Human Gene EPM2A (ENST00000639465.1) Description and Page Index
Description: Dual specificity protein phosphatase. May be involved in the control of glycogen metabolism, particularly in monitoring for and preventing the formation of poorly branched glycogen molecules (polyglucosans). Acts as a scaffold protein to facilitate PPP1R3C/PTG ubiquitination by NHLRC1/malin. Forms a complex with NHLRC1/malin and HSP70 and this complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Isoform 2, an inactive phosphatase, could function as a dominant-negative regulator for the phosphatase activity of isoform 1. (from UniProt O95278) Gencode Transcript: ENST00000639465.1 Gencode Gene: ENSG00000112425.16 Transcript (Including UTRs) Position: hg38 chr6:145,625,945-145,686,936 Size: 60,992 Total Exon Count: 4 Strand: - Coding Region Position: hg38 chr6:145,627,416-145,686,183 Size: 58,768 Coding Exon Count: 3
ID:EPM2A_HUMAN DESCRIPTION: RecName: Full=Laforin; EC=3.1.3.16; EC=3.1.3.48; AltName: Full=Lafora PTPase; Short=LAFPTPase; FUNCTION: Dual specificity protein phosphatase. May be involved in the control of glycogen metabolism, particularly in monitoring for and preventing the formation of poorly branched glycogen molecules (polyglucosans). Acts as a scaffold protein to facilitate PPP1R3C/PTG ubiquitination by NHLRC1/malin. Forms a complex with NHLRC1/malin and HSP70 and this complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Isoform 2, an inactive phosphatase, could function as a dominant-negative regulator for the phosphatase activity of isoform 1. CATALYTIC ACTIVITY: Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate. CATALYTIC ACTIVITY: A phosphoprotein + H(2)O = a protein + phosphate. SUBUNIT: Interacts with itself. Interacts also with PPP1R3C, HIRIP5 and EPM2AIP1. Binds glycogen and Lafora bodies. Interacts with NHLRC1/malin (via the NHL repeats). Forms a complex with NHLRC1/malin and HSP70. Isoform 2 does not bind glycogen. Isoform 1 and isoform 2 interact to form a heterodimeric complex inactive as phosphatase in vitro. Active phosphatase isoform 7 interacts with isoform 1 or isoform 2 to form a heterodimeric complex inactive as phosphatase in vitro. INTERACTION: Q9UQK1:PPP1R3C; NbExp=5; IntAct=EBI-2506661, EBI-2506727; SUBCELLULAR LOCATION: Cytoplasm. Note=Under glycogenolytic conditions localizes to the nucleus. SUBCELLULAR LOCATION: Isoform 1: Endoplasmic reticulum. Cell membrane. Note=Primarily associated with polyribosomes at the endoplasmic reticulum, also found at the plasma membrane. SUBCELLULAR LOCATION: Isoform 2: Endoplasmic reticulum. Cell membrane. Nucleus. Note=Also found in the nucleus. SUBCELLULAR LOCATION: Isoform 4: Cytoplasm. Nucleus. SUBCELLULAR LOCATION: Isoform 5: Cytoplasm. Nucleus. SUBCELLULAR LOCATION: Isoform 7: Cytoplasm. TISSUE SPECIFICITY: Expressed in heart, skeletal muscle, kidney, pancreas and brain. Isoform 4 is also expressed in the placenta. PTM: Polyubiquitinated by NHLRC1/malin. PTM: Phosphorylation on Ser-25 by AMPK affects the phosphatase activity of the enzyme and its ability to homodimerize and interact with NHLRC1, PPP1R3C or PRKAA2. DISEASE: Defects in EPM2A are a cause of progressive myoclonic epilepsy type 2 (EPM2) [MIM:254780]; 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. SIMILARITY: Belongs to the protein-tyrosine phosphatase family. SIMILARITY: Contains 1 CBM20 (carbohydrate binding type-20) domain. SIMILARITY: Contains 1 tyrosine-protein phosphatase domain. SEQUENCE CAUTION: Sequence=BAG51107.1; Type=Frameshift; Positions=223; WEB RESOURCE: Name=The Lafora progressive myoclonus epilepsy mutation and polymorphism database; URL="http://projects.tcag.ca/lafora/"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/EPM2A";
Protein Domain and Structure Information
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Other Names for This Gene
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Methods, Credits, and Use Restrictions
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