| Structural highlights
Disease
TM63A_HUMAN The disease is caused by variants affecting the gene represented in this entry.
Function
TM63A_HUMAN Mechanosensitive cation channel with low conductance and high activation threshold (PubMed:30382938, PubMed:31587869, PubMed:37543036). In contrast to TMEM63B, does not show phospholipid scramblase activity (PubMed:39716028). Acts as a regulator of lysosomal morphology by mediating lysosomal mechanosensitivity (By similarity). Important for the baby's first breath and respiration throughout life (PubMed:38127458). Upon lung inflation conducts cation currents in alveolar type 1 and 2 cells triggering lamellar body exocytosis and surfactant secretion into airspace (PubMed:38127458). Also acts as an osmosensitive cation channel preferentially activated by hypotonic stress (By similarity).[UniProtKB:Q91YT8][1] [2] [3] [4] [5]
References
- ↑ Murthy SE, Dubin AE, Whitwam T, Jojoa-Cruz S, Cahalan SM, Mousavi SAR, Ward AB, Patapoutian A. OSCA/TMEM63 are an Evolutionarily Conserved Family of Mechanically Activated Ion Channels. Elife. 2018 Nov 1;7:e41844. PMID:30382938 doi:10.7554/eLife.41844
- ↑ Yan H, Helman G, Murthy SE, Ji H, Crawford J, Kubisiak T, Bent SJ, Xiao J, Taft RJ, Coombs A, Wu Y, Pop A, Li D, de Vries LS, Jiang Y, Salomons GS, van der Knaap MS, Patapoutian A, Simons C, Burmeister M, Wang J, Wolf NI. Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result in Transient Hypomyelination during Infancy. Am J Hum Genet. 2019 Nov 7;105(5):996-1004. PMID:31587869 doi:10.1016/j.ajhg.2019.09.011
- ↑ Zheng W, Rawson S, Shen Z, Tamilselvan E, Smith HE, Halford J, Shen C, Murthy SE, Ulbrich MH, Sotomayor M, Fu TM, Holt JR. TMEM63 proteins function as monomeric high-threshold mechanosensitive ion channels. Neuron. 2023 Jul 28:S0896-6273(23)00512-3. PMID:37543036 doi:10.1016/j.neuron.2023.07.006
- ↑ Chen GL, Li JY, Chen X, Liu JW, Zhang Q, Liu JY, Wen J, Wang N, Lei M, Wei JP, Yi L, Li JJ, Ling YP, Yi HQ, Hu Z, Duan J, Zhang J, Zeng B. Mechanosensitive channels TMEM63A and TMEM63B mediate lung inflation-induced surfactant secretion. J Clin Invest. 2024 Dec 21;134(5):e174508. PMID:38127458 doi:10.1172/JCI174508
- ↑ Miyata Y, Nishimura M, Nagata A, Jing X, Sultan CS, Kuribayashi R, Takahashi K, Lee Y, Nishizawa T, Segawa K. Membrane structure-responsive lipid scramblase activity of the TMEM63/OSCA family. FEBS Lett. 2025 Mar;599(5):656-666. PMID:39716028 doi:10.1002/1873-3468.15084
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