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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 pregnant uterus, placenta, fetal and neonatal tissues, and thought to prevent premature exposure of developing fetal tissues to adult levels of thyroid hormones. It regulates circulating fetal thyroid hormone concentrations, and thus plays a critical role in mammalian development. Knockout mice lacking this gene exhibit abnormalities related to development and reproduction, and increased activity of this enzyme in infants with hemangiomas causes severe hypothyroidism. 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, May 2016]
DIO3 (Iodothyronine Deiodinase 3) is a Protein Coding gene. Diseases associated with DIO3 include Hypothyroidism and Uniparental Disomy Of Chromosome 14. Among its related pathways are Folate Metabolism and thyroid hormone metabolism I (via deiodination). Gene Ontology (GO) annotations related to this gene include thyroxine 5'-deiodinase activity and thyroxine 5-deiodinase activity. An important paralog of this gene is DIO2.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004800 | thyroxine 5'-deiodinase activity | TAS | -- |
GO:0016491 | oxidoreductase activity | IEA | -- |
GO:0033798 | thyroxine 5-deiodinase activity | IDA | 18566113 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005768 | endosome | IEA | -- |
GO:0005886 | plasma membrane | TAS | -- |
GO:0010008 | endosome membrane | IEA | -- |
GO:0016020 | membrane | IEA | -- |
GO:0016021 | integral component of membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Amine-derived hormones | ||
2 | thyroid hormone metabolism I (via deiodination) | ||
3 | Thyroid hormone signaling pathway | ||
4 | Metabolism |
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5 | Viral mRNA Translation |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0006590 | thyroid hormone generation | TAS | -- |
GO:0006915 | apoptotic process | IEA | -- |
GO:0008150 | biological_process | ND | -- |
GO:0040018 | positive regulation of multicellular organism growth | IEA | -- |
GO:0042403 | thyroid hormone metabolic process | IBA | 21873635 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Levothyroxine | Approved | Pharma | 0 | |||
Iopodic acid | Approved, Investigational, Withdrawn | Pharma | Target, antagonist | 0 | ||
Thyroid, porcine | Approved | Pharma | Enzyme, substrate | 0 | ||
Iodide | Approved, Experimental | Pharma | 0 | |||
Liothyronine | Approved, Vet_approved | Pharma | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
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Hydrogen Ion |
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I(-) |
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Thyroxine sulfate |
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77074-49-8 |
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This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Dog (Canis familiaris) |
Mammalia | DIO3 30 |
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Cow (Bos Taurus) |
Mammalia | DIO3 30 31 |
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OneToOne | |
Mouse (Mus musculus) |
Mammalia | Dio3 30 17 31 |
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OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Dio3 30 |
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Oppossum (Monodelphis domestica) |
Mammalia | DIO3 31 |
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OneToOne | |
Chicken (Gallus gallus) |
Aves | DIO3 30 |
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Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | dio3 30 |
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African clawed frog (Xenopus laevis) |
Amphibia | LOC397779 30 |
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Zebrafish (Danio rerio) |
Actinopterygii | dio3b 30 |
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dio3a 31 |
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OneToOne | |||
-- 30 |
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SNP ID | Clinical significance and condition | Chr 14 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
725300 | Benign: not provided | 101,562,327(+) | C/T | SYNONYMOUS_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
dgv1978n100 | CNV | gain | 25217958 |
dgv388n67 | CNV | gain | 20364138 |
esv3635530 | CNV | gain | 21293372 |
nsv1047869 | CNV | gain | 25217958 |
nsv1071171 | CNV | deletion | 25765185 |
nsv1143759 | CNV | deletion | 24896259 |
nsv565879 | CNV | loss | 21841781 |
nsv565880 | CNV | loss | 21841781 |
nsv565882 | CNV | loss | 21841781 |
nsv827060 | CNV | gain | 20364138 |
nsv827061 | CNV | gain | 20364138 |
nsv952247 | CNV | deletion | 24416366 |
Disorder | Aliases | PubMed IDs |
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hypothyroidism |
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uniparental disomy of chromosome 14 |
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hemangioma |
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neonatal thyrotoxicosis |
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temple syndrome |
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