Protein domains of estrogen receptor β1, β2 and β5 isoforms. All three isoforms contain an amino-terminal region (A/B), a DNA-binding region (C), a hinge region (D) and an LBD (E). ERβ1 also contains a carboxyl-terminal domain (F). Specific regions within C and E domains are important for receptor dimerization. Activation function 1 domain (AF-1) and AF-2 domains are required to transactivate gene expression. The N-terminal AF-1 domain and the C-terminal AF-2 domain correspond to ligand-independent and -dependent transactivation functions, respectively. The DNA-binding domain (DBD) shares a high degree of homology in the different ER isoforms. aa, Amino acids.