SARAF is an endoplasmic reticulum membrane resident protein that serves as a negative regulator of store-operated Ca2+ entry (SOCE) involved in protecting cells from Ca2+ overfilling. It is a single pass ER membrane protein whose systolic-facing domain is responsible for activity and whose luminary-facing domain carries out a regulatory function in conjunction with another membrane protein STIM, an ER single pass membrane protein that detects changes in ER Ca2+ levels through its EF-hand, conserved Ca2+ binding domain. STIM is the major target for SARAF regulation, and thus SARAF negatively regulates the SOCE entry of calcium into cells protecting them from overfilling [].
