Dio2 iodothyronine deiodinase 2 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Dio2provided by RGD
Official Full Name: iodothyronine deiodinase 2provided by RGD
Primary source: RGD:68418
See related: EnsemblRapid:ENSRNOG00000062383 AllianceGenome:RGD:68418
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: 5DII; DIOII
Summary: The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the conversion of prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4) to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by outer ring 5'-deiodination. This gene is expressed in a few tissues in rat, including brain, pituitary and brown adipose tissue. It is thought to be responsible for the 'local' production of T3, and thus important in influencing thyroid hormone action in these tissues. Studies in rat suggest that this gene may play an important role in the regulation of lipid metabolism and thermogenesis, and in osteoarthritis pathogenesis by enhancing the chondrocyte hypertrophy and inflammatory response. This protein is a selenoprotein containing the non-standard amino acid, selenocysteine (Sec), which is encoded by the UGA codon that 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. Unlike the other two members (DIO1 and DIO3) of this enzyme family, the mRNA for this gene contains an additional in-frame UGA codon that has been reported (in human) to function either as a Sec or a stop codon, resulting in two potential isoforms with one or two Sec residues; however, only the upstream Sec (conserved with the single Sec residue found at the active site in DIO1 and DIO3) was shown to be essential for enzyme activity (PMID:10403186). In addition, the lack of conservation of the protein extension past the second TGA codon suggests that the one-Sec containing isoform represents the canonical form. [provided by RefSeq, Oct 2018]
Expression: Biased expression in Uterus (RPKM 250.6), Brain (RPKM 51.8) and 2 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 6q31

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	6	NC_086024.1 (115396308..115410594, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	6	NC_051341.1 (109665523..109679809, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	6	NC_005105.4 (114475156..114489443, complement)

Chromosome 6 - NC_086024.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Glucocorticoids inhibited the adrenergic stimulation of Dio2 at the transcriptional level in brown adipocytes.
Title: Effect of glucocorticoids on the activity, expression and proximal promoter of type II deiodinase in rat brown adipocytes.
This study demonstrated that reduction of the Dio2 mRNA expression in hippocampus of thyroidectomized Wistar rats.
Title: Antidepressant behavior in thyroidectomized Wistar rats is induced by hippocampal hypothyroidism.
These studies reveal that tissue-specific differences in D2 ubiquitination are an inherent property of the TRH/TSH feedback mechanism
Title: Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine.
cold exposure is accompanied by concerted changes in the metabolism of BAT and oxidative and glycolytic skeletal muscles that are paralleled by type 2 deiodinase activation
Title: Type 2 iodothyronine deiodinase is upregulated in rat slow- and fast-twitch skeletal muscle during cold exposure.
results of the present study hypothesize that progesterone withdrawal may underlie the decrement in D2 expression, with consequent reduction in the peripheral conversion of T4 into T3 leading to a hypothyroid state.
Title: An evidence for the transcriptional regulation of iodothyronine deiodinase 2 by progesterone in ovarectomized rats.
Data suggest that type 2 deiodinase is induced in inflammation of tanycytes (as in inflammation of periventricular area, arcuate nucleus, and median eminence of hypothalamus); this enzyme induction appears to involve NFkappaB signaling.
Title: NFκB signaling is essential for the lipopolysaccharide-induced increase of type 2 deiodinase in tanycytes.
Data suggest that type 2 deiodinase induction (and kinetics of induction) in animal models of inflammation of leptomeninges, choroid plexus, and brain blood vessels is tissue specific and species specific.
Title: Inflammation-inducible type 2 deiodinase expression in the leptomeninges, choroid plexus, and at brain blood vessels in male rodents.
In rat articular cartilage, DIO2 is specifically expressed among deiodinases and dominantly expressed the same as in brown adipose tissue.
Title: Deiodinase 2 upregulation demonstrated in osteoarthritis patients cartilage causes cartilage destruction in tissue-specific transgenic rats.
Response of pituitary Dio1 and brown adipose tissue Dio2 is blunted in ovariectomized rats.
Title: Blunted response of pituitary type 1 and brown adipose tissue type 2 deiodinases to swimming training in ovariectomized rats.
Data indicate that low-iodine diets induces changes in deiodinase activities, especially in the thyroid, to counteract the low T(4) synthesis and secretion, contributing to maintain the local T(3) concentrations in the tissues with D2 activity.
Title: Deiodinase activities in thyroids and tissues of iodine-deficient female rats.

Submit: New GeneRIF Correction See all GeneRIFs (30)

General gene information

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Markers

RH142433 (e-PCR)
- UniSTS:231680

D6Wox25 (e-PCR)
- UniSTS:240445

Dio2 (e-PCR), detects polymorphism
- UniSTS:547395

RH138032 (e-PCR)
- UniSTS:220119

BE101746 (e-PCR)
- UniSTS:243706

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables hormone activity	IEA Inferred from Electronic Annotation more info
enables thyroxine 5'-deiodinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables thyroxine 5'-deiodinase activity	IDA Inferred from Direct Assay more info	PubMed
enables thyroxine 5'-deiodinase activity	ISO Inferred from Sequence Orthology more info
enables thyroxine 5-deiodinase activity	ISO Inferred from Sequence Orthology more info
enables ubiquitin protein ligase binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within brown fat cell differentiation	ISO Inferred from Sequence Orthology more info
involved_in hormone biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cold-induced thermogenesis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in response to lipopolysaccharide	IEP Inferred from Expression Pattern more info	PubMed
involved_in signal transduction	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within thyroid hormone catabolic process	ISO Inferred from Sequence Orthology more info
involved_in thyroid hormone generation	IDA Inferred from Direct Assay more info	PubMed
involved_in thyroid hormone metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in thyroid hormone metabolic process	IDA Inferred from Direct Assay more info	PubMed
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 extracellular region	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: type II iodothyronine deiodinase

Names: deiodinase, iodothyronine, type 2; deiodinase, iodothyronine, type II; type 2 DI; type-II 5'-deiodinase

NP_113908.4

EC 1.21.99.4

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.

mRNA and Protein(s)

NM_031720.5 → NP_113908.4 type II iodothyronine deiodinase

Status: REVIEWED

Source sequence(s)

JAXUCZ010000006

UniProtKB/Swiss-Prot

O70179, P70551

Related

ENSRNOP00000093973.1, ENSRNOT00000099607.2

Conserved Domains (1) summary

cl00388
Location:4 → 259

Thioredoxin_like; Protein Disulfide Oxidoreductases and Other Proteins with a Thioredoxin fold