Recombinant Human Laforin (EPM2A)

Uniprot Id

O95278

Target Species

Human

Target Name

EPM2A

Target Full Name

Laforin

Target Function

Plays an important role in preventing glycogen hyperphosphorylation and the formation of insoluble aggregates, via its activity as glycogen phosphatase, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with the E3 ubiquitin ligase NHLRC1/malin. Shows strong phosphatase activity towards complex carbohydrates in vitro, avoiding glycogen hyperphosphorylation which is associated with reduced branching and formation of insoluble aggregates. Dephosphorylates phosphotyrosine and synthetic substrates, such as para-nitrophenylphosphate (pNPP), and has low activity with phosphoserine and phosphothreonine substrates (in vitro). Has been shown to dephosphorylate MAPT. Forms a complex with NHLRC1/malin and HSP70, which suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Acts as a scaffold protein to facilitate PPP1R3C/PTG ubiquitination by NHLRC1/malin. Also promotes proteasome-independent protein degradation through the macroautophagy pathway.; does not bind to glycogen. Lacks phosphatase activity and might function as a dominant-negative regulator for the phosphatase activity of isoform 1 and isoform 7.; has phosphatase activity (in vitro).

Target Involvement

Epilepsy, progressive myoclonic 2 (EPM2)

Target Subcellular Location

Cytoplasm.; [Isoform 1]: Cytoplasm. Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Cell membrane.; [Isoform 2]: Cytoplasm. Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Cell membrane. Nucleus.; [Isoform 4]: Cytoplasm. Nucleus.; [Isoform 5]: Cytoplasm. Nucleus.; [Isoform 7]: Cytoplasm.

Target Protein Families

Protein-tyrosine phosphatase family

Target Tissue Specificity

Expressed in heart, skeletal muscle, kidney, pancreas and brain. Isoform 4 is also expressed in the placenta.

Target Synonyms

Epilepsy progressive myoclonus type 2 Lafora disease (laforin); Epilepsy progressive myoclonus type 2A Lafora disease (laforin); EPM2; Epm2a; Epm2a gene; EPM2A_HUMAN; Lafora PTPase; Laforin; LAFPTPase; LD; LDE; MELF; RP3-466P17.2

Target Background

This gene encodes a dual-specificity phosphatase and may be involved in the regulation of glycogen metabolism. The protein acts on complex carbohydrates to prevent glycogen hyperphosphorylation, thus avoiding the formation of insoluble aggregates. Loss-of-function mutations in this gene have been associated with Lafora disease, a rare, adult-onset recessive neurodegenerative disease, which results in myoclonus epilepsy and usually results in death several years after the onset of symptoms. The disease is characterized by the accumulation of insoluble particles called Lafora bodies, which are derived from glycogen.