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Protein

Laforin

Gene

EPM2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Has both dual-specificity protein phosphatase and glucan phosphatase activities. Together with the E3 ubiquitin ligase NHLRC1/malin, appears to be involved in the clearance of toxic polyglucosan and protein aggregates via multiple pathways. Dephosphorylates phosphotyrosine, 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. Isoform 2, an inactive phosphatase, could function as a dominant-negative regulator for the phosphatase activity of isoform 1.8 Publications

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei266Phosphocysteine intermediatePROSITE-ProRule annotation1 Publication1
Sitei329Required for homodimerization1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Autophagy, Carbohydrate metabolism, Glycogen metabolism

Enzyme and pathway databases

BioCyciZFISH:HS03569-MONOMER.
BRENDAi3.1.3.16. 2681.
ReactomeiR-HSA-3322077. Glycogen synthesis.
R-HSA-3785653. Myoclonic epilepsy of Lafora.
SIGNORiO95278.

Protein family/group databases

CAZyiCBM20. Carbohydrate-Binding Module Family 20.

Names & Taxonomyi

Protein namesi
Recommended name:
Laforin (EC:3.1.3.-, EC:3.1.3.16, EC:3.1.3.48)
Alternative name(s):
Glucan phosphatase
Lafora PTPase
Short name:
LAFPTPase
Gene namesi
Name:EPM2A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:3413. EPM2A.

Subcellular locationi

Isoform 1 :
Isoform 2 :

