Apr 13, 2012 · Using a functional-based high-throughput screen, we have identified the gene product of TMEM66, named hereafter as SARAF (for SOCE-associated regulatory factor) as a regulator of cellular Ca 2+ homeostasis. SARAF is a highly conserved protein in vertebrates and has poor functional annotation.

Apr 13, 2012 · STIM and Orai proteins have been identified as the essential components enabling the reconstitution of Ca(2+) release-activated Ca(2+) (CRAC) channels that mediate SOCE. Here, we report the molecular identification of SARAF as a negative regulator of SOCE.

Apr 12, 2016 · Here we present evidence for the dynamic interaction between the SOCE-associated regulatory factor (SARAF), STIM1 and Orai1. SARAF overexpression attenuated SOCE and the STIM1-Orai1...

The identification of the SOCE-associated regulatory factor (SARAF) and investigations of its role in SCDI have led to new functional and molecular insights into how SOCE is controlled. In this review, we provide an overview of the functional and molecular mechanisms underlying SCDI and discuss how the interaction between SARAF, STIM1, and ...

In this study we show that SARAF is an ER resi-dent protein, which responds to cytosolic Ca2+elevation after ER Ca2+ refilling by promoting a slow inactivation process of STIM2-dependent basal SOCE activity, as well as STIM1-medi-ated SOCE activity.

Sep 1, 2021 · Store-operated calcium entry-associated regulatory factor (SARAF) can downregulate SOCE. We sought to investigate the role of SARAF in the regulation of airway inflammation and remodeling in asthma mice models, as well as in the functional regulation of human airway smooth muscle cells (hASMCs).

Aug 19, 2021 · SARAF knockdown significantly enhances SOCE in MCF10A and MDA-MB-231 cells (Figure 2 c,e,f,h; n = 40 cells/day/3–5 days), which is compatible with a role of SARAF in cells where SOCE is predominantly mediated by STIM1 and Orai1 [13,16].

Feb 8, 2024 · The SOCE-Associated Regulatory Factor (SARAF) is the main Orai1-STIM1 regulator by inhibiting STIM1 activation, clustering, and potentiating Orai1-STIM1 Ca 2+-dependent inactivation mechanisms. As such, SARAF-STIM1 interaction constitutes the main molecular inhibitory checkpoint for SOCE regulation.

Mar 25, 2016 · SARAF is a 339 amino acid endoplasmic reticulum (ER)-resident protein that associates with STIM to facilitate slow Ca 2+ -dependent inactivation of store-operated Ca 2+ entry (SOCE), prevent STIM1 spontaneous activation and promote STIM1 deoligomerization after Ca 2+ store refilling.

Aug 10, 2020 · SOCE is negatively regulated by SOCE-associated regulatory factor (SARAF), an ER membrane protein that associates with STIM1 to facilitate a slow form of Ca 2+-dependent inactivation of SOCE, thus preventing excess Ca 2+ refilling and maintain proper intracellular Ca 2+ levels (Palty et al., 2012).