A site-2 regulated intramembrane protease (S2P) that cleaves the peptide bond between 'Ala-108' and 'Cys-109' in the transmembrane region of RseA. Part of a regulated intramembrane proteolysis (RIP) cascade. Acts on DegS-cleaved RseA to release the cytoplasmic domain of RseA, residue 'Val-148' of RseA may be required for this. This provides the cell with sigma-E (RpoE) activity through the proteolysis of RseA. Can also cleave sequences in transmembrane regions of other proteins (such as LacY) as well as liberated signal peptides of beta-lactamase, OmpF, LivK, SecM, PhoA, LivJ, OmpC, Lpp and TorA, probably within the membrane. Inhibited by Zn(2+) chelator 1,10-phenanthroline. Interacts with RseA; the third transmembrane domain can be cross-linked to the transmembrane domain of RseA. Part of the sigma-E regulon. Also has a primary sigma-70 factor promoter. The 2 circularly premutated PDZ domains act to negatively regulate protease action on intact RseA; mutations in PDZ 1 (PDZ-N) have a more deleterious effect than similar mutations in PDZ 2 (PDZ-C). A 31 residue insertion in PDZ-C (between Val-261 and Met-262) domain inhibits protease activity, whereas deletion of residues 203-279 alleviates the PDZ-inhibition, allowing cleavage of intact RseA. Essential. Depletion experiments lead to cessation of growth, elongated cells and limited lysis, as well as decreased amounts of sigma-E. Not essential in an rseA deletion strain, when sigma-E is overexpressed or in ompA-ompC deletion strain. In the latter has severely decreased growth at 20 degrees Celsius. Accumulation of an RseA proteolysis intermediate. 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), then within the membrane itself (site-2 protease, S2P, this enzyme), while cytoplasmic proteases finish degrading the regulatory protein, liberating the effector protein. Belongs to the peptidase M50B family. Was originally thought to be a negative regulator of sigma-E function and to act directly on sigma-E and RpoH; this may not be physiologically relevant.