STIM1 is cleaved by calpain.

Store-operated calcium entry (SOCE) is a pathway that moves Ca(2+) across the plasma membrane and is mediated by two major proteins, STIM1 and Orai1. Here, we discovered that the cytoplasmic domain of STIM1 is a target for calpains, a family of Ca(2+)-activated proteases. We found that calpain cleavage of STIM1 serves to control its cellular abundance and was noticeably increased under conditions of cellular stress and apoptosis. Dysregulation of STIM1 levels has been reported to have human disease consequences and our results suggest a mechanism for controlling STIM1 abundance.