Figure 6.

Mammalian SERCA2 oxidation at the cytosolic Cys674 modulates Ca²⁺ uptake into the ER in response to nitric oxide (NO). Cys674 (red circle) is located within the SERCA2 P domain, between the nucleotide binding domain (N) and the transmembrane domains (TMDs). The presence of NO in combination with cellular ROS and reduced glutathione results in SERCA2 glutathionylation (–SSG) and increased pumping of Ca²⁺ from the cytosol into the ER lumen. An accumulation of sulfonylated SERCA2 (–SO₃H) is associated with a lack of responsiveness to NO and various disease pathologies, including artherosclerosis. A, actuator domain.