Evolutionary Analysis of Post-translational Modification Sites in Translation Elongation Factor 1A

Evolutionary conservation is one of the powerful analyses to predict protein functional sites. There have been many studies proposing a variety of degrees of conservation. In this paper, we propose and compare two mathematical measures that calculate the degree of conservation at each site in the molecular evolutionary process, named "the degree of conservation" and "the degree of specific conservation". The degree of conservation can identify the sites which show a conserved pattern in all proteins of a protein family. The degree of specific conservation is the degree that can identify the sites conserved in a subfamily but variable in the whole family. In this study, the conservation analyses were applied to a protein that has many functions in the cell. Many researches of eukaryotic elongation factor 1A (eEF1A) revealed that eEF1A is involved in not only protein biosynthesis but also moonlighting functions such as cytoskeletal modification, apoptosis and viral infection. And functional divergences of the EF-Tu/1A protein family have occurred in the evolutionary process. Our results showed that the degree of conservation can predict the regions that are important for binding molecules of the eEF-Tu/1A proteins. The degree of specific conservation can predict the residues important for the functional divergences and post-translational modifications (PTMs). These results suggest that PTM sites of eEF1A are not conserved in the whole family but only conserved in a subfamily. It would be necessary to verify whether the conserved sites are responsible for the moonlighting functions of eEF1A to develop new drugs that can be effective for cancers.