NHLRC1 (malin) associates with the glycogen particle where it functions as a ubiquitin E3 ligase to mediate the polyubiquitination of EPM2A (laforin) and PPP1R3C (PTG). The two polyubiquitinated proteins are targeted for proteasome-mediated degradation, leaving a glycogen-GYG1 particle associated with GYS1 (Gentry et al. 2005, Worby et al. 2008). In NHLRC1 knockout mice, PPP1R3C levels are unchanged, rather than increased, suggesting that NHLRC1 does not target PPP1R3C for degradation. However, EPM2A protein levels are increased in this knockout consistent with NHLRC1's proposed role (DePaoli-Roach et al. 2010).
|NHLRC1||ubiquitin-protein transferase activity (0004842)|
|20538597||Genetic depletion of the malin E3 ubiquitin ligase in mice leads to lafora bodies and the accumulation of insoluble laforin||J. Biol. Chem.||2010|
|15930137||Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin||Proc. Natl. Acad. Sci. U.S.A.||2005|
|18070875||Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG)||J. Biol. Chem.||2008|