Member of the two-component regulatory system CusS/CusR involved in response to copper and silver. Acts as a copper/silver ion sensor. Activates CusR by phosphorylation. ATP + protein L-histidine = ADP + protein N-phospho-L-histidine. Autophosphorylated. Deletion mutant has higher susceptibility to silver and shows an increase in copper accumulation. The cus system plays an important role in copper tolerance under anaerobic growth and, under extreme copper stress, in aerobic growth. HprSR and CusSR form a unique regulation system, where both two-component systems recognize and regulate the same set of genes, but under different environmental conditions. HprSR plays a role in H(2)O(2) response regulation, while CusSR plays a role in Cu(2+) response regulation.