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB-SubCell
  • polysome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Epilepsy, progressive myoclonic 2 (EPM2)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive and severe form of adolescent-onset progressive epilepsy. Typically, as seizures increase in frequency, cognitive function declines towards dementia, and affected individuals die usually within 10 years after onset. EPM2 occurs worldwide, but it is particularly common in the mediterranean countries of southern Europe and northern Africa, in southern India and in the Middle East. At the cellular level, it 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. Among other conditions involving polyglucosans, EPM2 is unique in that the inclusions are in neuronal dendrites but not axons and the forming polyglucosan fibrils are associated with the endoplasmic reticulum.
See also OMIM:254780
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01946525S → P in EPM2; atypical form; does not affect glycogen binding. 2 Publications1
Natural variantiVAR_01946628E → K in EPM2; does not affect glycogen binding. 1 Publication1
Natural variantiVAR_01946732W → G in EPM2; affects phosphatase activity; abolishes glycogen binding; disrupts the interaction with PPP1R3C. 4 PublicationsCorresponds to variant rs104893955dbSNPEnsembl.1
Natural variantiVAR_01946984F → L in EPM2; affects phosphatase activity and glycogen binding; disrupts the interaction with PPP1R3C. 2 Publications1
Natural variantiVAR_01947088F → L in EPM2; does not affect glycogen binding. 1 Publication1
Natural variantiVAR_01947191R → P in EPM2; atypical form; learning difficuties with childhood-onset. 2 Publications1
Natural variantiVAR_019472108R → C in EPM2; loss of phosphatase activity; reduced self-interaction capacity; disrupts the interaction with PPP1R3C. 3 PublicationsCorresponds to variant rs137852915dbSNPEnsembl.1
Natural variantiVAR_046383140K → N in EPM2. 1 Publication1
Natural variantiVAR_046384148N → Y in EPM2. 1 Publication1
Natural variantiVAR_019474171R → H in EPM2; results in ubiquitin-positive perinuclear aggregates; may affect proper folding. 4 PublicationsCorresponds to variant rs137852916dbSNPEnsembl.1
Natural variantiVAR_019475187T → A in EPM2; abolishes interaction with NHLRC1. 1 Publication1
Natural variantiVAR_019476194T → I in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; reduced self-interaction capacity; abolishes interaction with NHLRC1, PPP1R3C and PRKAA2; no effect on phosphorylation of protein. 3 PublicationsCorresponds to variant rs375544596dbSNPEnsembl.1
Natural variantiVAR_046385210E → K in EPM2. 1 Publication1
Natural variantiVAR_019477240G → S in EPM2; very slight loss of phosphatase activity; does not affect glycogen binding; disrupts the interaction with PPP1R3C. 2 Publications1
Natural variantiVAR_019478279G → S in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 5 PublicationsCorresponds to variant rs137852917dbSNPEnsembl.1
Natural variantiVAR_019479293Q → L in EPM2; results in ubiquitin-positive perinuclear aggregates; may affect proper folding; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 4 PublicationsCorresponds to variant rs796052427dbSNPEnsembl.1
Natural variantiVAR_019480294Y → N in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 3 Publications1
Natural variantiVAR_019481301P → L in EPM2; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 2 PublicationsCorresponds to variant rs796052428dbSNPEnsembl.1
Natural variantiVAR_046386310L → W in EPM2; alters the subcellular localization of isoform 1; does not affect homodimerization of isoform 1 but prevents heterodimerization of isoform 1 and isoform 2. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi25S → 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. 1 Publication1
Mutagenesisi25S → 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. 1 Publication1
Mutagenesisi87K → A: Partial loss of phosphatase activity. Abolishes glycogen binding. 1 Publication1
Mutagenesisi109 – 110CC → SS: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication2
Mutagenesisi123C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication1
Mutagenesisi168S → A or D: Abolishes interaction with NHLRC1. 1 Publication1
Mutagenesisi169C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication1
Mutagenesisi187T → D: Abolishes interaction with NHLRC1. 1 Publication1
Mutagenesisi194T → D: Does not affect interaction with NHLRC1, PPP1R3C or PRKAA2. 1 Publication1
Mutagenesisi205C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication1
Mutagenesisi235D → A: Loss of phosphatase activity. Does not affect glycogen binding. 1 Publication1
Mutagenesisi250C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication1
Mutagenesisi266C → S: Complete loss of phosphatase activity. Does not affect glycogen binding. Does not affect self-interaction. Increases the interaction with PPP1R3C. 3 Publications1
Mutagenesisi329 – 331Missing : Fails to homodimerize. Does not affect carbohydrate binding or phosphatase activity. 1 Publication3
Mutagenesisi329C → S: Fails to homodimerize. Does not affect carbohydrate binding, interaction with NHLRC1, phosphatase activity, or ubiquitination by NHLRC1. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi7957.
MalaCardsiEPM2A.
MIMi254780. phenotype.
OpenTargetsiENSG00000112425.
Orphaneti501. Lafora disease.
PharmGKBiPA27832.

Chemistry databases

ChEMBLiCHEMBL2311242.

Polymorphism and mutation databases

BioMutaiRNF213.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000948381 – 331LaforinAdd BLAST331

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei25Phosphoserine; by AMPK1 Publication1

Post-translational modificationi

Polyubiquitinated by NHLRC1/malin.1 Publication
Phosphorylation on Ser-25 by AMPK affects the phosphatase activity of the enzyme and its ability to homodimerize and interact with NHLRC1, PPP1R3C or PRKAA2.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO95278.
PeptideAtlasiO95278.
PRIDEiO95278.

PTM databases

DEPODiO95278.
iPTMnetiO95278.
PhosphoSitePlusiO95278.

Expressioni

Tissue specificityi

Expressed in heart, skeletal muscle, kidney, pancreas and brain. Isoform 4 is also expressed in the placenta.1 Publication

Gene expression databases

BgeeiENSG00000112425.
CleanExiHS_EPM2A.
ExpressionAtlasiO95278. baseline and differential.
GenevisibleiO95278. HS.

Organism-specific databases

HPAiHPA053643.
HPA055468.

