Identification of novel phosphorylation modification sites in human proteins that originated after the human-chimpanzee divergence

Abstract

Motivation: Phosphorylation modifications of specific protein residues are involved in a wide range of biological processes such as modulation of intracellular signal networks. Here, we present the development and application of a bioinformatics procedure for systematic identification of human-specific phosphorylation sites in proteins that may have occurred after the human-chimpanzee divergence. Results: We collected annotated human phosphorylation sites and compared each site to orthologous mammalian proteins across taxa including chimpanzee, orangutan, rhesus macaque, marmoset, mouse, dog, cow, elephant, opossum and platypus. We identified 37 human-specific gains of annotated phosphorylation sites in 35 proteins: 22 serines, 12 threonines and 3 tyrosines. The novel phosphorylation sites are situated in highly conserved segments of the protein. Proteins with novel phosphorylation sites are involved in crucial biological processes such as cell division (AURKB, CASC5, MKI67 and PDCD4) and chromatin remodeling (HIRA, HIRIP3, HIST1H1T, NAP1L4 and LRWD1). Modified phosphorylatable residues produce novel target sites for protein kinases such as cyclin-dependent kinases and casein kinases, possibly resulting in rewiring and fine-tuning of phosphorylation regulatory networks. The potential human-specific phosphorylation sites identified in this study are useful as candidates for functional analysis to identify novel phenotypes in humans.