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Q1M199

- EPM2A_CANFA

UniProt

Q1M199 - EPM2A_CANFA

Protein

Laforin

Gene

EPM2A

Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - Annotation score: 4 out of 5- Protein inferred from homologyi
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    • History
      Entry version 59 (01 Oct 2014)
      Sequence version 1 (30 May 2006)
      Previous versions | rss
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    • Comment

    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 By similarity.By similarity

    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 annotation
    Sitei329 – 3291Required for homodimerizationBy similarity

    GO - Molecular functioni

    1. protein tyrosine/serine/threonine phosphatase activity Source: InterPro
    2. protein tyrosine phosphatase activity Source: UniProtKB-EC
    3. starch binding Source: InterPro

    GO - Biological processi

    1. autophagy Source: UniProtKB-KW
    2. glycogen metabolic process Source: UniProtKB-KW

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Biological processi

    Autophagy, Carbohydrate metabolism, Glycogen metabolism

    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
    OrganismiCanis familiaris (Dog) (Canis lupus familiaris)
    Taxonomic identifieri9615 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
    ProteomesiUP000002254: Unplaced

    Subcellular locationi

    Cytoplasm By similarity. Endoplasmic reticulum By similarity
    Note: Under glycogenolytic conditions localizes to the nucleus.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. endoplasmic reticulum Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 331331LaforinPRO_0000289592Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei25 – 251Phosphoserine; by AMPKBy similarity

    Post-translational modificationi

    Polyubiquitinated by NHLRC1/malin.By similarity
    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.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    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 By similarity.By similarity

    Protein-protein interaction databases

    STRINGi9615.ENSCAFP00000000457.

    Structurei

    3D structure databases

    ProteinModelPortaliQ1M199.
    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.
    InParanoidiQ1M199.

    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]

    Sequencei

    Sequence statusi: Complete.

    Q1M199-1 [UniParc]FASTAAdd to Basket

    « Hide

    MRFRFGVVVP PAGAGAAPEL LVVGSRPELG RWEPRGAVRL RPAGSAAGGG    50
    ARALQEPGLW LGEVELAPGE AARDGAEPAR VDTFWYKFLK REPGGALSWE 100
    GNGPHHDRCC TYNENNLVDG VYCLPIGHWI EATGHTNEMK HTTDFYFNIA 150
    GHQAMHYSRI LPNIWLGSCP RQVEHITIKL KHELGITAVM NFQTEWDIVQ 200
    NSSGCNRYPE PMTPDTMIKL YKEEGLVYIW MPTPDMSTEG RVQMLPQAVC 250
    LLHALLENGH TVYVHCNAGV GRSTAAVCGW LQYVMGWNLR KVQYFLMAKR 300
    PAVYIDEDAL ARAEEDFFQK FGKVRSSVCS V 331
    Length:331
    Mass (Da):36,900
    Last modified:May 30, 2006 - v1
    Checksum:i788A905A6D82835B
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY560906 Genomic DNA. Translation: ABE98181.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY560906 Genomic DNA. Translation: ABE98181.1 .

    3D structure databases

    ProteinModelPortali Q1M199.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9615.ENSCAFP00000000457.

    Protein family/group databases

    CAZyi CBM20. Carbohydrate-Binding Module Family 20.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Phylogenomic databases

    eggNOGi NOG243912.
    HOGENOMi HOG000285975.
    HOVERGENi HBG051493.
    InParanoidi Q1M199.

    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 [GENOMIC DNA].

    Entry informationi

    Entry nameiEPM2A_CANFA
    AccessioniPrimary (citable) accession number: Q1M199
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 29, 2007
    Last sequence update: May 30, 2006
    Last modified: October 1, 2014
    This is version 59 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3