Interactioni

Subunit structurei

Interacts with itself; however no biological function has been identified for the dimer. Interacts with PPP1R3B, PPP1R3C, 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. Isoform 2 does not bind glycogen. Isoform 1 and isoform 2 interact to form a heterodimeric complex inactive as phosphatase in vitro. Active phosphatase isoform 7 interacts with isoform 1 or isoform 2 to form a heterodimeric complex inactive as phosphatase in vitro. Interacts with PRDM8 (PubMed:22961547).9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
NHLRC1Q6VVB17EBI-2506661,EBI-6426628
PPP1R3CQ9UQK15EBI-2506661,EBI-2506727

Protein-protein interaction databases

BioGridi113679. 23 interactors.
IntActiO95278. 4 interactors.
STRINGi9606.ENSP00000356489.

Chemistry databases

BindingDBiO95278.

Structurei

Secondary structure

1331
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi1 – 9Combined sources9
Helixi11 – 14Combined sources4
Beta strandi19 – 26Combined sources8
Helixi27 – 29Combined sources3
Turni30 – 32Combined sources3
Helixi34 – 36Combined sources3
Beta strandi58 – 67Combined sources10
Beta strandi84 – 91Combined sources8
Beta strandi97 – 103Combined sources7
Helixi104 – 106Combined sources3
Beta strandi108 – 110Combined sources3
Helixi114 – 116Combined sources3
Beta strandi121 – 123Combined sources3
Helixi138 – 151Combined sources14
Beta strandi157 – 161Combined sources5
Beta strandi164 – 167Combined sources4
Helixi173 – 177Combined sources5
Helixi178 – 183Combined sources6
Beta strandi188 – 191Combined sources4
Helixi195 – 201Combined sources7
Helixi203 – 205Combined sources3
Beta strandi208 – 210Combined sources3
Helixi214 – 223Combined sources10
Beta strandi227 – 230Combined sources4
Helixi238 – 258Combined sources21
Beta strandi262 – 265Combined sources4
Helixi271 – 283Combined sources13
Helixi289 – 296Combined sources8
Beta strandi303 – 305Combined sources3
Helixi307 – 321Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4R30X-ray2.30A/B/C/D148-331[»]
4RKKX-ray2.40A/C1-329[»]
ProteinModelPortaliO95278.
SMRiO95278.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 124CBM20PROSITE-ProRule annotationAdd BLAST124
Domaini243 – 311Tyrosine-protein phosphataseAdd BLAST69

Sequence similaritiesi

Contains 1 CBM20 (carbohydrate binding type-20) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1716. Eukaryota.
COG2453. LUCA.
GeneTreeiENSGT00390000010101.
HOGENOMiHOG000285975.
HOVERGENiHBG051493.
KOiK14165.
OMAiRKVQYFV.
OrthoDBiEOG091G0GBM.
PhylomeDBiO95278.
TreeFamiTF332841.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.90.190.10. 1 hit.
InterProiIPR013784. Carb-bd-like_fold.
IPR002044. CBM_fam20.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR024950. DUSP.
IPR013783. Ig-like_fold.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR016130. Tyr_Pase_AS.
IPR000387. TYR_PHOSPHATASE_dom.
IPR020422. TYR_PHOSPHATASE_DUAL_dom.
[Graphical view]
PANTHERiPTHR10159. PTHR10159. 1 hit.
PfamiPF00686. CBM_20. 1 hit.
PF00782. DSPc. 1 hit.
[Graphical view]
SMARTiSM01065. CBM_2. 1 hit.
SM00195. DSPc. 1 hit.
[Graphical view]
SUPFAMiSSF49452. SSF49452. 1 hit.
SSF52799. SSF52799. 1 hit.
PROSITEiPS51166. CBM20. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: O95278-1) [UniParc]FASTAAdd to basket
Also known as: A, LDH1, Laf331

