DIO2 - iodothyronine deiodinase 2 Gene

Also Known as D2; 5DII; SelY; DIOII; TXDI2; SELENOY

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 1734

About DIO2

Cytogenetic location: 14q31.1 Genomic coordinates (GRCh38): 14:80,197,526-80,231,057 (from NCBI)

This gene has 10 transcripts (splice variants), 218 orthologues and 2 paralogues. Biased expression in thyroid (RPKM 69.7), endometrium (RPKM 13.6) and 2 other tissues.

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 widely expressed, including in thyroid and brain. It is thought to be responsible for the 'local' production of T3, and thus important in influencing thyroid hormone action in these tissues. It has also been reported to be highly expressed in thyroids of patients with Graves disease, and in follicular adenomas. The intrathyroidal T4 to T3 conversion by this enzyme may contribute significantly to the relative increase in thyroidal T3 production in these patients. 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, which can result in two 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). Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2018]

DIO2 Products (4)

mRNA	Protein	Name
NM_000793.6	NP_000784.3	type II iodothyronine deiodinase isoform b
NM_001324462.2	NP_001311391.2	type II iodothyronine deiodinase isoform b
NM_001366496.1	NP_001353425.1	type II iodothyronine deiodinase isoform b
NM_013989.5	NP_054644.1	type II iodothyronine deiodinase isoform a

Gene Ontology

Molecular Function
Biological Process

Molecular Function GO Annotation	Evidence	References	Source
enables thyroxine 5'-deiodinase activity	IDA IDA: Inferred from direct assay	19651899	GOA
enables thyroxine 5-deiodinase activity	IDA IDA: Inferred from direct assay	18566113	GOA
enables ubiquitin protein ligase binding	IPI IPI: Inferred from physical interaction	19651899	GOA

Biological Process GO Annotation	Evidence	References	Source
involved in thyroid hormone metabolic process	IDA IDA: Inferred from direct assay	19651899	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

DIO2 Protein Structure

T4_deiodinase

0
100
200
273 a.a.

Protein Preferred Names	Protein Names
type II iodothyronine deiodinase	deiodinase, iodothyronine type II

