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Updated: Jul 8, 2026

Nitropeptide Profiling and Identification Illustrated by Angiotensin II
Published on: June 16, 2019
Nitrotyrosine-modified SERCA2: a cellular sensor of reactive nitrogen species
1Cell Biology & Biochemistry, Biology Division, Pacific Northwest National Laboratory, P.O. Box 999, MS-P7-56, Richland, WA 99352, USA. diana.bigelow@pnl.gov
Abstract:
The endo-/sarcoplasmic reticulum Ca(2+)-Mg(2+)-adenosine triphosphatase (SERCA2) isoform of the sarco/endoplasmic reticulum Ca(2+)-ATPase is sensitive to cellular conditions of inflammation and oxidative stress as evidenced by the common appearance of 3-nitrotyrosine-modified forms of SERCA2 in aging and disease in both striated and smooth muscle of humans and rodent models. Structure-function studies of nitrated SERCA2 in aging heart and skeletal muscle demonstrate stoichiometric nitration of vicinal tyrosines, Tyr(294) and Tyr(295), on the lumenal side of the membrane-spanning helix, M4, which correlates with partial inhibition of Ca(2+)-ATPase activity suggesting a possible regulatory function in down-regulating mitochondrial energy production and the associated generation of reactive oxygen/nitrogen species. This review discusses recent work regarding the nitrative and oxidative sensitivity of SERCA2 in muscle with respect to general cellular mechanisms of turnover and repair of modified proteins.
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