Cyclins, TFIIB and RB play major roles in cell cycle and/or gene regulation. Earlier work has suggested common ancestry for the TFIIB repeats and RB pocket B which share 20% sequence identity. We now report that database searches with profiles based on a multiple alignment of cyclin core regions (the 'cyclin box') detect the TFIIB repeats with equivalent scores to divergent cyclins. Several features of the sequences support the notion of common ancestry: e.g. cyclins A/B, C and D share approximately 20-30% identity but each have approximately 15-20% identity with vertebrate TFIIB, showing that conserved cyclin features underlie the match. These results suggest the presence of a domain superfamily, which we term the TR domain, in nuclear regulatory proteins belonging to the TFIIB, cyclin and RB families, that has been duplicated many times during eukaryotic evolution. The TR domain appears to function in protein-protein interactions.