Tbio O95278 Laforin

Protein Summary

Description

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). This gene encodes a dual-specificity phosphatase and may be involved in the regulation of glycogen metabolism. The protein acts on complex carbohydrates to prevent glycogen hyperphosphorylation, thus avoiding the formation of insoluble aggregates. Loss-of-function mutations in this gene have been associated with Lafora disease, a rare, adult-onset recessive neurodegenerative disease, which results in myoclonus epilepsy and usually results in death several years after the onset of symptoms. The disease is characterized by the accumulation of insoluble particles called Lafora bodies, which are derived from glycogen. [provided by RefSeq, Jan 2018]

Uniprot Accession IDs

• O95278
• B3KMU5
• B4DRZ2
• O95483
• Q5T3F5
• Q6IS15
• Q8IU96
• Q8IX24
• Q8IX25
• Q9BS66
• Q9UEN2

Gene Name

• EPM2A

Ensembl ID

• ENST00000367519
• ENSP00000356489
• ENSG00000112425
• ENST00000435470
• ENSP00000405913
• ENST00000611340
• ENSP00000480268
• ENST00000618445
• ENSP00000480339
• ENST00000638262
• ENSP00000492876
• ENST00000638778
• ENSP00000491353
• ENST00000638783
• ENSP00000491338
• ENST00000639423
• ENSP00000492701
• ENST00000639465
• ENSP00000491180

Symbol

• EPM2
• MELF

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	0.99
histone modification site profile	0.88
transcription factor binding site profile	0.75
microRNA	0.73
cellular component	0.69

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 284.64   (req: < 5)

Gene RIFs: 51   (req: <= 3)

Antibodies: 507   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 284.64   (req: >= 5)

Gene RIFs: 51   (req: > 3)

Antibodies: 507   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 22

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0