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Protein

Laforin

Gene

EPM2A

Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Protein inferred from homologyi

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
Complete GO annotation...

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
Complete GO annotation...

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

        10         20         30         40         50
MRFRFGVVVP PAGAGAAPEL LVVGSRPELG RWEPRGAVRL RPAGSAAGGG
60 70 80 90 100
ARALQEPGLW LGEVELAPGE AARDGAEPAR VDTFWYKFLK REPGGALSWE
110 120 130 140 150
GNGPHHDRCC TYNENNLVDG VYCLPIGHWI EATGHTNEMK HTTDFYFNIA
160 170 180 190 200
GHQAMHYSRI LPNIWLGSCP RQVEHITIKL KHELGITAVM NFQTEWDIVQ
210 220 230 240 250
NSSGCNRYPE PMTPDTMIKL YKEEGLVYIW MPTPDMSTEG RVQMLPQAVC
260 270 280 290 300
LLHALLENGH TVYVHCNAGV GRSTAAVCGW LQYVMGWNLR KVQYFLMAKR
310 320 330
PAVYIDEDAL ARAEEDFFQK FGKVRSSVCS V
Length:331
Mass (Da):36,900
Last modified:May 30, 2006 - v1
Checksum:i788A905A6D82835B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY560906 Genomic DNA. Translation: ABE98181.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY560906 Genomic DNA. Translation: ABE98181.1.

3D structure databases

ProteinModelPortaliQ1M199.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000000457.

Protein family/group databases

CAZyiCBM20. Carbohydrate-Binding Module Family 20.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

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]
ProtoNetiSearch...

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: January 7, 2015
This is version 61 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.