Epm2a epilepsy, progressive myoclonic epilepsy, type 2 gene alpha [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Epm2aprovided by MGI
Official Full Name: epilepsy, progressive myoclonic epilepsy, type 2 gene alphaprovided by MGI
Primary source: MGI:MGI:1341085
See related: Ensembl:ENSMUSG00000055493 AllianceGenome:MGI:1341085
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: TG-B; Tg(TcraK,TcrbK)TG-BFlv
Summary: Enables identical protein binding activity; phosphatase activity; and starch binding activity. Involved in carbohydrate phosphorylation and glycogen metabolic process. Acts upstream of or within several processes, including glycogen biosynthetic process; habituation; and regulation of cellular protein metabolic process. Located in several cellular components, including cytoplasmic side of endoplasmic reticulum membrane; dendrite; and perikaryon. Is expressed in several structures, including brain. Used to study Lafora disease and lymphoma. Human ortholog(s) of this gene implicated in Lafora disease and progressive myoclonus epilepsy. Orthologous to human EPM2A (EPM2A glucan phosphatase, laforin). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in adrenal adult (RPKM 11.6), heart adult (RPKM 7.7) and 24 other tissues See more
Orthologs: human all
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Genomic context

Location:: 10 A1; 10 3.66 cM

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	10	NC_000076.7 (11218435..11335408)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	10	NC_000076.6 (11342691..11459664)

Chromosome 10 - NC_000076.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Epm2a[R240X] knock-in mice present earlier cognitive decline and more epileptic activity than Epm2a[-/-] mice.
Title: Epm2a(R240X) knock-in mice present earlier cognitive decline and more epileptic activity than Epm2a(-/-) mice.
Laforin targets malin to glycogen in Lafora progressive myoclonus epilepsy.
Title: Laforin targets malin to glycogen in Lafora progressive myoclonus epilepsy.
Structural and Functional Brain Abnormalities in Mouse Models of Lafora Disease.
Title: Structural and Functional Brain Abnormalities in Mouse Models of Lafora Disease.
Laforin knockout mice develop Cardiac Hypertrophy and marked Systolic Dysfunction. Histological assessment showed abundant glycogen aggregates inside the cardiomyocytes, including typical Lafora bodies.
Title: Lafora Disease Is an Inherited Metabolic Cardiomyopathy.
The present study analyzes possible inflammatory responses in the mouse lines Epm2a (-/-) (laforin knock-out) and Epm2b (-/-) (malin knock-out) with disease progression.
Title: Inflammation in Lafora Disease: Evolution with Disease Progression in Laforin and Malin Knock-out Mouse Models.
Laforin-silenced cells was able to induce autophagic flux, proteasomal activity and reduce the polyubiquitinated proteins by heat shock.
Title: Loss of malin, but not laforin, results in compromised autophagic flux and proteasomal dysfunction in cells exposed to heat shock.
This study also suggests a malin function independent of laforin, possibly in lysosomal biogenesis and/or lysosomal glycogen disposal.
Title: Protein degradation and quality control in cells from laforin and malin knockout mice.
loss of laforin results in activation of serum/glucocorticoid-induced kinase 1 in cellular and animals models
Title: Activation of serum/glucocorticoid-induced kinase 1 (SGK1) underlies increased glycogen levels, mTOR activation, and autophagy defects in Lafora disease.
expression of Epm2a blocks formation of Lafora bodies and restores the impairment in macroautophagy, preventing the development of Lafora bodies in Epm2a-deficient mice.
Title: The phosphatase activity of laforin is dispensable to rescue Epm2a-/- mice from Lafora disease.
in laforin-deficient mice, stress drastically accelerates Lafora bodies accumulation and Lafora disease.
Title: Laforin prevents stress-induced polyglucosan body formation and Lafora disease progression in neurons.

Submit: New GeneRIF Correction See all GeneRIFs (24)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Transgenic (1) 1 citation
Targeted (2) 1 citation
Endonuclease-mediated (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables carbohydrate binding	ISO Inferred from Sequence Orthology more info
enables carbohydrate phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables carbohydrate phosphatase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables carbohydrate phosphatase activity	ISO Inferred from Sequence Orthology more info
enables glycogen (starch) synthase activity	IEP Inferred from Expression Pattern more info	PubMed
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables myosin phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphoprotein phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables polysaccharide binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein serine/threonine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine phosphatase activity	ISO Inferred from Sequence Orthology more info
enables protein tyrosine phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein tyrosine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine phosphatase activity	ISO Inferred from Sequence Orthology more info
enables protein tyrosine/serine/threonine phosphatase activity	TAS Traceable Author Statement more info	PubMed
enables starch binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within L-glutamate transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within autophagosome assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within calcium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within carbohydrate metabolic process	IEA Inferred from Electronic Annotation more info
involved_in carbohydrate phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dephosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within glial cell proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in glycogen biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within glycogen biosynthetic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within glycogen biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glycogen biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within glycogen metabolic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within glycogen metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glycogen metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glycogen metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within habituation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within macromolecule metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mitochondrion organization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of TOR signaling	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of dephosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of peptidyl-serine phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of phosphatase activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within nervous system development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-tyrosine dephosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of macroautophagy	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of macroautophagy	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of macroautophagy	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within proteasome-mediated ubiquitin-dependent protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein dephosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of cell growth	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of glycogen (starch) synthase activity	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of proteasomal protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of protein import into nucleus	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of protein localization to plasma membrane	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of protein ubiquitination	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of ubiquitin protein ligase activity	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytoplasmic side of endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic side of rough endoplasmic reticulum membrane	ISO Inferred from Sequence Orthology more info
is_active_in cytosol	IMP Inferred from Mutant Phenotype more info	PubMed
located_in cytosol	ISO Inferred from Sequence Orthology more info	PubMed
located_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in perikaryon	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: laforin

Names: LAFPTPase; glucan phosphatase; lafora PTPase

NP_034276.2

EC 3.1.3.16

EC 3.1.3.48

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_010146.3 → NP_034276.2 laforin

See identical proteins and their annotated locations for NP_034276.2

Status: VALIDATED

Source sequence(s)

AC101984, AC157018

Consensus CDS

CCDS23698.1

UniProtKB/Swiss-Prot

G5E8E2, Q8BY80, Q9WUA5

Related

ENSMUSP00000066050.5, ENSMUST00000069106.5

Conserved Domains (2) summary

cd05806
Location:1 → 128

CBM20_laforin; Laforin protein tyrosine phosphatase, N-terminal CBM20 (carbohydrate-binding module, family 20) domain. Laforin, encoded by the EPM2A gene, is a dual-specificity phosphatase that dephosphorylates complex carbohydrates. Mutations in the gene encoding ...

cl21483
Location:157 → 303

PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...

RNA

NR_190354.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC101984, AC157018
NR_190355.1 RNA Sequence

Status: VALIDATED

Source sequence(s)

AC101984, AC157018