When looking at the differences between ERα and ERβ, Activating Function 1 (AF-1) and AF-2 are important. Together they play an important part in the interaction with other co-regulatory proteins that control gene transcription. AF-1 is located in the amino terminus of the ER and is only 20% homologous in ERα and ERβ. On the other hand, AF-2 is very similar in ERα and ERβ, and only one amino acid is different. Studies have shown that by switching AF-1 regions in ERα and ERβ, that there are specific differences in transcription activity. Generally, SERMs can partially activate engineered genes through ERα by an estrogen receptor element, but not through ERβ. Although, raloxifene and the active form of tamoxifen can stimulate AF-1-regulated reporter genes in both ERα and ERβ.