1.A.52.1.2
The ARC (Arachidonate-regulated Ca²⁺-selective) channel, a complex of STIM1, Orai1 and Orai3 (Mignen et al., 2008). It is a heteropentameric assembly of three Orai1 subunits and two Orai3 subunits (Mignen et al., 2009). (But see Demuro et al., 2011; 1.A.52.1.1). Molecular determinants within the N-terminus control channel activation and gating (Bergsmann et al., 2011).  Specifically activated by high concentrations (>50 microM) of 2-aminoethyl diphenylborinate (2-APB) (Amcheslavsky et al. 2014).  The CC1-SOAR region of STIM1 is a direct activation domain of temperature, leading to subsequent STIM1 activation, and the transmembrane (TM) region and K domain but not EF-SAM region were needed for this process. Furthermore, both the TM and SOAR domains exhibited similarities and differences between STIM1-mediated thermal sensation and store-operated calcium entry (SOCE), and the key sites of Orai1 showed similar roles in these two responses. Additionally, the TM23 (comprising TM2, loop2, and TM3) region of Orai1 was identified as the key domain determining the STIM1/Orai1 thermal response pattern (Liu et al. 2023).