Store-operated calcium entry-associated regulatory factor (SARAF)

Store-operated calcium entry-associated regulatory factor (SARAF) is a single-pass transmembrane protein primarily located in the endoplasmic reticulum membrane, encoded by the SARAF gene (previously TMEM66). SARAF plays a crucial regulatory role in intracellular calcium signaling by facilitating the slow calcium-dependent inactivation (SCDI) of store-operated calcium entry (SOCE), thus protecting cells from calcium overload. SARAF interacts with stromal interaction molecule 1 (STIM1) and Orai1 to modify calcium channel states, affecting both store-operated (CRAC) and store-independent (ARC) calcium channels. It functions as a negative regulator of cytosolic calcium signals and is also involved in shaping the amplitude and duration of calcium entry in response to stimuli. Altered SARAF expression influences cell survival pathways in cancer models and modulates response to agents such as arachidonic acid and retinoic acid, potentially impacting disease processes in cancer and possibly neurodegeneration[1][2][3].

Other names

TMEM66FOAP-7XTP3HSPC035NPD003PSEC0019UNQ1967/PRO4499SOCE-associated regulatory factorMGC8721HBV X-transactivated gene 3 proteinHBV XAg-transactivated protein 3testicular secretory protein Li 59Transmembrane protein 66

Not typically a direct drug target; functions by interacting with STIM1, Orai1, and ARC channel subunits to regulate calcium channel inactivation/activation[2][3]