Modulation of nuclear receptor activity by the F domain

•We review F domains found in the nuclear receptor superfamily.•The F domain can both stimulate and repress transcription.•The presence and/or absence of the F domain can be physiologically significant.•The F domain secondary structure (helix or beta strand) can be vital for function.•The F domain plus ligand binding domain can be covalently modified.

The F domain located at the C-terminus of proteins is one of the least conserved regions of the estrogen receptors alpha and beta, members of the nuclear hormone receptor superfamily. Indeed, many members of the superfamily lack the F domain. However, when present, removing the F domain entirely or mutating it alters transactivation, dimerization, and the responses to agonist and antagonist ligands. This review focuses on the functions of the F domain of the estrogen receptors, particularly in relation to other members of the superfamily.