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FLASH GENE
Symbol MBD2 contributors: mct/npt - updated : 03-07-2015
HGNC name methyl-CpG binding domain protein 2
HGNC id 6917
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal methyl CpG binding domain (MBD)
  • RG-rich domain
  • HOMOLOGY
    intraspecies homolog to MBD3 (93 p100)
    Homologene
    FAMILY
  • methyl-CpG-binding proteins family
  • CATEGORY enzyme , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome,heterochromosome
    basic FUNCTION
  • binding methylated DNA for demethylation
  • having demethylase activity that transforms methylated cytosine bases to cytosine (Bhattacharya 1999)
  • protein possessing both repressor and demethylase functions having evolved to coordinate a program that requires suppression of some methylated genes and activation of others
  • selective role in the methylation-mediated inhibition of ribosomal RNA gene expression
  • MBD2 and MBD3 assemble into mutually exclusive distinct Mi-2/NuRD-like complexes, called MBD2/NuRD and MBD3/NuRD (Le Guezennec 2006)
  • required for correct spatial gene expression in the gut (Berger 2007)
  • mediate the transcriptional silencing of hypermethylated genes (Chatagnon 2009)
  • general repressor of TERT in TERT-methylated telomerase-positive cells (Chatagnon 2009)
  • MBD2 and MECP2 regulate distinct transitional stages of olfactory receptor neuron (ORN) differentiation
  • role for MBD2 in cancer progression, providing support for the prospect of targeting MBD2 therapeutically in aggressive breast cancers
  • MBD2 is necessary for promoter binding and repressive function of NuRD complexes
  • MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes
  • putative role for MBD2 in breast cancer
  • CELLULAR PROCESS nucleotide, chromatin organization, methylation
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • of histone deacetylase complex
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • DNA methyl-CpG binding
  • association with the endogenous methylated rRNA promoter
  • associates with and colocalizes with MBD3L1
  • associates with the hypermethylated TERT promoter (Chatagnon 2009)
  • PRMT5 and its cofactor WDR77 are specific MBD2/NuRD interactors (PRMT5/MBD2 are recruited to CpG islands in a methylation-dependent manner) (Le Guezennec 2006)
  • association between MBD2 binding and transcriptional repression weakened as the distance between binding site and TSS increased, suggesting that MBD2 represses transcriptional initiation
  • MBD2 displays strong methyl-CpG binding activity that may aid in localizing NuRD complexes to inactive chromatin
  • MECP2 and MBD2 direct interactions could crosslink chromatin fibers and therefore give novel insight into the molecular mechanism of MBD mediated global heterochromatin architecture
  • MBD2-NuRD, in contrast to MBD3-NuRD, converts open chromatin with euchromatic histone modifications into tightly compacted chromatin with repressive histone marks
  • has a key role in promoting Treg-specific demethylation region (TSDR) demethylation, FOXP3 expression, and Treg-suppressive function
  • MBD2 colocalizes with the transcription factor CEBPA, and MBD2 binding at these positions is reduced upon CEBPA depletion
  • SFRS2 regulates AS of the methyl-CpG binding protein MBD2, whose isoforms play opposing roles in maintenance of and reprogramming to pluripotency
  • mainly recruited to CpG island promoters that are highly methylated
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    at the early stage of colorectal and stomach carcinogenesis
    tumoral somatic mutation      
    in colon and lung cancer
    constitutional       gain of function
    at specific stages of spermatogenesis, suggesting that they play an important role in the epigenetic reprogramming during spermatogenesis (Wawrzik 2009)
    constitutional     --low  
    decreased expression of MBD2 and MBD4 might involve in the pathogenesis of primary immune thrombocytopenia
    constitutional     --over  
    of the MBD2 and MBD4 genes in CD4+ T cells from systemic lupus erythematosus patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS