EPM2A
entrez
7957
canonical
uniprot
O95278
canonical
ensembl
ENSG00000112425
resolver
ensp
ENSP00000356489
resolver
ensp
ENSP00000405913
resolver
ensp
ENSP00000491353
resolver
ensp
ENSP00000492701
resolver
ensp
ENSP00000492876
resolver
ensp
ENSP00000786046
resolver
genesymbol
EPM2A
resolver
hgnc
HGNC:3413
resolver
uniprot
B3KMU5
resolver
uniprot
B4DRZ2
resolver
uniprot
O95483
resolver
uniprot
Q5T3F5
resolver
uniprot
Q6IS15
resolver
uniprot
Q8IU96
resolver
uniprot
Q8IX24
resolver
uniprot
Q8IX25
resolver
uniprot
Q9BS66
resolver
uniprot
Q9UEN2
resolver
uniprot_entry
EPM2A_HUMAN
resolver
uniprot_sec
B3KMU5
resolver
uniprot_sec
B4DRZ2
resolver
uniprot_sec
O95483
resolver
uniprot_sec
Q5T3F5
resolver
uniprot_sec
Q6IS15
resolver
uniprot_sec
Q8IU96
resolver
uniprot_sec
Q8IX24
resolver
uniprot_sec
Q8IX25
resolver
uniprot_sec
Q9BS66
resolver
uniprot_sec
Q9UEN2
resolver
amino_acid_sequence
MRFRFGVVVPPAVAGARPELLVVGSRPELGRWEPRGAVRLRPAGTAAGDGALALQEPGLWLGEVELAAEEAAQDGAEPGRVDTFWYKFLKREPGGELSWEGNGPHHDRCCTYNENNLVDGVYCLPIGHWIEATGHTNEMKHTTDFYFNIAGHQAMHYSRILPNIWLGSCPRQVEHVTIKLKHELGITAVMNFQTEWDIVQNSSGCNRYPEPMTPDTMIKLYREEGLAYIWMPTPDMSTEGRVQMLPQAVCLLHALLEKGHIVYVHCNAGVGRSTAAVCGWLQYVMGWNLRKVQYFLMAKRPAVYIDEEALARAQEDFFQKFGKVRSSVCSL
uniprot
proteins
disease_involvement
DISEASE: Myoclonic epilepsy of lafora 1 (MELF1) [MIM:254780]: A form of progressive myoclonic epilepsy, a clinically and genetically heterogeneous group of disorders defined by the combination of action and reflex myoclonus, other types of epileptic seizures, and progressive neurodegeneration and neurocognitive impairment. MELF1 is an autosomal recessive, severe form characterized by onset of progressive neurodegeneration between 8 and 18 years of age. Initial features can include headache, myoclonic jerks, generalized seizures, and often visual hallucination. Typically, as seizures increase in frequency, cognitive function declines towards dementia, and affected individuals die usually within 10 years after onset. At the cellular level, MELF1 is characterized by accumulation of starch-like polyglucosans called Lafora bodies (LBs) that are most abundant in organs with the highest glucose metabolism: brain, heart, liver and skeletal muscle. {ECO:0000269|PubMed:11001928, ECO:0000269|PubMed:11175283, ECO:0000269|PubMed:11739371, ECO:0000269|PubMed:12019207, ECO:0000269|PubMed:12560877, ECO:0000269|PubMed:14532330, ECO:0000269|PubMed:14706656, ECO:0000269|PubMed:14722920, ECO:0000269|PubMed:15009235, ECO:0000269|PubMed:18311786, ECO:0000269|PubMed:25544560, ECO:0000269|PubMed:26231210, ECO:0000269|PubMed:9771710, ECO:0000269|PubMed:9931343}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.3.-
uniprot
proteins
ec_number
3.1.3.16
uniprot
proteins
ec_number
3.1.3.48
uniprot
proteins
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. 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:25538239, PubMed:25544560, PubMed:26231210). 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:14722920, PubMed:16971387, PubMed:18617530, PubMed:22036712, PubMed:23922729). 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). {ECO:0000250|UniProtKB:Q9WUA5, ECO:0000269|PubMed:11001928, ECO:0000269|PubMed:11220751, ECO:0000269|PubMed:11739371, ECO:0000269|PubMed:14532330, ECO:0000269|PubMed:14722920, ECO:0000269|PubMed:16901901, ECO:0000269|PubMed:16971387, ECO:0000269|PubMed:18070875, ECO:0000269|PubMed:18617530, ECO:0000269|PubMed:19036738, ECO:0000269|PubMed:20453062, ECO:0000269|PubMed:22036712, ECO:0000269|PubMed:23624058, ECO:0000269|PubMed:23922729, ECO:0000269|PubMed:25538239, ECO:0000269|PubMed:25544560, ECO:0000269|PubMed:26231210}.; FUNCTION: [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). {ECO:0000269|PubMed:18617530, ECO:0000269|PubMed:22036712}.; FUNCTION: [Isoform 7]: Has phosphatase activity (in vitro). {ECO:0000269|PubMed:22036712}.
