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FLASH GENE
Symbol DNMT3B contributors: mct/npt/pgu - updated : 01-06-2016
HGNC name DNA (cytosine-5-)-methyltransferase 3 beta
HGNC id 2979
Corresponding disease
ICF Immunodeficiency, Centromeric instability, and Facial anomalies syndrome
Location 20q11.21      Physical location : 31.350.190 - 31.397.161
Synonym name
  • DNA MTase HsaIIIB
  • DNA cytosine-5 methyltransferase 3 beta
  • DNA methyltransferase HsaIIIB
  • Synonym symbol(s) CM3B, M.HsaIIIB
    EC.number 2.1.1.37
    DNA
    TYPE functioning gene
    STRUCTURE 46.97 kb     23 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • at least two TSPs (transcriptional start points ) which exist in different exons and the expression is controlled by different promoters (lacking typical TATA sequences, where one promoter contains a CpG-rich area near the TSP, the other promoter is CpG-poor)
  • MAPPING cloned Y linked N status confirmed
    Physical map
    RPL24P1 20q11 ribosomal protein L24 pseudogene 1 TSPYL3 20q11.1 TSPY-like 3 PLAGL2 20q11.1 pleiomorphic adenoma gene-like 2 POFUT1 20q11 protein O-fucosyltransferase 1 KIF3B 20p11.2-q11.21 kinesin family member 3B ASXL1 20q11 additional sex combs like 1 (Drosophila) DKFZP566G1424 20q11.1-q11.23 hypothetical protein DKFZp566G1424 C20orf112 20q11.1-q11.23 chromosome 20 open reading frame 112 LOC284804 20q11.21 hypothetical protein LOC284804 LOC149950 20q11.21 hypothetical LOC149950 FLJ33706 20q11.22 hypothetical protein FLJ33706 C20orf92 20q11.22 chromosome 20 open reading frame 92 DNMT3B 20q11.2 DNA (cytosine-5-)-methyltransferase 3 beta MAPRE1 20q11.1-q11.23 microtubule-associated protein, RP/EB family, member 1 LOC388795 20 similar to hypothetical protein FLJ33620 SPAG4L 20q11.21 sperm associated antigen 4-like BPIL1 20q11.21 bactericidal/permeability-increasing protein-like 1 BPIL3 20q11.22 bactericidal/permeability-increasing protein-like 3 LOC391242 20 similar to DNA segment, numerous copies, expressed probes (GS1 gene) C20orf185 20q11.21 chromosome 20 open reading frame 185 C20orf186 20q11.21 chromosome 20 open reading frame 186 C20orf70 20q11.21 chromosome 20 open reading frame 70 SOCS2P1 20 suppressor of cytokine signaling 2 pseudogene 1 BASE 20q11.21 suppressor of cytokine signaling 2 pseudogene 1 C20orf71 20q11.22 chromosome 20 open reading frame 71 PLUNC 20p11.1-q12 palate, lung and nasal epithelium carcinoma associated
    RNA
    TRANSCRIPTS type messenger
    text with at least two alternatively spliced isoforms
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    23 splicing 4353 - 853 ubiquitous except brain, muscle 2004 15148359
    22 splicing 4293 - 833 - 2004 15148359
    20 splicing 4104 - 770 - 2004 15148359
  • lacking exon 22-21
  • capable of DNA binding and contributing factor of DNA methylation
  • 22 splicing - - - ubiquitous except brain, lung, prostate, muscle 2004 15148359
    lacking exon 21
    22 splicing - - - testis (very low), brain, prostate 2004 15148359
    lacking exon 22
    22 splicing 4267 94.6 845 - 2004 15148359
    - - 3876 - 694 - 2004 15148359
    - - 3978 - 728 - 2004 15148359
    - - - - - expressed in pluripotent stem cells 2011 21698279
  • alternatively spliced exon 10
  • isoform is characteristic of the pluripotent state
  • - - - - - - 2009 19825994
  • lacking exon 5 within the N-terminal regulatory domain
  • possessed significantly enhanced DNA binding affinity and displayed an altered nuclear distribution
  • may play an important role in stem cell maintenance or differentiation and suggest that sequences encoded by exon 5 influence the functional properties of DNMT3B
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
     thymus    
    Digestiveintestinelarge intestinecolon  
     liver    
    Nervousbrain    
    Reproductivemale systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cell lineage abundantly in ES cells, barely detectable in differentiated cells
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal, pregnancy
    Text
  • liver, heart, kidney, placenta
  • highly expressed during early embryonic development and down-regulated in most differentiated somatic cells
  • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal PWWP domain central cysteine-rich region with homology with ATRX (XNP)
  • a PHD domain
  • five C terminal conserved catalytic domains functioning in the transmethylation reaction
  • a long N-terminal regulatory region linked to a conserved C-terminal domain responsible for the catalytic activity with a PWWP domain in the N-terminal region, chromatin/chromosome-targeting module essential for the chromatin targeting of the enzymes
  • HOMOLOGY
    interspecies homolog to murine Dnmt3b
