Phosphosite conservation in single domain orthologs versus paralogs: A way to combine differential regulation with redundant core functions

► Isoform co-expression in various tissues necessitates differential regulation. ► Conserved point mutations in single domain paralogs with similar core functions. ► Data mining indicates differential phosphorylation of vertebrate paralogs occurs. ► Paralog specific phosphosites exist in cofilins and profilins. ► Mapping phosphosites on 3D structures explains effects of differential regulation.