Property Summary

NCBI Gene PubMed Count 69
PubMed Score 254.09
PubTator Score 120.07

Knowledge Summary

Patent

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  Disease (5)

Expression

Protein-protein Interaction (1)

Gene RIF (48)

PMID Text
26648032 Laforin prevents the auto-degradation of malin by presenting itself as a substrate. Malin preferentially degrades the phosphatase-inactive laforin monomer.
26578817 Laforin-glycan interactions occur with a favourable enthalpic contribution counter-balanced by an unfavourable entropic contribution.
26216881 laforin is responsible for glycogen dephosphorylation during exercise and acts during the cytosolic degradation of glycogen
26102034 Lafora disease proteins laforin and malin negatively regulate the HIPK2-p53 cell death pathway.
25544560 The crystal structure of laforin bound to phosphoglucan product, reveals its unique integrated tertiary and quaternary structure.
25538239 novel molecular determinants in the laforin active site that help decipher the mechanism of glucan phosphatase activity.
25270369 This study identified some Mild Lafora disease have EPM2A mutation.
25246353 This study suggest that variations in phenotypes of EPM2A-deficient Lafora disease.
24770803 Studied the role of conformational changes in human laforin structure due to existing single mutation W32G and prepared double mutation W32G/K87A related to loss of glycogen binding.
24068615 Polyglucosan body degradation requires a protein assembly that includes laforin and malin.
23922729 These results suggest that cysteine 329 is specifically involved in the dimerization process of laforin.
23904258 This study identified the flexibility of K87A mutated laforin structure, with replacement of acidic amino acid to aliphatic amino acid in functional carbohydrate binding module domain, have more impact in abolishing glycogen binding that favors Lafora disease.
23313408 A new novel mutation of the EPM2A gene is identified that causes Lafora disease.
22815132 Malin forms a functional complex with laforin. This complex promotes the ubiquitination of proteins involved in glycogen metabolism and misregulation of pathways involved in this process results in Lafora body formation. (Review)
22364389 Studies indicate that laforin directly dephosphorylates glycogen.
22047982 This study identified that EPM2 gene mutations leading to Lafora disease in six Turkish families.
22036712 alternative splicing could possibly be one of the mechanisms by which EPM2A may regulate the cellular functions of the proteins it codes for
21930129 glycogen phosphorylation can be considered a catalytic error and laforin a repair enzyme.
21887368 laforin monomer is the dominant form of the protein and that it contains phosphatase activity.
21728993 results of the present study suggest that phosphorylation of laforin-Ser(25) by AMPK provides a mechanism to modulate the interaction between laforin and malin
21652633 Laforin and malin are defective in Lafora disease (LD), a neurodegenerative disorder associated with epileptic seizures
21371719 Genetic analysis showed a novel c.659 T>A mutation on exon 3 of the EPM2A gene, in a patient with Lafora's disease.
20738377 study described several novel mutations of EPM2A and NHLRC1 and brought additional data to genetic epidemiology of Lafora disease (LD); emphasized the high mutation rate in patients with classical LD as well as the high negativity rate of skin biopsy
20534808 These results suggest that the modification introduced by the laforin-malin complex could affect the subcellular distribution of AMPK beta subunits.
20453062 Laforin regulates autophagy.
19529779 laforin and malin play a role protecting cells from ER-stress, likely contributing to the elimination of unfolded proteins