Related Diseases

Diseases	Alias
Graves' Disease	Graves Disease Exophthalmic Goiter Basedow'S Disease Grave'S Disease Basedow Disease Toxic Diffuse Goiter Graves' Hyperthyroidism Parry Disease Autoimmune Hyperthyroidism Toxic Multinodular Goiter
Euthyroid Sick Syndrome	Euthyroid Sick Syndromes Sick-Euthyroid Syndrome Ess - [Euthyroid Sick Syndrome] Low-T3 Syndrome Ntis - [Non-Thyroidal Illness Syndrome] Tscitus - [Thyroid Allostasis In Critical Illness, Tumours, Uraemia And Starvation]
Kashin-Beck Disease	Kaschin-Beck Disease Kaschin-Beck Disease, Unspecified Site Kashin-Bek Disease Urov Disease
Hypothyroidism	Thyroid Diseases Thyroid Disease Thyroid Deficiency Thyroid Insufficiency Dysfunction Thyroid Thyroid Dysfunction
Allan-Herndon-Dudley Syndrome	AHDS Allan-Herndon Syndrome Monocarboxylate Transporter 8 Deficiency MCT8 DEFICIENCY Mental Retardation, X-Linked, With Hypotonia Triiodothyronine Resistance T3 Resistance Mental Retardation And Muscular Atrophy Mct8-Specific Thyroid Hormone Cell-Membrane Transporter Deficiency Intellectual Disability And Muscular Atrophy Monocarboxylate Transporter-8 Deficiency T3 Resisitence Triiodothyronine Resistence X-Linked Intellectual Disability With Hypotonia Mct8 -Specific Thyroid Hormone Cell Transporter Deficiency Monocarboxylate Transporter 8 Deficiency X-Linked Intellectual Disability-Hypotonia Syndrome
Graves Disease 1	Thyrotoxicosis Graves Disease, Susceptibility To, 1 GRD1 Grd Hyperthyroidism, Autoimmune Hyperthyroidism Hyperactive Thyroid Gland Overactive Thyroid Toxic Diffuse Goitre Toxic Primary Thyroid Hyperplasia Stokes Disease Thyrotoxicosis With Goitre Thyrotoxicosis Struma Graves Disease Goitre With Hyperthyroidism Basedow Disease Exophthalmic Goitre Exophthalmic Struma Flajani Disease Graves Disease With Exophthalmos Hyperthyroid Goitre Hyperthyroidism Struma Thyroid Exophthalmos Malignant Exophthalmos Parry Disease Toxic Diffuse Goitre With Exophthalmos Toxic Goitre Toxic Goitre Nos Thyrotoxicosis Due To Uninodular Goitre Toxic Thyroid Nodule Toxic Uninodular Goitre Uninodular Toxic Struma Uninodular Toxic Struma With Hyperthyroidism Thyrotoxicosis Due To Single Thyroid Nodule Toxic Uninodular Goitre With Hyperthyroidism Hyperthyroidism With Thyroid Nodule Thyrotoxicosis With Toxic Uninodular Goitre Uninodular Goitre In Hyperthyroidism Uninodular Goitre In Thyrotoxicosis Toxic Multinodular Goitre Multinodular Goitre With Thyrotoxicosis Thyrotoxicosis Nodular Goitre Nodular Goitre With Thyrotoxicosis Adenomatous Goitre With Hyperthyroidism Multinodular Goitre With Hyperthyroidism Nodular Goitre With Hyperthyroidism Nodular Struma With Hyperthyroidism Plummer Disease Thyrotoxicosis Adenomatous Goitre Thyrotoxicosis Adenomatous Struma Toxic Adenomatous Goitre Toxic Adenomatous Struma Toxic Nodular Goitre Nos Toxic Struma Nodosa Toxic Nodular Struma
Deafness, Autosomal Recessive 62	DFNB62 Autosomal Recessive Nonsyndromic Deafness 62 Autosomal Recessive Deafness 62
Follicular Adenoma	Follicular Adenoma Of The Thyroid Gland Thyroid Follicular Adenoma Adenoma Follicular Follicular Thyroid Adenoma Thyroid Gland Follicular Adenoma
Thyroid Hormone Resistance, Generalized, Autosomal Dominant	Thyroid Hormone Resistance Syndrome Thyroid Hormone Resistance GRTHD Gthr Thyroid Hormone Unresponsiveness Generalized Thyroid Hormone Resistance Hyperthyroxinemia, Familial Euthyroid, Secondary To Pituitary And Peripheral Thyroid Hormones Hyperthyroxinemia, Familial Euthyroid, Secondary To Pituitary And Peripheral Resistance To Thyroid Hormones Refetoff Syndrome Thyroid Hormone Responsiveness Defect Familial Euthyroid Hyperthyroxinemia, Secondary To Pituitary And Peripheral Resistance To Thyroid Hormones Thyroid Hormone Resistance, Generalized, Autosomal Recessive
Thyroid Gland Disease	Abnormality Of The Thyroid Gland Thyroid Diseases