uniprot
proteins
mass_dalton
37158
uniprot
proteins
mutagenesis
MUTAGEN 8; /note="V->A: Loss of phosphatase activity. No effect on glycogen binding."; /evidence="ECO:0000269|PubMed:25544560"; MUTAGEN 25; /note="S->A: Partial loss of phosphatase activity. Abolishes homodimerization. Abolishes interaction with NHLRC1, PPP1R3C and PRKAA2. Does not affect glycogen binding. Reduces stability of the protein."; /evidence="ECO:0000269|PubMed:21728993"; MUTAGEN 25; /note="S->D: Partial loss of phosphatase activity. Increases interaction with NHLRC1. Does not affect interaction with NHLRC1, PPP1R3C or PRKAA2. Does not affect binding to carbohydrate. Does not affect homodimerization."; /evidence="ECO:0000269|PubMed:21728993"; MUTAGEN 87; /note="K->A: Loss of phosphatase activity. Abolishes glycogen binding."; /evidence="ECO:0000269|PubMed:11739371, ECO:0000269|PubMed:25544560"; MUTAGEN 99; /note="W->A: Strongly reduces phosphatase activity. Strongly reduces glycogen binding."; /evidence="ECO:0000269|PubMed:25544560"; MUTAGEN 109..110; /note="CC->SS: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity."; /evidence="ECO:0000269|PubMed:23922729"; MUTAGEN 123; /note="C->S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity."; /evidence="ECO:0000269|PubMed:23922729"; MUTAGEN 126; /note="I->T: Strongly decreased phosphatase activity. No effect on glycogen binding."; /evidence="ECO:0000269|PubMed:25544560"; MUTAGEN 142; /note="T->A: Strongly decreased phosphatase activity. No effect on glycogen binding."; /evidence="ECO:0000269|PubMed:25544560"; MUTAGEN 168; /note="S->A,D: Abolishes interaction with NHLRC1."; /evidence="ECO:0000269|PubMed:21728993"; MUTAGEN 169; /note="C->S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity."; /evidence="ECO:0000269|PubMed:23922729"; MUTAGEN 169; /note="C->S: No effect on phosphatase activity."; /evidence="ECO:0000269|PubMed:25538239"; MUTAGEN 171; /note="R->A: No effect on phosphatase activity."; /evidence="ECO:0000269|PubMed:25538239"; MUTAGEN 187; /note="T->D: Abolishes interaction with NHLRC1."; /evidence="ECO:0000269|PubMed:21728993"; MUTAGEN 194; /note="T->D: Does not affect interaction with NHLRC1, PPP1R3C or PRKAA2."; /evidence="ECO:0000269|PubMed:21728993"; MUTAGEN 197; /note="D->A: Strongly decreased phosphatase activity. No effect on glycogen binding."; /evidence="ECO:0000269|PubMed:25538239, ECO:0000269|PubMed:25544560"; MUTAGEN 205; /note="C->S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity."; /evidence="ECO:0000269|PubMed:23922729"; MUTAGEN 235; /note="D->A: Complete loss of phosphatase activity. Does not affect glycogen binding."; /evidence="ECO:0000269|PubMed:14532330, ECO:0000269|PubMed:25538239"; MUTAGEN 236; /note="M->A: Complete loss of phosphatase activity. No effect on glycogen binding."; /evidence="ECO:0000269|PubMed:25544560"; MUTAGEN 250; /note="C->S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity."; /evidence="ECO:0000269|PubMed:23922729"; MUTAGEN 251; /note="L->A: Impairs protein stability. Strongly reduces phosphatase activity. No effect on glycogen binding."; /evidence="ECO:0000269|PubMed:25544560"; MUTAGEN 266; /note="C->S: Complete loss of phosphatase activity. Does not affect glycogen binding. Does not affect self-interaction. Increases the interaction with PPP1R3C."; /evidence="ECO:0000269|PubMed:11220751, ECO:0000269|PubMed:11739371, ECO:0000269|PubMed:14532330, ECO:0000269|PubMed:22036712, ECO:0000269|PubMed:23922729, ECO:0000269|PubMed:25538239, ECO:0000269|PubMed:25544560"; MUTAGEN 272; /note="R->A: Complete loss of phosphatase activity."; /evidence="ECO:0000269|PubMed:25538239"; MUTAGEN 321; /note="F->S: Impairs protein stability. Strongly reduces phosphatase activity. No effect on glycogen binding."; /evidence="ECO:0000269|PubMed:25544560"; MUTAGEN 329..331; /note="Missing: Fails to homodimerize. Does not affect carbohydrate binding or phosphatase activity."; /evidence="ECO:0000269|PubMed:23922729"; MUTAGEN 329; /note="C->S: Fails to homodimerize. Does not affect carbohydrate binding, interaction with NHLRC1, phosphatase activity, or ubiquitination by NHLRC1."; /evidence="ECO:0000269|PubMed:23922729"; MUTAGEN 329; /note="C->S: No effect on homodimerization."; /evidence="ECO:0000269|PubMed:25538239
uniprot
proteins
post_translational_modification
PTM: Polyubiquitinated by NHLRC1/malin. {ECO:0000269|PubMed:15930137}.; PTM: 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. {ECO:0000269|PubMed:21728993}.
