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FLASH GENE
Symbol NHLRC1 contributors: mct/npt - updated : 23-09-2020
HGNC name NHL repeat containing 1
HGNC id 21576
Corresponding disease
EPM2B myoclonic epilepsy, progressive, Lafora type 2B
Location 6p22.3      Physical location : 18.120.717 - 18.122.851
Synonym name malin
Synonym symbol(s) bA204B7.2, EPM2B, MGC119262, MGC119264, MGC119265, EPM2A, MALIN
EC.number 2.1.1.67/ 2.3.2.27
DNA
TYPE functioning gene
STRUCTURE 2.13 kb     1 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
1 - 2134 - 395 - 2015 26493215
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrinepancreas    
Nervousbrain    
Respiratorylung    
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a zinc finger of the RING type, acting as E3 ubiquitin ligase
  • six NHL repeat protein-protein interaction domains
  • HOMOLOGY
    interspecies ortholog to murine Nhlrc1
    ortholog to rattus nhlrc1
    Homologene
    FAMILY
  • RING-HCa family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • may be having an E3 ubiquitin ligase function
  • could function in concert or upstream of laforin in the control of glycogen phosphorylation (Tagliabracci 2008)
  • could regulate glycogen phosphorylation independently of laforin, for example down-regulating enzyme(s) responsible for introducing phosphate into glycogen (Tagliabracci 2008)
  • ubiquitinate and promote the clearance of its substrates through proteasomal degradation (Garyali 2009)
  • regulates WNT signaling pathway through the degradation of DVL2, suggesting possible deregulation of WNT signaling in Lafora disease
  • functions to regulate EPM2A and NHLRC1 deficiency at least in part causes Lafora bodies (LB) and Lafora disease (LD) through increased EPM2A binding to glycogen
  • role of the EPM2A/NHLRC1 complex in the activation of autophagy via regulation of the PI3KC3 complex that explain the defect in autophagy described in Lafora disease
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    ubiquitin-proteasomal pathway
    a component
  • EPM2A–NHLRC1 complex is a novel player in the neuronal response to misfolded proteins (Garyali 2009)
  • EPM2A–NHLRC1 complex negatively regulates glycogen synthesis by modulating cellular glucose uptake via glucose transporters
  • a functional EPM2A–NHLRC1 complex plays a critical role in disrupting Lafora bodies and relieving ER stress, implying that a causative pathogenic mechanism underlies their deficiency in Lafora disease
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • interacting with laforin, through their middle portions (promote the polyubiquitination and degradation of laforin)
  • interact with misfolded proteins and promote its degradation through the ubiquitin–proteasome system (Garyali 2009)
  • also interacts with HSPA4 (NHLRC1 is unstable, and the aggregate-prone protein and co-chaperone STUB1 can modulate its stability)
  • interacts with neuronatin (NNAT)and enhances its degradation through proteasome
  • interacts with DVL2, a key mediator of WNT signaling pathway
  • EPM2A-principle function is to control glycogen chain lengths, in a NHLRC1-dependent fashion, and loss of this control underlies LAFORA disease
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) EPM2B
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target could be with EPM2A potential therapeutic targets for neurodegenerative disorders associated with cytotoxic proteins (Garyali 2009)
    ANIMAL & CELL MODELS