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O95278

- EPM2A_HUMAN

UniProt

O95278 - EPM2A_HUMAN

Protein

Laforin

Gene

EPM2A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 2 (01 May 2000)
      Previous versions | rss
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    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 intermediate1 PublicationPROSITE-ProRule annotation
    Sitei329 – 3291Required for homodimerization

    GO - Molecular functioni

    1. carbohydrate phosphatase activity Source: Reactome
    2. phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity Source: RefGenome
    3. protein binding Source: UniProtKB
    4. protein serine/threonine phosphatase activity Source: UniProtKB
    5. protein tyrosine/serine/threonine phosphatase activity Source: RefGenome
    6. protein tyrosine phosphatase activity Source: UniProtKB
    7. starch binding Source: InterPro

    GO - Biological processi

    1. autophagy Source: UniProtKB-KW
    2. carbohydrate metabolic process Source: Reactome
    3. glucose metabolic process Source: Reactome
    4. glycogen biosynthetic process Source: Reactome
    5. glycogen metabolic process Source: UniProtKB
    6. habituation Source: Ensembl
    7. inositol phosphate dephosphorylation Source: RefGenome
    8. nervous system development Source: Ensembl
    9. peptidyl-tyrosine dephosphorylation Source: GOC
    10. protein dephosphorylation Source: UniProtKB
    11. small molecule metabolic process Source: Reactome

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Biological processi

    Autophagy, Carbohydrate metabolism, Glycogen metabolism

    Enzyme and pathway databases

    ReactomeiREACT_169208. Glycogen synthesis.
    REACT_200783. 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
    ProteomesiUP000005640: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:3413. EPM2A.

    Subcellular locationi

    Cytoplasm 5 Publications
    Note: Under glycogenolytic conditions localizes to the nucleus.
    Isoform 1 : Endoplasmic reticulum. Cell membrane
    Note: Primarily associated with polyribosomes at the endoplasmic reticulum, also found at the plasma membrane.
    Isoform 2 : Endoplasmic reticulum 1 Publication. Cell membrane 1 Publication. Nucleus 1 Publication
    Note: Also found in the nucleus.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: UniProtKB
    3. endoplasmic reticulum Source: UniProtKB-SubCell
    4. nucleus Source: RefGenome
    5. plasma membrane Source: UniProtKB-SubCell
    6. polysome Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Epilepsy, progressive myoclonic 2 (EPM2) [MIM:254780]: An 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.8 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti25 – 251S → P in EPM2; atypical form; does not affect glycogen binding. 1 Publication
    VAR_019465
    Natural varianti28 – 281E → K in EPM2; does not affect glycogen binding.
    VAR_019466
    Natural varianti32 – 321W → G in EPM2; affects phosphatase activity; abolishes glycogen binding; reduced binding to Lafora bodies; disrupts the interaction with PPP1R3C; significant protein amount targeted to the nucleus.
    VAR_019467
    Natural varianti84 – 841F → L in EPM2; affects phosphatase activity and glycogen binding; disrupts the interaction with PPP1R3C. 1 Publication
    VAR_019469
    Natural varianti88 – 881F → L in EPM2; does not affect glycogen binding.
    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. 2 Publications
    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. 3 Publications
    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. 1 Publication
    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. 1 Publication
    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. 3 Publications
    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. 2 Publications
    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. 1 Publication
    VAR_019480
    Natural varianti301 – 3011P → L in EPM2; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 1 Publication
    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.
    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

    MIMi254780. phenotype.
    Orphaneti501. Lafora disease.
    PharmGKBiPA27832.

    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 AMPK

    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.

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiO95278.
    PRIDEiO95278.

    PTM databases

    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

    ArrayExpressiO95278.
    BgeeiO95278.
    CleanExiHS_EPM2A.
    GenevestigatoriO95278.

    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.8 Publications

    Binary interactionsi

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

    Protein-protein interaction databases

    BioGridi113679. 13 interactions.
    IntActiO95278. 2 interactions.
    STRINGi9606.ENSP00000356489.

    Structurei

    3D structure databases

    ProteinModelPortaliO95278.
    SMRiO95278. Positions 8-108, 154-301.
    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

    eggNOGiNOG243912.
    HOGENOMiHOG000285975.
    HOVERGENiHBG051493.
    InParanoidiO95278.
    KOiK14165.
    OMAiHWIEVSG.
    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.
    IPR020422. Dual-sp_phosphatase_subgr_cat.
    IPR024950. DUSP.
    IPR013783. Ig-like_fold.
    IPR029021. Prot-tyrosine_phosphatase-like.
    IPR000387. Tyr/Dual-sp_Pase.
    IPR016130. Tyr_Pase_AS.
    [Graphical view]
    PANTHERiPTHR10159. PTHR10159. 1 hit.
    PfamiPF00686. CBM_20. 1 hit.
    PF00782. DSPc. 1 hit.
    [Graphical view]
    SMARTiSM01065. CBM_2. 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 (9)i

    Sequence statusi: Complete.

    This entry describes 9 isoformsi produced by alternative splicing and alternative initiation. Align

    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

    MRFRFGVVVP PAVAGARPEL LVVGSRPELG RWEPRGAVRL RPAGTAAGDG    50
    ALALQEPGLW LGEVELAAEE AAQDGAEPGR VDTFWYKFLK REPGGELSWE 100
    GNGPHHDRCC TYNENNLVDG VYCLPIGHWI EATGHTNEMK HTTDFYFNIA 150
    GHQAMHYSRI LPNIWLGSCP RQVEHVTIKL KHELGITAVM NFQTEWDIVQ 200
    NSSGCNRYPE PMTPDTMIKL YREEGLAYIW MPTPDMSTEG RVQMLPQAVC 250
    LLHALLEKGH IVYVHCNAGV GRSTAAVCGW LQYVMGWNLR KVQYFLMAKR 300
    PAVYIDEEAL ARAQEDFFQK FGKVRSSVCS L 331
    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 3 (identifier: O95278-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         75-100: GAEPGRVDTFWYKFLKREPGGELSWE → LVKIGSAPETRSKIFPRFTIRRRLSR

    Note: Produced by alternative splicing. No experimental confirmation available.

    Show »
    Length:331
    Mass (Da):37,188
    Checksum:i65E7EC44AE20B083
    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.

    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 BAG51107.1 differs from that shown. Reason: Frameshift at position 223.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti193 – 1931Q → K in AAH70047. (PubMed:15489334)Curated
    Sequence conflicti248 – 2481A → P in AAO15523. 1 PublicationCurated
    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. 1 Publication
    VAR_019465
    Natural varianti28 – 281E → K in EPM2; does not affect glycogen binding.
    VAR_019466
    Natural varianti32 – 321W → G in EPM2; affects phosphatase activity; abolishes glycogen binding; reduced binding to Lafora bodies; disrupts the interaction with PPP1R3C; significant protein amount targeted to the nucleus.
    VAR_019467
    Natural varianti46 – 461A → P Does not affect glycogen binding. 2 Publications
    VAR_019468
    Natural varianti84 – 841F → L in EPM2; affects phosphatase activity and glycogen binding; disrupts the interaction with PPP1R3C. 1 Publication
    VAR_019469
    Natural varianti88 – 881F → L in EPM2; does not affect glycogen binding.
    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. 2 Publications
    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. 3 Publications
    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. 1 Publication
    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. 1 Publication
    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. 3 Publications
    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. 2 Publications
    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. 1 Publication
    VAR_019480
    Natural varianti301 – 3011P → L in EPM2; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 1 Publication
    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 sequencei75 – 10026GAEPG…ELSWE → LVKIGSAPETRSKIFPRFTI RRRLSR in isoform 3. 1 PublicationVSP_011014Add
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF084535 mRNA. Translation: AAC83347.2.
    AF284580 mRNA. Translation: AAG18377.1.
    AF454491 mRNA. Translation: AAO15523.1.
    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_006715564.1. [O95278-5]
    XP_006715628.1. XM_006715565.1. [O95278-7]
    UniGeneiHs.486696.

    Genome annotation databases

    EnsembliENST00000367519; ENSP00000356489; ENSG00000112425. [O95278-1]
    GeneIDi7957.
    KEGGihsa:7957.
    UCSCiuc003qku.3. human. [O95278-7]
    uc003qkv.3. human. [O95278-2]
    uc003qkw.3. human. [O95278-1]
    uc010khr.3. human. [O95278-5]

    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF084535 mRNA. Translation: AAC83347.2 .
    AF284580 mRNA. Translation: AAG18377.1 .
    AF454491 mRNA. Translation: AAO15523.1 .
    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 .
    CCDSi CCDS5206.1. [O95278-1 ]
    RefSeqi NP_001018051.1. NM_001018041.1. [O95278-2 ]
    NP_005661.1. NM_005670.3. [O95278-1 ]
    XP_006715627.1. XM_006715564.1. [O95278-5 ]
    XP_006715628.1. XM_006715565.1. [O95278-7 ]
    UniGenei Hs.486696.

    3D structure databases

    ProteinModelPortali O95278.
    SMRi O95278. Positions 8-108, 154-301.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113679. 13 interactions.
    IntActi O95278. 2 interactions.
    STRINGi 9606.ENSP00000356489.

    Chemistry

    ChEMBLi CHEMBL2311242.

    Protein family/group databases

    CAZyi CBM20. Carbohydrate-Binding Module Family 20.

    PTM databases

    PhosphoSitei O95278.

    Proteomic databases

    PaxDbi O95278.
    PRIDEi O95278.

    Protocols and materials databases

    DNASUi 7957.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000367519 ; ENSP00000356489 ; ENSG00000112425 . [O95278-1 ]
    GeneIDi 7957.
    KEGGi hsa:7957.
    UCSCi uc003qku.3. human. [O95278-7 ]
    uc003qkv.3. human. [O95278-2 ]
    uc003qkw.3. human. [O95278-1 ]
    uc010khr.3. human. [O95278-5 ]

    Organism-specific databases

    CTDi 7957.
    GeneCardsi GC06M145822.
    GeneReviewsi EPM2A.
    HGNCi HGNC:3413. EPM2A.
    HPAi HPA053643.
    HPA055468.
    MIMi 254780. phenotype.
    607566. gene.
    neXtProti NX_O95278.
    Orphaneti 501. Lafora disease.
    PharmGKBi PA27832.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG243912.
    HOGENOMi HOG000285975.
    HOVERGENi HBG051493.
    InParanoidi O95278.
    KOi K14165.
    OMAi HWIEVSG.
    PhylomeDBi O95278.
    TreeFami TF332841.

    Enzyme and pathway databases

    Reactomei REACT_169208. Glycogen synthesis.
    REACT_200783. Myoclonic epilepsy of Lafora.

    Miscellaneous databases

    GenomeRNAii 7957.
    NextBioi 30475.
    PROi O95278.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O95278.
    Bgeei O95278.
    CleanExi HS_EPM2A.
    Genevestigatori O95278.

