NHLRC1 mediated ubiquitination of EPM2A (laforin) and PPP1RC3 (PTG) associated with glycogen-GYG2
Species Homo sapiens
NHLRC1 (malin) associates with the glycogen particle where it functions as a ubiquitin E3 ligase to mediate the polyubiquitination of EPM2A (laforin) and PPP1R3C (protein phosphatase 1 regulatory subunit 3C, PTG). The two polyubiquitinated proteins are targeted for proteasome-mediated degradation, leaving a glycogen-GYG2 particle associated with glycogen synthase 2 GYS2 (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). This process is inferred from studies of muscle glycogen and from the fact that defects in either EPM2A or NHLRC1 lead to formation of similar aberrant glycogen particles in both tissues.
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