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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:

Alanay, Y., B. Ergüner, E. Utine, O. Haçariz, P.O. Kiper, E.Z. Taşkıran, F. Perçin, E. Uz, M.&.#.3.5.0.;. Sağiroğlu, B. Yuksel, K. Boduroglu, and N.A. Akarsu. (2014). TMCO1 deficiency causes autosomal recessive cerebrofaciothoracic dysplasia. Am J Med Genet A 164A: 291-304. 24194475
Batchelor-Regan, H., B. Xin, A. Zhou, and H. Wang. (2021). From Disease Description and Gene Discovery to Functional Cell Pathway: A Decade-Long Journey for TMCO1. Front Genet 12: 652400. 34093650
Li, C.F., W.R. Wu, T.C. Chan, Y.H. Wang, L.R. Chen, W.J. Wu, B.W. Yeh, S.S. Liang, and Y.L. Shiue. (2017). Transmembrane and Coiled-Coil Domain 1 Impairs the AKT Signaling Pathway in Urinary Bladder Urothelial Carcinoma: A Characterization of a Tumor Suppressor. Clin Cancer Res 23: 7650-7663. 28972042
Li, J., C. Liu, Y. Li, Q. Zheng, Y. Xu, B. Liu, W. Sun, Y. Li, S. Ji, M. Liu, J. Zhang, D. Zhao, R. Du, Z. Liu, G. Zhong, C. Sun, Y. Wang, J. Song, S. Zhang, J. Qin, S. Ling, X. Wang, and Y. Li. (2019). TMCO1-mediated Ca leak underlies osteoblast functions via CaMKII signaling. Nat Commun 10: 1589. 30962442
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
Wunderlich, J. (2022). Updated List of Transport Proteins in. Front Cell Infect Microbiol 12: 926541. 35811673
Yang, K.Y., S. Zhao, H. Feng, J. Shen, Y. Chen, S.T. Wang, S.J. Wang, Y.X. Zhang, Y. Wang, C. Guo, H. Liu, and T.S. Tang. (2022). Ca homeostasis maintained by TMCO1 underlies corpus callosum development via ERK signaling. Cell Death Dis 13: 674. 35927240
Zhang, N., M. Tang, M. Wen, Y. Cao, and B. OuYang. (2020). Expression, purification and characterization of TMCO1 for structural studies. Protein Expr Purif 179: 105803. [Epub: Ahead of Print] 33253810
Zhong, W., X. Wang, L. Yang, Y. Wang, Q. Xiao, S. Yu, R.D. Cannon, Y. Bai, C. Zhang, D. Chen, P. Ji, X. Gao, and J. Song. (2022). Nanocarrier-Assisted Delivery of Metformin Boosts Remodeling of Diabetic Periodontal Tissue via Cellular Exocytosis-Mediated Regulation of Endoplasmic Reticulum Homeostasis. ACS Nano. [Epub: Ahead of Print] 36259964