Dio2 deiodinase, iodothyronine, type II [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Dio2provided by MGI
Official Full Name: deiodinase, iodothyronine, type IIprovided by MGI
Primary source: MGI:MGI:1338833
See related: Ensembl:ENSMUSG00000007682 AllianceGenome:MGI:1338833
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
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 highly expressed in brain, placenta and mammary gland. It is thought to be responsible for the 'local' production of T3, and thus important in influencing thyroid hormone action in these tissues. Knockout studies in mice suggest that this gene may play an important role in brown adipose tissue lipogenesis, auditory function, and bone formation. 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 subcutaneous fat pad adult (RPKM 14.7), frontal lobe adult (RPKM 8.9) and 4 other tissues See more
Orthologs: human all
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Genomic context

Location:: 12 D3; 12 44.05 cM

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	12	NC_000078.7 (90691326..90705812, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	12	NC_000078.6 (90724552..90739038, complement)

Chromosome 12 - NC_000078.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Diabetes Modulates Iodothyronine Deiodinase 2 Expression in the Mouse Retina: A Role for Thyroid Hormone in the Pathogenesis of Diabetic Retinopathy.
Title: Diabetes Modulates Iodothyronine Deiodinase 2 Expression in the Mouse Retina: A Role for Thyroid Hormone in the Pathogenesis of Diabetic Retinopathy.
Type 2 Deiodinase Thr92Ala Polymorphism and Aging Are Associated with a Decreased Pituitary Sensitivity to Thyroid Hormone.
Title: Type 2 Deiodinase Thr92Ala Polymorphism and Aging Are Associated with a Decreased Pituitary Sensitivity to Thyroid Hormone.
Brain Gene Expression in Systemic Hypothyroidism and Mouse Models of MCT8 Deficiency: The Mct8-Oatp1c1-Dio2 Triad.
Title: Brain Gene Expression in Systemic Hypothyroidism and Mouse Models of MCT8 Deficiency: The Mct8-Oatp1c1-Dio2 Triad.
Cochlear Fibrocyte and Osteoblast Lineages Expressing Type 2 Deiodinase Identified with a Dio2CreERt2 Allele.
Title: Cochlear Fibrocyte and Osteoblast Lineages Expressing Type 2 Deiodinase Identified with a Dio2CreERt2 Allele.
A Type 2 Deiodinase-Dependent Increase in Vegfa Mediates Myoblast-Endothelial Cell Crosstalk During Skeletal Muscle Regeneration.
Title: A Type 2 Deiodinase-Dependent Increase in Vegfa Mediates Myoblast-Endothelial Cell Crosstalk During Skeletal Muscle Regeneration.
Adult Mice Lacking Mct8 and Dio2 Proteins Present Alterations in Peripheral Thyroid Hormone Levels and Severe Brain and Motor Skill Impairments.
Title: Adult Mice Lacking Mct8 and Dio2 Proteins Present Alterations in Peripheral Thyroid Hormone Levels and Severe Brain and Motor Skill Impairments.
Hepatic Inactivation of the Type 2 Deiodinase Confers Resistance to Alcoholic Liver Steatosis.
Title: Hepatic Inactivation of the Type 2 Deiodinase Confers Resistance to Alcoholic Liver Steatosis.
FoxO1-Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth.
Title: FoxO1-Dio2 signaling axis governs cardiomyocyte thyroid hormone metabolism and hypertrophic growth.
Results indicate that type 2 iodothyronine-deiodinase (D2) loss leads to significant changes in skeletal muscle contractile function and fiber type composition.
Title: A Global Loss of Dio2 Leads to Unexpected Changes in Function and Fiber Types of Slow Skeletal Muscle in Male Mice.
Type 2 deiodinase polymorphism causes ER stress and hypothyroidism in the brain.
Title: Type 2 deiodinase polymorphism causes ER stress and hypothyroidism in the brain.

Submit: New GeneRIF Correction See all GeneRIFs (60)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (3) 1 citation
Endonuclease-mediated (7) 1 citation

General gene information

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Markers

D6Wox25 (e-PCR)
- UniSTS:240445

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

AI324267 (e-PCR)
- UniSTS:180436

RH138032 (e-PCR)
- UniSTS:220119

Dio2 (e-PCR), detects polymorphism
- UniSTS:506846

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables oxidoreductase 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	IMP Inferred from Mutant Phenotype 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	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cellular lipid metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within hormone biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cold-induced thermogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within thyroid hormone catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in thyroid hormone generation	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-stimulating hormone secretion	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: type II iodothyronine deiodinase

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

NP_034180.2

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_010050.4 → NP_034180.2 type II iodothyronine deiodinase

Status: REVIEWED

Source sequence(s)

AK032038, AK045607, BQ033571, CT573100

Consensus CDS

CCDS36514.1

UniProtKB/TrEMBL

A0A8Z1S5Q0

Related

ENSMUSP00000081013.6, ENSMUST00000082432.7

Conserved Domains (1) summary

cl00388
Location:4 → 259

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