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Q1M199

- EPM2A_CANFA

UniProt

Q1M199 - EPM2A_CANFA

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Protein

Laforin

Gene
EPM2A
Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - 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.

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. 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 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

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

STRINGi9615.ENSCAFP00000000457.

Structurei

3D structure databases

ProteinModelPortaliQ1M199.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 124124CBM20Add
BLAST
Domaini243 – 31169Tyrosine-protein phosphataseAdd
BLAST

Sequence similaritiesi

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

MRFRFGVVVP PAGAGAAPEL LVVGSRPELG RWEPRGAVRL RPAGSAAGGG    50
ARALQEPGLW LGEVELAPGE AARDGAEPAR VDTFWYKFLK REPGGALSWE 100
GNGPHHDRCC TYNENNLVDG VYCLPIGHWI EATGHTNEMK HTTDFYFNIA 150
GHQAMHYSRI LPNIWLGSCP RQVEHITIKL KHELGITAVM NFQTEWDIVQ 200
NSSGCNRYPE PMTPDTMIKL YKEEGLVYIW MPTPDMSTEG RVQMLPQAVC 250
LLHALLENGH TVYVHCNAGV GRSTAAVCGW LQYVMGWNLR KVQYFLMAKR 300
PAVYIDEDAL ARAEEDFFQK FGKVRSSVCS V 331
Length:331
Mass (Da):36,900
Last modified:May 30, 2006 - v1
Checksum:i788A905A6D82835B
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY560906 Genomic DNA. Translation: ABE98181.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY560906 Genomic DNA. Translation: ABE98181.1 .

3D structure databases

ProteinModelPortali Q1M199.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9615.ENSCAFP00000000457.

Protein family/group databases

CAZyi CBM20. Carbohydrate-Binding Module Family 20.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Phylogenomic databases

eggNOGi NOG243912.
HOGENOMi HOG000285975.
HOVERGENi HBG051493.
InParanoidi Q1M199.

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

  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: July 9, 2014
This is version 58 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

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