Sigma factors are initiation factors that promote the attachment of RNA polymerase (RNAP) to specific initiation sites and are then released. Extracytoplasmic function (ECF) sigma-E controls the envelope stress response, responding to periplasmic protein stress, increased levels of periplasmic lipopolysaccharide (LPS) as well as acid stress, heat shock and oxidative stress; it controls protein processing in the extracytoplasmic compartment. ECF sigma-E is held in an inactive form by its cognate anti-sigma factor (RseA) until released by regulated intramembrane proteolysis (RIP). RIP occurs when an extracytoplasmic signal (periplasmic, acid or heat stress) triggers a concerted proteolytic cascade to transmit information and elicit cellular responses. In S.typhimurium there are 2 cascades, the heat shock response which depends on DegS and RseP, and acid response which depends only on RseP. The anti-sigma factor RseA is an inner membrane protein, binding sigma-E in the cytoplasm and RseB in the periplasm. RseA is first cut extracytoplasmically (site-1 protease, S1P, by DegS), then within the membrane itself (site-2 protease, S2P, by RseP), while cytoplasmic proteases (predominantly ClpX-ClpP) finish degrading the regulatory protein, liberating sigma-E. Degradation of RseA requires 2 signals to activate DegS; an outer membrane protein (OMP) signal activates DegS, while an LPS signal causes release of RseB from RseA, freeing RseA to be cleaved. OMP stress can be abrogated by overexpression of the sRNA rybB. Interacts transiently with the RNAP catalytic core formed by RpoA, RpoB, RpoC and RpoZ (2 alpha, 1 beta, 1 beta' and 1 omega subunit) to form the RNAP holoenzyme that can initiate transcription. Interacts 1:1 with anti-sigma-E factor RseA which prevents binding to RNAP catalytic core (Probable). Associates with the inner membrane via RseA. Poorly expressed in logarithmic growth, induced in stationary phase. By acid stress (pH 4.5), heat shock. Has 3 promoters, the first 2 are sigma-70-dependent, the third is positively auto-regulated. The sigma-70 factor domain-2 mediates sequence-specific interaction with the -10 element in promoter DNA, and plays an important role in melting the double-stranded DNA and the formation of the transcription bubble. The sigma-70 factor domain-2 mediates interaction with the RNA polymerase subunits RpoB and RpoC (By similarity). The sigma-70 factor domain-4 contains a helix-turn-helix (H-T-H) motif that mediates interaction with the -35 element in promoter DNA. The domain also mediates interaction with the RNA polymerase subunit RpoA. Interactions between sigma-70 factor domain-4 and anti-sigma factors prevents interaction of sigma factors with the RNA polymerase catalytic core (By similarity). Not essential. Increased sensitivity to oxidative stress. 100-fold decreased survival in acidified murine macrophages, slightly reduced growth at pH 7.0, delayed growth at pH 4.5, severely delayed growth at pH 3.0. Loss of sigma-E-dependent acid tolerance response, loss of acid and heat stress response. Belongs to the sigma-70 factor family. ECF subfamily.