Methionine sulfoxide reduction is an important process, by which cells regulate biological processes and cope with oxidative stress. MsrA, a protein involved in the reduction of methionine sulfoxides in proteins, has been known for four decades and has been extensively characterized with respect to structure and function. However, recent studies revealed that MsrA is only specific for methionine-S-sulfoxides. Because oxidized methionines occur in a mixture of R and S isomers in vivo, it was unclear how stereo-specific MsrA could be responsible for the reduction of all protein methionine sulfoxides. It appears that a second methionine sulfoxide reductase, SelR, evolved that is specific for methionine-R-sulfoxides, the activity that is different but complementary to that of MsrA. Thus, these proteins, working together, could reduce both stereoisomers of methionine sulfoxide. This domain is found both in SelR proteins and fused with the peptide methionine sulfoxide reductase enzymatic domain pfam01625. The domain has two conserved cysteine and histidines. The domain binds both selenium and zinc. The final cysteine is found to be replaced by the rare amino acid selenocysteine in some members of the family. This family has methionine-R-sulfoxide reductase activity.