1.A.17.4.14
Tmc4 (MBOAT7) of 712 aas and 10 TMSs (Mancina et al. 2016). It is a calcium-dependent chloride channel that may play a role in nonalcoholic fatty liver disease (NAFLD) (Sookoian et al. 2018) but is not associated with a risk of hepatocellular carcinoma or persistent hepatitis B infection (Wang et al. 2021). Ibuprofen only minimally inhibits the taste response of the ENaC to NaCl, but it significantly inhibits the TMC4 response to NaCl with an IC50 at 1.45 mM. Thus, ibuprofen interferes with detection of salty taste via inhibition of TMC4 (Kasahara et al. 2021). This agrees with the fact that TMC4 is a chloride channel involved in high-concentration salt taste sensation (Kasahara et al. 2021). TMC4 is involved in pH and temperature-dependent modulation of salty taste (Kasahara et al. 2021). Salt-enhancing peptides were identified based on the allosteric sites in TMC4 (Shen et al. 2022). Mechanisms of salt taste reception and the properties of TMC4 as a  salt taste-related molecule have been reviewed (Kasahara et al. 2022). Genetic polymorphisms in TMC4 predispose organisms to a higher risk of liver diseases (Rivera-Iñiguez et al. 2022). Umami peptides bind to the TMC4 receptor to enhance saltiness (Xie et al. 2023). Salt-enhancing peptides can effectively reduce sodium consumption from Largemouth bass myosin through virtual hydrolysis, molecular simulation, and sensory evaluation (Bu et al. 2024). Human TMC4 was constructed using Alphafold2. DAF, QIF, RPAL, and IPVM significantly enhanced the saltiness perception, and QIF exhibited the most pronounced effect in enhancing saltiness (P < 0.05). The residues Ala258, Ser546, Ser603, Phe259, Cys265, Glu539, Lys278 and Ser585 were identified as key binding sites (Bu et al. 2024).