8.A.111.  The Store-operated Ca²⁺ Entry-associated Regulatory Factor (SARAF) Family. 

Members of this family can be found in animals and many other eukaryotes of many types, but not in prokaryotes. SARAF is a negative regulator of store-operated Ca²⁺ entry (SOCE) involved in protecting cells from Ca²⁺ overfilling. In response to cytosolic Ca²⁺ elevation after endoplasmic reticulum Ca²⁺ refilling, a slow inactivation of STIM (STIM1 or STIM2)-dependent SOCE activity occurs. This mechanisms possibly acts by facilitating the deoligomerization of STIM to efficiently turn off ORAI when the endoplasmic reticulum lumen is filled with the appropriate Ca²⁺ levels. It would thus prevent the overload of the cell with excessive Ca²⁺ ions (Dai et al. 2018). Overexpressing SARAF ameliorates pressure overload-induced cardiac hypertrophy through supprssing STIM1-Orai in mice. Thus, overexpression of SARAF in the heart prevents cardiac hypertrophy, probably by suppressing the upregulation of STIM1/Orai1 (Dai et al. 2018).