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Q1M199 (EPM2A_CANFA) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 56. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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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
OrganismCanis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]
Taxonomic identifier9615 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis

Protein attributes

Sequence length331 AA.
Sequence statusComplete.
Protein existenceInferred from homology

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.

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_0000289592

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

Sequences

Sequence LengthMass (Da)Tools
Q1M199 [UniParc].

Last modified May 30, 2006. Version 1.
Checksum: 788A905A6D82835B

FASTA33136,900
        10         20         30         40         50         60 
MRFRFGVVVP PAGAGAAPEL LVVGSRPELG RWEPRGAVRL RPAGSAAGGG ARALQEPGLW 

        70         80         90        100        110        120 
LGEVELAPGE AARDGAEPAR VDTFWYKFLK REPGGALSWE GNGPHHDRCC TYNENNLVDG 

       130        140        150        160        170        180 
VYCLPIGHWI EATGHTNEMK HTTDFYFNIA GHQAMHYSRI LPNIWLGSCP RQVEHITIKL 

       190        200        210        220        230        240 
KHELGITAVM NFQTEWDIVQ NSSGCNRYPE PMTPDTMIKL YKEEGLVYIW MPTPDMSTEG 

       250        260        270        280        290        300 
RVQMLPQAVC LLHALLENGH TVYVHCNAGV GRSTAAVCGW LQYVMGWNLR KVQYFLMAKR 

       310        320        330 
PAVYIDEDAL ARAEEDFFQK FGKVRSSVCS V 

« Hide

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY560906 Genomic DNA. Translation: ABE98181.1.

3D structure databases

ProteinModelPortalQ1M199.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9615.ENSCAFP00000000457.

Protein family/group databases

CAZyCBM20. Carbohydrate-Binding Module Family 20.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

eggNOGNOG243912.
HOGENOMHOG000285975.
HOVERGENHBG051493.
InParanoidQ1M199.

Family and domain databases

Gene3D2.60.40.10. 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.
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.
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...

Entry information

Entry nameEPM2A_CANFA
AccessionPrimary (citable) accession number: Q1M199
Entry history
Integrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 30, 2006
Last modified: April 16, 2014
This is version 56 of the entry and version 1 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