating fetal thyroid hormone concentration. This protein is a selenoprotein, containing the rare selenocysteine (Sec) amino acid at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. [provided by RefSeq, Jun 2016]
Orthologs: human mouse all
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Genomic context

Location:: 6q32

Exon count:: 1

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	6	NC_086024.1 (135107072..135108933)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	6	NC_051341.1 (129285747..129287608)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	6	NC_005105.4 (134627278..134629139)

Chromosome 6 - NC_086024.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Adaptive Thermogenesis Driving Catch-Up Fat Is Associated With Increased Muscle Type 3 and Decreased Hepatic Type 1 Iodothyronine Deiodinase Activities: A Functional and Proteomic Study.
Title: Adaptive Thermogenesis Driving Catch-Up Fat Is Associated With Increased Muscle Type 3 and Decreased Hepatic Type 1 Iodothyronine Deiodinase Activities: A Functional and Proteomic Study.
findings suggest that translational repression of Dio3 is an important determinant of the reduced D3 protein expression following liver damage
Title: Decreased translation of Dio3 mRNA is associated with drug-induced hepatotoxicity.
ischemia/hypoxia induces an Hsp40-mediated translocation of Dio3 to the nucleus, facilitating thyroid hormone inactivation proximal to the thyroid hormone receptors
Title: Neuronal hypoxia induces Hsp40-mediated nuclear import of type 3 deiodinase as an adaptive mechanism to reduce cellular metabolism.
Data suggest that genetic background and sex modify vulnerability to prenatal alcohol via brain region-specific expression of Dio3.
Title: Strain-specific vulnerability to alcohol exposure in utero via hippocampal parent-of-origin expression of deiodinase-III.
we show marked expression of D3 by granulocytes and macrophages in spinal cord inflammatory lesions of EAE rats. We further confirm induction of D3 expression in vitro in monocytes that were activated toward proinflammatory or immunomodulatory phenotypes
Title: Type 3 deiodinase expression in inflammatory spinal cord lesions in rat experimental autoimmune encephalomyelitis.
Dio3 is important in the modulation of thyroid hormone levels in the regenerating liver, in which decrease in cellular T3 permits an increase in proliferation.
Title: Large induction of type III deiodinase expression after partial hepatectomy in the regenerating mouse and rat liver.
a mechanism of metabolic regulation during hypoxic-ischemic injury in which HIF-1 reduces local thyroid hormone signaling through induction of D3.
Title: Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats.
Acute decrease in serum T(4) and T(3) after myocardial infarction is due to increased thyroid hormone catabolism from ectopic D3 expression in the heart.
Title: Thyroid function disturbance and type 3 iodothyronine deiodinase induction after myocardial infarction in rats a time course study.
genomic imprinting and gene expression at the Dlk1/Dio3 imprinted domain may play a role in the regulation of adipocyte proliferation and differentiation
Title: Gene expression from the imprinted Dio3 locus is associated with cell proliferation of cultured brown adipocytes.
Induction of D3 activity begins immediately after implantation and increases markedly over next 72 hours. In spontaneously cycling female rats, both D2 and D3 were observed to be 3- to 8-fold higher in proestrus, compared with diestrus.
Title: Determinants of iodothyronine deiodinase activities in rodent uterus.

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General gene information

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Markers

UniSTS:489530 (e-PCR)
- UniSTS:489530

RH128338 (e-PCR)
- UniSTS:211646

NoName (e-PCR)
- UniSTS:532166

Dio3 (e-PCR), detects polymorphism
- UniSTS:532166

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables thyroxine 5'-deiodinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables thyroxine 5'-deiodinase activity	ISO Inferred from Sequence Orthology more info
enables thyroxine 5'-deiodinase activity	TAS Traceable Author Statement more info	PubMed
enables thyroxine 5-deiodinase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in brown fat cell proliferation	IEP Inferred from Expression Pattern more info	PubMed
involved_in hormone biosynthetic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of multicellular organism growth	ISO Inferred from Sequence Orthology more info
involved_in response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within retinal cone cell apoptotic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of retinal cone cell development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within retinal cone cell development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within thyroid hormone catabolic process	ISO Inferred from Sequence Orthology more info
involved_in thyroid hormone catabolic process	ISO Inferred from Sequence Orthology more info
involved_in thyroid hormone metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in thyroid hormone metabolic process	ISO Inferred from Sequence Orthology more info
involved_in thyroid hormone metabolic process	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in endosome membrane	IEA Inferred from Electronic Annotation more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: thyroxine 5-deiodinase

Names: deiodinase, iodothyronine, type 3; deiodinase, iodothyronine, type III; type 3 DI; type III iodothyronine deiodinase; type-III 5'-deiodinase

NP_058906.3

EC 1.21.99.3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.