Illustration of UT-A1 ubiquitination, internalization, and degradation. In normal conditions, cytosolic UT-A1 (including misfolded UT-A1 from endoplasmic reticulum) and constitutively internalized cell surface UT-A1 (mostly from the caveolae-mediated endocytic pathway) is polyubiquitinated and degraded in a 26S proteasome system. However, upon AVP/FSK stimulation, UT-A1 is phosphorylated and processed for monoubiquitination at the cell surface and internalized via the clathrin-coated pits (CCP) pathway. The internalized monoubiquitinated UT-A1 is trafficked to early endosome, then targeted to the lysosome for degradation. AVP, arginine vasopressin; PKA, protein kinase A.