Abstract
Phosphorylation is essential for protein function and signal transduction in eukaryotic cells. With the rapid development of mass spectrometry technology, a large number of phosphosites are identified. However, high-throughput methods of functional characterization for phosphosites are still scarce. In this study, we inspected if the co-evolution property can be used as an indicator to explore function of phosphosites through investigating co-evolutionary relationship between functionally associated phosphosites in human. In practice, the evolution attributes of phosphosites were represented with phylogenetic profiles, and then co-evolutionary correlations of functionally associated phosphosites were detected on three levels: (1) phosphosites within one protein; (2) phosphosites in different proteins participating in the same signal transduction pathways, and (3) general phosphosites. Results of the detection show that co-evolution is a general property of functionally associated phosphosites. This finding suggests to some degree that it is feasible to use the co-evolution property in exploring the function of phosphosites and investigating the functional association between them.
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Acknowledgments
We greatly appreciate the anonymous reviewers for their help to improve the manuscript. The authors gratefully acknowledge the support of SA-SIBS scholarship program. This work was supported by the National Basic Research program of China (973) (No. 2011CB910204), the Main Direction Program of Knowledge Innovation of Chinese Academy of Sciences (No. KSCX2-EW-R-04), the National Natural Science Foundation of China (No. 31100957, No. 31070752, No. 31301032), China Postdoctoral Science Foundation Fund (No. 20110490758), and Shanghai Postdoctoral Scientific Program (13R21417300).
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The authors declare that they have no conflict of interest.
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Communicated by S. Hohmann.
Z. Liu and G. Zheng contributed equally to this work.
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438_2014_881_MOESM1_ESM.xlsx
Table S1—statistics of the Homologene database. The first column is species information; the second column is initial gene number of a species; the third column is the number of genes having homology for a species; and the fourth column is the number of homology groups for a species (XLSX 11 kb)
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Table S2—information of phosphosites involved in KEGG pathways. Detailed phylogenetic profile information of phosphosites participated in human signalling transduction pathways is provided (XLSX 19 kb)
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Table S3—information of multi-phosphorylated proteins. Phylogenetic profile information of phosphosites within proteins is provided in the first sheet. Profile correlation values of functional associated phosphosite-pairs and the average correlation values of phosphosite-pairs within proteins are provided in the second sheet (XLSX 15 kb)
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Table S4—Phylogenetic profile information of phosphosites in the mTor, MAPK, and PI3K-AKT pathway. The first three sheets present the phosphosites and their phylogenetic pattern information in the mTor pathway, MAPK pathway, and PI3K-AKT pathway respectively. The last three sheets present correlation values of phylogenetic profile for target and control phosphosite-pairs in the mTor pathway, MAPK pathway, and PI3K-AKT pathway, respectively (XLSX 21 kb)
438_2014_881_MOESM5_ESM.xlsx
Table S5—information of interacted proteins regulated by same kinases. The detailed information of interacted proteins, kinases, phosphosites, and phylogenetic profile correlation values are provided. The last two columns are correlation values of phosphosite-pairs with functional association and the average correlation value of all phosphosite-pairs within interacted proteins, respectively (XLSX 85 kb)
438_2014_881_MOESM6_ESM.xlsx
Table S6—distance information of intra-group and inter-group phosphosites. For a protein, its phosphosites with identical profiles are classified into a pattern group. Then the average distance are calculated between sites in one group (intra-group) as well as sites of different groups (inter-group). The last two columns present the distance of sites intra-group and inter-group, respectively (XLSX 290 kb)
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Liu, Z., Zheng, G., Dong, X. et al. Investigating co-evolution of functionally associated phosphosites in human. Mol Genet Genomics 289, 1217–1223 (2014). https://doi.org/10.1007/s00438-014-0881-x
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DOI: https://doi.org/10.1007/s00438-014-0881-x