A site-1 protease (S1P) that cleaves the peptide bond between 'Val-148' and 'Ser-149' in RseA. 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 heat shock-induced degradation of RseA but not for acid stress response in this strain. 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. Homotrimer. Deletion of the PDZ domain eliminates the heat shock response of the sigma-E regulon, but not the acid stress response. Loss of heat shock but not acid stress response of sigma-E regulon. 10-fold decreased survival in acidified murine macrophages. 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.