DIO2

DIO2
Identifiers
Aliases	DIO2 , 5DII, D2, DIOII, SelY, TXDI2, deiodinase, iodothyronine, type II, iodothyronine deiodinase 2, SELENOY
External IDs	OMIM: 601413 MGI: 1338833 HomoloGene: 621 GeneCards: DIO2
Gene location (Human)
Chr.	Chromosome 14 (human)
End	80,387,757 bp
Gene location (Mouse)
Chr.	Chromosome 12 (mouse)
End	90,705,212 bp
RNA expression pattern
	Top expressed in
	body of tongue; ; superior surface of tongue; ; cavity of mouth; ; thyroid gland; ; right lobe of thyroid gland; ; nipple; ; human penis; ; left lobe of thyroid gland; ; urethra; ; pituitary gland;
	More reference expression data
	n/a
Gene ontology
Molecular function	oxidoreductase activity ; selenium binding ; thyroxine 5'-deiodinase activity ; ubiquitin protein ligase binding ;
Cellular component	integral component of membrane ; plasma membrane ; membrane ;
Biological process	thyroid hormone metabolic process ; thyroid hormone generation ; selenocysteine incorporation ; hormone biosynthetic process ; positive regulation of cold-induced thermogenesis ;
	Sources:Amigo / QuickGO
Orthologs
	1734
	13371
	ENSG00000211448
	ENSMUSG00000007682
	Q92813
	Q9Z1Y9
NM_013989 ; NM_000793 ; NM_001007023 ; NM_001242503 ; NM_001324462 ;
	NM_001366496
	NM_010050
	NP_000784 ; NP_001311391 ; NP_054644 ; NP_001353425
	NP_034180
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated June 14, 2022

Type II iodothyronine deiodinase (iodothyronine 5'-deiodinase, iodothyronine 5'-monodeiodinase) is an enzyme that in humans is encoded by the DIO2 gene.^[5]^[6]^[7]

Function

The protein encoded by this gene belongs to the iodothyronine deiodinase family. It activates thyroid hormone by converting the prohormone thyroxine (T₄) by outer ring deiodination (ORD) to bioactive 3,3',5-triiodothyronine (T₃). It is highly expressed in the thyroid, and may contribute significantly to the relative increase in thyroidal T₃ production in patients with Graves' disease and thyroid adenomas. This protein contains selenocysteine (Sec) residues 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. Alternative splicing results in multiple transcript variants encoding different isoforms.^[7]

Interactions

DIO2 has been shown to interact with USP33.^[8]

Related Research Articles

Iodothyronine deiodinase Class of enzymes

Iodothyronine deiodinases (EC 1.21.99.4 and EC 1.21.99.3) are a subfamily of deiodinase enzymes important in the activation and deactivation of thyroid hormones. Thyroxine (T₄), the precursor of 3,5,3'-triiodothyronine (T₃) is transformed into T₃ by deiodinase activity. T₃, through binding a nuclear thyroid hormone receptor, influences the expression of genes in practically every vertebrate cell. Iodothyronine deiodinases are unusual in that these enzymes contain selenium, in the form of an otherwise rare amino acid selenocysteine.

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. This enzyme catalyses the following chemical reaction

The gastric inhibitory polypeptide receptor (GIP-R), also known as the glucose-dependent insulinotropic polypeptide receptor, is a protein that in humans is encoded by the GIPR gene. GIP-R is a member of the 7-transmembrane protein family, a class of G protein coupled receptors. GIP-R is found on beta-cells in the pancreas where it serves as the receptor for the hormone Gastric inhibitory polypeptide (GIP).

The sodium/iodide cotransporter, also known as the sodium/iodide symporter (NIS), is a protein that in humans is encoded by the SLC5A5 gene. It is a transmembrane glycoprotein with a molecular weight of 87 kDa and 13 transmembrane domains, which transports two sodium cations (Na⁺) for each iodide anion (I⁻) into the cell. NIS mediated uptake of iodide into follicular cells of the thyroid gland is the first step in the synthesis of thyroid hormone.

Homeobox expressed in ES cells 1, also known as homeobox protein ANF, is a homeobox protein that in humans is encoded by the HESX1 gene.

The human gene SRD5A2 encodes the 3-oxo-5α-steroid 4-dehydrogenase 2 enzyme, also known as 5α-reductase type 2 (5αR2), one of three isozymes of 5α-reductase.

The G protein-coupled bile acid receptor 1 (GPBAR1) also known G-protein coupled receptor 19 (GPCR19), membrane-type receptor for bile acids (M-BAR) or TGR5 as is a protein that in humans is encoded by the GPBAR1 gene.

Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the NR1H3 gene.

Somatostatin receptor type 5 is a protein that in humans is encoded by the SSTR5 gene.

