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1.A.106 The Calcium Load-activated Calcium Channel (CLAC) Family 

Maintaining homeostasis of Ca2+ stores in the endoplasmic reticulum (ER) is crucial for proper Ca2+ signaling and key cellular functions. The Ca2+-release-activated Ca2+ (CRAC) channel is responsible for Ca2+ influx and refilling after store depletion. Transmembrane and coiled-coil domains protein 1 (TMCO1) is an ER transmembrane protein with 3 TMSs that actively prevents Ca2+ stores from overfilling, acting as a 'Cacium Load-activated Calcium channel' or 'CLAC' channel. TMCO1 undergoes reversible homotetramerization in response to ER Ca2+ overloading and disassembly upon Ca2+ depletion and forms a Ca2+-selective ion channel in liposomes. TMCO1 knockout mice reproduce the main clinical features of human cerebrofaciothoracic (CFT) dysplasia spectrum, a developmental disorder linked to TMCO1 dysfunction, and exhibit severe mishandling of ER Ca2+ in cells. Thus, TMCO1 provides a protective mechanism to prevent overfilling of ER stores with Calcium ions (Wang et al. 2016).  The CLAC Family was formerly the DUF106 Family.

References associated with 1.A.106 family:

Sun, Z., H. Zhang, X. Wang, Q.C. Wang, C. Zhang, J.Q. Wang, Y.H. Wang, C.Q. An, K.Y. Yang, Y. Wang, F. Gao, C. Guo, and T.S. Tang. (2018). TMCO1 is essential for ovarian follicle development by regulating ER Castore of granulosa cells. Cell Death Differ. [Epub: Ahead of Print] 29467381
Wang, Q.C., Q. Zheng, H. Tan, B. Zhang, X. Li, Y. Yang, J. Yu, Y. Liu, H. Chai, X. Wang, Z. Sun, J.Q. Wang, S. Zhu, F. Wang, M. Yang, C. Guo, H. Wang, Q. Zheng, Y. Li, Q. Chen, A. Zhou, and T.S. Tang. (2016). TMCO1 Is an ER Ca2+ Load-Activated Ca2+ Channel. Cell 165: 1454-1466. 27212239