@article {Renz575241, author = {Christian Renz and Vera Tr{\"o}ster and Thomas K. Albert and Olivier Santt and Susan C. Jacobs and Anton Khmelinskii and Helle D. Ulrich}, title = {The ubiquitin-conjugating enzyme Ubc13-Mms2 cooperates with a family of FYVE-type-RING ubiquitin protein ligases in K63-polyubiquitylation at internal membranes}, elocation-id = {575241}, year = {2019}, doi = {10.1101/575241}, publisher = {Cold Spring Harbor Laboratory}, abstract = {The heterodimeric ubiquitin-conjugating enzyme (E2), Ubc13-Mms2, catalyses K63-specific polyubiquitylation in genome maintenance and inflammatory signalling. In budding yeast, the only ubiquitin protein ligase (E3) known to cooperate with Ubc13-Mms2 so far is a nuclear RING finger protein, Rad5, involved in the replication of damaged DNA. We have now identified a family of membrane-associated FYVE-(type)-RING finger proteins as cognate E3s for Ubc13-Mms2 in several species. We show that budding yeast Pib1, a FYVE-RING finger E3 associated with internal membranes, exhibits exquisite selectivity for Ubc13-Mms2 and cooperates with the E2 in the multivesicular body pathway. Phenotypic analysis indicates that the contribution of Ubc13-Mms2 to membrane trafficking goes beyond its cooperation with Pib1, suggesting an involvement with additional E3s in the endocytic compartment. These results widely implicate Ubc13-Mms2 in the regulation of membrane protein sorting.}, URL = {https://www.biorxiv.org/content/early/2019/03/12/575241}, eprint = {https://www.biorxiv.org/content/early/2019/03/12/575241.full.pdf}, journal = {bioRxiv} }