How many human proteoforms are there?

TY - JOUR

T1 - How many human proteoforms are there?

AU - Aebersold, Ruedi

AU - Agar, Jeffrey N

AU - Amster, I Jonathan

AU - Baker, Mark S

AU - Bertozzi, Carolyn R

AU - Boja, Emily S

AU - Costello, Catherine E

AU - Cravatt, Benjamin F

AU - Fenselau, Catherine

AU - Garcia, Benjamin A

AU - Ge, Ying

AU - Gunawardena, Jeremy

AU - Hendrickson, Ronald C

AU - Hergenrother, Paul J

AU - Huber, Christian G

AU - Ivanov, Alexander R

AU - Jensen, Ole N

AU - Jewett, Michael C

AU - Kelleher, Neil L

AU - Kiessling, Laura L

AU - Krogan, Nevan J

AU - Larsen, Martin R

AU - Loo, Joseph A

AU - Ogorzalek Loo, Rachel R

AU - Lundberg, Emma

AU - MacCoss, Michael J

AU - Mallick, Parag

AU - Mootha, Vamsi K

AU - Mrksich, Milan

AU - Muir, Tom W

AU - Patrie, Steven M

AU - Pesavento, James J

AU - Pitteri, Sharon J

AU - Rodriguez, Henry

AU - Saghatelian, Alan

AU - Sandoval, Wendy

AU - Schlüter, Hartmut

AU - Sechi, Salvatore

AU - Slavoff, Sarah A

AU - Smith, Lloyd M

AU - Snyder, Michael P

AU - Thomas, Paul M

AU - Uhlén, Mathias

AU - Van Eyk, Jennifer E

AU - Vidal, Marc

AU - Walt, David R

AU - White, Forest M

AU - Williams, Evan R

AU - Wohlschlager, Therese

AU - Wysocki, Vicki H

AU - Yates, Nathan A

AU - Young, Nicolas L

AU - Zhang, Bing

PY - 2018/2/14

Y1 - 2018/2/14

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/nchembio.2576

DO - 10.1038/nchembio.2576

M3 - SCORING: Journal article

C2 - 29443976

VL - 14

SP - 206

EP - 214

JO - NAT CHEM BIOL

JF - NAT CHEM BIOL

SN - 1552-4450

IS - 3

ER -