Comparative kinomics of human and chimpanzee reveal unique kinship and functional diversity generated by new domain combinations
- Equal contributors
1 Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India
2 INRA UR1077, Unité Mathématique Informatique et Génome, F-78350 Jouy-en-Josas, France
3 Université de Lyon, Lyon, France; Université Lyon 1; IFR 128; CNRS, UMR 5086; IBCP, Institut de Biologie et Chimie des Protéines, 7 passage du Vercors, Lyon, F-69367, France
BMC Genomics 2008, 9:625 doi:10.1186/1471-2164-9-625Published: 23 December 2008
Phosphorylation by protein kinases is a common event in many cellular processes. Further, many kinases perform specialized roles and are regulated by non-kinase domains tethered to kinase domain. Perturbation in the regulation of kinases leads to malignancy. We have identified and analysed putative protein kinases encoded in the genome of chimpanzee which is a close evolutionary relative of human.
The shared core biology between chimpanzee and human is characterized by many orthologous protein kinases which are involved in conserved pathways. Domain architectures specific to chimp/human kinases have been observed. Chimp kinases with unique domain architectures are characterized by deletion of one or more non-kinase domains in the human kinases. Interestingly, counterparts of some of the multi-domain human kinases in chimp are characterized by identical domain architectures but with kinase-like non-kinase domain. Remarkably, out of 587 chimpanzee kinases no human orthologue with greater than 95% sequence identity could be identified for 160 kinases. Variations in chimpanzee kinases compared to human kinases are brought about also by differences in functions of domains tethered to the catalytic kinase domain. For example, the heterodimer forming PB1 domain related to the fold of ubiquitin/Ras-binding domain is seen uniquely tethered to PKC-like chimpanzee kinase.
Though the chimpanzee and human are evolutionary very close, there are chimpanzee kinases with no close counterpart in the human suggesting differences in their functions. This analysis provides a direction for experimental analysis of human and chimpanzee protein kinases in order to enhance our understanding on their specific biological roles.