3-Oxo-5α-steroid 4-dehydrogenase 1 is an enzyme that in humans is encoded by the SRD5A1 gene. It is one of three forms of steroid 5α-reductase.

Thyroid hormone receptor beta (TR-beta) also known as nuclear receptor subfamily 1, group A, member 2 (NR1A2), is a nuclear receptor protein that in humans is encoded by the THRB gene.

NK2 homeobox 1 (NKX2-1), also known as thyroid transcription factor 1 (TTF-1), is a protein which in humans is encoded by the NKX2-1 gene.

Ubiquitin carboxyl-terminal hydrolase 33 is an enzyme that in humans is encoded by the USP33 gene.

Mu-crystallin homolog also known as NADP-regulated thyroid-hormone-binding protein (THBP) is a protein that in humans is encoded by the CRYM gene. Multiple alternatively spliced transcript variants have been found for this gene.

Ubiquitin carboxyl-terminal hydrolase 20 is an enzyme that in humans is encoded by the USP20 gene.

Inhibin, beta B, also known as INHBB, is a protein which in humans is encoded by the INHBB gene. INHBB is a subunit of both activin and inhibin, two closely related glycoproteins with opposing biological effects.

High mobility group nucleosome-binding domain-containing protein 3 is a protein that in humans is encoded by the HMGN3 gene.

Glycoprotein hormone beta-5 is a protein that in humans is encoded by the GPHB5 gene.

Iodotyrosine deiodinase, also known as iodotyrosine dehalogenase 1, is a type of deiodinase enzyme that scavenges iodide by removing it from iodinated tyrosine residues in the thyroid gland. These iodinated tyrosines are produced during thyroid hormone biosynthesis. The iodide that is scavenged by iodotyrosine deiodinase is necessary to again synthesize the thyroid hormones. After synthesis, the thyroid hormones circulate through the body to regulate metabolic rate, protein expression, and body temperature. Iodotyrosine deiodinase is thus necessary to keep levels of both iodide and thyroid hormones in balance.

Monocarboxylate transporter 10, also known as aromatic amino acid transporter 1 and T-type amino acid transporter 1 (TAT1) and solute carrier family 16 member 10 (SLC16A10), is a protein that in humans is encoded by the SLC16A10 gene. SLC16A10 is a member of the solute carrier family.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000211448 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000007682 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Croteau W, Davey JC, Galton VA, St Germain DL (Sep 1996). "Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues". J Clin Invest. 98 (2): 405–417. doi:10.1172/JCI118806. PMC 507444 . PMID 8755651.
↑ Araki O, Murakami M, Morimura T, Kamiya Y, Hosoi Y, Kato Y, Mori M (Jun 1999). "Assignment of type II iodothyronine deiodinase gene (DIO2) to human chromosome band 14q24.2→q24.3 by in situ hybridization". Cytogenet Cell Genet. 84 (1–2): 73–74. doi:10.1159/000015218. PMID 10343107. S2CID 19715942.
1 2 "Entrez Gene: DIO2 deiodinase, iodothyronine, type II".
↑ Curcio-Morelli C, Zavacki AM, Christofollete M, Gereben B, de Freitas BC, Harney JW, Li Z, Wu G, Bianco AC (July 2003). "Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation". J. Clin. Invest. 112 (2): 189–96. doi:10.1172/JCI18348. PMC 164294 . PMID 12865408.

Gereben B, Salvatore D (2006). "Pretranslational regulation of type 2 deiodinase". Thyroid. 15 (8): 855–864. doi:10.1089/thy.2005.15.855. PMID 16131328.
Andersson B, Wentland MA, Ricafrente JY, et al. (1996). "A "double adaptor" method for improved shotgun library construction". Anal. Biochem. 236 (1): 107–113. doi:10.1006/abio.1996.0138. PMID 8619474.
Salvatore D, Tu H, Harney JW, Larsen PR (1996). "Type 2 iodothyronine deiodinase is highly expressed in human thyroid". J. Clin. Invest. 98 (4): 962–968. doi:10.1172/JCI118880. PMC 507511 . PMID 8770868.
Yu W, Andersson B, Worley KC, et al. (1997). "Large-scale concatenation cDNA sequencing". Genome Res. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC 139146 . PMID 9110174.
Buettner C, Harney JW, Larsen PR (1999). "The 3'-untranslated region of human type 2 iodothyronine deiodinase mRNA contains a functional selenocysteine insertion sequence element". J. Biol. Chem. 273 (50): 33374–33378. doi: 10.1074/jbc.273.50.33374 . PMID 9837913.
Bartha T, Kim SW, Salvatore D, et al. (2000). "Characterization of the 5'-flanking and 5'-untranslated regions of the cyclic adenosine 3',5'-monophosphate-responsive human type 2 iodothyronine deiodinase gene". Endocrinology. 141 (1): 229–237. doi: 10.1210/en.141.1.229 . PMID 10614643.
Baqui MM, Gereben B, Harney JW, et al. (2000). "Distinct subcellular localization of transiently expressed types 1 and 2 iodothyronine deiodinases as determined by immunofluorescence confocal microscopy". Endocrinology. 141 (11): 4309–4312. doi: 10.1210/endo.141.11.7872 . PMID 11089566.
Ohba K, Yoshioka T, Muraki T (2001). "Identification of two novel splicing variants of human type II iodothyronine deiodinase mRNA". Mol. Cell. Endocrinol. 172 (1–2): 169–175. doi:10.1016/S0303-7207(00)00368-3. PMID 11165050. S2CID 19110385.
Imai Y, Toyoda N, Maeda A, et al. (2002). "Type 2 iodothyronine deiodinase expression is upregulated by the protein kinase A-dependent pathway and is downregulated by the protein kinase C-dependent pathway in cultured human thyroid cells". Thyroid. 11 (10): 899–907. doi:10.1089/105072501753210957. PMID 11716036.
Molnár I, Balázs C, Szegedi G, Sipka S (2002). "Inhibition of type 2,5'-deiodinase by tumor necrosis factor alpha, interleukin-6 and interferon gamma in human thyroid tissue". Immunol. Lett. 80 (1): 3–7. doi:10.1016/S0165-2478(01)00301-7. PMID 11716958.
Kuiper GG, Klootwijk W, Visser TJ (2002). "Substitution of cysteine for a conserved alanine residue in the catalytic center of type II iodothyronine deiodinase alters interaction with reducing cofactor". Endocrinology. 143 (4): 1190–1198. doi: 10.1210/en.143.4.1190 . PMID 11897672.
Gereben B, Kollár A, Harney JW, Larsen PR (2003). "The mRNA structure has potent regulatory effects on type 2 iodothyronine deiodinase expression". Mol. Endocrinol. 16 (7): 1667–1679. doi: 10.1210/mend.16.7.0879 . PMID 12089359.
Baur A, Buchfelder M, Köhrle J (2002). "Expression of 5'-deiodinase enzymes in normal pituitaries and in various human pituitary adenomas". Eur. J. Endocrinol. 147 (2): 263–268. doi: 10.1530/eje.0.1470263 . PMID 12153750.
Botero D, Gereben B, Goncalves C, et al. (2003). "Ubc6p and ubc7p are required for normal and substrate-induced endoplasmic reticulum-associated degradation of the human selenoprotein type 2 iodothyronine monodeiodinase". Mol. Endocrinol. 16 (9): 1999–2007. doi: 10.1210/me.2002-0135 . PMID 12198238.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. doi: 10.1073/pnas.242603899 . PMC 139241 . PMID 12477932.
Curcio-Morelli C, Gereben B, Zavacki AM, et al. (2003). "In vivo dimerization of types 1, 2, and 3 iodothyronine selenodeiodinases". Endocrinology. 144 (3): 937–946. doi: 10.1210/en.2002-220960 . PMID 12586771.
Ambroziak M, Pachucki J, Chojnowski K, et al. (2003). "Pax-8 expression correlates with type II 5' deiodinase expression in thyroids from patients with Graves' disease". Thyroid. 13 (2): 141–148. doi:10.1089/105072503321319440. PMID 12699588.
Dentice M, Morisco C, Vitale M, et al. (2004). "The different cardiac expression of the type 2 iodothyronine deiodinase gene between human and rat is related to the differential response of the Dio2 genes to Nkx-2.5 and GATA-4 transcription factors". Mol. Endocrinol. 17 (8): 1508–1521. doi: 10.1210/me.2002-0348 . PMID 12775767.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000211448 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000007682 - 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.

[pmid8755651-5] Croteau W, Davey JC, Galton VA, St Germain DL (Sep 1996). "Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues". J Clin Invest. 98 (2): 405–417. doi:10.1172/JCI118806. PMC 507444 . PMID 8755651.

[pmid10343107-6] Araki O, Murakami M, Morimura T, Kamiya Y, Hosoi Y, Kato Y, Mori M (Jun 1999). "Assignment of type II iodothyronine deiodinase gene (DIO2) to human chromosome band 14q24.2→q24.3 by in situ hybridization". Cytogenet Cell Genet. 84 (1–2): 73–74. doi:10.1159/000015218. PMID 10343107. S2CID 19715942.

[entrez-7] 1 2 "Entrez Gene: DIO2 deiodinase, iodothyronine, type II".

[pmid12865408-8] Curcio-Morelli C, Zavacki AM, Christofollete M, Gereben B, de Freitas BC, Harney JW, Li Z, Wu G, Bianco AC (July 2003). "Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation". J. Clin. Invest. 112 (2): 189–96. doi:10.1172/JCI18348. PMC 164294 . PMID 12865408.

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DIO2

Contents

Function

Interactions

See also

Related Research Articles

References

Further reading