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Tethering Ubl4a to BAGS domain This is the C-terminal domain of Ubiquitin-like protein 4A an ortholog of yeast Get5. In budding yeast, GET proteins directly mediate the insertion of newly synthesized TA proteins into endoplasmic reticulum membranes. Similarly, mammalian BAG6, Ubl4a, and SGTA make up a trimeric complex that binds TA proteins post-translationally and then loads them onto the cytosolic ATPase TRC40, which in turn targets them to the endoplasmic reticulum. Structural studies show that this C-terminal TUGS domain of Ubl4a is essential for BAG6 tethering. Given that BAG6 mediates oligomeric complex formation of Ubl4a, TRC35, and TRC40 (mammalian counterparts of Get5, Get4, and Get3, respectively), the C-terminal TUGS domain might be crucial for supporting BAG6-mediated Ubl4a-TRC35 complex formation in humans as an alternative to the direct Get5-Get4 interaction in yeast.
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Jiyao W et al.(2023). "The conserved domain database in 2023.",