Functional Analysis of Genetic Variation in the SECIS Element of Thyroid Hormone Activating Type 2 Deiodinase.

Context: Thyroid hormone is important for normal brain development. The type 2 deiodinase (D2) controls thyroid hormone action in the brain by activating T4 to T3. The enzymatic activity of D2 depends on the incorporation of selenocysteine for which the selenocysteine-insertion sequence (SECIS) element located in the 3' untranslated region is indispensable.

Functional analysis of novel genetic variation in the thyroid hormone activating type 2 deiodinase.

Context: Thyroid hormones (TH) are important for normal brain development and abnormal TH regulation in the brain results in neurocognitive impairments. The type 2 deiodinase (D2) is important for local TH control in the brain by generating the active hormone T3 from its precursor T4. Dysfunction of D2 likely results in a neurocognitive phenotype.

The role of Arg445 and Asp498 in the human thyroid hormone transporter MCT8.

Monocarboxylate transporter 8 (MCT8) facilitates cellular influx and efflux of the thyroid hormones (THs) T(4) and T(3). Mutations in MCT8 lead to severe psychomotor retardation. Here, we studied the importance of 2 highly conserved residues (Arg445 in transmembrane domain 8 and Asp498 in transmembrane domain 10) for substrate recognition and helix interactions.

Mutations in MCT8 in patients with Allan-Herndon-Dudley-syndrome affecting its cellular distribution.

Monocarboxylate transporter 8 (MCT8) is a thyroid hormone (TH)-specific transporter. Mutations in the MCT8 gene are associated with Allan-Herndon-Dudley Syndrome (AHDS), consisting of severe psychomotor retardation and disturbed TH parameters. To study the functional consequences of different MCT8 mutations in detail, we combined functional analysis in different cell types with live-cell imaging of the cellular distribution of seven mutations that we identified in patients with AHDS.

A nonselenoprotein from amphioxus deiodinates triac but not T3: is triac the primordial bioactive thyroid hormone?

Thyroid hormone (TH) is important for metamorphosis in many species, including the cephalochordate Branchiostoma floridae, a marine invertebrate (amphioxus) living in warmer coastal areas. Branchiostoma expresses a TH receptor, which is activated by 3,3',5-triiodothyroacetic acid (TA(3)) but not by T(3). The Branchiostoma genome also contains multiple genes coding for proteins homologous to iodothyronine deiodinases in vertebrates, selenoproteins catalyzing the activation or inactivation of TH.