Meta‐analysis Of Nuclear Targets Of Tyrosine Phosphorylation: Identifying Nodes that Regulate Nuclear Activity

PhosphoSitePlus ® (PSP)* contains the largest and deepest repository of tyrosine phosphorylation sites (pYPsites) available, curated from thousands of phosphoproteomic studies and from literature reports derived from low‐throughput experiments. PSP is thus an ideal resource of data that can enable proteome‐wide studies of the distribution of pYSites in all cellular compartments. We present here a meta‐analysis of the pYSites of nuclear proteins, as well as the proteins that regulate traffic into and out of the nucleus. The goal of this work is to identify proteins that are relatively enriched or depleted of pYSites, and sites that may regulate important nuclear activities including transcription, splicing, and nuclear trafficking. For example, tyrosine phosphorylation is rare in nuclear receptors, suggesting very little cross talk between nuclear receptors and receptors that activate tyrosine kinases. Tyrosine phosphorylation is dramatically increased in specific sites that may regulate nuclear translocation, transcription, and RNA processing. By way of contrast, other modification types such as serine and threonine phosphorylation, acetylation and methylation are compared to tyrosine phosphorylation, identifying compartments and processes that are enriched/depleted in each of these modification types.