Twenty-nine proteins from 16 different species of prokaryotes revealed an extensive sequence homology with the cytoplasmic domain of the Escherichia coli aspartate receptor. The high percentage of identity indicated that they constitute a superfamily of proteins. A consensus secondary structure consisting mostly of alpha-helices was predicted. The occurrence of a seven-residue repeat (a-b-c-d-e-f-g), in which both the a and d residues were hydrophobic with few exceptions, provided additional evidence for a conserved alpha-helical conformation. Sequence alignments, together with the predicted secondary structure, led to identification of the boundaries for the functional units constituting the cytoplasmic domain. Putative methylation sites were assigned for all the members of this superfamily. These proteins could be grouped into three classes based on the presence of 14-residue insertion/deletion regions found within both the signalling and the methylation functional units of the cytoplasmic domain. The gene coding for the C-terminal cytoplasmic domain of these proteins apparently evolved through gene duplication from a common ancestor in which the four original 14-residue insertion/deletion regions were deleted two by two during evolution.