    Family and domain databases

    Gene3Di 2.60.40.10. 1 hit.
    3.90.190.10. 1 hit.
    InterProi IPR013784. Carb-bd-like_fold.
    IPR002044. CBM_fam20.
    IPR000340. Dual-sp_phosphatase_cat-dom.
    IPR020422. Dual-sp_phosphatase_subgr_cat.
    IPR024950. DUSP.
    IPR013783. Ig-like_fold.
    IPR029021. Prot-tyrosine_phosphatase-like.
    IPR000387. Tyr/Dual-sp_Pase.
    IPR016130. Tyr_Pase_AS.
    [Graphical view ]
    PANTHERi PTHR10159. PTHR10159. 1 hit.
    Pfami PF00686. CBM_20. 1 hit.
    PF00782. DSPc. 1 hit.
    [Graphical view ]
    SMARTi SM01065. CBM_2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49452. SSF49452. 1 hit.
    SSF52799. SSF52799. 1 hit.
    PROSITEi PS51166. CBM20. 1 hit.
    PS00383. TYR_PHOSPHATASE_1. 1 hit.
    PS50056. TYR_PHOSPHATASE_2. 1 hit.
    PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING, PROBABLE FUNCTION, TISSUE SPECIFICITY, VARIANTS EPM2 CYS-108; SER-279 AND LEU-293, VARIANT ASP-114.
    2. "Laforin, defective in the progressive myoclonus epilepsy of Lafora type, is a dual-specificity phosphatase associated with polyribosomes."
      Ganesh S., Agarwala K.L., Ueda K., Akagi T., Shoda K., Usui T., Hashikawa T., Osada H., Delgado-Escueta A.V., Yamakawa K.
      Hum. Mol. Genet. 9:2251-2261(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTIONAL CHARACTERIZATION, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS EPM2 HIS-171 AND LEU-293.
      Tissue: Fetal brain.
    3. Lee J.R., Scherer S.W.
      Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    4. "Cloning of differentially spliced transcripts of the EPM2A gene."
      Ganesh S., Yamakawa K.
      Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 8), NUCLEOTIDE SEQUENCE [MRNA] OF 25-331 (ISOFORM 4), NUCLEOTIDE SEQUENCE [MRNA] OF 75-331 (ISOFORM 3).
      Tissue: Cerebellum and Fetal brain.
    5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 7 AND 8).
      Tissue: Fetal brain and Teratocarcinoma.
    6. "The DNA sequence and analysis of human chromosome 6."
      Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
      Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 6).
      Tissue: Hypothalamus and Kidney.
    9. "A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2)."
      Serratosa J.M., Gomez-Garre P., Gallardo M.E., Anta B., de Bernabe D.B., Lindhout D., Augustijn P.B., Tassinari C.A., Malafosse R.M., Topcu M., Grid D., Dravet C., Berkovic S.F., de Cordoba S.R.
      Hum. Mol. Genet. 8:345-352(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 82-331 (ISOFORMS 1 AND 2), VARIANTS EPM2 HIS-171; ILE-194; SER-279 AND ASN-294.
    10. "Laforin is a cell membrane and endoplasmic reticulum-associated protein tyrosine phosphatase."
      Minassian B.A., Andrade D.M., Ianzano L., Young E.J., Chan E., Ackerley C.A., Scherer S.W.
      Ann. Neurol. 49:271-275(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION.
    11. "Alternative splicing modulates subcellular localization of laforin."
      Ganesh S., Suzuki T., Yamakawa K.
      Biochem. Biophys. Res. Commun. 291:1134-1137(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING, SUBCELLULAR LOCATION (ISOFORM 2).
    12. "A unique carbohydrate binding domain targets the Lafora disease phosphatase to glycogen."
      Wang J., Stuckey J.A., Wishart M.J., Dixon J.E.
      J. Biol. Chem. 277:2377-2380(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOGEN-BINDING, SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT EPM2 GLY-32, ACTIVE SITE, MUTAGENESIS OF LYS-87 AND CYS-266.
    13. "Identification of a novel protein interacting with laforin, the EPM2A progressive myoclonus epilepsy gene product."
      Ianzano L., Zhao X.C., Minassian B.A., Scherer S.W.
      Genomics 81:579-587(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EPM2AIP1.
    14. "The Lafora disease gene product laforin interacts with HIRIP5, a phylogenetically conserved protein containing a NifU-like domain."
      Ganesh S., Tsurutani N., Suzuki T., Ueda K., Agarwala K.L., Osada H., Delgado-Escueta A.V., Yamakawa K.
