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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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei266 – 2661Phosphocysteine intermediatePROSITE-ProRule annotation1 Publication
Sitei329 – 3291Required for homodimerization

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

BRENDAi3.1.3.16. 2681.
ReactomeiR-HSA-3322077. Glycogen synthesis.
R-HSA-3785653. Myoclonic epilepsy of Lafora.

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti25 – 251S → P in EPM2; atypical form; does not affect glycogen binding. 2 Publications
VAR_019465
Natural varianti28 – 281E → K in EPM2; does not affect glycogen binding. 1 Publication
VAR_019466
Natural varianti32 – 321W → G in EPM2; affects phosphatase activity; abolishes glycogen binding; disrupts the interaction with PPP1R3C. 4 Publications
Corresponds to variant rs104893955 [ dbSNP | Ensembl ].
VAR_019467
Natural varianti84 – 841F → L in EPM2; affects phosphatase activity and glycogen binding; disrupts the interaction with PPP1R3C. 2 Publications
VAR_019469
Natural varianti88 – 881F → L in EPM2; does not affect glycogen binding. 1 Publication
VAR_019470
Natural varianti91 – 911R → P in EPM2; atypical form; learning difficuties with childhood-onset. 2 Publications
VAR_019471
Natural varianti108 – 1081R → C in EPM2; loss of phosphatase activity; reduced self-interaction capacity; disrupts the interaction with PPP1R3C. 3 Publications
Corresponds to variant rs137852915 [ dbSNP | Ensembl ].
VAR_019472
Natural varianti140 – 1401K → N in EPM2. 1 Publication
VAR_046383
Natural varianti148 – 1481N → Y in EPM2. 1 Publication
VAR_046384
Natural varianti171 – 1711R → H in EPM2; results in ubiquitin-positive perinuclear aggregates; may affect proper folding. 4 Publications
Corresponds to variant rs137852916 [ dbSNP | Ensembl ].
VAR_019474
Natural varianti187 – 1871T → A in EPM2; abolishes interaction with NHLRC1. 1 Publication
VAR_019475
Natural varianti194 – 1941T → 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 Publications
Corresponds to variant rs375544596 [ dbSNP | Ensembl ].
VAR_019476
Natural varianti210 – 2101E → K in EPM2. 1 Publication
VAR_046385
Natural varianti240 – 2401G → S in EPM2; very slight loss of phosphatase activity; does not affect glycogen binding; disrupts the interaction with PPP1R3C. 2 Publications
VAR_019477
Natural varianti279 – 2791G → S in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 5 Publications
Corresponds to variant rs137852917 [ dbSNP | Ensembl ].
VAR_019478
Natural varianti293 – 2931Q → 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 Publications
Corresponds to variant rs796052427 [ dbSNP | Ensembl ].
VAR_019479
Natural varianti294 – 2941Y → N in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 3 Publications
VAR_019480
Natural varianti301 – 3011P → L in EPM2; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 2 Publications
Corresponds to variant rs796052428 [ dbSNP | Ensembl ].
VAR_019481
Natural varianti310 – 3101L → 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 Publication
VAR_046386

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi25 – 251S → 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 Publication
Mutagenesisi25 – 251S → 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 Publication
Mutagenesisi87 – 871K → A: Partial loss of phosphatase activity. Abolishes glycogen binding. 1 Publication
Mutagenesisi109 – 1102CC → SS: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication
Mutagenesisi123 – 1231C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication
Mutagenesisi168 – 1681S → A or D: Abolishes interaction with NHLRC1. 1 Publication
Mutagenesisi169 – 1691C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication
Mutagenesisi187 – 1871T → D: Abolishes interaction with NHLRC1. 1 Publication
Mutagenesisi194 – 1941T → D: Does not affect interaction with NHLRC1, PPP1R3C or PRKAA2. 1 Publication
Mutagenesisi205 – 2051C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication
Mutagenesisi235 – 2351D → A: Loss of phosphatase activity. Does not affect glycogen binding. 1 Publication
Mutagenesisi250 – 2501C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication
Mutagenesisi266 – 2661C → S: Complete loss of phosphatase activity. Does not affect glycogen binding. Does not affect self-interaction. Increases the interaction with PPP1R3C. 3 Publications
Mutagenesisi329 – 3313Missing : Fails to homodimerize. Does not affect carbohydrate binding or phosphatase activity. 1 Publication
Mutagenesisi329 – 3291C → S: Fails to homodimerize. Does not affect carbohydrate binding, interaction with NHLRC1, phosphatase activity, or ubiquitination by NHLRC1. 1 Publication

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

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

Chemistry

ChEMBLiCHEMBL2311242.

