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).