Human Gene DNMT3B (ENST00000348286.6) Description and Page Index
  Description: Homo sapiens DNA methyltransferase 3 beta (DNMT3B), transcript variant 3, mRNA. (from RefSeq NM_175849)
RefSeq Summary (NM_175849): CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase which is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes primarily to the nucleus and its expression is developmentally regulated. Mutations in this gene cause the immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. Eight alternatively spliced transcript variants have been described. The full length sequences of variants 4 and 5 have not been determined. [provided by RefSeq, May 2011].
Gencode Transcript: ENST00000348286.6
Gencode Gene: ENSG00000088305.18
Transcript (Including UTRs)
   Position: hg38 chr20:32,762,424-32,809,356 Size: 46,933 Total Exon Count: 20 Strand: +
Coding Region
   Position: hg38 chr20:32,780,324-32,807,903 Size: 27,580 Coding Exon Count: 19 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesGeneReviewsMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr20:32,762,424-32,809,356)mRNA (may differ from genome)Protein (770 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: DNM3B_HUMAN
DESCRIPTION: RecName: Full=DNA (cytosine-5)-methyltransferase 3B; Short=Dnmt3b; EC=2.1.1.37; AltName: Full=DNA methyltransferase HsaIIIB; Short=DNA MTase HsaIIIB; Short=M.HsaIIIB;
FUNCTION: Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co- repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing (By similarity). In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Function as transcriptional corepressor by associating with ZHX1.
CATALYTIC ACTIVITY: S-adenosyl-L-methionine + DNA = S-adenosyl-L- homocysteine + DNA containing 5-methylcytosine.
ENZYME REGULATION: Activated by binding to the regulatory factor DNMT3L (By similarity).
SUBUNIT: Interacts with BAZ2A/TIP5, SUV39H1 and CBX4. Interacts with UHRF1 (By similarity). Interacts with DNMT1 and DNMT3A, SETDB1, UBL1, UBE2I9 and ZHX1. Interacts with the PRC2/EED-EZH2 complex.
INTERACTION: O75530:EED; NbExp=4; IntAct=EBI-80125, EBI-923794; Q15910:EZH2; NbExp=6; IntAct=EBI-80125, EBI-530054; P63165:SUMO1; NbExp=4; IntAct=EBI-80125, EBI-80140; P63279:UBE2I; NbExp=3; IntAct=EBI-80125, EBI-80168; Q9UKY1:ZHX1; NbExp=4; IntAct=EBI-6083193, EBI-347767;
SUBCELLULAR LOCATION: Nucleus.
TISSUE SPECIFICITY: Ubiquitous; highly expressed in fetal liver, heart, kidney, placenta, and at lower levels in spleen, colon, brain, liver, small intestine, lung, peripheral blood mononuclear cells, and skeletal muscle. Isoform 1 is expressed in all tissues except brain, skeletal muscle and PBMC, 3 is ubiquitous, 4 is expressed in all tissues except brain, skeletal muscle, lung and prostate and 5 is detectable only in testis and at very low level in brain and prostate.
DOMAIN: The PWWP domain is essential for targeting to pericentric heterochromatin.
PTM: Sumoylated.
DISEASE: Defects in DNMT3B are a cause of immunodeficiency- centromeric instability-facial anomalies syndrome type 1 (ICF1) [MIM:242860]. A rare disorder characterized by a variable immunodeficiency, facial anomalies, and branching of chromosomes 1, 9, and 16. Other variable symptoms include growth retardation, failure to thrive, and psychomotor retardation. Laboratory studies show limited hypomethylation of DNA in a small fraction of the genome in some, but not all, patients.
SIMILARITY: Belongs to the C5-methyltransferase family.
SIMILARITY: Contains 1 ADD domain.
SIMILARITY: Contains 1 GATA-type zinc finger.
SIMILARITY: Contains 1 PHD-type zinc finger.
SIMILARITY: Contains 1 PWWP domain.
WEB RESOURCE: Name=DNMT3Bbase; Note=DNMT3B mutation db; URL="http://bioinf.uta.fi/DNMT3Bbase/";