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRFRFGVVVP PAVAGARPEL LVVGSRPELG RWEPRGAVRL RPAGTAAGDG
60 70 80 90 100
ALALQEPGLW LGEVELAAEE AAQDGAEPGR VDTFWYKFLK REPGGELSWE
110 120 130 140 150
GNGPHHDRCC TYNENNLVDG VYCLPIGHWI EATGHTNEMK HTTDFYFNIA
160 170 180 190 200
GHQAMHYSRI LPNIWLGSCP RQVEHVTIKL KHELGITAVM NFQTEWDIVQ
210 220 230 240 250
NSSGCNRYPE PMTPDTMIKL YREEGLAYIW MPTPDMSTEG RVQMLPQAVC
260 270 280 290 300
LLHALLEKGH IVYVHCNAGV GRSTAAVCGW LQYVMGWNLR KVQYFLMAKR
310 320 330
PAVYIDEEAL ARAQEDFFQK FGKVRSSVCS L
Length:331
Mass (Da):37,158
Last modified:May 1, 2000 - v2
Checksum:iDD79F917262AB458
GO
Isoform 2 (identifier: O95278-2) [UniParc]FASTAAdd to basket
Also known as: B, C-terISO, Laf317

The sequence of this isoform differs from the canonical sequence as follows:
     310-320: LARAQEDFFQK → ASQDTFPL
     321-331: Missing.

Note: Produced by alternative splicing.
Show »
Length:317
Mass (Da):35,519
Checksum:i5646A039398AC24D
GO
Isoform 4 (identifier: O95278-4) [UniParc]FASTAAdd to basket
Also known as: Laf152

The sequence of this isoform differs from the canonical sequence as follows:
     102-199: NGPHHDRCCT...MNFQTEWDIV → IASRRLPPAQ...VPAHSPGDLG
     200-331: Missing.

Note: Produced by alternative splicing. May be due to an intron retention.
Show »
Length:152
Mass (Da):15,804
Checksum:i60CD9293F2267EC4
GO
Isoform 5 (identifier: O95278-5) [UniParc]FASTAAdd to basket
Also known as: Laf224

The sequence of this isoform differs from the canonical sequence as follows:
     160-293: Missing.
     294-331: YFLMAKRPAV...GKVRSSVCSL → PSTDAAPGGV...PHGQEAGCLH

Note: Produced by alternative splicing.
Show »
Length:224
Mass (Da):24,134
Checksum:i66ECE43870086B2A
GO
Isoform 6 (identifier: O95278-6) [UniParc]FASTAAdd to basket
Also known as: Laf88

The sequence of this isoform differs from the canonical sequence as follows:
     1-243: Missing.

Note: Produced by alternative initiation at Met-244 of isoform 1. Transcript amplified but protein not detected.
Show »
Length:88
Mass (Da):9,933
Checksum:iD28FAB18CC285D07
GO
Isoform 7 (identifier: O95278-7) [UniParc]FASTAAdd to basket
Also known as: Laf177

The sequence of this isoform differs from the canonical sequence as follows:
     1-159: MRFRFGVVVP...AGHQAMHYSR → MIFNK

Note: Produced by alternative splicing. Active phosphatase.
Show »
Length:177
Mass (Da):20,256
Checksum:i5AE29B26B72E7BF7
GO
Isoform 8 (identifier: O95278-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-138: Missing.

Note: Produced by alternative splicing. No experimental confirmation available.
Show »
Length:193
Mass (Da):22,160
Checksum:i3DC9436A9885B915
GO
Isoform 9 (identifier: B3EWF7-1) [UniParc]FASTAAdd to basket
Also known as: POCR
The sequence of this isoform can be found in the external entry B3EWF7.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by alternative initiation. Arises due to the use of an alternative initiation codon in exon 1 out of frame with isoform 1 and results in a completely different isoform.
Length:344
Mass (Da):35,169
GO

