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Aliases for EPM2A Gene

Aliases for EPM2A Gene

  • Epilepsy, Progressive Myoclonus Type 2A, Lafora Disease (Laforin) 2 3 5
  • Epilepsy, Progressive Myoclonus Type 2, Lafora Disease (Laforin) 2 3
  • Glucan Phosphatase 3 4
  • Lafora PTPase 3 4
  • LAFPTPase 3 4
  • EC 3.1.3.16 4
  • EC 3.1.3.48 4
  • EC 3.1.3.- 4
  • EPM2 3
  • MELF 3

External Ids for EPM2A Gene

Previous GeneCards Identifiers for EPM2A Gene

  • GC06M145569
  • GC06M145794
  • GC06M145927
  • GC06M145988
  • GC06M145822
  • GC06M143510

Summaries for EPM2A Gene

Entrez Gene Summary for EPM2A Gene

  • This gene encodes a dual-specificity phosphatase that associates with polyribosomes. The encoded protein may be involved in the regulation of glycogen metabolism. Mutations in this gene have been associated with myoclonic epilepsy of Lafora. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

GeneCards Summary for EPM2A Gene

EPM2A (Epilepsy, Progressive Myoclonus Type 2A, Lafora Disease (Laforin)) is a Protein Coding gene. Diseases associated with EPM2A include Epilepsy, Progressive Myoclonic 2B and Epm2a-Related Lafora Disease. Among its related pathways are Glycosaminoglycan metabolism and Diseases of metabolism. GO annotations related to this gene include carbohydrate binding and protein tyrosine phosphatase activity.

UniProtKB/Swiss-Prot for EPM2A Gene

  • Has both dual-specificity protein phosphatase and glucan phosphatase activities. Together with the E3 ubiquitin ligase NHLRC1/malin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. Dephosphorylates phosphotyrosine, phosphoserine and phosphothreonine substrates in vitro. Has also been shown to dephosphorylate MAPT. Shows strong phosphatase activity towards complex carbohydrates in vitro, avoiding glycogen hyperphosphorylation which is associated with reduced branching and formation of insoluble aggregates. 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. Isoform 2, an inactive phosphatase, could function as a dominant-negative regulator for the phosphatase activity of isoform 1.

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for EPM2A Gene

Genomics for EPM2A Gene

Regulatory Elements for EPM2A Gene

Enhancers for EPM2A Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around EPM2A on UCSC Golden Path with GeneCards custom track

Promoters for EPM2A Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around EPM2A on UCSC Golden Path with GeneCards custom track

Genomic Location for EPM2A Gene

Chromosome:
6
Start:
145,500,777 bp from pter
End:
145,736,303 bp from pter
Size:
235,527 bases
Orientation:
Minus strand

Genomic View for EPM2A Gene

Genes around EPM2A on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
EPM2A Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for EPM2A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EPM2A Gene

Proteins for EPM2A Gene

  • Protein details for EPM2A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    B3EWF7-EP2A2_HUMAN
    Recommended name:
    Laforin, isoform 9
    Protein Accession:
    B3EWF7

    Protein attributes for EPM2A Gene

    Size:
    344 amino acids
    Molecular mass:
    35169 Da
    Quaternary structure:
    • Interacts with isoform 1 and isoform 2.

    Alternative splice isoforms for EPM2A Gene

  • Protein details for EPM2A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O95278-EPM2A_HUMAN
    Recommended name:
    Laforin
    Protein Accession:
    O95278
    Secondary Accessions:
    • B3KMU5
    • B4DRZ2
    • O95483
    • Q5T3F5
    • Q6IS15
    • Q8IU96
    • Q8IX24
    • Q8IX25
    • Q9BS66
    • Q9UEN2

    Protein attributes for EPM2A Gene

    Size:
    331 amino acids
    Molecular mass:
    37158 Da
    Quaternary structure:
    • Interacts with itself; however no biological function has been identified for the dimer. Interacts with PPP1R3B, 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. Interacts with PPP1R3D; in the presence of NHLC1/malin the interaction leads to ubiquitination and autophagic degradation of PPP1R3D. Interacts (via the phosphatase domain) with MAPT/Tau; the interaction dephosphorylates MAPT. 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. Interacts with PRDM8 (PubMed:22961547).
    SequenceCaution:
    • Sequence=BAG51107.1; Type=Frameshift; Positions=223; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for EPM2A Gene

