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FLASH GENE
Symbol EPM2A contributors: mct - updated : 23-04-2012
HGNC name epilepsy, progressive myoclonus type 2A, Lafora disease (laforin)
HGNC id 3413
Corresponding disease
EPM2A myoclonic epilepsy, progressive, Lafora type 2A
Location 6q24.3      Physical location : 145.946.445 - 146.056.991
Synonym name
  • laforin
  • progressive myoclonus epilepsy with polyglucosan bodies
  • LAFPTPase
  • Synonym symbol(s) MELF, LD, LDE, EPM2
    EC.number 3.1.1.48, 3.1.3.16
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head
    STRUCTURE 110.55 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    HIVEP2 6q23-q24 human immunodeficiency virus type I enhancer binding protein 2 AIG1 6q24.1 androgen-induced 1 DEADC1 6q24.1 deaminase domain containing 1 LOC391977 6 similar to dJ20N2.2 (novel protein similar to tubulin, beta polypeptide 4, member Q (TUBB4Q)) PEX3 6q23-q24 peroxisomal biogenesis factor 3 FUCA2 6q25-qter fucosidase, alpha-L- 2, plasma C6orf56 6q24.1 chromosome 6 open reading frame 56 C6orf93 6q24.1 chromosome 6 open reading frame 93 LOC153918 6q24.1 similar to CGI-62 protein PLAGL1 6q25 pleiomorphic adenoma gene-like 1 SF3B5 6q24.1 splicing factor 3b, subunit 5, 10kDa MRPL42P3 6q24.2 splicing factor 3b, subunit 5, 10kDa STX11 6q23.1-q25.3 syntaxin 11 LOC285741 6q24.1 similar to Translationally controlled tumor protein (TCTP) (p23) (Histamine-releasing factor) (HRF) UTRN 6q24 utrophin (homologous to dystrophin) LOC391978 6 similar to ZNF131 protein EPM2A 6q24.3 epilepsy, progressive myoclonus type 2A, Lafora disease (laforin) FBXO30 6q24 F-box protein 30 SHPRH 6q24.2 SNF2 histone linker PHD RING helicase GRM1 6q24 glutamate receptor, metabotropic 1 RAB32 6q24.3 RAB32, member RAS oncogene family LOC389431 6 similar to hypothetical protein 9130014G24 STXBP5 6q24.3 syntaxin binding protein 5 (tomosyn) LOC391979 6 similar to yes-associated protein 2 LOC389432 6 similar to RIKEN cDNA E130306M17 gene SASH1 6q24.3 similar to RIKEN cDNA E130306M17 gene LOC340151 6q24.3 similar to laminin receptor 1 (ribosomal protein SA); P40-3, functional; P40-8, functional; laminin receptor 1 (67kD, ribosomal protein SA)
    RNA
    TRANSCRIPTS type messenger
    text alternative splicing in the 5' and 3' end regions,transcripts group A,B,C,D (PMID: 9931343)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 3474 38 331 - 2008 18617530
  • also called EPM2A or laf331
  • using exons 4a, 1, 2, 3, 4
  • predominantly cytoplasmic
  • with laf317 form dimers
  • dual-specificity phosphatase
  • 5 - 1711 - 317 - 2008 18617530
  • also called EPM2B or laf317
  • using exons 4b, 1, 2, 3, 4b
  • localized both in nucleus and cytoplasm
  • with laf331 form dimers
  • inactive phosphatase that competes with laf331 for the substrate and regulates the activity of laf331 by forming heterodimers
  • interacting with malin (degraded by malin, NHLRC1)
  • - splicing 2800 - 250 brain 1999 9931343
    also called EMP2A1
    - splicing 1030 - 236 brain 1999 9931343
    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
  • 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
  • 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