Functional domains of the human estrogen receptors. ERα and ERβ share a highly conserved central DNA-binding domain and moderately conserved C-terminal ligand-binding domain. The ligand-dependent transcriptional activities of the ERs are mediated through a C-terminal activation function (AF-2). ERα contains a constitutive AF-1 in the N terminus; no apparent AF-1 domain is present in the human ERβ (6). Numbers in boxes indicate the number of residues in each protein region.