@article{3251, keywords = {Protein Biosynthesis, Humans, Mass Spectrometry, Phenotype, Protein Processing, Post-Translational, Proteomics, Proteome, Databases, Protein, Proteins, Genome, Human, Ubiquitin, Protein Isoforms}, author = {Ruedi Aebersold and Jeffrey Agar and I Jonathan Amster and Mark Baker and Carolyn Bertozzi and Emily Boja and Catherine Costello and Benjamin Cravatt and Catherine Fenselau and Benjamin Garcia and Ying Ge and Jeremy Gunawardena and Ronald Hendrickson and Paul Hergenrother and Christian Huber and Alexander Ivanov and Ole Jensen and Michael Jewett and Neil Kelleher and Laura Kiessling and Nevan Krogan and Martin Larsen and Joseph Loo and Rachel Loo and Emma Lundberg and Michael MacCoss and Parag Mallick and Vamsi Mootha and Milan Mrksich and Tom Muir and Steven Patrie and James Pesavento and Sharon Pitteri and Henry Rodriguez and Alan Saghatelian and Wendy Sandoval and Hartmut Schl{\"u}ter and Salvatore Sechi and Sarah Slavoff and Lloyd Smith and Michael Snyder and Paul Thomas and Mathias Uhl{\'e}n and Jennifer Van Eyk and Marc Vidal and David Walt and Forest White and Evan Williams and Therese Wohlschlager and Vicki Wysocki and Nathan Yates and Nicolas Young and Bing Zhang}, 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.
}, year = {2018}, journal = {Nat Chem Biol}, volume = {14}, pages = {206-214}, month = {2018 Feb 14}, issn = {1552-4469}, doi = {10.1038/nchembio.2576}, language = {eng}, }