NHLRC1

The RING domain is essential for ubiquitin E3 ligase activity.

E3 ubiquitin-protein ligase. Together with the phosphatase EPM2A/laforin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. In complex with EPM2A/laforin and HSP70, suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Ubiquitinates the glycogen-targeting protein phosphatase subunits PPP1R3C/PTG and PPP1R3D in a laforin-dependent manner and targets them for proteasome-dependent degradation, thus decreasing glycogen accumulation. Polyubiquitinates EPM2A/laforin and ubiquitinates AGL and targets them for proteasome-dependent degradation. Also promotes proteasome-independent protein degradation through the macroautophagy pathway.

Myoclonic epilepsy of Lafora 2

MELF2

A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. MELF2 is an autosomal recessive, severe form characterized by onset of progressive neurodegeneration between 8 and 18 years of age. Initial features can include headache, myoclonic jerks, generalized seizures, and often visual hallucination. Typically, as seizures increase in frequency, cognitive function declines towards dementia, and affected individuals die usually within 10 years after onset. At the cellular level, MELF2 is characterized by accumulation of starch-like polyglucosans called Lafora bodies (LBs) that are most abundant in organs with the highest glucose metabolism: brain, heart, liver and skeletal muscle.

None

The disease is caused by variants affecting the gene represented in this entry.

Protein modification; protein ubiquitination.

Expressed in brain, cerebellum, spinal cord, medulla, heart, liver, skeletal muscle and pancreas.

• Endoplasmic reticulum
• Nucleus
• Localizes at the endoplasmic reticulum and, to a lesser extent, in the nucleus.

EPM2B, NHLRC1, E3 ubiquitin-protein ligase NHLRC1, Malin, NHL repeat-containing protein 1, RING-type E3 ubiquitin transferase NHLRC1

• entrezGene:378884
• omim:608072
• swissprot:Q6VVB1

Proteins

Neuroscience

42293Da