The Dio2 gene is composed of 3 exons comprising 14656 bp of the genomic DNA.

The length of transcribed mRNA is about 6,8 kb and generates three variants of mRNA. Transcript variant 1 represents the longest transcript and encodes isoform a. Transcript variant 2 differs in the 5UTR when compared to variant 1. Both variants 1 and 2 encode isoform a. Transcript variant 3 includes an alternate in-frame exon in the coding region, compared to variant 1. Variant 3 encodes isoform b, which is longer than isoform a.

No pseudogene have been described.

The protein encoded by this gene belongs to the iodothyronine deiodinase family. This enzyme activates thyroid hormone by converting the prohormone thyroxine (T4) by outer ring deiodination 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 often signals the end of process of translation. The 3UTR 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 a stop signal. Alternative splicing results in multiple transcript variants encoding different isoforms. Ubiquitination can also regulate proteins by transiently inactivating enzymatic function through conformational change in a dimeric enzyme, which can be reversed upon deubiquitination (post-translational).

Ohba et al. (2001) identified 2 alternatively spliced DIO2 transcripts that include intronic sequences between the 2 invariant DIO2 exons. These splice variants showed tissue-specific expression in brain, thyroid, liver, thymus, anterior pituitary gland and brown adipose tissue. In mesothelioma cell lysates, Curcio et al. (2001) determined that endogenous DIO2 gene had an apparent molecular mass of 31 kD. In normal tissues, D2 activity/mRNA ratio is variable, but the enzyme is expressed in rodents in the developing and adult testis, heart, muscle, thyroid, BAT, brain, pituitary, thymus, skin, spinal cord, placenta, liver and pancreas. In humans D2 is expressed in brain, BAT, heart, thyroid, muscle, placenta, skin and vascular smooth muscle cells.

Immuno location of the protein in cells showed D2 as an endoplasmic reticulum resident protein.

Type 2 deiodinase converts intracellular pro-hormone-3,3,5,5-tetraiodothyronine (T4) into the active thyroid hormone 3,3,5-triiodothyronine (T3) thereby regulating intracellular levels of active T3 in target tissues.
Thermogenesis
The expression of D2 is increased in response to cold stimulation in brown adipocytes isolated from mice. Dio2 activation in the brown adipose tissue (BAT) of human newborns and rodents is known to play a role in adaptive energy expenditure during cold exposure.
Development
D2 activity is present in human placenta through all pregnancy, and is highly expressed during the first trimester. The level of activity is low in the non-pregnant uterus, but in pregnancy the level rises progressively to a maximum at gestation day 17 when it is increased threefold.

Several homologues of Dio2 have been identified in Pan troglodytes and Macaca mulatta (100%). The chicken and mouse have similar domain structures with human Dio2 (97%). Human Dio2 homology with D3 is expressed in Sus scrofia, Equus caballus, Cricetus cricetus, Oryctolagus cuniculus, Pituophis deppei (92% similarity) and limited domains with human D3 and D1.

No germinal or somatic mutations has been described. However, the polymorphism Thr92Ala in Dio2 gene is associated with increased risk of mental retardation, insulin resistance in type 2 diabetic patients, reduced glucose availability in obese women, symptomatic osteoarthritis, Graves disease and arterial hypertension.