All proteins on one site
Atlas of human proteins has been created
Photos from the website proteinatlas.orgThe efforts of a large group of specialists have brought together all the available data on the proteins of the human body and their number in different tissues and cells.
As a result, an interactive "Atlas of Human Proteins" became available – an electronic resource that allows you to see all the information on all specific proteins, and not only literary data, but also the author's experimental research on the evaluation of the volumes of tissue-specific proteins and corresponding transcripts. This product is very promising for the search for new drugs that can balance the metabolism disrupted by the disease.
We have already gone very far from seeing man as a vessel with four harmoniously balanced fluids – blood, phlegm, black and yellow bile – and four elements – air, water, earth and fire. Now a person is a vessel with a thousand interacting chemical substances, naturally placed in this complex vessel. In order for movement to continue in this vessel, an exact coordination of each of the substances is needed; the addition of one substance in one place or another will cause a small shift in another, and this will cascade through the whole body. Any chemical intervention (read – eating or taking medications) requires knowledge about such cascading risks, and with time and space scans. We need accurate small-scale maps of these chemical interactions. And they are created, such maps.
In fact, their time has come now – there are both tools and resources for their creation, and their exceptional relevance is also clear. We are constantly being informed about the start or completion of projects aimed at creating genetic and metabolic patterns of interaction in the human body. We have already told readers about some of them. So, in the course of work on the ENCODE project, an encyclopedia of human gene functions is being created. The FANTOM project is aimed at identifying tissue-specific genes and determining the level of their expression in various tissues. Also important is a project to study the entire array of specific and non-specific metabolites (metabolome) in various tissues and organs.
If genes are the starting point of human biochemistry, then metabolites are the end point of the path: what is tracked during the synthesis of the main cellular product – building and membrane proteins and enzymes. And the squirrels themselves? How are they distributed in cellular tissues?
To outline the distribution of proteins and their corresponding transcripts in various tissues of the human body is the goal of the international Human Proteome Project and its part – The Human Protein Atlas ("Atlas of Human Proteins").
Within the framework of this project, the Atlas of Human Proteins, an inventory of human proteins was carried out: where, how many and which proteins are synthesized in the adult human body. The routine method of protein determination and estimation of their quantity was carried out using immunohistochemical analyses of individual cells in combination with quantitative analysis of transcripts (matrix RNAs) in individual tissues. About 13 million immunotests involving the verification of 17 thousand protein-coding genes and 24 thousand transcripts themselves in 44 types of tissues – this is the approximate amount of work carried out by the project participants.
Tissues and organs for which lists of proteins have been compiled and their relative amount has been estimated; tissues where only immunohistochemical methods were used (only for proteins) are marked in gray, and those for which both protein and their mRNA were determined are marked in black. A drawing from the discussed article in ScienceThis colossal work makes it possible to look in general at the protein universe of man.
Here you can view this universe from all sides, at different levels of detail, from the general characteristics to the proteins of individual organs, tissues and cells, with all possible literary sources. Specialists related to this field of knowledge will certainly use this voluminous resource, especially since it is freely available. And what is useful for non-specialists to know about this work?
The authors of the project, with a full understanding of the enormous prospects – both academic and practical – of their capital work, pointed out several important conclusions. So, in various human tissues, about 8.8 thousand similar protein-coding genes work in each cell (this is about 44% of all protein-coding genes and 42% of the proteins themselves), and their relative number is approximately the same. These are the proteins that are needed to maintain the existence of the cell itself. 60% of them are proteins that serve cellular metabolism. These are the proteins that should be paid attention to when analyzing the general features of the functioning of living cells and their evolution.
The ratio of protein-coding genes that are expressed the same in all tissues (blue) and those that have an increased level of expression in various tissues: purple – the amount of mRNA is 5 times higher than the maximum level for other tissues, yellow – the amount of mRNA for a small group of tissues is five times higher than on average for all tissues, red is a slightly elevated level compared to the average for all tissues. A drawing from the discussed article in ScienceOf the remaining protein-coding genes, 34% have an increased level of expression in certain tissues.
These are genes that determine the functional specifics of organs and tissues. The tissues of the testes, liver and skeletal muscles are most distinguished by this feature. At the same time, according to the total volume of all tissue-specific transcripts, the liver and pancreas win, the muscles, brain and testes are behind them. The meaning of this difference will be discussed in future papers. It is important to take into account which proteins create a characteristic protein portrait of certain tissues, general reasoning in this case is meaningless.
The number of mRNAs (expressed as FPKM – Fragments Per Kilobase Of Exon Per Million Fragments Mapped) for tissue-specific genes (those that are more intensively expressed in a particular tissue than others). The results for 13 tissues are shown. It can be seen that out of these 13 variants, the testes, brain and liver are especially distinguished; the proportion of membrane proteins in the brain is increased, in the liver – those that are released from the cell, in the testes – the proportion of soluble proteins. A drawing from the discussed article in ScienceA review of tissue-specific proteins allowed us to draw some conclusions regarding the drugs used.
About a third (30%) of drugs aimed at working with specific proteins in specific tissues are not actually tissue-specific. Their intended targets are in fact equally present in all other tissues. This means that these 30% of medications can have many side effects. But pharmacologists working with new drugs are given the opportunity to choose new tissue-specific targets and select effective regulators for them. According to the authors of the project, there are about a thousand proteins promising for the search for new drugs (see the section The druggable proteome).
Source: Mathias Uhlen et al., Tissue-based map of the human proteome // Science. 2015. V. 347. P. 394.
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