How many human proteoforms are there?

Ruedi Aebersold; Jeffrey N Agar; I Jonathan Amster; Mark S Baker; Carolyn R Bertozzi; Emily S Boja; Catherine E Costello; Benjamin F Cravatt; Catherine Fenselau; Benjamin A Garcia; Ying Ge; Jeremy Gunawardena; Ronald C Hendrickson; Paul J Hergenrother; Christian G Huber; Alexander R Ivanov; Ole N Jensen; Michael C Jewett; Neil L Kelleher; Laura L Kiessling; Nevan J Krogan; Martin R Larsen; Joseph A Loo; Rachel R Ogorzalek Loo; Emma Lundberg; Michael J MacCoss; Parag Mallick; Vamsi K Mootha; Milan Mrksich; Tom W Muir; Steven M Patrie; James J Pesavento; Sharon J Pitteri; Henry Rodriguez; Alan Saghatelian; Wendy Sandoval; Hartmut Schlüter; Salvatore Sechi; Sarah A Slavoff; Lloyd M Smith; Michael P Snyder; Paul M Thomas; Mathias Uhlén; Jennifer E Van Eyk; Marc Vidal; David R Walt; Forest M White; Evan R Williams; Therese Wohlschlager; Vicki H Wysocki; Nathan A Yates; Nicolas L Young; Bing Zhang

doi:10.1038/nchembio.2576

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Journal article

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How many human proteoforms are there?

Ruedi Aebersold, Jeffrey N Agar, I Jonathan Amster, Mark S Baker, Carolyn R Bertozzi, Emily S Boja, Catherine E Costello, Benjamin F Cravatt, Catherine Fenselau, Benjamin A Garcia, …

Nature chemical biology, Vol.14(3), pp.206-214

2018-02-14

DOI: https://doi.org/10.1038/nchembio.2576

PMID: 29443976

Abstract

Databases, Protein

Genome, Human

Humans

Mass Spectrometry

Phenotype

Protein Biosynthesis

Protein Isoforms - chemistry

Protein Processing, Post-Translational

Proteins - chemistry

Proteome - chemistry

Proteomics - methods

Ubiquitin - chemistry

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.

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Title: How many human proteoforms are there?
Creators: Ruedi Aebersold - ETH Zurich
Jeffrey N Agar - Northeastern University
I Jonathan Amster - University of Georgia
Mark S Baker - Macquarie University
Carolyn R Bertozzi - Stanford University
Emily S Boja - Cancer Clinic
Catherine E Costello - Boston University
Benjamin F Cravatt - Scripps Research Institute
Catherine Fenselau - University of Maryland, College Park
Benjamin A Garcia - University of Pennsylvania
Ying Ge - University of Wisconsin–Madison
Jeremy Gunawardena - Center for Systems Biology
Ronald C Hendrickson - Memorial Sloan Kettering Cancer Center
Paul J Hergenrother - University of Illinois Urbana-Champaign
Christian G Huber - University of Salzburg
Alexander R Ivanov - Northeastern University
Ole N Jensen - University of Southern Denmark
Michael C Jewett - Northwestern University
Neil L Kelleher - Northwestern University
Laura L Kiessling - Massachusetts Institute of Technology
Nevan J Krogan - University of California, San Francisco
Martin R Larsen - University of Southern Denmark
Joseph A Loo - University of California, Los Angeles
Rachel R Ogorzalek Loo - University of California, Los Angeles
Emma Lundberg - KTH Royal Institute of Technology
Michael J MacCoss - University of Washington
Parag Mallick - Stanford University
Vamsi K Mootha - Center for Systems Biology
Milan Mrksich - Northwestern University
Tom W Muir - Princeton University
Steven M Patrie - Northwestern University
James J Pesavento - Saint Mary's College of California
Sharon J Pitteri - Stanford University
Henry Rodriguez - Cancer Clinic
Alan Saghatelian - Salk Institute for Biological Studies
Wendy Sandoval - Abterra Biosciences
Hartmut Schlüter - University Medical Center Hamburg-Eppendorf
Salvatore Sechi - National Institute of Diabetes and Digestive and Kidney Diseases
Sarah A Slavoff - Yale University
Lloyd M Smith - Energy Center of Wisconsin
Michael P Snyder - Stanford University
Paul M Thomas - Northwestern University
Mathias Uhlén - KTH Royal Institute of Technology
Jennifer E Van Eyk - Cedars-Sinai Medical Center
Marc Vidal - Harvard University
David R Walt - Harvard University
Forest M White - Massachusetts Institute of Technology
Evan R Williams - University of California, Berkeley
Therese Wohlschlager - University of Salzburg
Vicki H Wysocki - The Ohio State University
Nathan A Yates - University of Pittsburgh
Nicolas L Young - Baylor College of Medicine
Bing Zhang - Baylor College of Medicine
Publication Details: Nature chemical biology, Vol.14(3), pp.206-214
Grant note: R01 GM021248 / NIGMS NIH HHS S10 OD019938 / NIH HHS P01 CA196539 / NCI NIH HHS R01 HL132075 / NHLBI NIH HHS P01 HL112730 / NHLBI NIH HHS P30 CA008748 / NCI NIH HHS P30 CA014195 / NCI NIH HHS R01 HL111362 / NHLBI NIH HHS R01 GM110174 / NIGMS NIH HHS P41 GM108569 / NIGMS NIH HHS
Academic Unit: Miller School of Medicine; Microbiology and Immunology Research; Biochemistry & Molecular Biology Research
Language: English
Resource Type: Journal article
PMID: 29443976
Record Identifier: 991032905813102976