Sequence cautioni

The sequence AAO15523 differs from that shown. Probable cloning artifact.Curated
The sequence BAG51107 differs from that shown. Reason: Frameshift at position 223.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti193Q → K in AAH70047 (PubMed:15489334).Curated1
Sequence conflicti248A → P in AAO15523 (Ref. 4) Curated1
Sequence conflicti258K → E in BAG61454 (PubMed:14702039).Curated1
Sequence conflicti294Y → H in BAG61454 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01946525S → P in EPM2; atypical form; does not affect glycogen binding. 2 Publications1
Natural variantiVAR_01946628E → K in EPM2; does not affect glycogen binding. 1 Publication1
Natural variantiVAR_01946732W → G in EPM2; affects phosphatase activity; abolishes glycogen binding; disrupts the interaction with PPP1R3C. 4 PublicationsCorresponds to variant rs104893955dbSNPEnsembl.1
Natural variantiVAR_01946846A → P Does not affect glycogen binding. 3 PublicationsCorresponds to variant rs374338349dbSNPEnsembl.1
Natural variantiVAR_01946984F → L in EPM2; affects phosphatase activity and glycogen binding; disrupts the interaction with PPP1R3C. 2 Publications1
Natural variantiVAR_01947088F → L in EPM2; does not affect glycogen binding. 1 Publication1
Natural variantiVAR_01947191R → P in EPM2; atypical form; learning difficuties with childhood-onset. 2 Publications1
Natural variantiVAR_019472108R → C in EPM2; loss of phosphatase activity; reduced self-interaction capacity; disrupts the interaction with PPP1R3C. 3 PublicationsCorresponds to variant rs137852915dbSNPEnsembl.1
Natural variantiVAR_019473114E → D.1 Publication1
Natural variantiVAR_046383140K → N in EPM2. 1 Publication1
Natural variantiVAR_046384148N → Y in EPM2. 1 Publication1
Natural variantiVAR_019474171R → H in EPM2; results in ubiquitin-positive perinuclear aggregates; may affect proper folding. 4 PublicationsCorresponds to variant rs137852916dbSNPEnsembl.1
Natural variantiVAR_019475187T → A in EPM2; abolishes interaction with NHLRC1. 1 Publication1
Natural variantiVAR_019476194T → I in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; reduced self-interaction capacity; abolishes interaction with NHLRC1, PPP1R3C and PRKAA2; no effect on phosphorylation of protein. 3 PublicationsCorresponds to variant rs375544596dbSNPEnsembl.1
Natural variantiVAR_046385210E → K in EPM2. 1 Publication1
Natural variantiVAR_019477240G → S in EPM2; very slight loss of phosphatase activity; does not affect glycogen binding; disrupts the interaction with PPP1R3C. 2 Publications1
Natural variantiVAR_019478279G → S in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 5 PublicationsCorresponds to variant rs137852917dbSNPEnsembl.1
Natural variantiVAR_019479293Q → L in EPM2; results in ubiquitin-positive perinuclear aggregates; may affect proper folding; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 4 PublicationsCorresponds to variant rs796052427dbSNPEnsembl.1
Natural variantiVAR_019480294Y → N in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 3 Publications1
Natural variantiVAR_019481301P → L in EPM2; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 2 PublicationsCorresponds to variant rs796052428dbSNPEnsembl.1
Natural variantiVAR_046386310L → W in EPM2; alters the subcellular localization of isoform 1; does not affect homodimerization of isoform 1 but prevents heterodimerization of isoform 1 and isoform 2. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0424941 – 243Missing in isoform 6. 1 PublicationAdd BLAST243
Alternative sequenceiVSP_0424951 – 159MRFRF…MHYSR → MIFNK in isoform 7. 1 PublicationAdd BLAST159
Alternative sequenceiVSP_0424931 – 138Missing in isoform 8. 2 PublicationsAdd BLAST138
Alternative sequenceiVSP_011015102 – 199NGPHH…EWDIV → IASRRLPPAQSGSSGPHPQP GPRPRAGPAGPGGARPGLFA RVPAHSPGDLG in isoform 4. 1 PublicationAdd BLAST98
Alternative sequenceiVSP_042496160 – 293Missing in isoform 5. CuratedAdd BLAST134
Alternative sequenceiVSP_011016200 – 331Missing in isoform 4. 1 PublicationAdd BLAST132
Alternative sequenceiVSP_042497294 – 331YFLMA…SVCSL → PSTDAAPGGVPAACAAGEGT HRVRALQRWGGPLHRGCLRL APVCDGLESEEGAVFPHGQE AGCLH in isoform 5. CuratedAdd BLAST38
Alternative sequenceiVSP_011017310 – 320LARAQEDFFQK → ASQDTFPL in isoform 2. 2 PublicationsAdd BLAST11
Alternative sequenceiVSP_011018321 – 331Missing in isoform 2. 2 PublicationsAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF084535 mRNA. Translation: AAC83347.2.
AF284580 mRNA. Translation: AAG18377.1.
AF454491 mRNA. Translation: AAO15523.1. Sequence problems.
AF454492 mRNA. Translation: AAO15524.1.
AF454493 mRNA. Translation: AAO15525.1.
AF454494 mRNA. Translation: AAO15526.1.
AK022721 mRNA. Translation: BAG51107.1. Frameshift.
AK299497 mRNA. Translation: BAG61454.1.
AL023806, AL365193 Genomic DNA. Translation: CAI21419.1.
AL365193, AL023806 Genomic DNA. Translation: CAI21675.1.
CH471051 Genomic DNA. Translation: EAW47844.1.
BC005286 mRNA. Translation: AAH05286.1.
BC070047 mRNA. Translation: AAH70047.1.
AJ130763 mRNA. Translation: CAA10199.1.
AJ130764 mRNA. Translation: CAA10200.1.
CCDSiCCDS5206.1. [O95278-1]
RefSeqiNP_001018051.1. NM_001018041.1. [O95278-2]
NP_005661.1. NM_005670.3. [O95278-1]
XP_006715627.1. XM_006715564.3. [O95278-5]
XP_011534418.1. XM_011536116.1. [O95278-8]
XP_016866789.1. XM_017011300.1. [O95278-7]
XP_016866790.1. XM_017011301.1. [O95278-7]
XP_016866791.1. XM_017011302.1. [O95278-7]
UniGeneiHs.486696.

