The THRα and THRβ isoforms have considerable homology. The DBDs of all THR isoforms are highly homologous and each of these proteins can form heterodimers and homodimers. Alternative splicing and use of alternative transcription sites results in the generation of four THR isoforms that able to bind T3 (THRα1 and THRβ1-3). The AF-1 and AF-2 regions of the proteins have some sequence variability across the isoforms; the THRα2 and THRα3 isoforms are truncated and, as a result of having no AF-2 domains, they are unable to bind T3. Abbreviations: AF-1, activation function 1; AF-2, activation function 2; DBD, DNA-binding domain; LBD, ligand-binding domain.