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FLASH GENE
Symbol MBD4 contributors: mct - updated : 11-05-2022
HGNC name methyl-CpG binding domain protein 4
HGNC id 6919
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveesophagus   highly
Endocrinepancreas   highly
Lymphoid/Immunethymus   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N-proximal methyl-CpG binding domain (MBD), N-terminal MBD (MBD4MBD)
  • a C-terminal mismatch-specific glycosylase domain, which is an important molecule believed to be involved in maintaining of genome stability
  • conjugated sumoylated
    HOMOLOGY
    Homologene
    FAMILY DNA glycosylase superfamily, helix-hairpin-helix (HhH) superfamily.
    CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • encoding an MLH1 interactor
  • acting as a tumor suppressor involved in genetic stability and participating in DNA damage checkpoint
  • important roles in maintaining genome stability through base excision repair (BER) processes and mismatch repair (MMR) processes
  • wide role for MBD4 in DNA damage response and maintaining chromosomal stability
  • efficiently processed T/G mismatches within the nucleosome
  • excises thymine from mutagenic G·T mispairs generated by deamination of 5-methylcytosine, and downstream base excision repair proteins restore a G·C pair
  • provides selective interactions with the mismatched guanine (N1H, N2H(2)) that are not compatible with adenine, which likely confer mismatch specificity
  • is upregulated at the protein level upon oxidative stress, and is essential for cell survival following oxidative stress
  • is likely a component of mismatch repair (MMR)-directed DNA end processing
  • is also involved in DNA damage response and transcriptional regulation
  • MBD4 excises thymine from G·T mispairs, suppressing mutations caused by deamination of 5-methylcytosine, and it removes uracil and modified uracils (e.g., 5-hydroxymethyluracil) mispaired with guanine
  • encodes a glycosylase involved in repair of G:T mismatches resulting from deamination of 5&
  • 8242;-methylcytosine
    CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • DNA methyl-CpG binding
  • interact with RET through its transcriptional repression domain
  • MBD4 (AAs 413–454) represses hypermethylated MLH1 promoters, because of its interaction with the MLHL1
  • MBD4 is required for TGFB1-dependent DNA demethylation
  • interaction between DNMT1 and MBD4 is involved in controlling gene expression and responding to oxidative stress
  • UHRF1 and USP7 are two new interaction partners for MBD4
  • both DNMT1 and methyl-CpG-binding domain Protein 4 (MBD4) bind to the TNFRSF18
  • cell & other
    REGULATION
    Other is sumoylated in a DNA damage-specific manner, suggesting that sumoylation serves to regulate its repair activity and could be compromised in cancer
    ASSOCIATED DISORDERS
    corresponding disease(s) COLPEN
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    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
    tumoral       loss of function
    may contribute to tumorigenesis, acting as a modifier of mismatch repair (MMR)-deficient cancer phenotype
    constitutional   LOI    
    in Abdominal arterial aneurysm (AAA)
    Susceptibility
  • to rheumatoid arthritis
  • to Uveal melanoma (UM)
  • Variant & Polymorphism SNP , other
  • MBD4-8666 and MBD4-922 are associated to RA
  • MBD4 variants associated to Uveal melanoma (UM)
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS