Understanding the functional difference between growth arrest-specific protein 6 and protein S: an evolutionary approach.
Although protein S (PROS1) and growth arrest-specific protein 6 (GAS6) proteins are homologous with a high degree of structural similarity, they are functionally different. The objectives of this study were to identify the evolutionary origins from which these functional differences arose. Bioinformatics methods were used to estimate the evolutionary divergence time and to detect the amino acid residues under functional divergence between GAS6 and PROS1. The properties of these residues were analysed in the light of their three-dimensional structures, such as their stability effects, the identification of electrostatic patches and the identification potential protein-protein interaction. The divergence between GAS6 and PROS1 probably occurred during the whole-genome duplications in vertebrates. A total of 78 amino acid sites were identified to be under functional divergence. One of these sites, Asn463, is involved in N-glycosylation in GAS6, but is mutated in PROS1, preventing this post-translational modification. Sites experiencing functional divergence tend to express a greater diversity of stabilizing/destabilizing effects than sites that do not experience such functional divergence. Three electrostatic patches in the LG1/LG2 domains were found to differ between GAS6 and PROS1. Finally, a surface responsible for protein-protein interactions was identified. These results may help researchers to analyse disease-causing mutations in the light of evolutionary and structural constraints, and link genetic pathology to clinical phenotypes.
['Studer|Romain A|RA|', 'Opperdoes|Fred R|FR|', 'Nicolaes|Gerry A F|GA|', 'Mulder|André B|AB|', 'Mulder|René|R|']
D000465:Algorithms D000596:Amino Acids D000818:Animals D001665:Binding Sites D001798:Blood Proteins D002938:Ciona intestinalis D019295:Computational Biology D030562:Databases, Protein D019143:Evolution, Molecular D006031:Glycosylation D006801:Humans D036341:Intercellular Signaling Peptides and Proteins D009154:Mutation D010641:Phenotype D010802:Phylogeny D011485:Protein Binding D025941:Protein Interaction Mapping D011499:Protein Processing, Post-Translational D017293:Protein S D017433:Protein Structure, Secondary D017434:Protein Structure, Tertiary D055672:Static Electricity
growth arrest-specific protein 6 protein S evolution