-  MalaCards Disease Associations
  MalaCards Gene Search: DNMT3B
Diseases sorted by gene-association score: immunodeficiency-centromeric instability-facial anomalies syndrome 1* (1332), immunodeficiency-centromeric instability-facial anomalies syndrome* (402), fascioscapulohumeral muscular dystrophy 2, digenic* (212), testicular spermatocytic seminoma (11), thrombocytopenic purpura, autoimmune (8), early-onset schizophrenia (8), testis seminoma (6), mutagen sensitivity (4), colorectal cancer (3), nasopharyngeal carcinoma (2), breast cancer (2), myelodysplastic syndrome (2), lung cancer (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 5.66 RPKM in Testis
Total median expression: 43.30 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -136.90282-0.485 Picture PostScript Text
3' UTR -427.601453-0.294 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR025766 - ADD
IPR018117 - C5_DNA_meth_AS
IPR001525 - C5_MeTfrase
IPR025811 - C5_MeTrfase_3
IPR000313 - PWWP
IPR011011 - Znf_FYVE_PHD
IPR013083 - Znf_RING/FYVE/PHD

Pfam Domains:
PF00145 - C-5 cytosine-specific DNA methylase
PF00855 - PWWP domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

3FLG
- X-ray MuPIT

3QKJ
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9UBC3
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003714 transcription corepressor activity
GO:0003886 DNA (cytosine-5-)-methyltransferase activity
GO:0005515 protein binding
GO:0008168 methyltransferase activity
GO:0009008 DNA-methyltransferase activity
GO:0016740 transferase activity
GO:0042826 histone deacetylase binding
GO:0046872 metal ion binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001666 response to hypoxia
GO:0006306 DNA methylation
GO:0009636 response to toxic substance
GO:0010212 response to ionizing radiation
GO:0010468 regulation of gene expression
GO:0010628 positive regulation of gene expression
GO:0014823 response to activity
GO:0031000 response to caffeine
GO:0032259 methylation
GO:0032355 response to estradiol
GO:0033189 response to vitamin A
GO:0042220 response to cocaine
GO:0042493 response to drug
GO:0045666 positive regulation of neuron differentiation
GO:0045814 negative regulation of gene expression, epigenetic
GO:0051571 positive regulation of histone H3-K4 methylation
GO:0051573 negative regulation of histone H3-K9 methylation
GO:0071455 cellular response to hyperoxia
GO:0071549 cellular response to dexamethasone stimulus
GO:0090116 C-5 methylation of cytosine

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0043231 intracellular membrane-bounded organelle


