Title | How many human proteoforms are there? |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Aebersold, R, Agar, JN, I Amster, J, Baker, MS, Bertozzi, CR, Boja, ES, Costello, CE, Cravatt, BF, Fenselau, C, Garcia, BA, Ge, Y, Gunawardena, J, Hendrickson, RC, Hergenrother, PJ, Huber, CG, Ivanov, AR, Jensen, ON, Jewett, MC, Kelleher, NL, Kiessling, LL, Krogan, NJ, Larsen, MR, Loo, JA, Loo, RROgorzale, Lundberg, E, MacCoss, MJ, Mallick, P, Mootha, VK, Mrksich, M, Muir, TW, Patrie, SM, Pesavento, JJ, Pitteri, SJ, Rodriguez, H, Saghatelian, A, Sandoval, W, Schlüter, H, Sechi, S, Slavoff, SA, Smith, LM, Snyder, MP, Thomas, PM, Uhlén, M, Van Eyk, JE, Vidal, M, Walt, DR, White, FM, Williams, ER, Wohlschlager, T, Wysocki, VH, Yates, NA, Young, NL, Zhang, B |
Journal | Nat Chem Biol |
Volume | 14 |
Issue | 3 |
Pagination | 206-214 |
Date Published | 2018 02 14 |
ISSN | 1552-4469 |
Keywords | Databases, Protein, Genome, Human, Humans, Mass Spectrometry, Phenotype, Protein Biosynthesis, Protein Isoforms, Protein Processing, Post-Translational, Proteins, Proteome, Proteomics, Ubiquitin |
Abstract | <p>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.</p> |
DOI | 10.1038/nchembio.2576 |
Alternate Journal | Nat Chem Biol |
PubMed ID | 29443976 |
PubMed Central ID | PMC5837046 |
Grant List | P01 CA196539 / CA / NCI NIH HHS / United States P41 GM108569 / GM / NIGMS NIH HHS / United States R01 GM114292 / GM / NIGMS NIH HHS / United States P30 CA014195 / CA / NCI NIH HHS / United States P01 HL112730 / HL / NHLBI NIH HHS / United States R01 HL132075 / HL / NHLBI NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States S10 OD019938 / OD / NIH HHS / United States R01 AI118891 / AI / NIAID NIH HHS / United States R01 GM110174 / GM / NIGMS NIH HHS / United States R01 GM115739 / GM / NIGMS NIH HHS / United States R01 GM021248 / GM / NIGMS NIH HHS / United States |