      Hum. Mol. Genet. 12:2359-2368(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HIRIP5.
    15. "Laforin, the dual-phosphatase responsible for Lafora disease, interacts with R5 (PTG), a regulatory subunit of protein phosphatase-1 that enhances glycogen accumulation."
      Fernandez-Sanchez M.E., Criado-Garcia O., Heath K.E., Garcia-Fojeda B., Medrano-Fernandez I., Gomez-Garre P., Sanz P., Serratosa J.M., Rodriguez de Cordoba S.
      Hum. Mol. Genet. 12:3161-3171(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: SELF-INTERACTION, INTERACTION WITH PPP1R3C, MUTAGENESIS OF ASP-235 AND CYS-266, CHARACTERIZATION OF VARIANTS EPM2 GLY-32; LEU-84; CYS-108; ILE-194; SER-240; SER-279; LEU-293; ASN-294 AND LEU-301.
    16. "The carbohydrate-binding domain of Lafora disease protein targets Lafora polyglucosan bodies."
      Ganesh S., Tsurutani N., Suzuki T., Hoshii Y., Ishihara T., Delgado-Escueta A.V., Yamakawa K.
      Biochem. Biophys. Res. Commun. 313:1101-1109(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: BINDING TO LAFORA BODIES, CHARACTERIZATION OF VARIANTS EPM2 PRO-25; LYS-28; GLY-32 AND LEU-88, CHARACTERIZATION OF VARIANT PRO-46.
    17. "Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin."
      Gentry M.S., Worby C.A., Dixon J.E.
      Proc. Natl. Acad. Sci. U.S.A. 102:8501-8506(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NHLRC1, POLYUBIQUITINATION.
    18. "Laforin, a dual specificity phosphatase that dephosphorylates complex carbohydrates."
      Worby C.A., Gentry M.S., Dixon J.E.
      J. Biol. Chem. 281:30412-30418(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS A GLUCAN PHOSPHATASE, INTERACTION WITH PPP1R3B; PPP1R3C AND PPP1R3D.
    19. "A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori's disease."
      Cheng A., Zhang M., Gentry M.S., Worby C.A., Dixon J.E., Saltiel A.R.
      Genes Dev. 21:2399-2409(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    20. "Modulation of functional properties of laforin phosphatase by alternative splicing reveals a novel mechanism for the EPM2A gene in Lafora progressive myoclonus epilepsy."
      Dubey D., Ganesh S.
      Hum. Mol. Genet. 17:3010-3020(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, HOMODIMERIZATION, HETERODIMERIZATION, SUBCELLULAR LOCATION.
    21. "Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG)."
      Worby C.A., Gentry M.S., Dixon J.E.
      J. Biol. Chem. 283:4069-4076(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH PPP1R3C.
    22. "The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system."
      Garyali P., Siwach P., Singh P.K., Puri R., Mittal S., Sengupta S., Parihar R., Ganesh S.
      Hum. Mol. Genet. 18:688-700(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, COMPLEX FORMATION WITH NHLRC1 AND HSP70.
    23. "Hyperphosphorylation and aggregation of Tau in laforin-deficient mice, an animal model for Lafora disease."
      Puri R., Suzuki T., Yamakawa K., Ganesh S.
      J. Biol. Chem. 284:22657-22663(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MAPT.
    24. "Laforin, the most common protein mutated in Lafora disease, regulates autophagy."
      Aguado C., Sarkar S., Korolchuk V.I., Criado O., Vernia S., Boya P., Sanz P., de Cordoba S.R., Knecht E., Rubinsztein D.C.
      Hum. Mol. Genet. 19:2867-2876(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    25. "Laforin, a dual-specificity phosphatase involved in Lafora disease, is phosphorylated at Ser25 by AMP-activated protein kinase."
      Roma-Mateo C., Solaz-Fuster Mdel C., Gimeno-Alcaniz J.V., Dukhande V.V., Donderis J., Worby C.A., Marina A., Criado O., Koller A., Rodriguez De Cordoba S., Gentry M.S., Sanz P.
      Biochem. J. 439:265-275(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-25 (ISOFORM 1), MUTAGENESIS OF SER-25; SER-168; THR-187 AND THR-194.
    26. "Identification and characterization of novel splice variants of the human EPM2A gene mutated in Lafora progressive myoclonus epilepsy."
      Dubey D., Parihar R., Ganesh S.
      Genomics 99:36-43(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ALTERNATIVE SPLICING (ISOFORMS 4; 5; 6; 7 AND 9).
