*4.4. PTM Prediction*

We predicted phosphorylation sites using NetPhos 3.1 (http://www.cbs.dtu.dk/services/ NetPhos/) [78] to infer PTM sites conserved between human CDKL5, FOXG1, and MeCP2 sequences and their orthologs. The predictions had values ranging from 0 (strong propensity for obtaining a negative result) to 1 (strong propensity for obtaining a positive result); we used 0.75 as a cut-off to divide the negative and positive results. The prediction results for each sequence were plotted following multiple sequence alignment of each protein dataset. Predicted PTM sites in each dataset were considered as conserved through evolution if they had a positive value according to the 50% majority rule of the amount of sequence in the alignment.
