A site-1 protease (S1P) that cleaves the peptide bond between 'Val-148' and 'Ser-149' in RseA. Part of a regulated intramembrane proteolysis (RIP) cascade. When heat shock or other environmental stresses disrupt protein folding in the periplasm, DegS senses the accumulation of unassembled outer membrane porins (OMP) and then initiates RseA (anti sigma-E factor) degradation by cleaving its periplasmic domain, making it a substrate for subsequent cleavage by RseP. This cascade ultimately leads to the sigma-E-driven expression of a variety of factors dealing with folding stress in the periplasm and OMP assembly. Required for basal and stress-induced degradation of RseA (By similarity). Acts on substrates that are at least partially unfolded. The cleavage site P1 residue is normally between a pair of hydrophobic residues, such as Val-|-Val. Allosterically activated by the C-terminus of exposed OMP peptides (consensus Tyr-X-Phe-COOH); cleavage only occurs in the presence of peptides. Inhibited when RseB is bound to RseA. Homotrimer. The PDZ domain probably binds peptides ending with C-terminal Tyr-X-Phe sequences, which activates proteolysis. In the absence of OMP peptides the PDZ domain inhibits peptidase activity (By similarity). Regulated intramembrane proteolysis (RIP) occurs when an extracytoplasmic signal triggers a concerted proteolytic cascade to transmit information and elicit cellular responses. A membrane-spanning regulatory substrate protein is first cut extracytoplasmically (site-1 protease, S1P, this enzyme), then within the membrane itself (site-2 protease, S2P), while cytoplasmic proteases finish degrading the regulatory protein, liberating the effector protein (By similarity). Belongs to the peptidase S1C family.