Polymorphism and mutation databases

BioMutaiRNF213.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 331331LaforinPRO_0000094838Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei25 – 251Phosphoserine; by AMPK1 Publication

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.
PhosphoSiteiO95278.

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 interactions.
IntActiO95278. 4 interactions.
STRINGi9606.ENSP00000356489.

Chemistry

BindingDBiO95278.

Structurei

Secondary structure

331
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi1 – 99Combined sources
Helixi11 – 144Combined sources
Beta strandi19 – 268Combined sources
Helixi27 – 293Combined sources
Turni30 – 323Combined sources
Helixi34 – 363Combined sources
Beta strandi58 – 6710Combined sources
Beta strandi84 – 918Combined sources
Beta strandi97 – 1037Combined sources
Helixi104 – 1063Combined sources
Beta strandi108 – 1103Combined sources
Helixi114 – 1163Combined sources
Beta strandi121 – 1233Combined sources
Helixi138 – 15114Combined sources
Beta strandi157 – 1615Combined sources
Beta strandi164 – 1674Combined sources
Helixi173 – 1775Combined sources
Helixi178 – 1836Combined sources
Beta strandi188 – 1914Combined sources
Helixi195 – 2017Combined sources
Helixi203 – 2053Combined sources
Beta strandi208 – 2103Combined sources
Helixi214 – 22310Combined sources
Beta strandi227 – 2304Combined sources
Helixi238 – 25821Combined sources
Beta strandi262 – 2654Combined sources
Helixi271 – 28313Combined sources
Helixi289 – 2968Combined sources
Beta strandi303 – 3053Combined sources
Helixi307 – 32115Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4R30X-ray2.30A/B/C/D148-331[»]
4RKKX-ray2.40A/C1-329[»]
ProteinModelPortaliO95278.
SMRiO95278. Positions 1-331.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 124124CBM20PROSITE-ProRule annotationAdd
BLAST
Domaini243 – 31169Tyrosine-protein phosphataseAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti193 – 1931Q → K in AAH70047 (PubMed:15489334).Curated
Sequence conflicti248 – 2481A → P in AAO15523 (Ref. 4) Curated
Sequence conflicti258 – 2581K → E in BAG61454 (PubMed:14702039).Curated
Sequence conflicti294 – 2941Y → H in BAG61454 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti25 – 251S → P in EPM2; atypical form; does not affect glycogen binding. 2 Publications
VAR_019465
Natural varianti28 – 281E → K in EPM2; does not affect glycogen binding. 1 Publication
VAR_019466
Natural varianti32 – 321W → G in EPM2; affects phosphatase activity; abolishes glycogen binding; disrupts the interaction with PPP1R3C. 4 Publications
Corresponds to variant rs104893955 [ dbSNP | Ensembl ].
VAR_019467
Natural varianti46 – 461A → P Does not affect glycogen binding. 3 Publications
Corresponds to variant rs374338349 [ dbSNP | Ensembl ].
VAR_019468
Natural varianti84 – 841F → L in EPM2; affects phosphatase activity and glycogen binding; disrupts the interaction with PPP1R3C. 2 Publications
VAR_019469
Natural varianti88 – 881F → L in EPM2; does not affect glycogen binding. 1 Publication
VAR_019470
Natural varianti91 – 911R → P in EPM2; atypical form; learning difficuties with childhood-onset. 2 Publications
VAR_019471
Natural varianti108 – 1081R → C in EPM2; loss of phosphatase activity; reduced self-interaction capacity; disrupts the interaction with PPP1R3C. 3 Publications
Corresponds to variant rs137852915 [ dbSNP | Ensembl ].
VAR_019472
Natural varianti114 – 1141E → D.1 Publication
VAR_019473
Natural varianti140 – 1401K → N in EPM2. 1 Publication
VAR_046383
Natural varianti148 – 1481N → Y in EPM2. 1 Publication
VAR_046384
Natural varianti171 – 1711R → H in EPM2; results in ubiquitin-positive perinuclear aggregates; may affect proper folding. 4 Publications
Corresponds to variant rs137852916 [ dbSNP | Ensembl ].
VAR_019474
Natural varianti187 – 1871T → A in EPM2; abolishes interaction with NHLRC1. 1 Publication
VAR_019475
Natural varianti194 – 1941T → 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 Publications
Corresponds to variant rs375544596 [ dbSNP | Ensembl ].
VAR_019476
Natural varianti210 – 2101E → K in EPM2. 1 Publication
VAR_046385
Natural varianti240 – 2401G → S in EPM2; very slight loss of phosphatase activity; does not affect glycogen binding; disrupts the interaction with PPP1R3C. 2 Publications
VAR_019477
Natural varianti279 – 2791G → S in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 5 Publications
Corresponds to variant rs137852917 [ dbSNP | Ensembl ].
VAR_019478
Natural varianti293 – 2931Q → 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 Publications
Corresponds to variant rs796052427 [ dbSNP | Ensembl ].
VAR_019479
Natural varianti294 – 2941Y → N in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 3 Publications
VAR_019480
Natural varianti301 – 3011P → L in EPM2; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 2 Publications
Corresponds to variant rs796052428 [ dbSNP | Ensembl ].
VAR_019481
Natural varianti310 – 3101L → 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 Publication
VAR_046386

