How many human proteoforms are there?

TitleHow many human proteoforms are there?
Publication TypeJournal Article
Year of Publication2018
AuthorsAebersold, 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
JournalNat Chem Biol
Volume14
Issue3
Pagination206-214
Date Published2018 02 14
ISSN1552-4469
KeywordsDatabases, 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>

DOI10.1038/nchembio.2576
Alternate JournalNat. Chem. Biol.
PubMed ID29443976
PubMed Central IDPMC5837046
Grant ListP01 CA196539 / CA / NCI NIH HHS / United States
P41 GM108569 / GM / NIGMS NIH HHS / United States
R01 GM114292 / GM / NIGMS 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