How many human proteoforms are there? Journal Article

Authors: Aebersold, R.; Agar, J. N.; Amster, I. J.; Baker, M. S.; Bertozzi, C. R.; Boja, E. S.; Costello, C. E.; Cravatt, B. F.; Fenselau, C.; Garcia, B. A.; Ge, Y.; Gunawardena, J.; Hendrickson, R. C.; Hergenrother, P. J.; Huber, C. G.; Ivanov, A. R.; Jensen, O. N.; Jewett, M. C.; Kelleher, N. L.; Kiessling, L. L.; Krogan, N. J.; Larsen, M. R.; Loo, J. A.; Ogorzalek Loo, R. R.; Lundberg, E.; MacCoss, M. J.; Mallick, P.; Mootha, V. K.; Mrksich, M.; Muir, T. W.; Patrie, S. M.; Pesavento, J. J.; Pitteri, S. J.; Rodriguez, H.; Saghatelian, A.; Sandoval, W.; Schlüter, H.; Sechi, S.; Slavoff, S. A.; Smith, L. M.; Snyder, M. P.; Thomas, P. M.; Uhlén, M.; Van Eyk, J. E.; Vidal, M.; Walt, D. R.; White, F. M.; Williams, E. R.; Wohlschlager, T.; Wysocki, V. H.; Yates, N. A.; Young, N. L.; Zhang, B.
Article Title: How many human proteoforms are there?
Abstract: Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype. © Nature Publishing Group 2018. All rights reserved.
Keywords: review; protein function; phenotype; gene; protein; assay; rna; dna; protein processing; protein synthesis; protein structure; reagent; human; priority journal
Journal Title: Nature Chemical Biology
Volume: 14
Issue: 3
ISSN: 1552-4450
Publisher: Nature Publishing Group  
Date Published: 2018-03-01
Start Page: 206
End Page: 214
Language: English
DOI: 10.1038/nchembio.2576
PROVIDER: scopus
PMCID: PMC5837046
PUBMED: 29443976
Notes: Review -- Export Date: 1 March 2018 -- Source: Scopus
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