Proteomics and the human proteome project may help to estimate the total number of proteins and their functions.
The Human Proteome Project (HPP) is a collaborative effort coordinated by the Human Proteome Organization (HUPO) with the stated goal of experimentally observing all of the proteins produced by the sequences translated from the human genome (Mol Cell Proteomics. 10:M111.009993 (2011). Human proteome projects are of course useful but should include ideally include RNA as well. It makes sense to encourage multiple groups and countries to collaborate to make progress on large and complex problems. For example, we do not know the activities or state of many human proteins. Even for microbial systems the metalloproteome is largely unknown (Nature 2010 466, 779-82), so the status on metal ions and their functions in human proteins is far from defined and may be misunderstood from recombinant metal ion artifacts. Such knowledge effects metal ion needs for nutrition, pathogens responses, and disease states spanning from cancer to neurodegenerative diseases. The current project focus involves Mass Spectrometry (MS), Antibodies (Abs), and the Knowledgebase (KB). This gives the current project a top-down emphasis. With high throughput structural methods such as small angle X-ray scattering (SAXS), it should be possible to add efforts to define the shape, assembly, conformational states, and interactions of human proteins and their complexes (Nature Methods 2009 6, 606-12). Such bottom up mechanistic approaches would be useful to understand and predict biological outcomes from disease, environmental stress, and aging. In general there is a need to deal with the growing gap between sequence information and experimental structures that methods such as SAXS could reduce (Annu Rev Biophys. 2013 42, 415-41).
One of the great advantages of these projects is that their scale and ambition often helps to drive methodological improvements. This was certainly the case for the Human Genome Project, and some of the Structural Genomics approaches. The protein level is in dire need of tool improvements to help keep up with the vast quantity of nucleic acid data that is being produced. Hopefully this project will provide protein science with some wonderful new tools as a side-product.
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