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Protein

Laforin

Gene

EPM2A

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

Functioni

Plays an important role in preventing glycogen hyperphosphorylation and the formation of insoluble aggregates, via its activity as glycogen phosphatase, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with the E3 ubiquitin ligase NHLRC1/malin. Dephosphorylates phosphotyrosine and synthetic substrates, such as para-nitrophenylphosphate (pNPP), and has low activity with 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.PROSITE-ProRule annotation
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei32SubstrateBy similarity1
Binding sitei87SubstrateBy similarity1
Binding sitei197SubstrateBy similarity1
Binding sitei235SubstrateBy similarity1
Binding sitei241SubstrateBy similarity1
Active sitei266Phosphocysteine intermediatePROSITE-ProRule annotation1
Binding sitei304SubstrateBy similarity1
Sitei329Required for homodimerizationBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protein phosphatase
Biological processAutophagy, 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.-By similarity, EC:3.1.3.16, EC:3.1.3.48By similarity)
Alternative name(s):
Glucan phosphatase
Lafora PTPase
Short name:
LAFPTPase
Gene namesi
Name:EPM2A
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Unplaced

Subcellular locationi

  • Cytoplasm By similarity
  • Endoplasmic reticulum membrane By similarity; Peripheral membrane protein By similarity; Cytoplasmic side By similarity
  • Cell membrane By similarity

  • Note: Colocalizes with glycogen synthase in punctate structures in the cytoplasm. Primarily associated with polyribosomes at the rough endoplasmic reticulum, and also detected at the plasma membrane. Under glycogenolytic conditions localizes to the nucleus.By similarity

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002895921 – 331LaforinAdd BLAST331

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei25Phosphoserine; by AMPKBy similarity1

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

PaxDbiQ1M199.

Interactioni

Subunit structurei

Homodimer. Interacts with itself. Interacts with PPP1R3B, PPP1R3C, PPP1R3D, 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. Interacts with PRDM8.By similarity

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000030595.

Structurei

3D structure databases

ProteinModelPortaliQ1M199.
SMRiQ1M199.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 124CBM20PROSITE-ProRule annotationAdd BLAST124
Domaini243 – 311Tyrosine-protein phosphataseAdd BLAST69

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni103 – 107Substrate bindingBy similarity5
Regioni267 – 272Substrate bindingBy similarity6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi266 – 272Glucan phosphatase signature motif CXAGXGRBy similarity7

Domaini

The CBM20 domain mediates binding to cytoplasmic glycogen and to Lafora polyglucosan bodies.By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1716. Eukaryota.
COG2453. LUCA.
HOGENOMiHOG000285975.
HOVERGENiHBG051493.
InParanoidiQ1M199.

Family and domain databases

CDDicd05806. CBM20_laforin. 1 hit.
Gene3Di2.60.40.10. 1 hit.
3.90.190.10. 1 hit.
InterProiView protein in InterPro
IPR013784. Carb-bd-like_fold.
IPR034831. CBM20_laforin.
IPR002044. CBM_fam20.
IPR000340. Dual-sp_phosphatase_cat-dom.
IPR024950. DUSP.
IPR013783. Ig-like_fold.
IPR029021. Prot-tyrosine_phosphatase-like.
IPR016130. Tyr_Pase_AS.
IPR000387. TYR_PHOSPHATASE_dom.
IPR020422. TYR_PHOSPHATASE_DUAL_dom.
PANTHERiPTHR10159. PTHR10159. 1 hit.
PfamiView protein in Pfam
PF00686. CBM_20. 1 hit.
PF00782. DSPc. 1 hit.
SMARTiView protein in SMART
SM01065. CBM_2. 1 hit.
SM00195. DSPc. 1 hit.
SUPFAMiSSF49452. SSF49452. 1 hit.
SSF52799. SSF52799. 1 hit.
PROSITEiView protein in PROSITE
PS51166. CBM20. 1 hit.
PS00383. TYR_PHOSPHATASE_1. 1 hit.
PS50056. TYR_PHOSPHATASE_2. 1 hit.
PS50054. TYR_PHOSPHATASE_DUAL. 1 hit.

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.

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 one 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.

Entry informationi

Entry nameiEPM2A_CANLF
AccessioniPrimary (citable) accession number: Q1M199
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 29, 2007
Last sequence update: May 30, 2006
Last modified: June 7, 2017
This is version 69 of the entry and version 1 of the sequence. See 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