NHLRC1 mediated ubiquitination of EPM2A (laforin) and PPP1RC3 (PTG) associated with glycogen-GYG2

Stable Identifier
Reaction [omitted]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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.
Literature References
PubMed ID Title Journal Year
15930137 Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin

Gentry, MS, Worby, CA, Dixon, JE

Proc. Natl. Acad. Sci. U.S.A. 2005
18070875 Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG)

Gentry, MS, Worby, CA, Dixon, JE

J. Biol. Chem. 2008
20538597 Genetic depletion of the malin E3 ubiquitin ligase in mice leads to lafora bodies and the accumulation of insoluble laforin

Segvich, DM, Meyer, CM, Roach, PJ, Irimia, JM, Tagliabracci, VS, DePaoli-Roach, AA

J. Biol. Chem. 2010
Catalyst Activity

ubiquitin-protein transferase activity of NHLRC1 [cytosol]

Cite Us!