    Alternative splice isoforms for EPM2A Gene

neXtProt entry for EPM2A Gene

Proteomics data for EPM2A Gene at MOPED

Post-translational modifications for EPM2A Gene

  • 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.
  • Polyubiquitinated by NHLRC1/malin.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for EPM2A Gene

Antibody Products

  • R&D Systems Antibodies for EPM2A (Laforin/EPM2A)
  • Abcam antibodies for EPM2A

No data available for DME Specific Peptides for EPM2A Gene

Domains & Families for EPM2A Gene

Gene Families for EPM2A Gene

Graphical View of Domain Structure for InterPro Entry

O95278

UniProtKB/Swiss-Prot:

EPM2A_HUMAN :
  • Contains 1 CBM20 (carbohydrate binding type-20) domain.
  • Belongs to the protein-tyrosine phosphatase family.
Domain:
  • Contains 1 CBM20 (carbohydrate binding type-20) domain.
  • Contains 1 tyrosine-protein phosphatase domain.
Family:
  • Belongs to the protein-tyrosine phosphatase family.
genes like me logo Genes that share domains with EPM2A: view

Function for EPM2A Gene

Molecular function for EPM2A Gene

GENATLAS Biochemistry:
laforin,tyrosine phosphatase with two alternative C terminini,putatively governing the localization of the protein either in cytoplasmic membrane or in the nucleus
UniProtKB/Swiss-Prot CatalyticActivity:
Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.
UniProtKB/Swiss-Prot CatalyticActivity:
[a protein]-serine/threonine phosphate + H(2)O = [a protein]-serine/threonine + phosphate.
UniProtKB/Swiss-Prot Function:
Has both dual-specificity protein phosphatase and glucan phosphatase activities. Together with the E3 ubiquitin ligase NHLRC1/malin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. Dephosphorylates phosphotyrosine, phosphoserine and phosphothreonine substrates in vitro. Has also been shown to dephosphorylate MAPT. Shows strong phosphatase activity towards complex carbohydrates in vitro, avoiding glycogen hyperphosphorylation which is associated with reduced branching and formation of insoluble aggregates. 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. Isoform 2, an inactive phosphatase, could function as a dominant-negative regulator for the phosphatase activity of isoform 1.

Enzyme Numbers (IUBMB) for EPM2A Gene

Gene Ontology (GO) - Molecular Function for EPM2A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 12915448
GO:0030246 carbohydrate binding IEA --
genes like me logo Genes that share ontologies with EPM2A: view
genes like me logo Genes that share phenotypes with EPM2A: view

Human Phenotype Ontology for EPM2A Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for EPM2A Gene

MGI Knock Outs for EPM2A:

Animal Model Products

miRNA for EPM2A Gene

miRTarBase miRNAs that target EPM2A

No data available for Transcription Factor Targets and HOMER Transcription for EPM2A Gene

Localization for EPM2A Gene

Subcellular locations from UniProtKB/Swiss-Prot for EPM2A Gene

Nucleus.
Cytoplasm. Note=Under glycogenolytic conditions localizes to the nucleus.
Isoform 1: Endoplasmic reticulum. Cell membrane. Note=Primarily associated with polyribosomes at the endoplasmic reticulum, also found at the plasma membrane.
Isoform 2: Endoplasmic reticulum. Cell membrane. Nucleus. Note=Also found in the nucleus.
Isoform 4: Cytoplasm. Nucleus.
Isoform 5: Cytoplasm. Nucleus.
Isoform 7: Cytoplasm.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for EPM2A Gene COMPARTMENTS Subcellular localization image for EPM2A gene
Compartment Confidence
cytosol 5
endoplasmic reticulum 5
nucleus 5
plasma membrane 5
extracellular 2
lysosome 1
mitochondrion 1
peroxisome 1
vacuole 1

No data available for Gene Ontology (GO) - Cellular Components for EPM2A Gene

Pathways & Interactions for EPM2A Gene

genes like me logo Genes that share pathways with EPM2A: view

Pathways by source for EPM2A Gene

Gene Ontology (GO) - Biological Process for EPM2A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005978 glycogen biosynthetic process TAS --
GO:0006006 glucose metabolic process TAS --
GO:0006470 protein dephosphorylation IEA,IDA 11001928
GO:0006914 autophagy IEA --
GO:0035335 peptidyl-tyrosine dephosphorylation NAS 9931343
genes like me logo Genes that share ontologies with EPM2A: view

No data available for SIGNOR curated interactions for EPM2A Gene

Drugs & Compounds for EPM2A Gene

(2) Drugs for EPM2A Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
calcium Nutra 0

(8) Additional Compounds for EPM2A Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Glycogen
  • Animal starch
  • Glycogen
  • Liver starch
  • Lyoglycogen
  • Phytoglycogen
9005-79-2
Phosphate
  • NFB Orthophosphate
  • O-Phosphoric acid
  • Ortho-phosphate
  • Orthophosphate (PO43-)
  • Orthophosphate(3-)
14265-44-2
phosphoric acid
  • Acide phosphorique (FRENCH)
  • Acido fosforico [Italian]
  • Acidum phosphoricum
  • Diphosphate tetrasodium
  • Fosforzuuroplossingen [Dutch]
7664-38-2
Water
  • Dihydrogen oxide
  • Steam
7732-18-5
genes like me logo Genes that share compounds with EPM2A: view

Transcripts for EPM2A Gene

Unigene Clusters for EPM2A Gene

Epilepsy, progressive myoclonus type 2A, Lafora disease (laforin):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for EPM2A Gene

ExUns: 1a · 1b ^ 2a · 2b · 2c · 2d ^ 3 ^ 4 ^ 5 ^ 6 ^ 7a · 7b · 7c · 7d ^ 8a · 8b
SP1: -
SP2: - - - - -
SP3: - - - - - -
SP4: - -
SP5: - - - - - - -
SP6: - - -
SP7:

Relevant External Links for EPM2A Gene

GeneLoc Exon Structure for
EPM2A
ECgene alternative splicing isoforms for
EPM2A

Expression for EPM2A Gene

mRNA expression in normal human tissues for EPM2A Gene

mRNA differential expression in normal tissues according to GTEx for EPM2A Gene

This gene is overexpressed in Muscle - Skeletal (x6.9).

Protein differential expression in normal tissues from HIPED for EPM2A Gene

This gene is overexpressed in Pancreatic juice (11.3), Heart (11.2), Spinal cord (9.3), and Fetal Brain (7.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for EPM2A Gene



SOURCE GeneReport for Unigene cluster for EPM2A Gene Hs.486696

mRNA Expression by UniProt/SwissProt for EPM2A Gene

B3EWF7-EP2A2_HUMAN
Tissue specificity: Expressed in heart, skeletal muscle, kidney, pancreas and brain. Isoform 4 is also expressed in the placenta.
genes like me logo Genes that share expression patterns with EPM2A: view

Protein tissue co-expression partners for EPM2A Gene

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for EPM2A Gene

Orthologs for EPM2A Gene

This gene was present in the common ancestor of chordates.

Orthologs for EPM2A Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia EPM2A 35
  • 91.44 (n)
  • 95.17 (a)
EPM2A 36
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia EPM2A 35
  • 91.81 (n)
  • 96.12 (a)
EPM2A 36
  • 80 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Epm2a 35
  • 86.77 (n)
  • 89.7 (a)
Epm2a 16
Epm2a 36
  • 90 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia EPM2A 35
  • 99.4 (n)
  • 99.7 (a)
EPM2A 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Epm2a 35
  • 86.51 (n)
  • 90.94 (a)
oppossum
(Monodelphis domestica)
Mammalia EPM2A 36
  • 78 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia EPM2A 36
  • 87 (a)
OneToOne
chicken
(Gallus gallus)
Aves EPM2A 35
  • 75.58 (n)
  • 78.03 (a)
EPM2A 36
  • 76 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia EPM2A 36
  • 85 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia epm2a 35
  • 68.48 (n)
  • 69.97 (a)
zebrafish
(Danio rerio)
Actinopterygii epm2a 35
  • 67.97 (n)
  • 66.12 (a)
epm2a 36
  • 64 (a)
OneToOne
Species with no ortholog for EPM2A:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for EPM2A Gene

ENSEMBL:
Gene Tree for EPM2A (if available)
TreeFam:
Gene Tree for EPM2A (if available)

Paralogs for EPM2A Gene

No data available for Paralogs for EPM2A Gene

Variants for EPM2A Gene

Sequence variations from dbSNP and Humsavar for EPM2A Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
VAR_019465 Epilepsy, progressive myoclonic 2 (EPM2)
VAR_019466 Epilepsy, progressive myoclonic 2 (EPM2)
VAR_019467 Epilepsy, progressive myoclonic 2 (EPM2)
VAR_019468 -
VAR_019469 Epilepsy, progressive myoclonic 2 (EPM2)

Variation tolerance for EPM2A Gene

Residual Variation Intolerance Score: 44.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.39; 42.30% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for EPM2A Gene

Human Gene Mutation Database (HGMD)
EPM2A

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for EPM2A Gene

Disorders for EPM2A Gene

MalaCards: The human disease database

(11) MalaCards diseases for EPM2A Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
epilepsy, progressive myoclonic 2b
  • epilepsy, progressive myoclonic 2a
epm2a-related lafora disease
  • progressive myoclonus epilepsy 2a
myoclonus
progressive myoclonus epilepsy
  • unverricht-lundborg syndrome
early myoclonic encephalopathy
  • epileptic seizures - myoclonic
- elite association - COSMIC cancer census association via MalaCards
Search EPM2A in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

EPM2A_HUMAN
  • Epilepsy, progressive myoclonic 2 (EPM2) [MIM:254780]: 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. {ECO:0000269 PubMed:11175283, ECO:0000269 PubMed:12019207, ECO:0000269 PubMed:12560877, ECO:0000269 PubMed:14722920, ECO:0000269 PubMed:15009235, ECO:0000269 PubMed:18311786, ECO:0000269 PubMed:9771710, ECO:0000269 PubMed:9931343}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for EPM2A

Genetic Association Database (GAD)
EPM2A
Human Genome Epidemiology (HuGE) Navigator
EPM2A
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
EPM2A
genes like me logo Genes that share disorders with EPM2A: view

No data available for Genatlas for EPM2A Gene

Publications for EPM2A Gene

  1. Laforin, the dual-phosphatase responsible for Lafora disease, interacts with R5 (PTG), a regulatory subunit of protein phosphatase-1 that enhances glycogen accumulation. (PMID: 14532330) Fernandez-Sanchez M.E. … Rodriguez de Cordoba S. (Hum. Mol. Genet. 2003) 3 4 23 67
  2. The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system. (PMID: 19036738) Garyali P. … Ganesh S. (Hum. Mol. Genet. 2009) 3 23
  3. AMP-activated protein kinase phosphorylates R5/PTG, the glycogen targeting subunit of the R5/PTG-protein phosphatase 1 holoenzyme, and accelerates its down-regulation by the laforin-malin complex. (PMID: 19171932) Vernia S. … Sanz P. (J. Biol. Chem. 2009) 3 23
  4. Deletions and missense mutations of EPM2A exacerbate unfolded protein response and apoptosis of neuronal cells induced by endoplasm reticulum stress. (PMID: 19403557) Liu Y. … Zheng P. (Hum. Mol. Genet. 2009) 3 23
  5. Increased endoplasmic reticulum stress and decreased proteasomal function in lafora disease models lacking the phosphatase laforin. (PMID: 19529779) Vernia S. … Sanz P. (PLoS ONE 2009) 3 23

Products for EPM2A Gene

Sources for EPM2A Gene

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