Explaining functional and contextual divergence by clustering the functional distance of protein sequences from helix-turn-helix (HTH) DNA binding domains and RAM domains of FFRPs in H. salinarum . A. Hierarchically clustered tree of the functional distance between HTH DNA binding domains of FFRPs. B. Putative DNA recognition motifs for each FFRP. C. Upper triangle of matrix displays significant pairwise FFRP DNA recognition motif similarity as black boxes (Benjamini-Hochberg corrected p-value <0.05). Lower triangle displays pairwise FFRP target gene overlap as percent overlap as intensity of red boxes and significant overlap using black outline for boxes (p-value <0.05 and percent overlap <50%). D. Hierarchically clustered tree of the functional distance between RAM domains of FFRPs. E. Key amino acid residues used to predict the most likely effector molecules for each FFRP. F. Predicted effector molecule preferences for RAM or additional domain. Arg=arginine, Gln=glutamine, Lys=lysine, Ile=isoleucine, Leu=leucine, Val=valine, Asn=asparagine, and Asp=aspartic acid. The two additional domains are predicted to sense the effector molecules: K+=potassium ion, NAD+=nicotinamide adenine dinucleotide, Cu(II)=copper, and =unkown. Interesting groupings from clustering the functional distance are denoted by a red bracket below the effector molecule preferences.