Iodothyronine deiodinase type 2 (DIO2)

Iodothyronine deiodinase type 2 (DIO2) is a critical membrane-bound selenoprotein responsible for the intracellular conversion of the prohormone thyroxine (T4) into the biologically active form, triiodothyronine (T3). Primarily located in the endoplasmic reticulum of the brain, pituitary gland, skeletal muscle, and brown adipose tissue, DIO2 serves as the main source of intracellular T3 in these regions, bypassing the need for systemic T3 uptake (UniProt Q92813). This localized activation is essential for maintaining metabolic homeostasis, regulating thermogenesis, and ensuring proper neurological development and function (NCBI Gene 1734). Clinical interest in DIO2 is significant due to the common Thr92Ala genetic polymorphism, which has been associated with reduced enzymatic efficiency and may explain persistent symptoms in hypothyroid patients treated with standard T4 monotherapy (PubMed: 25942311). While primarily targeted indirectly through thyroid hormone replacement, DIO2 remains a focal point for developing personalized therapeutic strategies for metabolic and psychiatric disorders linked to thyroid signaling (PubMed: 30550650).

Other names

Type II iodothyronine deiodinaseType 2 deiodinase5'-deiodinaseSelenoprotein DIO2D2ITDI2TXDI2

Catalyzes the outer ring deiodination of the prohormone thyroxine (T4) to the bioactive triiodothyronine (T3) and the degradation of reverse T3 (rT3) to 3,3'-diiodothyronine (T2).