<p>Two-component signal transduction systems enable bacteria to sense, respond, and adapt to a wide range of environments, stressors, and growth conditions [<cite idref="PUB00042804"/>]. Some bacteria can contain up to as many as 200 two-component systems that need tight regulation to prevent unwanted cross-talk [<cite idref="PUB00042805"/>]. These pathways have been adapted to response to a wide variety of stimuli, including nutrients, cellular redox state, changes in osmolarity, quorum signals, antibiotics, and more [<cite idref="PUB00010651"/>]. Two-component systems are comprised of a sensor histidine kinase (HK) and its cognate response regulator (RR) [<cite idref="PUB00011096"/>]. The HK catalyses its own auto-phosphorylation followed by the transfer of the phosphoryl group to the receiver domain on RR; phosphorylation of the RR usually activates an attached output domain, which can then effect changes in cellular physiology, often by regulating gene expression. Some HK are bifunctional, catalysing both the phosphorylation and dephosphorylation of their cognate RR. The input stimuli can regulate either the kinase or phosphatase activity of the bifunctional HK.</p><p>A variant of the two-component system is the phospho-relay system. Here a hybrid HK auto-phosphorylates and then transfers the phosphoryl group to an internal receiver domain, rather than to a separate RR protein. The phosphoryl group is then shuttled to histidine phosphotransferase (HPT) and subsequently to a terminal RR, which can evoke the desired response [<cite idref="PUB00042806"/>, <cite idref="PUB00042807"/>].</p><p>This entry represents a response regulator receiver domain and an associated transcriptional regulatory region. This group is separated phylogenetically from related proteins with similar architecture and contains a number of proteins associated with heavy metal resistance efflux systems for copper, silver, cadmium, and/or zinc. Most members are encoded by genes adjacent to genes which code for a member of the heavy metal sensor histidine kinase family (<db_xref db="INTERPRO" dbkey="IPR006290"/>), its partner in the two-component response regulator system. </p> Signal transduction response regulator, heavy metal response