Q91XQ2 · EPM2A_RAT
- ProteinLaforin
- GeneEpm2a
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids331 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
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
- H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 32 | substrate | ||||
Sequence: W | ||||||
Binding site | 87 | substrate | ||||
Sequence: K | ||||||
Binding site | 103-107 | substrate | ||||
Sequence: GPHHD | ||||||
Binding site | 197 | substrate | ||||
Sequence: D | ||||||
Binding site | 235 | substrate | ||||
Sequence: D | ||||||
Binding site | 241 | substrate | ||||
Sequence: R | ||||||
Active site | 266 | Phosphocysteine intermediate | ||||
Sequence: C | ||||||
Binding site | 267-272 | substrate | ||||
Sequence: NAGVGR | ||||||
Binding site | 304 | substrate | ||||
Sequence: Y | ||||||
Site | 329 | Required for homodimerization | ||||
Sequence: C |
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameLaforin
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ91XQ2
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Peripheral membrane protein
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
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000094840 | 1-331 | Laforin | |||
Sequence: MLFRFGVVVPPAVAGTRLELLLAGSRPELGRWEPRGAVRLRPAGTAAGAAALALQEPGLWLAEVELAPEEEAADGAEPGRIDTFWYKFLQREPGGELHWEGNGPHHDRCCTYNENNLVDGVYCLPVGHWIEATGHTNEMKHTTDFYFNIAGHQAMHYSRILPNIWLGSCPRQLEHVTIKLKHELGITAVMNFQTEWDIIQNSSGCNRYPEPMTPDTMMKLYKEEGLAYIWMPTPDMSTEGRVQMLPQAVCLLHALLENGHTVYVHCNAGVGRSTAAVCGWLHYVIGWSLRKVQYFIMAKRPAVYIDEEALAQAQQDFFQKFGKVHSSICTL | ||||||
Modified residue | 25 | Phosphoserine; by AMPK | ||||
Sequence: S |
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
- PTM
Proteomic databases
PTM databases
Expression
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1-124 | CBM20 | ||||
Sequence: MLFRFGVVVPPAVAGTRLELLLAGSRPELGRWEPRGAVRLRPAGTAAGAAALALQEPGLWLAEVELAPEEEAADGAEPGRIDTFWYKFLQREPGGELHWEGNGPHHDRCCTYNENNLVDGVYCL | ||||||
Domain | 156-323 | Tyrosine-protein phosphatase | ||||
Sequence: HYSRILPNIWLGSCPRQLEHVTIKLKHELGITAVMNFQTEWDIIQNSSGCNRYPEPMTPDTMMKLYKEEGLAYIWMPTPDMSTEGRVQMLPQAVCLLHALLENGHTVYVHCNAGVGRSTAAVCGWLHYVIGWSLRKVQYFIMAKRPAVYIDEEALAQAQQDFFQKFGK | ||||||
Motif | 266-272 | Glucan phosphatase signature motif CXAGXGR | ||||
Sequence: CNAGVGR |
Domain
The CBM20 domain mediates binding to cytoplasmic glycogen and to Lafora polyglucosan bodies.
Sequence similarities
Belongs to the protein-tyrosine phosphatase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length331
- Mass (Da)37,144
- Last updated2014-04-16 v2
- ChecksumC97D07AA55A534FC
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8L2QTS7 | A0A8L2QTS7_RAT | Epm2a | 347 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 9-10 | in Ref. 3; AAK60619 | ||||
Sequence: VP → DQ |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |