Zinc metalloprotease that mediates intramembrane proteolysis of proteins such as ATF6, ATF6B, SREBF1/SREBP1 and SREBF2/SREBP2 (, ). Catalyzes the second step in the proteolytic activation of the sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2: cleaves SREBPs within the first transmembrane segment, thereby releasing the N-terminal segment with a portion of the transmembrane segment attached ( ). Mature N-terminal SREBP fragments shuttle to the nucleus and activate gene transcription ( ). Also mediates the second step in the proteolytic activation of the cyclic AMP-dependent transcription factor ATF-6 (ATF6 and ATF6B) . Involved in intramembrane proteolysis during bone formation . In astrocytes and osteoblasts, upon DNA damage and ER stress, mediates the second step of the regulated intramembrane proteolytic activation of the transcription factor CREB3L1, leading to the inhibition of cell-cycle progression .
Subcellular locations: Membrane, Cytoplasm, Golgi apparatus membrane
Expressed in heart, brain, placenta, lung, liver, muscle, kidney and pancreas.