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How many human proteoforms are there?
Nature Chemical Biology ( IF 12.9 ) Pub Date : 2018-02-14 , DOI: 10.1038/nchembio.2576
Ruedi Aebersold 1 , Jeffrey N Agar 2 , I Jonathan Amster 3 , Mark S Baker 4 , Carolyn R Bertozzi 5 , Emily S Boja 6 , Catherine E Costello 7 , Benjamin F Cravatt 8 , Catherine Fenselau 9 , Benjamin A Garcia 10 , Ying Ge 11, 12 , Jeremy Gunawardena 13 , Ronald C Hendrickson 14 , Paul J Hergenrother 15 , Christian G Huber 16 , Alexander R Ivanov 2 , Ole N Jensen 17 , Michael C Jewett 18 , Neil L Kelleher 19 , Laura L Kiessling 20 , Nevan J Krogan 21 , Martin R Larsen 17 , Joseph A Loo 22 , Rachel R Ogorzalek Loo 22 , Emma Lundberg 23, 24 , Michael J MacCoss 25 , Parag Mallick 5 , Vamsi K Mootha 13 , Milan Mrksich 18 , Tom W Muir 26 , Steven M Patrie 19 , James J Pesavento 27 , Sharon J Pitteri 5 , Henry Rodriguez 6 , Alan Saghatelian 28 , Wendy Sandoval 29 , Hartmut Schlüter 30 , Salvatore Sechi 31 , Sarah A Slavoff 32 , Lloyd M Smith 12, 33 , Michael P Snyder 24 , Paul M Thomas 19 , Mathias Uhlén 34 , Jennifer E Van Eyk 35 , Marc Vidal 36 , David R Walt 37 , Forest M White 38 , Evan R Williams 39 , Therese Wohlschlager 16 , Vicki H Wysocki 40 , Nathan A Yates 41 , Nicolas L Young 42 , Bing Zhang 42
Affiliation  

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.



中文翻译:

人类有多少种蛋白质?

尽管几十年来积累了有关蛋白质及其翻译后修饰 (PTM) 的知识,但有关其分子组成和生物功能的许多问题仍然存在。最基本的问题之一是 DNA、RNA 和 PTM 水平变异的组合在多大程度上会导致人类蛋白质组的复杂性爆炸。在这里,我们概述了我们从当前数据库和测量策略(包括基于质谱的蛋白质组学)中了解到的信息。在此过程中,我们研究了关于人类蛋白质上显示的修饰数量以及它们如何结合以产生健康和疾病背后的蛋白质多样性的流行观念。我们提出了有关确定蛋白质水平变异和 PTM 的核心问题,包括当今该领域存在的一些悖论。我们使用这个框架来评估现有数据并提出以下问题:“20,300 个人类基因创建了多少种不同的蛋白质一级结构(蛋白质形式)?” 我们还探索了改进测量的前景,以更好地规范蛋白质水平生物学并有效地将 PTM 与功能和表型相关联。

更新日期:2018-02-14
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