19403557 Mutations of EPM2A formed aggregates and elicited endoplasm reticulum stress in neuronal cell.
19267391 Meta-analysis of gene-disease association. (HuGE Navigator)
19171932 phosphorylation of R5/PTG at Ser-8 by AMPK accelerates its laforin/malin-dependent ubiquitination and subsequent proteasomal degradation, which results in a decrease of its glycogenic activity.
19036738 Laforin and malin interact with misfolded proteins and promote their degradation through the ubiquitin-proteasome system.
18617530 EPM2A regulated by alternative splicing plays roles in Lafora progressive myoclonus epilepsy.
18311786 Results suggest that the altered subcellular localization of mutant proteins of the EPM2A and NHLRC1 genes could be one of the molecular bases of the Lafora disease phenotype.
18070875 Laforin acts as a scaffold that allows the E3 ubiquitin ligase malin to ubiquitinate protein targeting to glycogen (PTG). These results suggest an additional mechanism, involving laforin and malin, in regulating glycogen metabolism.
18029386 Regulation of glycogen synthesis by the laforin-malin complex is modulated by the AMP-activated protein kinase pathway.
17646401 Laforin is conserved in all vertebrates and a small class of protists; it is not found in other organisms. Additionally, laforin is a functional equivalent of the plant phosphatase SEX4, and it may function to dephosphorylate complex carbohydrates.
17509003 study concludse that considerable variability in the age at onset of Lafora disease can occur within families; identical mutations can be associated with the classic adolescent presentation, as well as late-onset cases
17337485 Defects in laforin may lead to increased levels of misfolded and/or target proteins, which may eventually affect the physiological processes of the neuron, and likely to be the primary trigger in the physiopathology of lafora disease.
16971387 results demonstrate a critical role of dimerization in Laforin function and suggest an important new dimension in protein phosphatase function and in molecular pathogenesis of Lafora's disease
16959610 Inactivation of Epm2a resulted in increased Wnt signaling and tumorigenesis
16901901 Laforin does not dephosphorylate GSK3B (beta) in vitro, but possesses the unique ability to utilize a phosphorylated complex carbohydrate as a substrate and this function may be necessary for the maintenance of normal cellular glycogen.
16115820 Laforin is a Glycogen-Synthase-Kinase-3 Ser 9 phosphatase, and therefore capable of inactivating GS through GSK3.
14722920 Six novel mutations were identified, one of which is the first mutation specific to the cytoplasmic laforin isoform, implicating this isoform in disease pathogenesis.
14706656 encodes a 331 amino acid protein that contains an N-terminal carbohydrate-binding domain (CBD) and a C-terminal dual-specificity phosphatase domain. The CBD of laforin targets the protein to Lafora inclusion bodies.
14643920 Up to 20% cases of LD are not genetically linked to chromosome 6. We report two sisters affected from bioptically diagnosed LD but without evidence of EPM2A mutation
12915448 Laforin interacts with HIRPI5.
12782127 The EPM2AIP1 gene was identified and characterized in a screen for laforin-interacting proteins with a human brain cDNA library; the specificity of the interaction was confirmed; subcellular colocalization of laforin and EPM2AIP1 protein was demonstrated
12019207 identification of mutations in EPM2A with phenotypes of 22 patients (14 families) and identification of two subsyndromes
11883934 Laforin is an active phosphatase; therefore, isoforms targeted to different cellular compartments might dephosphorylate and regulate distinct cellular substrates.

