The five residues involved in sugar binding are conserved in GNE (N516, D517, E566, H569, E588, GNE numbering).
Likewise, R353, R399 and F441, where substitutions strongly affected RNA binding, are conserved in Prp3 orthologs.
Moreover, the DISC1 arginine-rich motif required for TRAK1 binding is conserved in mouse, apart from a conservative substitution of glutamine for the first arginine (27).
This autosome-specific binding is conserved in evolution, as demonstrated by the F element specificity (also detected, for instance, in Drosophila pseudoobscura and Drosophila virilis).
RIM8 protein alignments showed that in the C-terminal domain, the residue Ile-331 of A. nidulans, involved in PalF-PalH receptor binding, was conserved in all the fungi sequences (it is located in position Ile-320 in P. brasiliensis).
W-575, which is important for the substrate binding was conserved in some of the bPOPs, while in a few other bPOPs it was substituted by other amino acids.
While the sites homologous to the poorly characterized phosphorylation sites of 4E-BP1 (S83, S101 and S112; numbered according to human 4E-BP1) are strikingly absent, the principal phosphorylation sites (T37, T46, S65 and T70; numbered according to human 4E-BP1) involved in the regulation of eIF4E-binding are conserved in the sea urchin 4E-BP sequence.
In both CRB-1 and EAT-20, the essential residues of the FERM-binding motif and the PDZ-domain binding motif are conserved in the intracellular region (Klebes and Knust, 2000; Klose et al., 2013).
It is striking that, unlike for MCT4, all the key binding residues are conserved in MCT2 except for two conservative changes (Leu to Ile and Ser to Ala).
Although most of the cofactor binding sites are conserved in plant JMJD6 proteins, the first KG binding site has been substituted by Ser and Ala in plant JMJD6A and JMJD6B proteins, respectively.
By assuming that TF binding sites are conserved in the genome of an organism, these models described gene expression as a function of TF binding affinity, which they estimated using TF expression and TF binding motifs [ 8- 10].
