NHLRC1 Antibody – Rabbit Polyclonal

The protein encoded by this gene is a single subunit E3 ubiquitin ligase. Laforin is polyubiquitinated by the encoded protein. Defects in this intronless gene lead to an accumulation of laforin and onset of Lafora disease, also known as progressive myoclonic epilepsy type 2 (EPM2).[provided by RefSeq, Mar 2010]

NHLRC1: E3 ubiquitin-protein ligase which 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 PPP1R3C/PTG in a laforin-dependent manner, and targets it for proteasome-dependent degradation and this degradation decreases glycogen accumulation. Polyubiquitinates EPM2A/laforin and ubiquitinates AGL and targets them for proteasome-dependent degradation. Defects in NHLRC1 are a cause of progressive myoclonic epilepsy type 2 (EPM2); also known as Lafora disease. EPM2 is an autosomal recessive and severe form of adolescent-onset progressive epilepsy. Typically, as seizures increase in frequency, cognitive function declines towards dementia, and affected individuals die usually within 10 years after onset. EPM2 occurs worldwide, but it is particularly common in the mediterranean countries of southern Europe and northern Africa, in southern India and in the Middle East. At the cellular level, it 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. Among other conditions involving polyglucosans, EPM2 is unique in that the inclusions are in neuronal dendrites but not axons and the forming polyglucosan fibrils are associated with the endoplasmic reticulum.

Protein type: EC 6.3.2.19; Ubiquitin conjugating system; Ligase; EC 6.3.2.-; Ubiquitin ligase

Chromosomal Location of Human Ortholog: 6p22.3

Cellular Component: cytosol; endoplasmic reticulum; nucleus; perinuclear region of cytoplasm

Molecular Function: ligase activity; protein binding; ubiquitin-protein ligase activity; zinc ion binding

Biological Process: autophagy; glycogen biosynthetic process; positive regulation of protein ubiquitination; proteasomal ubiquitin-dependent protein catabolic process; protein polyubiquitination

Disease: Myoclonic Epilepsy Of Lafora