1.A.17.1.30
Anoctamin-8, Ano8 or TMEM16H, of 1232 aas and 9 TMSs. It tethers the endoplasmic reticulum and plasma membrane for assembly of Ca²⁺ signaling complexes at the ER/PM compartment (Jha et al. 2019). ANO8 is a key tether in the formation of the ER/PM junctions that are essential for STIM1-STIM1 interaction and STIM1-Orai1 interaction and channel activation at a ER/PM PI(4,5)P₂-rich compartment. Moreover, ANO8 assembles all core Ca²⁺ signaling proteins: Orai1, PMCA, STIM1, IP₃ receptors, and SERCA2 at the ER/PM junctions to mediate a novel form of Orai1 channel inactivation by markedly facilitating SERCA2-mediated Ca²⁺ influx into the ER. This controls the efficiency of receptor-stimulated Ca²⁺ signaling, Ca²⁺ oscillations, and the duration of Orai1 activity to prevent Ca²⁺ toxicity (Jha et al. 2019).