Genome annotation databases

EnsembliENST00000367519; ENSP00000356489; ENSG00000112425. [O95278-1]
ENST00000611340; ENSP00000480268; ENSG00000112425. [O95278-8]
ENST00000618445; ENSP00000480339; ENSG00000112425. [O95278-2]
GeneIDi7957.
KEGGihsa:7957.
UCSCiuc003qkw.4. human. [O95278-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

The Lafora progressive myoclonus epilepsy mutation and polymorphism database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF084535 mRNA. Translation: AAC83347.2.
AF284580 mRNA. Translation: AAG18377.1.
AF454491 mRNA. Translation: AAO15523.1. Sequence problems.
AF454492 mRNA. Translation: AAO15524.1.
AF454493 mRNA. Translation: AAO15525.1.
AF454494 mRNA. Translation: AAO15526.1.
AK022721 mRNA. Translation: BAG51107.1. Frameshift.
AK299497 mRNA. Translation: BAG61454.1.
AL023806, AL365193 Genomic DNA. Translation: CAI21419.1.
AL365193, AL023806 Genomic DNA. Translation: CAI21675.1.
CH471051 Genomic DNA. Translation: EAW47844.1.
BC005286 mRNA. Translation: AAH05286.1.
BC070047 mRNA. Translation: AAH70047.1.
AJ130763 mRNA. Translation: CAA10199.1.
AJ130764 mRNA. Translation: CAA10200.1.
CCDSiCCDS5206.1. [O95278-1]
RefSeqiNP_001018051.1. NM_001018041.1. [O95278-2]
NP_005661.1. NM_005670.3. [O95278-1]
XP_006715627.1. XM_006715564.3. [O95278-5]
XP_011534418.1. XM_011536116.1. [O95278-8]
XP_016866789.1. XM_017011300.1. [O95278-7]
XP_016866790.1. XM_017011301.1. [O95278-7]
XP_016866791.1. XM_017011302.1. [O95278-7]
UniGeneiHs.486696.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4R30X-ray2.30A/B/C/D148-331[»]
4RKKX-ray2.40A/C1-329[»]
ProteinModelPortaliO95278.
SMRiO95278.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113679. 23 interactors.
IntActiO95278. 4 interactors.
STRINGi9606.ENSP00000356489.

