EPM2A | Laforin
 
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Sequence Viewer
Gene
Synonyms
-
Protein Name
Laforin
UniProt ID
O95278 [go to UniProt ] [go to PDBe-KB ]
Ensembl Gene ID
NCBI Gene ID
Molecular Weight
37158
Protein Length
331
Protein Domain
3D Structure
(PDB ID : 4r30)
Target by Small Molecules
Protein-protein Interaction Database
Gene Expression
Drugs and Diseases
Enzyme Class
3.1.3.-; 3.1.3.16; 3.1.3.48; (BRENDA)
Catalytic Site
Catalytic Activity
H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphateH2O + O-phospho-L-seryl-[protein] = L-seryl-[protein] + phosphateH2O + O-phospho-L-threonyl-[protein] = L-threonyl-[protein] + phosphate
Localization
Cytoplasm;Isoform 1: Cytoplasm,Endoplasmic reticulum membrane,Cell membrane;Isoform 2: Cytoplasm,Endoplasmic reticulum membrane,Cell membrane,Nucleus;Isoform 4: Cytoplasm,Nucleus;Isoform 5: Cytoplasm,Nucleus;Isoform 7: Cytoplasm;
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. Shows strong phosphatase activity towards complex carbohydrates in vitro, avoiding glycogen hyperphosphorylation which is associated with reduced branching and formation of insoluble aggregates (PubMed:16901901, PubMed:23922729, PubMed:26231210, PubMed:25538239, PubMed:25544560). Dephosphorylates phosphotyrosine and synthetic substrates, such as para-nitrophenylphosphate (pNPP), and has low activity with phosphoserine and phosphothreonine substrates (in vitro) (PubMed:11001928, PubMed:11220751, PubMed:11739371, PubMed:14532330, PubMed:16971387, PubMed:18617530, PubMed:22036712, PubMed:23922729, PubMed:14722920). Has been shown to dephosphorylate MAPT (By similarity). 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 (PubMed:23922729). Also promotes proteasome-independent protein degradation through the macroautophagy pathway (PubMed:20453062).Isoform 2: does not bind to glycogen (PubMed:18617530). Lacks phosphatase activity and might function as a dominant-negative regulator for the phosphatase activity of isoform 1 and isoform 7 (PubMed:18617530, PubMed:22036712).Isoform 7: has phosphatase activity (in vitro).
Gene Ontology
GO:0005737; GO:0098556; GO:0005829; GO:0005654; GO:0005634; GO:0005886; GO:0030246; GO:0019203; GO:2001069; GO:0016791; GO:0046983; GO:0042803; GO:0004722; GO:0004725; GO:0008138; GO:2001070; GO:0006914; GO:0016311; GO:0005978; GO:0005977; GO:0046959; GO:0035305; GO:0010923; GO:0007399; GO:0035335; GO:0046838; GO:0016239; GO:0006470
 
Gene Ontology