Thyroid Dyshormonogenesis 4	Deiodinase Deficiency TDH4 Iodotyrosine Dehalogenase Deficiency Thyroid Hormonogenesis, Genetic Defect In, 4 Hypothyroidism, Congenital, Due To Dyshormonogenesis, 4 Genetic Defect In Thyroid Hormonogenesis 4 Chdh4 Congenital Hypothyroidism Due To Dyshormonogenesis Type 4 Genetic Defect In Thyroid Hormonogenesis Type 4
Staphyloenterotoxemia	Staphylococcal Food Poisoning Staphylococcal Toxaemia Due To Food Staphyloenterotoxicosis
Type 2 Diabetes Mellitus	Insulin Resistance NIDDM Type 2 Diabetes Diabetes Mellitus, Non-Insulin-Dependent T2D Noninsulin-Dependent Diabetes Mellitus Diabetes Mellitus, Type Ii Maturity-Onset Diabetes Insulin Resistance, Severe, Digenic Diabetes Mellitus, Type 2 Diabetes Mellitus, Noninsulin-Dependent Diabetes Mellitus, Noninsulin-Dependent, Association With Diabetes Mellitus, Noninsulin-Dependent, Late Onset Hypertension, Insulin Resistance-Related, Susceptibility To Insulin Resistance, Susceptibility To Non-Insulin-Dependent Diabetes Mellitus Type Ii Diabetes Mellitus Adult-Onset Diabetes Mellitus Maturity-Onset Diabetes Mellitus Diabetes Mellitus Type 2 Type Ii Diabetes Type 2 Diabetes Mellitus, Susceptibility To Diabetes, Type 2 Diabetes Mellitus, Noninsulin-Dependent, Susceptibility To Diabetes Mellitus, Non-Insulin-Dependent, Susceptibility To Diabetes Mellitus, Type 2, Susceptibility To Diabetes Mellitus, Noninsulin-Dependent, 2 Diabetes Mellitus, Type Ii, Susceptibility To Hypertension, Insulin Resistance-Related Adult-Onset Diabetes Aodm Diabetes Mellitus, Adult-Onset Diabetes Mellitus Type Ii Diabetes Mellitus Type 2, Susceptibility To Diabetes, Type Ii, Susceptibility To Diabetes Type 2 Diabetes Mellitus Adult Onset Diabetes Maturity Onset Diabetes Nonketotic Diabetes Non-Insulin Dependent Diabetes Mellitus T2dm - [Type 2 Diabetes Mellitus] Niddm - [Non Insulin Dependent Diabetes Mellitus] Dm2 Dm Type Ii Diabetic Type 2 Insulin Requiring Type 2 Diabetes Noninsulin Dependent Diabetes Non-Insulin-Dependent Diabetes Mellitus Without Complications Diabetes Due To Insulin Secretory Defect Diabetes Mellitus Due To Insulin Secretory Defect Non-Insulin-Dependent Diabetes Of The Young Senile Diabetes Nonketotic Hyperglycaemia Stable Diabetes
Familial Thyroid Dyshormonogenesis	Thyroid Dyshormonogenesis Familial Dyshormonogenetic Goiter
Loeys-Dietz Syndrome 1	Furlong Syndrome Loeys-Dietz Aortic Aneurysm Syndrome LDS1 Aat5 Loeys-Dietz Syndrome Type 1 Aortic Aneurysm, Familial Thoracic 5 Familial Throacic Aortic Aneurysm 5 Loeys-Dietz Syndrome Aortic Aneurysm Syndrome, Loeys-Dietz Type Familial Thoracic Aortic Aneurysm 5 Ldas Marfanoid Disorder-Craniosynostosis Syndrome Aneurysm, Aortic, Thoracic, Familial, Type 5 Loeys-Dietz Syndrome, Type 1 Loeys-Dietz Syndrome, Type 2a
Congenital Hypothyroidism	Cretinism Neonatal Hypothyroidism Ch Cht Congenital Myxedema Myxedema, Congenital Endemic Cretinism Congenital Iodine-Deficiency Syndrome Fetal Iodine Deficiency Syndrome Congenital Iodine-Deficiency Hypothyroidism Nos
Diabetes Mellitus	Diabetes
Body Mass Index Quantitative Trait Locus 11	OBESITY Obesity, Susceptibility To Leanness, Inherited Obesity, Susceptibility To, Bmiq11 Obesity, Mild, Early-Onset Obesity, Association With Obesity, Early-Onset, Susceptibility To Obesity, Severe Obesity, Severe, And Type Ii Diabetes Obesity, Late-Onset Obesity , Susceptibility To BMIQ11 Obesity Bmiq11 Obesity, Early-Onset Simple Obesity Nos Excess Fat Obesity, Not Elsewhere Classified, Body Mass Index Not Elsewhere Classified Adiposis

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Pre-clinical Phase

Pre-clinical Phase

Bioactive Molecules (2)

Cat. No.	상품명	효과	Purity	Rare Diseases
HY-RS03770	DIO2 Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-402216	N-b-Hydroxyethyl oleyl imidazoline	Inhibitor	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Felis catus	DIO2	VGNC	VGNC:80987
Mus musculus	DIO2	MGD	MGI:1338833
Canis familiaris	DIO2	VGNC	VGNC:56059
Rattus norvegicus	DIO2	RGD	RGD:68418
Bos taurus	DIO2	VGNC	VGNC:106710
Others	DIO2	NCBI