ER (estrogen receptor 1) a member of the steroid receptor superfamily, contains highly conserved DNA binding (DBD) and ligand binding domains (LBD). Through its estrogen-independent and estrogen-dependent activation domains (AF-1 and AF-2, respectively), ER regulates transcription by recruiting coactivator proteins and interacting with general transcriptional machinery. Phosphorylation provides an important mechanism to regulate ER activity. ER is phosphorylated on multiple sites.