Estimating the total number of phosphoproteins and phosphorylation sites in eukaryotic proteomes

Background: Phosphorylation is the most frequent post-translational modification made to proteins and may regulate protein activity as either a molecular digital switch or a rheostat. Despite the cornucopia of high-throughput (HTP) phosphoproteomic data in the last decade, it remains unclear how many proteins are phosphorylated and how many phosphorylation sites (p-sites) can exist in total within a eukaryotic proteome. We present the first reliable estimates of the total number of phosphoproteins and phosphorylation sites (p-sites), for four eukaryotes (human, mouse, Arabidopsis, and yeast).

Results: In all, 187 HTP phosphoproteomic datasets were filtered, compiled and studied along with two low-throughput (LTP) compendia. Estimates of the number of phosphoproteins and p-sites were inferred by two methods: Capture-Recapture, and fitting the saturation curve of cumulative redundant vs. cumulative non-redundant phosphoproteins/p-sites. Estimates were also adjusted for different levels of noise within the individual datasets and other confounding factors. We estimate that in total, 13,000, 11,000 and 3,000 phosphoproteins and 230,000, 156,000 and 40,000 p-sites exist in human, mouse and yeast, respectively, whereas estimates for Arabidopsis were not as reliable.

Conclusions: Most of the phosphoproteins have been discovered for human, mouse and yeast, while the dataset for Arabidopsis is still far from complete. The datasets for p-sites are not as close to saturation as those for phosphoproteins, Integration of the LTP data suggests that current HTP phosphoproteomics appears to be capable of capturing 70-95% of total phosphoproteins, but only 40-60% of total p-sites.

Vlastaridis, P., Kyriakidou, P., Chaliotis, A., Van de Peer, Y., Oliver, S., Amoutzias, G. (2016) Estimating the total number of phosphoproteins and phosphorylation sites in eukaryotic proteomes. GigaScience (In Press).

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