The Cpx system is one of extracytoplasmic stress response systems (ESR) found in Gram-negative bacteria. ESRs are operated by a two-component signaling system which consists of a sensory histidine kinase (HK) and a response regulator (RR) as basal elements. In the Cpx system, CpxA is the inner membrane-spanning, sensory HK. Members of this superfamily share the structure of the periplasmic domain of CpxA, involved in the recognition of a specific envelope stress. This event triggers signal transduction to the cytoplasmic domain, which results in the autophosphorylation of a conserved histidine residue (His248 in Escherichia coli CpxA). Then, the phosphate group is transferred to its cognate RR, CpxR, which controls the transcription of the genes involved in the ESRS PMID:22760860.