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FLASH GENE
Symbol EPM2A contributors: mct - updated : 23-07-2015
HGNC name epilepsy, progressive myoclonus type 2A, Lafora disease (laforin)
HGNC id 3413
EXPRESSION
Type widely
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Digestiveliver    
Endocrineneuroendocrinepituitary  highly
Lymphoid/Immunelymph node   highly
Reproductivemale systemprostate  moderately
Respiratorylung   moderately
Skin/Tegumentskin    
Urinarykidney   moderately
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Epithelialbarrier/lining   
Muscularstriatumskeletal  
Nervouscentral   
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousneuron
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • carbohydrate binding domain (CB-D) at the N-terminus, critical for association with glycogen, and targeting the protein to Lafora inclusion bodies (only phosphatase in the animal kingdom that contains a carbohydrate-binding module)
  • dual specificity phosphatase catalytic domain (DSPD) at the C-terminus
  • conjugated PhosphoP
    mono polymer monomer , dimer
    HOMOLOGY
    interspecies homolog to murine Epm2a
    homolog to C.elegans W01a11.1
    Homologene
    FAMILY
  • protein-tyrosine phosphatase family
  • family of glucan phosphatases
  • CATEGORY enzyme , secretory , receptor membrane tyrosine phosphatase
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum ,rough,smooth
    intracellular,cytoplasm,cytosolic
    text
  • localized in dendrites but not in axons of neurons
  • co-localize with EPM2B in endoplasmic reticulum (ER)
  • basic FUNCTION
  • a polysaccharide phosphatase, involved in translational regulation and in protein amino acid dephosphorylation
  • involved in the regulation of glycogen metabolism throught the interaction with PP1R3C
  • involved in glycogen metabolic pathway regulating the disposal of pathogenic polyglucosan inclusions
  • detecting polyglucosan appearances during glycogen synthesis and initiating mechanisms to downregulate glycogen synthase
  • dual specificity phosphatase that dephosphorylates complex carbohydrates
  • having functions to suppress excessive glycogen phosphorylation and is an essential component of the metabolism of normally structured glycogen
  • regulates autophagy via the mammalian target of rapamycin kinase-dependent pathway
  • modulates autophagy either at the level of TSC2 or above this protein
  • regulator of insulin sensitivity, and this phosphatase is a potential novel component of the insulin signaling cascade
  • laforin monomer is the dominant form of the protein and it contains phosphatase activity
  • role of the EPM2A/NHLRC1 complex in the activation of autophagy via regulation of the PI3KC3 complex that explain the defect in autophagy described in Lafora disease
  • CELLULAR PROCESS protein, translation regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
    glycogen metabolism, ubiquitin-proteasomal pathway
    a component
  • EPM2A–NHLRC1 complex is a novel player in the neuronal response to misfolded proteins
  • prevalently exists as a monomer with a small dimer fraction
  • EPM2A–NHLRC1 complex negatively regulates glycogen synthesis by modulating cellular glucose uptake via glucose transporters
  • a functional EPM2A–NHLRC1 complex plays a critical role in disrupting Lafora bodies and relieving ER stress, implying that a causative pathogenic mechanism underlies their deficiency in Lafora disease
  • INTERACTION
    DNA
    RNA
    small molecule other,
  • binding polyglucosans
  • protein
  • with HIRIP5 (dephosphorylation of HIRIP5)
  • with PPAR3C (binding with EPM2A critical for its function)
  • binds glycogen, but also starch, amylose and cyclodextrin
  • interacting with malin, through their middle portions (malin degrading the laforin)
  • glycogen, as well as amylopectin, is a substrate for laforin
  • interacts with proteins known to be involved in glycogen metabolism and rule out several of these proteins as potential substrates
  • interact with misfolded proteins and promote its degradation through the ubiquitin–proteasome system
  • critical partner for malin cellular functions
  • NHLRC1 functions to regulate EPM2A and NHLRC1 deficiency at least in part causes Lafora bodies (LB) and Lafora disease (LD) through increased EPM2A binding to glycogen
  • EPM2A-principle function is to control glycogen chain lengths, in a NHLRC1-dependent fashion, and loss of this control underlies LAFORA disease
  • cell & other
    REGULATION
    Phosphorylated by Ser(25) is phosphorylated by AMPK
    ASSOCIATED DISORDERS
    corresponding disease(s) EPM2A
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyneurodegenerative 
    could be with NHLRC1 potential therapeutic targets for neurodegenerative disorders associated with cytotoxic proteins
    ANIMAL & CELL MODELS
  • mice lacking laforin (epm2a-/-) have enhanced insulin response leading to altered whole-body energy balance