The SERCA pump is localized to the Sarcoplasmic Reticulum (SR) membrane and is responsible for pumping calcium ions back into the SR following muscle contraction. SERCA is an ATPase pump and is thus powered by energy from ATP hydrolysis, allowing it to establish a concentration gradient of calcium across the SR membrane. It is typically characterized by its three cytosolic domains, canonically labeled "N", where nucleotide binding occurs, "A", the actuator domain, and "P", where phosphorylation occurs . After nucleotide binding to the N domain, the N and A domains move within a closer proximity and phosphorylation occurs at ASP351, which allows for further conformational changes in the protein, eventually leading to calcium release into the SR . Further, SERCA contains 10 transmembrane helices, typically labeled M1 through M10, where calcium binding occurs . Specifically, calcium from the cytosol binds between helices M4, M5, M6, and M8. Helices M1 and M2 make up part of the calcium entry pathway into these binding sites . Two calcium ions bind per hydrolyzed ATP, at two sites within this region. Calcium binds cooperatively, and binding of calcium to the first binding site increases the affinity of the second binding site for calcium .