uniprot
proteins
protein_family
Protein-tyrosine phosphatase family
uniprot
proteins
pubmed
11001928
uniprot
proteins
pubmed
11175283
uniprot
proteins
pubmed
11220751
uniprot
proteins
pubmed
11735300
uniprot
proteins
pubmed
11739371
uniprot
proteins
pubmed
11883934
uniprot
proteins
pubmed
12019207
uniprot
proteins
pubmed
12560877
uniprot
proteins
pubmed
12782127
uniprot
proteins
pubmed
12915448
uniprot
proteins
pubmed
14532330
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14706656
uniprot
proteins
pubmed
14722920
uniprot
proteins
pubmed
15009235
uniprot
proteins
pubmed
15102711
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15930137
uniprot
proteins
pubmed
16021330
uniprot
proteins
pubmed
16901901
uniprot
proteins
pubmed
16971387
uniprot
proteins
pubmed
17908927
uniprot
proteins
pubmed
18070875
uniprot
proteins
pubmed
18311786
uniprot
proteins
pubmed
18617530
uniprot
proteins
pubmed
19036738
uniprot
proteins
pubmed
19542233
uniprot
proteins
pubmed
20453062
uniprot
proteins
pubmed
21728993
uniprot
proteins
pubmed
22036712
uniprot
proteins
pubmed
22961547
uniprot
proteins
pubmed
23624058
uniprot
proteins
pubmed
23922729
uniprot
proteins
pubmed
25538239
uniprot
proteins
pubmed
25544560
uniprot
proteins
pubmed
26231210
uniprot
proteins
pubmed
9771710
uniprot
proteins
pubmed
9931343
uniprot
proteins
sequence_length
331
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11001928, ECO:0000269|PubMed:11220751, ECO:0000269|PubMed:11739371, ECO:0000269|PubMed:15102711, ECO:0000269|PubMed:17908927}. Note=Under glycogenolytic conditions localizes to the nucleus. {ECO:0000269|PubMed:17908927}.; SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm {ECO:0000269|PubMed:11001928, ECO:0000269|PubMed:11739371, ECO:0000269|PubMed:11883934, ECO:0000269|PubMed:14532330, ECO:0000269|PubMed:18311786, ECO:0000269|PubMed:18617530, ECO:0000269|PubMed:22036712}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:11001928, ECO:0000269|PubMed:14722920, ECO:0000269|PubMed:18311786}; Peripheral membrane protein {ECO:0000269|PubMed:11001928, ECO:0000269|PubMed:18311786}; Cytoplasmic side {ECO:0000269|PubMed:11001928, ECO:0000269|PubMed:18311786}. Cell membrane {ECO:0000269|PubMed:11220751}. Note=Colocalizes with glycogen synthase in punctate structures in the cytoplasm (PubMed:11739371, PubMed:14532330). Primarily associated with polyribosomes at the rough endoplasmic reticulum, and also detected at the plasma membrane (PubMed:11001928, PubMed:11220751, PubMed:11883934, PubMed:18311786). {ECO:0000269|PubMed:11001928, ECO:0000269|PubMed:11220751, ECO:0000269|PubMed:11739371, ECO:0000269|PubMed:11883934, ECO:0000269|PubMed:14532330, ECO:0000269|PubMed:18311786}.; SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000269|PubMed:18617530}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:11883934}; Peripheral membrane protein {ECO:0000269|PubMed:11883934}; Cytoplasmic side {ECO:0000269|PubMed:11883934}. Cell membrane {ECO:0000269|PubMed:11883934}. Nucleus {ECO:0000269|PubMed:11883934, ECO:0000269|PubMed:14722920, ECO:0000269|PubMed:18617530}. Note=Also found in the nucleus. {ECO:0000269|PubMed:11883934, ECO:0000269|PubMed:18617530}.; SUBCELLULAR LOCATION: [Isoform 4]: Cytoplasm {ECO:0000269|PubMed:22036712}. Nucleus {ECO:0000269|PubMed:22036712}.; SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm {ECO:0000269|PubMed:22036712}. Nucleus {ECO:0000269|PubMed:22036712}.; SUBCELLULAR LOCATION: [Isoform 7]: Cytoplasm {ECO:0000269|PubMed:22036712}.
uniprot
proteins