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CRACR2A is a Ca(2+)-binding protein that plays a key role in store-operated Ca(2+) entry (SOCE) in T-cells by regulating CRAC channel activation. CRACR2A acts as a cytoplasmic calcium-sensor that facilitates the clustering of ORAI1 and STIM1 at the junctional regions between the plasma membrane and the endoplasmic reticulum upon low Ca(2+) concentration. Further, CRACR2A regulates CRAC channel activation, including translocation and clustering of ORAI1 and STIM1. Upon increase of cytoplasmic Ca(2+) resulting from opening of CRAC channels, CRACR2A dissociates from ORAI1 and STIM1, thereby destabilizing the ORAI1-STIM1 complex.
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