Distribution of Proteoforms Numbers in a Human Cell according to Their Abundance is Following Zipf’s Law

Human cells contain many thousands of protein components, protein species/proteoforms, whose cooperation provides the complicated functional mechanisms of the cellular proteome. Though recent methods still do not allow us to obtain the whole picture of this cooperation, they at least provide an opportunity to develop a representation of the proteome size and quantitative distribution of proteoforms inside the proteome. Using 2DE analysis followed by both protein staining and ESI LC-MS/MS analysis, we performed an analysis of the quantitative distribution of different proteoforms in human cells. We have analyzed several human cancer cell lines (HepG2, glioblastoma, MCF7) along with the primary liver cells from tissue samples and found that the dependence of the number of proteoforms on their abundance is described by Zipf's law: y = ax-1 (1), where y stands for the number of proteoforms (N), x stands for the abundance. In the case where the abundance is expressed as %V, and a = 14, the final equation is: N=14/%V (2). It is highly likely that this type of distribution reflects the fundamental functional organization of the human cellular proteome since it is the same in all types of cells analyzed.