Chemistry databases

BindingDBiO95278.
ChEMBLiCHEMBL2311242.

Protein family/group databases

CAZyiCBM20. Carbohydrate-Binding Module Family 20.

PTM databases

DEPODiO95278.
iPTMnetiO95278.
PhosphoSitePlusiO95278.

Polymorphism and mutation databases

BioMutaiRNF213.

Proteomic databases

PaxDbiO95278.
PeptideAtlasiO95278.
PRIDEiO95278.

Protocols and materials databases

DNASUi7957.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000367519; ENSP00000356489; ENSG00000112425. [O95278-1]
ENST00000611340; ENSP00000480268; ENSG00000112425. [O95278-8]
ENST00000618445; ENSP00000480339; ENSG00000112425. [O95278-2]
GeneIDi7957.
KEGGihsa:7957.
UCSCiuc003qkw.4. human. [O95278-1]

Organism-specific databases

CTDi7957.
DisGeNETi7957.
GeneCardsiEPM2A.
GeneReviewsiEPM2A.
HGNCiHGNC:3413. EPM2A.
HPAiHPA053643.
HPA055468.
MalaCardsiEPM2A.
MIMi254780. phenotype.
607566. gene.
neXtProtiNX_O95278.
OpenTargetsiENSG00000112425.
Orphaneti501. Lafora disease.
PharmGKBiPA27832.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1716. Eukaryota.
COG2453. LUCA.
GeneTreeiENSGT00390000010101.
HOGENOMiHOG000285975.
HOVERGENiHBG051493.
KOiK14165.
OMAiRKVQYFV.
OrthoDBiEOG091G0GBM.
PhylomeDBiO95278.
TreeFamiTF332841.

Enzyme and pathway databases

BioCyciZFISH:HS03569-MONOMER.
BRENDAi3.1.3.16. 2681.
ReactomeiR-HSA-3322077. Glycogen synthesis.
R-HSA-3785653. Myoclonic epilepsy of Lafora.
SIGNORiO95278.

Miscellaneous databases

ChiTaRSiEPM2A. human.
GenomeRNAii7957.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112425.
CleanExiHS_EPM2A.
ExpressionAtlasiO95278. baseline and differential.
GenevisibleiO95278. HS.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
3.90.190.10. 1 hit.
InterProiIPR013784. Carb-bd-like_fold.
IPR002044. CBM_fam20.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR024950. DUSP.
IPR013783. Ig-like_fold.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR016130. Tyr_Pase_AS.
IPR000387. TYR_PHOSPHATASE_dom.
IPR020422. TYR_PHOSPHATASE_DUAL_dom.
[Graphical view]
PANTHERiPTHR10159. PTHR10159. 1 hit.
PfamiPF00686. CBM_20. 1 hit.
PF00782. DSPc. 1 hit.
[Graphical view]
SMARTiSM01065. CBM_2. 1 hit.
SM00195. DSPc. 1 hit.
[Graphical view]
SUPFAMiSSF49452. SSF49452. 1 hit.
SSF52799. SSF52799. 1 hit.
PROSITEiPS51166. CBM20. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEPM2A_HUMAN
AccessioniPrimary (citable) accession number: O95278
Secondary accession number(s): B3KMU5
, B4DRZ2, O95483, Q5T3F5, Q6IS15, Q8IU96, Q8IX24, Q8IX25, Q9BS66, Q9UEN2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 2000
Last modified: November 2, 2016
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.