Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q91XQ2

- EPM2A_RAT

UniProt

Q91XQ2 - EPM2A_RAT

Protein

Laforin

Gene

Epm2a

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 91 (01 Oct 2014)
      Sequence version 2 (16 Apr 2014)
      Previous versions | rss
    • Help video
    • Feedback
    • 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. phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity Source: RefGenome
    2. protein tyrosine/serine/threonine phosphatase activity Source: RefGenome
    3. protein tyrosine phosphatase activity Source: UniProtKB-EC
    4. starch binding Source: InterPro

    GO - Biological processi

    1. autophagy Source: UniProtKB-KW
    2. glycogen metabolic process Source: UniProtKB-KW
    3. inositol phosphate dephosphorylation Source: RefGenome
    4. protein dephosphorylation Source: RefGenome

    Keywords - Molecular functioni

    Hydrolase, Protein phosphatase

    Keywords - Biological processi

    Autophagy, Carbohydrate metabolism, Glycogen metabolism

    Enzyme and pathway databases

    ReactomeiREACT_207828. Myoclonic epilepsy of Lafora.
    REACT_214969. Glycogen synthesis.

    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
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi71047. Epm2a.

    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
    3. nucleus Source: RefGenome

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 331331LaforinPRO_0000094840Add
    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

    Proteomic databases

    PRIDEiQ91XQ2.

    Expressioni

    Tissue specificityi

    Widely expressed.1 Publication

    Gene expression databases

    GenevestigatoriQ91XQ2.

    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

    STRINGi10116.ENSRNOP00000058646.

    Structurei

    3D structure databases

    ProteinModelPortaliQ91XQ2.
    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.
    GeneTreeiENSGT00390000010101.
    HOGENOMiHOG000285975.
    HOVERGENiHBG051493.
    InParanoidiQ91XQ2.
    KOiK14165.
    OMAiHWIEVSG.

    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.

    Q91XQ2-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLFRFGVVVP PAVAGTRLEL LLAGSRPELG RWEPRGAVRL RPAGTAAGAA    50
    ALALQEPGLW LAEVELAPEE EAADGAEPGR IDTFWYKFLQ REPGGELHWE 100
    GNGPHHDRCC TYNENNLVDG VYCLPVGHWI EATGHTNEMK HTTDFYFNIA 150
    GHQAMHYSRI LPNIWLGSCP RQLEHVTIKL KHELGITAVM NFQTEWDIIQ 200
    NSSGCNRYPE PMTPDTMMKL YKEEGLAYIW MPTPDMSTEG RVQMLPQAVC 250
    LLHALLENGH TVYVHCNAGV GRSTAAVCGW LHYVIGWSLR KVQYFIMAKR 300
    PAVYIDEEAL AQAQQDFFQK FGKVHSSICT L 331
    Length:331
    Mass (Da):37,144
    Last modified:April 16, 2014 - v2
    Checksum:iC97D07AA55A534FC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti9 – 102VP → DQ in AAK60619. (PubMed:11355878)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AABR06000316 Genomic DNA. No translation available.
    AABR06000317 Genomic DNA. No translation available.
    AABR06000318 Genomic DNA. No translation available.
    AABR06000319 Genomic DNA. No translation available.
    AABR06000320 Genomic DNA. No translation available.
    AABR06000321 Genomic DNA. No translation available.
    AABR06000322 Genomic DNA. No translation available.
    AABR06000323 Genomic DNA. No translation available.
    AABR06000324 Genomic DNA. No translation available.
    AABR06000325 Genomic DNA. No translation available.
    AABR06000326 Genomic DNA. No translation available.
    AABR06000327 Genomic DNA. No translation available.
    AABR06000328 Genomic DNA. No translation available.
    CH473994 Genomic DNA. Translation: EDL93717.1.
    AF347030 mRNA. Translation: AAK60619.1.
    RefSeqiNP_001263691.1. NM_001276762.1.
    UniGeneiRn.121954.

    Genome annotation databases

    EnsembliENSRNOT00000061930; ENSRNOP00000058646; ENSRNOG00000040242.
    GeneIDi114005.
    KEGGirno:114005.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AABR06000316 Genomic DNA. No translation available.
    AABR06000317 Genomic DNA. No translation available.
    AABR06000318 Genomic DNA. No translation available.
    AABR06000319 Genomic DNA. No translation available.
    AABR06000320 Genomic DNA. No translation available.
    AABR06000321 Genomic DNA. No translation available.
    AABR06000322 Genomic DNA. No translation available.
    AABR06000323 Genomic DNA. No translation available.
    AABR06000324 Genomic DNA. No translation available.
    AABR06000325 Genomic DNA. No translation available.
    AABR06000326 Genomic DNA. No translation available.
    AABR06000327 Genomic DNA. No translation available.
    AABR06000328 Genomic DNA. No translation available.
    CH473994 Genomic DNA. Translation: EDL93717.1 .
    AF347030 mRNA. Translation: AAK60619.1 .
    RefSeqi NP_001263691.1. NM_001276762.1.
    UniGenei Rn.121954.

    3D structure databases

    ProteinModelPortali Q91XQ2.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000058646.

    Proteomic databases

    PRIDEi Q91XQ2.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000061930 ; ENSRNOP00000058646 ; ENSRNOG00000040242 .
    GeneIDi 114005.
    KEGGi rno:114005.

    Organism-specific databases

    CTDi 7957.
    RGDi 71047. Epm2a.

    Phylogenomic databases

    eggNOGi NOG243912.
    GeneTreei ENSGT00390000010101.
    HOGENOMi HOG000285975.
    HOVERGENi HBG051493.
    InParanoidi Q91XQ2.
    KOi K14165.
    OMAi HWIEVSG.

    Enzyme and pathway databases

    Reactomei REACT_207828. Myoclonic epilepsy of Lafora.
    REACT_214969. Glycogen synthesis.

    Miscellaneous databases

    NextBioi 35576258.

    Gene expression databases

    Genevestigatori Q91XQ2.

    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. "Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
      Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M.
      , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
      Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Brown Norway.
    2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "Regional and developmental expression of Epm2a gene and its evolutionary conservation."
      Ganesh S., Agarwala K.L., Amano K., Suzuki T., Delgado-Escueta A.V., Yamakawa K.
      Biochem. Biophys. Res. Commun. 283:1046-1053(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-331, TISSUE SPECIFICITY.
      Strain: Sprague-Dawley.
      Tissue: Brain cortex.

    Entry informationi

    Entry nameiEPM2A_RAT
    AccessioniPrimary (citable) accession number: Q91XQ2
    Secondary accession number(s): F1LPW7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 19, 2004
    Last sequence update: April 16, 2014
    Last modified: October 1, 2014
    This is version 91 of the entry and version 2 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