The human secretome

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.

Facets of individual-specific health signatures determined from longitudinal plasma proteome profiling

“…All 14 unique proteins were annotated to be secreted into blood and primarily expressed by the liver [9] and the longitudinal profiles stratified by genotypes are shown in Fig. 6A-O. Following our previous observations [14] and recent insights connecting the circulating proteome with genetic variation [23], we investigated if differences in detected proteins can be linked to protein polymorphisms.…”

“…Protein features that represent a family of several proteins are denoted with one gene name followed by "*". Feature names are colored red if predicted to be actively secreted into blood, or blue if they appear in blood due to cell leakage [9,39]. Protein examples: TNFRSF1B, DAPK1, CKAP2, GDF9, TBK1…”

“…For the circulating plasma proteome, nearly 5,000 proteins have this far been detected when combing discoveries from all assays and technologies [8]. Surprisingly, only 730 proteins are predicted to be actively secreted into the circulation [9], attributing many of the currently detected proteins to cellular leakage that may possibly occur during sample preparation [10]. Even though highly multiplexed assays have enabled large scale assessment of pre-symptomatic health states [3], additional investigations will complement our molecular description and understanding of the facets of health in healthy individuals.…”

Direct trafficking pathways from the Golgi apparatus to the plasma membrane

“…Membrane trafficking allows delivery of nascently biosynthesised proteins and lipids to the plasma membrane. Approximately 11-15% of human proteins are secreted as soluble proteins to the extracellular space [1][2][3] and an additional 10% localise to the plasma membrane [4]. This represents over 3500 proteins with a vast array of functions, including antibodies, signalling molecules, and integral endomembrane proteins which traffic to the plasma membrane before being internalised to the endolysosomal system.…”

CIRFESS: An interactive resource for querying the set of theoretically detectable peptides for cell surface and extracellular enrichment proteomic studies

“…Such proteomic approaches include enrichment strategies which exploit the biophysical properties of membranes - such as density gradient flotation, differential centrifugation, or silica-bead capture 11–15 - or affinity-based approaches that use proximity labels 16–18 , lectins 19 , metabolic 20–22 or chemical labels 23–27 to enrich cell surface proteins. Application of these approaches have supported efforts to catalog the cell surface and secretome and have led to large scale efforts in experimentation 28 and collation 29 . As with most proteomic methods, currently available strategies to probe the cell surface and secreted proteome are biased towards proteins that contain specific features (e.g.…”