title: Phosphosite conservation in single domain orthologs versus paralogs: a way to combine differential regulation with redundant core functions.
abstract: Evolutionary conservation for structure function relations is commonly accepted. Here we hypothesize that closely related single domain paralogous proteins, having similar expression profiles and redundant biochemical core functions, additionally evolved to allow and maintain isoform specific differential regulation by single conserved amino acid substitutions. To substantiate this, we considered two families of closely related actin binding proteins combined with data mining of phosphorylated residues in human and mouse proteins. We show that such residues are identical in other orthologs whereas paralogs have a different, but also conserved, non-phosphorylatable residue at the equivalent positions.
authors.affiliation: Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
authors.forename: Lynn
authors.initials: L
authors.lastname: Huyck
authors.forename: Marleen
authors.initials: M
authors.lastname: Van Troys
authors.forename: Christophe
authors.initials: C
authors.lastname: Ampe
mesh_terms: D051339:Actin Depolymerizing Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D010750:Phosphoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D040681:Structural Homology, Protein
chemical_list: D051339:Actin Depolymerizing Factors; D008840:Microfilament Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms