1.A.154. The Tentonin or TMEM150 (TMEM150) Family Tentonin proteins (TMEM150) were orignally shown to be regulators of Piezo1 and Piezo2, and were therefore listed as members of TC family 8.A.113 but subsequently were shown to be ion channels themselves. While this last conclusion was initially questioned, it now seems to have been confirmed in several labs. Consequently these proteins may both regulate Piezo channels and be ion channels (Kang and Lee 2024). Only the best characteriized such channel is included here, so 1.A.154.1.1 and 8.A.113.1.1 are the same protein listed twice in TCDB.
References:
Anderson, E.O., E.R. Schneider, J.D. Matson, E.O. Gracheva, and S.N. Bagriantsev. (2018). TMEM150C/Tentonin3 Is a Regulator of Mechano-gated Ion Channels. Cell Rep 23: 701-708.
Hong, G.S., B. Lee, J. Wee, H. Chun, H. Kim, J. Jung, J.Y. Cha, T.R. Riew, G.H. Kim, I.B. Kim, and U. Oh. (2016). Tentonin 3/TMEM150c Confers Distinct Mechanosensitive Currents in Dorsal-Root Ganglion Neuron.s with Proprioceptive Function. Neuron. 91: 107-118.
Kang, H. and C.J. Lee. (2024). Transmembrane proteins with unknown function (TMEMs) as ion channels: electrophysiological properties, structure, and pathophysiological roles. Exp Mol Med 56: 850-860.
Ojeda-Alonso, J., V. Bégay, J.A. Garcia-Contreras, A.F. Campos-Pérez, B. Purfürst, and G.R. Lewin. (2022). Lack of evidence for participation of TMEM150C in sensory mechanotransduction. J Gen Physiol 154:.
Pak, S., H. Ryu, S. Lim, T.L. Nguyen, S. Yang, S. Kang, Y.G. Yu, J. Woo, C. Kim, C. Fenollar-Ferrer, J.N. Wood, M.O. Lee, G.S. Hong, K. Han, T.S. Kim, and U. Oh. (2024). Tentonin 3 is a pore-forming subunit of a slow inactivation mechanosensitive channel. Cell Rep 43: 114334.
Examples:
TC#	Name	Organismal Type	Example
1.A.154.1.1	TMEM150c/Tentonin 3 of 249 aas and 6 TMSs. According to Anderson et al. 2018, it reglulates channels such as Piezo 1 and Piezo 2. According to Hong et al. 2016, it has inherent channel activity, but Ojeda-Alonso et al. 2022 could not demonstrate this, Nevertheless, Pak et al. 2024 showed that tentonin 3 is a pore-forming subunit of a slow inactivation mechanosensitive channel. They reported that tentonin 3/TMEM150C (TTN3) confers mechanically activating (MA) currents with slow inactivation kinetics in somato- and barosensory neurons. Thus, purified TTN3 proteins incorporated into the lipid bilayer displayed spontaneous and pressure-sensitive channel currents. These MA currents were conserved across vertebrates and differ from Piezo1 in activation threshold and pharmacological response. Deep neural network structure prediction programs coupled with mutagenetic analysis predicted a rectangular-shaped, tetrameric structure with six transmembrane helices and a pore at the inter-subunit center. The putative pore aligned with two helices of each subunit and had constriction sites whose mutations changed the MA currents. These findings suggest that TTN3 is a pore-forming subunit of a distinct slow inactivation MA channel, potentially possessing a tetrameric structure (Pak et al. 2024). It appears that Tentonin 3 may both modify some channels and be one as well. Kang and Lee 2024 have confirmed the ion channel activity of tentonin and examined its structure.		Tentonin, TMEM150c, of Homo sapiens