    Homologene
    FAMILY
  • C5 (cytosine-5) methyltransferase family
  • CATEGORY enzyme , DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome,nucleosome
    intracellular,nucleus,chromatin/chromosome,heterochromosome
    intracellular,nucleus,chromatin/chromosome,centromere
    text
  • co-localizing with condensin and KIF4A on condensed chromosomes throughout mitosis
  • localizes to both centromeric and pericentromeric regions
  • almost all of the cellular contents of DNMT3A/3B, but not DNMT1, are strongly anchored to a subset of nucleosomes
  • basic FUNCTION
  • essential for de novo DNA methylation and development (at least in mouse) and catalytically methylating cytosines in CpG pairs
  • functions as a co-repressor of polycomb protein in inducing transcriptional repression independent of DNA methylation
  • playing a role in chromosome condensation machinery
  • plays a critical role in chromosomal stability and maintenance of peri-/centromeric region chromatin structure
  • DNMT3A and DNMT3B, but not the maintenance enzyme DNMT1, are redox-dependent DNA dehydroxymethylase
  • DNA dehydroxymethylation by DNMT3A, DNMT3B provides a simpler pathway to reduce DNA hydroxymethylation and methylation
  • DNMT3A, DNMT3B, DNMT1 roles in Ca(2+) ion-dependent biological processes, including the genome-wide/local DNA demethylation during early embryogenesis, cell differentiation, neuronal activity-regulated gene expression, and carcinogenesis
  • DNMT3A and DNMT3B have overlapping and distinct functions in hematopoietic stem cells
  • DNMT3A and DNMT3B are critical to regulate the onset of IGK light chain rearrangement during early B-cell development
  • DNMT3A and DNMT3B are primarily responsible for de novo methylation of specific cytosine residues in CpG dinucleotides during mammalian development
  • subtelomeric DNA undergoes methylation during development by DNMT3B, including the CpG-rich promoters of the long non-coding RNA (TERRA) embedded in these regions
  • CELLULAR PROCESS nucleotide
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
  • universal repressor complex containing DNMT3B and
  • ZHX1
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • HDAC
  • interacting with HDAC1, HDAC2, HP1 proteins, SUV39H1, and components of the histone methylation system, the ATP-dependent chromatin remodeling enzyme SMARCA5
  • interacting with DNMT3L (stimulating the catalytic activity of DNMT3)
  • interacting with CBX4 through its N-terminal regulatory domain
  • interaction between DNMT3B and constitutive centromere protein CENPC1, itself essential for mitosis
  • link between DNMT3B and centromere dynamics, suggesting that CENPC1 and DNMT3B mutually reinforce each other's recruitment and play a significant role in regulating epigenetic marks at the centromere
  • HOXB3 binds to DNMT3B and increases its expression and in turn, is recruited to the RASSF1A promoter, resulting in hypermethylation and silencing of RASSF1A expression (
  • TCL1A physically interacts with DNA methylthansferases DNMT3A and DNMT3B
  • ability of HELLS to bind ATP and the cellular concentration of DNMT3B are critical for cell-autonomous de novo DNA methylation in somatic cells
  • ZBTB24 is a transcriptional regulator that coordinates with DNMT3B to control DNA methylation
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) ICF
    related resource DNMT3Bbase: Mutation registry for ICF syndrome
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    DNMT3B isoform 4 is overexpressed in hepatocellular carcinoma (hypomethylation)
    tumoral       gain of function
    in leukemia
    tumoral        
    DeltaDNMT3B is the major expression form of DNMT3B in NSCLC
    tumoral     --over  
    overexpression was identified as an independent prognostic factor for predicting shortened survival of patients with diffuse large B-cell lymphomas
    tumoral   amplification    
    in pancreatic and breast cancer, and is associated with increased resistance to the growth-inhibitory effect mediated by DNA demethylating agents
    constitutional germinal mutation      
    heterozygous DNMT3B mutations, only when combined with smaller D4Z4 repeat arrays, can derepress DUX4 in somatic cells and cause FSHMD1a or FSHD2
    constitutional       loss of function
    disruption of DNMT3A or DNMT3B individually as well as of both enzymes in tandem results in viable, pluripotent cell lines with distinct effects on the DNA methylation landscape
    Susceptibility to hereditary nonpolyposis colorectal cancer
    Variant & Polymorphism other polymorphisms associated to nonpolyposis colorectal cancer with early age of onset
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS