Definition of Protein Superfamily

Margaret O. Dayhoff introduced the term protein superfamily in 1974 [1,2,3]. Since that time, the sequences in the PIR-International Protein Sequence Database have been classified into protein superfamilies. Prior to about 1990, the superfamily classification permitted a sequence to be assigned to a single superfamily only. The recognition of mosaic, multidomain proteins, whose component domains appear to have had separate evolutionary histories, has made this approach no longer effective. Moreover, the term superfamily has come into common usage and its meaning is no longer well defined. Although originally defined as a group of evolutionarily related proteins, it also has been used in the published literature to refer to a group of structurally or functionally related proteins not necessarily of common evolutionary origin.