ERβ splice variants. The AF1 and AF2 domains exhibit the least homology between ERβ1 and ERα. ERβ2 is nearly identical to ERβ1 except that the last 61 amino acids (aa) are replaced by 26 novel aa (indicated by the green portion of the receptor). As such, the β2 splice variant is comprised of 495 aa. Similarly, the last 65 aa of ERβ5 has been replaced by 7 other aa resulting in a 472 aa protein. Of note, truncation of the LBD/AF1 domains of β2 and β5 results in loss of ligand-binding activity, while conservation of their DBD maintains the likelihood of ERE binding. Estrogen binding to the delta5 splice variant is compromised by deletion of nucleotides 812–950 (139 base pairs (bp)) in the LBD. The result of the 18 aa insertion into what is essentially ERβ2 markedly diminishes ligand binding.
