Estrogen receptor alpha (ER alpha) is a nuclear protein and member of the steroid hormone receptor family. ER alpha possesses both DNA binding and ligand binding domains, and exerts a significant role in activating the transcription of certain genes. Ligand-dependent dimerization and phosphorylation both function to regulate the transcriptional activation of ER alpha. Particularly, phosphorylation of serines 104 and 106, located in the N-terminal transcription activation function-1 domain (AF-1), plays a large role in regulating ER alpha activity.