-  Descriptions from all associated GenBank mRNAs
  AB208880 - Homo sapiens mRNA for DNA cytosine-5 methyltransferase 3 beta isoform 6 variant protein.
AF331857 - Homo sapiens DNA cytosine methyltransferase 3 beta (DNMT3B) mRNA, complete cds.
DQ321787 - Homo sapiens DNA methyltransferase (DNMT3B) mRNA, DNMT3B-7 allele, complete cds, alternatively spliced.
AK300857 - Homo sapiens cDNA FLJ60900 complete cds, highly similar to DNA (cytosine-5)-methyltransferase 3B (EC 2.1.1.37).
AK299915 - Homo sapiens cDNA FLJ56945 complete cds, highly similar to DNA (cytosine-5)-methyltransferase 3B (EC 2.1.1.37).
AF156487 - Homo sapiens DNA cytosine-5 methyltransferase 3 beta 3 (DNMT3B) mRNA, complete cds.
AF156488 - Homo sapiens DNA cytosine-5 methyltransferase 3 beta 1 (DNMT3B) mRNA, complete cds.
AK295176 - Homo sapiens cDNA FLJ57837 complete cds, highly similar to DNA (cytosine-5)-methyltransferase 3B (EC 2.1.1.37).
AK299821 - Homo sapiens cDNA FLJ61375 complete cds, highly similar to Homo sapiens DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B), transcript variant 3, mRNA.
AK299776 - Homo sapiens cDNA FLJ52873 complete cds, highly similar to DNA (cytosine-5)-methyltransferase 3B (EC 2.1.1.37).
JD522839 - Sequence 503863 from Patent EP1572962.
JD407002 - Sequence 388026 from Patent EP1572962.
JD157412 - Sequence 138436 from Patent EP1572962.
JD497254 - Sequence 478278 from Patent EP1572962.
JD458955 - Sequence 439979 from Patent EP1572962.
JD129615 - Sequence 110639 from Patent EP1572962.
AF176228 - Homo sapiens DNA cytosine-5 methyltransferase 3B (DNMT3B) mRNA, complete cds.
AB527132 - Synthetic construct DNA, clone: pF1KE0347, Homo sapiens DNMT3B gene for DNA (cytosine-5-)-methyltransferase 3 beta, without stop codon, in Flexi system.
BC111933 - Synthetic construct Homo sapiens clone IMAGE:40080753, MGC:133466 DNMT3B protein (DNMT3B) mRNA, encodes complete protein.
BC118502 - Synthetic construct Homo sapiens clone IMAGE:40080762, MGC:155335 DNMT3B protein (DNMT3B) mRNA, encodes complete protein.
KX447429 - Homo sapiens DNA cytosine-5--methyltransferase 3 beta transcript variant 9 (DNMT3B) mRNA, complete cds, alternatively spliced.
AK001191 - Homo sapiens cDNA FLJ10329 fis, clone NT2RM2000594, highly similar to DNA (cytosine-5)-methyltransferase 3B (EC 2.1.1.37).
AF129267 - Homo sapiens DNA methyltransferase 3 beta 1 (DNMT3B) mRNA, alternate splice product, partial cds.
AF129268 - Homo sapiens DNA methyltransferase 3 beta 4 (DNMT3B) mRNA, alternate splice product, partial cds.
AF129269 - Homo sapiens DNA methyltransferase 3 beta 5 (DNMT3B) mRNA, alternate splice product, partial cds.
JD456749 - Sequence 437773 from Patent EP1572962.
JD391094 - Sequence 372118 from Patent EP1572962.
JD386720 - Sequence 367744 from Patent EP1572962.
JD283939 - Sequence 264963 from Patent EP1572962.
JD474337 - Sequence 455361 from Patent EP1572962.
JD118118 - Sequence 99142 from Patent EP1572962.
JD118926 - Sequence 99950 from Patent EP1572962.
JD210976 - Sequence 192000 from Patent EP1572962.
JD231446 - Sequence 212470 from Patent EP1572962.
JD144796 - Sequence 125820 from Patent EP1572962.
JD230515 - Sequence 211539 from Patent EP1572962.
JD151521 - Sequence 132545 from Patent EP1572962.
JD457962 - Sequence 438986 from Patent EP1572962.
JD326076 - Sequence 307100 from Patent EP1572962.
JD231182 - Sequence 212206 from Patent EP1572962.
JD280531 - Sequence 261555 from Patent EP1572962.
JD362536 - Sequence 343560 from Patent EP1572962.
JD163715 - Sequence 144739 from Patent EP1572962.
JD442482 - Sequence 423506 from Patent EP1572962.
JD126632 - Sequence 107656 from Patent EP1572962.
JD130356 - Sequence 111380 from Patent EP1572962.
JD373660 - Sequence 354684 from Patent EP1572962.
JD374010 - Sequence 355034 from Patent EP1572962.
JD538606 - Sequence 519630 from Patent EP1572962.
JD328803 - Sequence 309827 from Patent EP1572962.
JD563559 - Sequence 544583 from Patent EP1572962.
L32168 - Homo sapiens (clone tec12) mRNA.
JD037534 - Sequence 18558 from Patent EP1572962.
JD040361 - Sequence 21385 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00270 - Cysteine and methionine metabolism
hsa01100 - Metabolic pathways

Reactome (by CSHL, EBI, and GO)

Protein Q9UBC3 (Reactome details) participates in the following event(s):

R-HSA-427409 Nucleolar Remodelling Complex (NoRC) binds intergenic region of rDNA
R-HSA-5334164 DNMT3B:DNMT3L binds chromatin
R-HSA-212222 PRC2 recruits DNA methyltransferases
R-HSA-5227490 NoRC:HDAC:DNMT methylates cytosine of the rRNA genes
R-HSA-5334097 DNMT3B:DNMT3L methylates cytosine in DNA
R-HSA-427413 NoRC negatively regulates rRNA expression
R-HSA-5334118 DNA methylation
R-HSA-212300 PRC2 methylates histones and DNA
R-HSA-5250941 Negative epigenetic regulation of rRNA expression
R-HSA-212165 Epigenetic regulation of gene expression
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: A2A2E2, DNM3B_HUMAN, E1P5M6, E1P5M7, NM_175849, Q9UBC3, Q9UBD4, Q9UJQ5, Q9UKA6, Q9UNE5, Q9Y5R9, Q9Y5S0, uc002wye.1, uc002wye.2, uc002wye.3, uc002wye.4
UCSC ID: uc002wye.4
RefSeq Accession: NM_175849
Protein: Q9UBC3 (aka DNM3B_HUMAN or DM3B_HUMAN)
CCDS: CCDS13207.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene DNMT3B:
fsh (Facioscapulohumeral Muscular Dystrophy)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.