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 expressed in brain, thyroid and lung. It is thought to be responsible for the \'local\' production of T3, and thus important in influencing thyroid hormone action in these tissues. 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, resulting in two potential 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). In addition, the lack of conservation of the protein extension past the second TGA codon suggests that the one-Sec containing isoform represents the canonical form. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2018]

NM_001324555.3; NM_204114.6

NP_001311484.2; NP_989445.3