AA Sequence

MRFRFGVVVPPAVAGARPELLVVGSRPELGRWEPRGAVRLRPAGTAAGDGALALQEPGLWLGEVELAAEE      1 - 70
AAQDGAEPGRVDTFWYKFLKREPGGELSWEGNGPHHDRCCTYNENNLVDGVYCLPIGHWIEATGHTNEMK     71 - 140
HTTDFYFNIAGHQAMHYSRILPNIWLGSCPRQVEHVTIKLKHELGITAVMNFQTEWDIVQNSSGCNRYPE    141 - 210
PMTPDTMIKLYREEGLAYIWMPTPDMSTEGRVQMLPQAVCLLHALLEKGHIVYVHCNAGVGRSTAAVCGW    211 - 280
LQYVMGWNLRKVQYFLMAKRPAVYIDEEALARAQEDFFQKFGKVRSSVCSL                       281 - 331
//

Text Mined References (73)

PMID Year Title
26648032 2015 Interdependence of laforin and malin proteins for their stability and functions could underlie the molecular basis of locus heterogeneity in Lafora disease.
26578817 2016 Biophysical characterization of laforin-carbohydrate interaction.
26216881 2015 Muscle glycogen remodeling and glycogen phosphate metabolism following exhaustive exercise of wild type and laforin knockout mice.
26102034 2015 Lafora disease proteins laforin and malin negatively regulate the HIPK2-p53 cell death pathway.
25544560 2015 Structural mechanism of laforin function in glycogen dephosphorylation and lafora disease.
25538239 2015 Dimeric quaternary structure of human laforin.
25270369 2014 Mild Lafora disease: clinical, neurophysiologic, and genetic findings.
25246353 2014 Late onset Lafora disease and novel EPM2A mutations: breaking paradigms.
24837458 2014 The carbohydrate-binding domain of overexpressed STBD1 is important for its stability and protein-protein interactions.
24770803 2014 Molecular dynamics simulations and principal component analysis on human laforin mutation W32G and W32G/K87A.
24068615 2014 Laforin-malin complex degrades polyglucosan bodies in concert with glycogen debranching enzyme and brain isoform glycogen phosphorylase.
23922729 2013 Dimerization of the glucan phosphatase laforin requires the participation of cysteine 329.
23904258 2013 Exploring the structural insights on human laforin mutation K87A in Lafora disease--a molecular dynamics study.
23624058 2013 Glycogenic activity of R6, a protein phosphatase 1 regulatory subunit, is modulated by the laforin-malin complex.
23313408 2013 A novel nonsense mutation of the EPM2A gene in northwest Greece causing myoclonic epilepsy.
22961547 2012 Early-onset Lafora body disease.
22815132 2012 Deciphering the role of malin in the lafora progressive myoclonus epilepsy.
22364389 2013 Laforin, a protein with many faces: glucan phosphatase, adapter protein, et alii.
22047982 2012 Four novel and two recurrent NHLRC1 (EPM2B) and EPM2A gene mutations leading to Lafora disease in six Turkish families.
22036712 2012 Identification and characterization of novel splice variants of the human EPM2A gene mutated in Lafora progressive myoclonus epilepsy.
21930129 2011 Are there errors in glycogen biosynthesis and is laforin a repair enzyme?
21887368 2011 Laforin, a dual specificity phosphatase involved in Lafora disease, is present mainly as monomeric form with full phosphatase activity.
21728993 2011 Laforin, a dual-specificity phosphatase involved in Lafora disease, is phosphorylated at Ser25 by AMP-activated protein kinase.
21652633 2011 Malin and laforin are essential components of a protein complex that protects cells from thermal stress.
21505799 2011 Lafora progressive myoclonus epilepsy: NHLRC1 mutations affect glycogen metabolism.
21371719 2011 A novel exon 3 mutation in a Tunisian patient with Lafora's disease.
20738377 2010 Novel mutations in EPM2A and NHLRC1 widen the spectrum of Lafora disease.
20534808 2010 The laforin-malin complex, involved in Lafora disease, promotes the incorporation of K63-linked ubiquitin chains into AMP-activated protein kinase beta subunits.
20453062 2010 Laforin, the most common protein mutated in Lafora disease, regulates autophagy.
19542233 2009 Hyperphosphorylation and aggregation of Tau in laforin-deficient mice, an animal model for Lafora disease.
19529779 2009 Increased endoplasmic reticulum stress and decreased proteasomal function in lafora disease models lacking the phosphatase laforin.
19403557 2009 Deletions and missense mutations of EPM2A exacerbate unfolded protein response and apoptosis of neuronal cells induced by endoplasm reticulum stress.
19267391 2009 Lafora progressive myoclonus epilepsy: a meta-analysis of reported mutations in the first decade following the discovery of the EPM2A and NHLRC1 genes.
19171932 2009 AMP-activated protein kinase phosphorylates R5/PTG, the glycogen targeting subunit of the R5/PTG-protein phosphatase 1 holoenzyme, and accelerates its down-regulation by the laforin-malin complex.
