Research ResourceBiochemistry

The human secretome

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Science Signaling  26 Nov 2019:
Vol. 12, Issue 609, eaaz0274
DOI: 10.1126/scisignal.aaz0274

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Secrets of secreted proteins

Although proteins that are actively secreted from cells constitute a large proportion of the targets of pharmaceutical drugs, we lack a complete understanding of the size and composition of this group of proteins, collectively referred to as the human “secretome.” Uhlén et al. analyzed the genes of the Human Protein Atlas that encode proteins that are predicted to be secreted and combined this with data derived from antibody- and mass spectrometry–based analyses of the relative abundances, sites of origin, and final locations of proteins within the body. Their analysis suggests that many proteins that were thought to be secreted are retained intracellularly, and that another group of secreted proteins are retained locally rather than being released into the blood. These data serve as a resource for future research on this important class of proteins.

Abstract

The proteins secreted by human cells (collectively referred to as the secretome) are important not only for the basic understanding of human biology but also for the identification of potential targets for future diagnostics and therapies. Here, we present a comprehensive analysis of proteins predicted to be secreted in human cells, which provides information about their final localization in the human body, including the proteins actively secreted to peripheral blood. The analysis suggests that a large number of the proteins of the secretome are not secreted out of the cell, but instead are retained intracellularly, whereas another large group of proteins were identified that are predicted to be retained locally at the tissue of expression and not secreted into the blood. Proteins detected in the human blood by mass spectrometry–based proteomics and antibody-based immunoassays are also presented with estimates of their concentrations in the blood. The results are presented in an updated version 19 of the Human Protein Atlas in which each gene encoding a secretome protein is annotated to provide an open-access knowledge resource of the human secretome, including body-wide expression data, spatial localization data down to the single-cell and subcellular levels, and data about the presence of proteins that are detectable in the blood.

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