Involved in regulated intramembrane proteolysis and the subsequent release of functional polypeptides from their membrane anchors. Known substrate: EFNB3 (By similarity). Cleaves type-1 transmembrane domains using a catalytic dyad composed of serine and histidine that are contributed by different transmembrane domains. Proteolytic processing of the proenzyme produces an N- and a C-terminal fragment. The processing is required for activation of the protease (By similarity). Belongs to the peptidase S54 family.