19036738 2009 The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system.
18617530 2008 Modulation of functional properties of laforin phosphatase by alternative splicing reveals a novel mechanism for the EPM2A gene in Lafora progressive myoclonus epilepsy.
18311786 2008 Lafora disease in the Indian population: EPM2A and NHLRC1 gene mutations and their impact on subcellular localization of laforin and malin.
18070875 2008 Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG).
18029386 2008 Regulation of glycogen synthesis by the laforin-malin complex is modulated by the AMP-activated protein kinase pathway.
17908927 2007 A role for AGL ubiquitination in the glycogen storage disorders of Lafora and Cori's disease.
17646401 2007 The phosphatase laforin crosses evolutionary boundaries and links carbohydrate metabolism to neuronal disease.
17509003 2007 Founder effect with variable age at onset in Arab families with Lafora disease and EPM2A mutation.
17337485 2007 Lafora disease proteins malin and laforin are recruited to aggresomes in response to proteasomal impairment.
16971387 2006 Dimerization of Laforin is required for its optimal phosphatase activity, regulation of GSK3beta phosphorylation, and Wnt signaling.
16959610 2006 Epm2a suppresses tumor growth in an immunocompromised host by inhibiting Wnt signaling.
16901901 2006 Laforin, a dual specificity phosphatase that dephosphorylates complex carbohydrates.
16115820 2005 Novel glycogen synthase kinase 3 and ubiquitination pathways in progressive myoclonus epilepsy.
16021330 2005 Mutations in the NHLRC1 gene are the common cause for Lafora disease in the Japanese population.
15930137 2005 Insights into Lafora disease: malin is an E3 ubiquitin ligase that ubiquitinates and promotes the degradation of laforin.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15009235 2004 A novel exon 1 mutation in a patient with atypical lafora progressive myoclonus epilepsy seen as childhood-onset cognitive deficit.
14722920 2004 Loss of function of the cytoplasmic isoform of the protein laforin (EPM2A) causes Lafora progressive myoclonus epilepsy.
14706656 2004 The carbohydrate-binding domain of Lafora disease protein targets Lafora polyglucosan bodies.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14643920 2003 Bioptically demonstrated Lafora disease without EPM2A mutation: a clinical and neurophysiological study of two sisters.
14574404 2003 The DNA sequence and analysis of human chromosome 6.
14532330 2003 Laforin, the dual-phosphatase responsible for Lafora disease, interacts with R5 (PTG), a regulatory subunit of protein phosphatase-1 that enhances glycogen accumulation.
12915448 2003 The Lafora disease gene product laforin interacts with HIRIP5, a phylogenetically conserved protein containing a NifU-like domain.
12782127 2003 Identification of a novel protein interacting with laforin, the EPM2a progressive myoclonus epilepsy gene product.
12560877 2003 Two novel mutations in the EPM2A gene in a Korean patient with Lafora's progressive myoclonus epilepsy.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12019207 2002 Genotype-phenotype correlations for EPM2A mutations in Lafora's progressive myoclonus epilepsy: exon 1 mutations associate with an early-onset cognitive deficit subphenotype.
11883934 2002 Alternative splicing modulates subcellular localization of laforin.
11739371 2002 A unique carbohydrate binding domain targets the lafora disease phosphatase to glycogen.
11735300 2001 Mutation screening for Japanese Lafora's disease patients: identification of novel sequence variants in the coding and upstream regulatory regions of EPM2A gene.
11220751 2001 Laforin is a cell membrane and endoplasmic reticulum-associated protein tyrosine phosphatase.
11175283 2000 Mutational spectrum of the EPM2A gene in progressive myoclonus epilepsy of Lafora: high degree of allelic heterogeneity and prevalence of deletions.
11001928 2000 Laforin, defective in the progressive myoclonus epilepsy of Lafora type, is a dual-specificity phosphatase associated with polyribosomes.
9931343 1999 A novel protein tyrosine phosphatase gene is mutated in progressive myoclonus epilepsy of the Lafora type (EPM2).
9771710 1998 Mutations in a gene encoding a novel protein tyrosine phosphatase cause progressive myoclonus epilepsy.
9345091 1997 Lafora progressive myoclonus epilepsy: narrowing the chromosome 6q24 locus by recombinations and homozygosities.
9222970 1997 Identification of a recombination event narrowing the Lafora disease gene region.
7485240 1995 Lafora disease is not linked to the Unverricht-Lundborg locus.