9.B.26 The Regulator of ER Stress and Autophagy TMEM208 (TMEM208) Family

TMEM208 family proteins are small protein of about 175 aas and 4 TMSs that appear to play roles in ER stress and autophagy regulation (Zhao et al. 2013).  These proteins are constituents of the SRP-independent targeting (SND) Family (TC# 9.A.64) (Aviram et al. 2016). Understanding protein targeting to the endoplasmic reticulum (ER) was expanded by the discovery of multiple pathways that function in parallel to the signal recognition particle (SRP). Guided entry of tail-anchored proteins and SRP independent (SND) systems are two such targeting pathways described in yeast. hSnd2 is the first constituent of the human SND pathway able to support substrate-specific protein targeting to the ER. Similar to its yeast counterpart, hSnd2 is assumed to function as a membrane-bound receptor preferentially targeting precursors carrying C-terminal transmembrane domains. Thus, hSnd2 is part of a complex network of targeting and translocation that is dynamically regulated (Haßdenteufel et al. 2017). ER stress seems to play a role in differentiation of cells of mesenchymal origin (Turishcheva et al. 2022).  O-linked N-acetylglucosamine protein modification regulaties autophagy (Zhu et al. 2024).

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