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Ubiquitin is a carbon dioxide-binding protein

Linthwaite, V.L.; Pawloski, W.; Pegg, H.B.; Townsend, P.D.; Thomas, M.J.; Brown, A.P.; Hodgson, D.R.W.; Lorimer, G.H.; Fushman, D.; Cann, M.J.

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V.L. Linthwaite

W. Pawloski

H.B. Pegg

P.D. Townsend

M.J. Thomas

G.H. Lorimer

D. Fushman


The identification of CO2-binding proteins is crucial to understanding CO2-regulated molecular processes. CO2 can form a reversible posttranslational modification through carbamylation of neutral N-terminal -amino or lysine -amino groups. We have previously developed triethyloxonium (TEO) ion as a chemical proteomics tool for covalent trapping of carbamates, and here, we deploy TEO to identify ubiquitin as a mammalian CO2-binding protein. We use 13C-NMR spectroscopy to demonstrate that CO2 forms carbamates on the ubiquitin N terminus and -amino groups of lysines 6, 33, 48, and 63. We demonstrate that biologically relevant pCO2 levels reduce ubiquitin conjugation at lysine-48 and down-regulate ubiquitin-dependent NF-B pathway activation. Our results show that ubiquitin is a CO2-binding protein and demonstrates carbamylation as a viable mechanism by which mammalian cells can respond to fluctuating pCO2


Linthwaite, V., Pawloski, W., Pegg, H., Townsend, P., Thomas, M., Brown, A., …Cann, M. (2021). Ubiquitin is a carbon dioxide-binding protein. Science Advances, 7(39), Article eabi5507.

Journal Article Type Article
Acceptance Date Nov 26, 2020
Online Publication Date Sep 24, 2021
Publication Date 2021-09
Deposit Date Nov 26, 2020
Publicly Available Date Oct 7, 2021
Journal Science Advances
Publisher American Association for the Advancement of Science
Peer Reviewed Peer Reviewed
Volume 7
Issue 39
Article Number eabi5507
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Published Journal Article (520 Kb)

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Copyright Statement
Copyright © 2021
The Authors, some
rights reserved;
exclusive licensee
American Association
for the Advancement
of Science. No claim to
original U.S.Government
Works. Distributed
under a Creative
Commons Attribution
License 4.0 (CC BY).

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