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Q91XQ2

- EPM2A_RAT

UniProt

Q91XQ2 - EPM2A_RAT

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Protein
Laforin
Gene
Epm2a
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript 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 By similarity.

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei266 – 2661Phosphocysteine intermediate By similarity
Sitei329 – 3291Required for homodimerization By similarity

GO - Molecular functioni

  1. phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity Source: RefGenome
  2. protein tyrosine phosphatase activity Source: UniProtKB-EC
  3. protein tyrosine/serine/threonine phosphatase activity Source: RefGenome
  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
Complete GO annotation...

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
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 331331Laforin
PRO_0000094840Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei25 – 251Phosphoserine; by AMPK By 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.

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000058646.

Structurei

3D structure databases

ProteinModelPortaliQ91XQ2.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 124124CBM20
Add
BLAST
Domaini243 – 31169Tyrosine-protein phosphatase
Add
BLAST

Sequence similaritiesi

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti9 – 102VP → DQ in AAK60619. 1 Publication

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 90 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

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