1.A.119.1.2
The TMEM120A or TACAN protein of 343 aas and 7 TMSs.  It may function in adipogenesis (Batrakou et al. 2015). TACAN is reported to be a Ca²⁺-transporting ion channel involved in sensing mechanical pain. It is expressed in a subset of nociceptors in humans, and its heterologous expression increases mechanically evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel that transports Ca²⁺ (Beaulieu-Laroche et al. 2020). However, Niu et al. 2021 failed to detect the proposed mechanosensitive ion channel activity of TACAN. Using membrane reconstitution methods, they found that TACAN, at high protein concentrations, produces heterogeneous conduction levels that are not mechanosensitive and are most consistent with disruptions of the lipid bilayer. They determined the structure of TACAN using single-particle cryo-EM and observed that it is a symmetrical dimeric transmembrane protein. Each protomer contains an intracellular-facing cleft with a coenzyme A cofactor, confirmed by mass spectrometry. The TACAN protomer is related in three-dimensional structure to a fatty acid elongase, ELOVL7. Thus, TACAN may not be a mechanosensitive ion channel. It may not mediate poking- or stretch-induced channel activities (Rong et al. 2021; Xue et al. 2021). TMEM120A genome organisation functions affect many adipose functions, and its loss may yield adiposity spectrum disorders, including an miRNA-based mechanism that could explain muscle hypertrophy in human lipodystrophy (Czapiewski et al. 2022). TACAN is an ion channel-like protein that may be involved in sensing mechanical pain. Chen et al. 2022 presented the cryo-EM structure of human TACAN (hTACAN). It forms a dimer in which each protomer consists of a transmembrane globular domain (TMD) containing six helices and an intracellular domain (ICD) containing two helices. Molecular dynamic simulations suggest that each protomer contains a putative ion conduction pore. A single-point mutation of the key residue Met207 greatly increases membrane pressure-activated currents, and each hTACAN subunit binds one cholesterol molecule. The wild-type hTACAN may be in a closed state (Chen et al. 2022). TMEM120A can detect mechanical pain stimuli as a mechanosensitive channel, contributes to adipocyte differentiation/functions by regulating genome organization and promotes STING trafficking to active cellular innate immune responses (Qian et al. 2022). These multiple proposed functions of TMEM120A have been reviewed and a molecular mechanism underlying TMEM120A's role in fatty acid metabolism and STING signaling has been proposed (Qian et al. 2022). See also TC# 1.A.5.2.1. TMEM120A/TACAN has been reported to be a regulator of ion channels, mechanosensation, and lipid metabolism (Gabrielle and Rohacs 2023).