Difference and similarity between the ubiquitous secretory pathway Ca2+-ATPases, SERCA2b, and SPCA1a

P1B-type and P2-type ATPases play fundamental roles in maintaining intracellular metal ion homeostasis, which is essential for various cellular processes including protein folding, trafficking and signaling. SERCA2b, a member of the P2A-type subfamily, pumps Ca2+ into the endoplasmic reticulum (ER) lumen, whereas SPCA1a, which also belongs to the P2A-type subfamily, mediates the transport of both Ca2+ and Mn2+ into the Golgi apparatus. With recent advances in their structural studies, researchers, including ourselves, have thoroughly characterized high-energy intermediates of these two Ca2+ pumps, which likely serve to facilitate transitions during the catalytic cycle by conformationally bridging the preceding and subsequent reaction states. In addition, we present a comparative analysis of the differences in cytosolic-domain rearrangements and transmembrane helix movements during the Ca2+ transport cycle, highlighting distinct metal ion transport mechanisms and kinetics between SERCA2b and SPCA1a. Notably, we identify unique structural elements involved in Ca2+ release and propose a potential SPCA1a-specific Ca2+ release pathway. The present review provides insights into the subfamily-specific variations in Ca2+ pump mechanisms.