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).
References:
Dai, F., Y. Zhang, Q. Wang, Li, Y. Yang, S. Ma, and D. Yang. (2018). Overexpression of SARAF Ameliorates Pressure Overload-Induced Cardiac Hypertrophy Through Suppressing STIM1-Orai1 in Mice. Cell Physiol Biochem 47: 817-826.
Saldías, M.P., P. Cruz, I. Silva, O. Orellana-Serradell, B. Lavanderos, D. Maureira, R. Pinto, and O. Cerda. (2023). The Cytoplasmic Region of SARAF Reduces Triple-Negative Breast Cancer Metastasis through the Regulation of Store-Operated Calcium Entry. Int J Mol Sci 24:.
Yang, J., S. Li, Q. Wang, and D. Yang. (2019). Transmembrane protein 66 attenuates neointimal hyperplasia after carotid artery injury by SOCE inactivation. Mol Med Rep 20: 1436-1442.
Examples:
TC#	Name	Organismal Type	Example
8.A.111.1.1	Store operated calcium entry (SOCE)-associated regulatory factor, SARAF, ia of 339 aas with 2 or 3 TMSs. Overexpression of SARAF in the heart prevents cardiac hypertrophy, probably through suppressing the upregulation of STIM1/Orai1 (Dai et al. 2018). TMEM66 attenuates neointimal hyperplasia after carotid artery injury by store operated calcium entry (SOCE) inactivation. It confers vascular protection against balloon injury (Yang et al. 2019). Regulating the activity of the SOCE response via SARAF activity may allow therapeutic strategies for triple-negative breast cancer (Saldías et al. 2023).		SARAF of Homo sapiens

8.A.111.1.2	SARAF of 316 aas and 2 or 3 TMSs.		SARAF of Caenorhabditis elegans

8.A.111.1.3	DUF1183 domain-containing protein of 357 aas and 2 TMSs.		SARAF homologue of Neurospora crassa

8.A.111.1.4	Uncharacterized protein of 299 aas and 3 TMSs.		UP of Chondrus crispus (Carrageen Irish moss) (Polymorpha crispa)

8.A.111.1.5	Uncharacterized protein of 253 aas and 2 or 3 TMSs.		UP of Bifiguratus adelaidae

8.A.111.1.6	Uncharacterized protein of 765 aas and 2 or 3 TMSs		UP of Tropilaelaps mercedesae

8.A.111.1.7	Uncharacterized protein of 310 aas and 3 TMSs		UP of Chara braunii

8.A.111.1.8	Uncharacterized protein of 351 aas and 2 TMSs		UP of Ectocarpus siliculosus

8.A.111.1.9	Uncharacterized protein of 802 aas and 2 TMSs.		UP of Crassostrea virginica