    27. "Glycogenic activity of R6, a protein phosphatase 1 regulatory subunit, is modulated by the laforin-malin complex."
      Rubio-Villena C., Garcia-Gimeno M.A., Sanz P.
      Int. J. Biochem. Cell Biol. 45:1479-1488(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH PPP1R3D.
    28. "Dimerization of the glucan phosphatase laforin requires the participation of cysteine 329."
      Sanchez-Martin P., Raththagala M., Bridges T.M., Husodo S., Gentry M.S., Sanz P., Roma-Mateo C.
      PLoS ONE 8:E69523-E69523(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF 109-CYS-CYS-110; CYS-123; CYS-169; CYS-205; CYS-250; CYS-266; CYS-329 AND 329-CYS--CYS-331.
    29. "Mutational spectrum of the EPM2A gene in progressive myoclonus epilepsy of Lafora: high degree of allelic heterogeneity and prevalence of deletions."
      Gomez-Garre P., Sanz Y., Rodriguez de Cordoba S.R., Serratosa J.M.
      Eur. J. Hum. Genet. 8:946-954(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS EPM2 LEU-84; SER-240 AND LEU-301.
    30. "Mutation screening for Japanese Lafora's disease patients: identification of novel sequence variants in the coding and upstream regulatory regions of EPM2A gene."
      Ganesh S., Shoda K., Amano K., Uchiyama A., Kumada S., Moriyama N., Hirose S., Yamakawa K.
      Mol. Cell. Probes 15:281-289(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PRO-46.
    31. "Genotype-phenotype correlations for EPM2A mutations in Lafora's progressive myoclonus epilepsy: exon 1 mutations associate with an early-onset cognitive deficit subphenotype."
      Ganesh S., Delgado-Escueta A.V., Suzuki T., Francheschetti S., Riggio C., Avanzini G., Rabinowicz A., Bohlega S., Bailey J., Alonso M.E., Rasmussen A., Thomson A.E., Ochoa A., Prado A.J., Medina M.T., Yamakawa K.
      Hum. Mol. Genet. 11:1263-1271(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS EPM2 PRO-25; CYS-108; HIS-171 AND LEU-293, CHARACTERIZATION OF VARIANTS EPM2 GLY-32; CYS-108; ILE-194; SER-279 AND ASN-294.
    32. "Two novel mutations in the EPM2A gene in a Korean patient with Lafora's progressive myoclonus epilepsy."
      Ki C.S., Kong S.Y., Seo D.W., Hong S.B., Kim H.J., Kim J.W.
      J. Hum. Genet. 48:51-54(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT EPM2 ALA-187.
    33. "A novel exon 1 mutation in a patient with atypical Lafora progressive myoclonus epilepsy seen as childhood-onset cognitive deficit."
      Annesi G., Sofia V., Gambardella A., Ciro Candiano I.C., Spadafora P., Annesi F., Cutuli N., De Marco E.V., Civitelli D., Carrideo S., Tarantino P., Barone R., Zappia M., Quattrone A.
      Epilepsia 45:294-295(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT EPM2 PRO-91.
    34. "Loss of function of the cytoplasmic isoform of the protein laforin (EPM2A) causes Lafora progressive myoclonus epilepsy."
      Ianzano L., Young E.J., Zhao X.C., Chan E.M., Rodriguez M.T., Torrado M.V., Scherer S.W., Minassian B.A.
      Hum. Mutat. 23:170-176(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS EPM2 PRO-91; HIS-171 AND SER-279.
    35. "Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population."
      Singh S., Suzuki T., Uchiyama A., Kumada S., Moriyama N., Hirose S., Takahashi Y., Sugie H., Mizoguchi K., Inoue Y., Kimura K., Sawaishi Y., Yamakawa K., Ganesh S.
      J. Hum. Genet. 50:347-352(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PRO-46.
    36. "Lafora disease in the Indian population: EPM2A and NHLRC1 gene mutations and their impact on subcellular localization of laforin and malin."
      Singh S., Satishchandra P., Shankar S.K., Ganesh S.
      Hum. Mutat. 29:E1-12(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS EPM2 ASN-140; TYR-148; LYS-210 AND TRP-310, CHARACTERIZATION OF VARIANT EPM2 TRP-310.

    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: October 1, 2014
    This is version 126 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

    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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3