A protein complex that has aspartic-type endopeptidase activity and contains a presenilin catalytic subunit (either PSEN1 or PSEN2), an APH1 subunit (multiple genes and splice variants exist), nicastrin (NCT), and presenilin enhancer (aka PEN-2 or Psenen), as the core complex. Variants of the complex with different subunit compositions differ in localization and specific substrates. Additionally, variants of the complex exist that contain a additional regulatory subunit as well as the four core subunits; known regulatory subunits include gamma-secretase-activating protein (aka gSAP), TMP1 (aka TMED10), and CD147 antigen (aka basigin). Gamma-secretase cleaves type I transmembrane protein substrates, including the cell surface receptor Notch and the amyloid-beta precursor protein.
PS2 complex