Q91XQ2 · EPM2A_RAT

Function

function

Plays an important role in preventing glycogen hyperphosphorylation and the formation of insoluble aggregates, via its activity as glycogen phosphatase, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with the E3 ubiquitin ligase NHLRC1/malin. Dephosphorylates phosphotyrosine and synthetic substrates, such as para-nitrophenylphosphate (pNPP), and has low activity with 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.

Catalytic activity

Features

Showing features for binding site, active site, site.

TypeIDPosition(s)Description
Binding site32substrate
Binding site87substrate
Binding site103-107substrate
Binding site197substrate
Binding site235substrate
Binding site241substrate
Active site266Phosphocysteine intermediate
Binding site267-272substrate
Binding site304substrate
Site329Required for homodimerization

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytoplasmic side of endoplasmic reticulum membrane
Cellular Componentcytoplasmic side of rough endoplasmic reticulum membrane
Cellular Componentcytosol
Cellular Componentdendrite
Cellular Componentnucleus
Cellular Componentperikaryon
Cellular Componentplasma membrane
Molecular Functioncarbohydrate binding
Molecular Functioncarbohydrate phosphatase activity
Molecular Functionglycogen (starch) synthase activity
Molecular Functionglycogen binding
Molecular Functionidentical protein binding
Molecular Functionmyosin phosphatase activity
Molecular Functionphosphatase activity
Molecular Functionphosphoprotein phosphatase activity
Molecular Functionpolysaccharide binding
Molecular Functionprotein homodimerization activity
Molecular Functionprotein serine/threonine phosphatase activity
Molecular Functionprotein tyrosine phosphatase activity
Molecular Functionstarch binding
Biological Processautophagosome assembly
Biological Processautophagy
Biological Processcalcium ion transport
Biological Processcarbohydrate phosphorylation
Biological Processdephosphorylation
Biological Processglial cell proliferation
Biological Processglycogen biosynthetic process
Biological Processglycogen metabolic process
Biological Processhabituation
Biological ProcessL-glutamate transmembrane transport
Biological Processmitochondrion organization
Biological Processnegative regulation of cell cycle
Biological Processnegative regulation of gene expression
Biological Processnegative regulation of peptidyl-serine phosphorylation
Biological Processnegative regulation of TOR signaling
Biological Processnervous system development
Biological Processpositive regulation of macroautophagy
Biological Processproteasome-mediated ubiquitin-dependent protein catabolic process
Biological Processregulation of cell growth
Biological Processregulation of gene expression
Biological Processregulation of proteasomal protein catabolic process
Biological Processregulation of protein import into nucleus
Biological Processregulation of protein localization to plasma membrane
Biological Processregulation of protein phosphorylation
Biological Processregulation of protein ubiquitination
Biological ProcessWnt signaling pathway

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

Gene names

    • Name
      Epm2a

Organism names

  • Taxonomic identifier
  • Strains
    • Brown Norway
    • Sprague-Dawley
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    Q91XQ2
  • Secondary accessions
    • F1LPW7

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Endoplasmic reticulum membrane
; Peripheral membrane protein
Cell membrane
Note: Colocalizes with glycogen synthase in punctate structures in the cytoplasm. Primarily associated with polyribosomes at the rough endoplasmic reticulum, and also detected at the plasma membrane. Under glycogenolytic conditions localizes to the nucleus.

Keywords

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00000948401-331Laforin
Modified residue25Phosphoserine; by AMPK

Post-translational modification

Polyubiquitinated by NHLRC1/malin.
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.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Widely expressed.

Gene expression databases

Interaction

Subunit

Homodimer. Interacts with itself. Interacts with PPP1R3B, PPP1R3C, PPP1R3D, 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. Interacts with PRDM8.

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for domain, motif.

TypeIDPosition(s)Description
Domain1-124CBM20
Domain156-323Tyrosine-protein phosphatase
Motif266-272Glucan phosphatase signature motif CXAGXGR

Domain

The CBM20 domain mediates binding to cytoplasmic glycogen and to Lafora polyglucosan bodies.

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    331
  • Mass (Da)
    37,144
  • Last updated
    2014-04-16 v2
  • Checksum
    C97D07AA55A534FC
MLFRFGVVVPPAVAGTRLELLLAGSRPELGRWEPRGAVRLRPAGTAAGAAALALQEPGLWLAEVELAPEEEAADGAEPGRIDTFWYKFLQREPGGELHWEGNGPHHDRCCTYNENNLVDGVYCLPVGHWIEATGHTNEMKHTTDFYFNIAGHQAMHYSRILPNIWLGSCPRQLEHVTIKLKHELGITAVMNFQTEWDIIQNSSGCNRYPEPMTPDTMMKLYKEEGLAYIWMPTPDMSTEGRVQMLPQAVCLLHALLENGHTVYVHCNAGVGRSTAAVCGWLHYVIGWSLRKVQYFIMAKRPAVYIDEEALAQAQQDFFQKFGKVHSSICTL

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8L2QTS7A0A8L2QTS7_RATEpm2a347

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict9-10in Ref. 3; AAK60619

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AABR06000316
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AABR06000317
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AABR06000318
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AABR06000319
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AABR06000320
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AABR06000321
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AABR06000322
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AABR06000323
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AABR06000324
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AABR06000325
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AABR06000326
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AABR06000327
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AABR06000328
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH473994
EMBL· GenBank· DDBJ
EDL93717.1
EMBL· GenBank· DDBJ
Genomic DNA
AF347030
EMBL· GenBank· DDBJ
AAK60619.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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