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Q91XQ2 (EPM2A_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 89. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Epm2a
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length331 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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 activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

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

Subunit structure

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.

Subcellular location

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

Tissue specificity

Widely expressed. Ref.3

Post-translational modification

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.

Sequence similarities

Belongs to the protein-tyrosine phosphatase family.

Contains 1 CBM20 (carbohydrate binding type-20) domain.

Contains 1 tyrosine-protein phosphatase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 331331Laforin
PRO_0000094840

Regions

Domain1 – 124124CBM20
Domain243 – 31169Tyrosine-protein phosphatase

Sites

Active site2661Phosphocysteine intermediate By similarity
Site3291Required for homodimerization By similarity

Amino acid modifications

Modified residue251Phosphoserine; by AMPK By similarity

Experimental info

Sequence conflict9 – 102VP → DQ in AAK60619. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q91XQ2 [UniParc].

Last modified April 16, 2014. Version 2.
Checksum: C97D07AA55A534FC

FASTA33137,144
        10         20         30         40         50         60 
MLFRFGVVVP PAVAGTRLEL LLAGSRPELG RWEPRGAVRL RPAGTAAGAA ALALQEPGLW 

        70         80         90        100        110        120 
LAEVELAPEE EAADGAEPGR IDTFWYKFLQ REPGGELHWE GNGPHHDRCC TYNENNLVDG 

       130        140        150        160        170        180 
VYCLPVGHWI EATGHTNEMK HTTDFYFNIA GHQAMHYSRI LPNIWLGSCP RQLEHVTIKL 

       190        200        210        220        230        240 
KHELGITAVM NFQTEWDIIQ NSSGCNRYPE PMTPDTMMKL YKEEGLAYIW MPTPDMSTEG 

       250        260        270        280        290        300 
RVQMLPQAVC LLHALLENGH TVYVHCNAGV GRSTAAVCGW LHYVIGWSLR KVQYFIMAKR 

       310        320        330 
PAVYIDEEAL AQAQQDFFQK FGKVHSSICT L 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001263691.1. NM_001276762.1.
UniGeneRn.121954.

3D structure databases

ProteinModelPortalQ91XQ2.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000058646.

Proteomic databases

PRIDEQ91XQ2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000061930; ENSRNOP00000058646; ENSRNOG00000040242.
GeneID114005.
KEGGrno:114005.

Organism-specific databases

RGD71047. Epm2a.

Phylogenomic databases

eggNOGNOG243912.
GeneTreeENSGT00390000010101.
HOGENOMHOG000285975.
HOVERGENHBG051493.
InParanoidQ91XQ2.
OMAHWIEVSG.

Gene expression databases

GenevestigatorQ91XQ2.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
3.90.190.10. 1 hit.
InterProIPR013784. 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]
PANTHERPTHR10159. PTHR10159. 1 hit.
PfamPF00686. CBM_20. 1 hit.
PF00782. DSPc. 1 hit.
[Graphical view]
SMARTSM01065. CBM_2. 1 hit.
[Graphical view]
SUPFAMSSF49452. SSF49452. 1 hit.
SSF52799. SSF52799. 1 hit.
PROSITEPS51166. CBM20. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio35576258.

Entry information

Entry nameEPM2A_RAT
AccessionPrimary (citable) accession number: Q91XQ2
Secondary accession number(s): F1LPW7
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: April 16, 2014
Last modified: July 9, 2014
This is version 89 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families