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 243243Missing in isoform 6. 1 PublicationVSP_042494Add
BLAST
Alternative sequencei1 – 159159MRFRF…MHYSR → MIFNK in isoform 7. 1 PublicationVSP_042495Add
BLAST
Alternative sequencei1 – 138138Missing in isoform 8. 2 PublicationsVSP_042493Add
BLAST
Alternative sequencei102 – 19998NGPHH…EWDIV → IASRRLPPAQSGSSGPHPQP GPRPRAGPAGPGGARPGLFA RVPAHSPGDLG in isoform 4. 1 PublicationVSP_011015Add
BLAST
Alternative sequencei160 – 293134Missing in isoform 5. CuratedVSP_042496Add
BLAST
Alternative sequencei200 – 331132Missing in isoform 4. 1 PublicationVSP_011016Add
BLAST
Alternative sequencei294 – 33138YFLMA…SVCSL → PSTDAAPGGVPAACAAGEGT HRVRALQRWGGPLHRGCLRL APVCDGLESEEGAVFPHGQE AGCLH in isoform 5. CuratedVSP_042497Add
BLAST
Alternative sequencei310 – 32011LARAQEDFFQK → ASQDTFPL in isoform 2. 2 PublicationsVSP_011017Add
BLAST
Alternative sequencei321 – 33111Missing in isoform 2. 2 PublicationsVSP_011018Add
BLAST

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]
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]
UniGeneiHs.486696.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4R30X-ray2.30A/B/C/D148-331[»]
4RKKX-ray2.40A/C1-329[»]
ProteinModelPortaliO95278.
SMRiO95278. Positions 1-331.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113679. 23 interactions.
IntActiO95278. 4 interactions.
STRINGi9606.ENSP00000356489.

Chemistry

BindingDBiO95278.
ChEMBLiCHEMBL2311242.

Protein family/group databases

CAZyiCBM20. Carbohydrate-Binding Module Family 20.

PTM databases

DEPODiO95278.
iPTMnetiO95278.
PhosphoSiteiO95278.

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

Phylogenomic databases

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

Enzyme and pathway databases

BRENDAi3.1.3.16. 2681.
ReactomeiR-HSA-3322077. Glycogen synthesis.
R-HSA-3785653. Myoclonic epilepsy of Lafora.

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: September 7, 2016
This is version 148 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.