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The Human Secretome defined – a unique resource to study human biology and diseases

A novel map of all proteins secreted to human blood is described in a paper by Mathias Uhlen et al. entitled “The Human Secretome”, published in the journal Science Signaling.

The paper provides a first comprehensive annotation of all proteins secreted by the human cells. In addition, an analysis of the concentrations of the proteins circulating in the human blood is described. This map provides a unique resource to study human biology and diseases, in particular for immune-based research and efforts to develop new, effective treatments in oncology and autoimmune diseases.

The “human secretome”

An important class of proteins are those that are actively transported out of the human cells. This collection of secreted proteins, herein referred to as the “human secretome”, constitutes a large fraction of the targets for pharmaceutical drugs, but these are also important as targets for both the current clinical chemistry and for future diagnostics. Many of these proteins are also involved in signaling functions, including proteins such as cytokines, growth factors, and hormones. In recent years, many biological drugs targeting these proteins have been introduced in the clinic and improved the lives of numerous patients with cancer and autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and psoriasis. Despite the huge interest in secreted proteins, there have been few attempts to define the entire human secretome.

In the paper, an analysis of all proteins predicted to be secreted in humans is presented. It suggests, somewhat surprisingly, that the number of proteins predicted to be secreted into blood is just around 700. This corresponds to less than 4% of all human protein-coding genes and is thus far less than previously estimated. Among the proteins identified are the classical plasma proteins, the inflammation proteins (cytokines and interleukins), well-known hormones and receptors, but also close to one hundred proteins with no known function yet.

A quest for the future

The proteins circulating in human blood were also analyzed to define those that have been detected by mass spectrometry–based proteomics and antibody-based immunoassay. The analysis revealed that assays are lacking for a large fraction of the secreted blood proteins. A quest for the future is therefore to extend the respective assays and measure all the actively secreted proteins, providing a secretome-wide tool box of assays for the proteins in the blood and accelerate the possibilities to study human health and diseases.

The results are presented in an updated version 19 of the Human Protein Atlas to provide an open-access knowledge resource of the human secretome to facilitate basic and applied research involving this important class of proteins.

“We are excited to provide to the research community with this open access resource to facilitate future efforts to understand human biology and to improve patient care, in particular in fields such as immune-based therapies and blood-based assays,” says Mathias Uhlen, Director of the Human Protein Atlas program and senior author on the paper.

The work was funded by the Erling Persson Foundation and the Knut and Alice Wallenberg Foundation.

Source: SciLifeLab

Photo of Mathias Uhlén: KTH/Jens Lasthein

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