ID:DNM3A_HUMAN DESCRIPTION: RecName: Full=DNA (cytosine-5)-methyltransferase 3A; Short=Dnmt3a; EC=2.1.1.37; AltName: Full=DNA methyltransferase HsaIIIA; Short=DNA MTase HsaIIIA; Short=M.HsaIIIA; 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. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZNF238. Can actively repress transcription through the recruitment of HDAC activity (By similarity). 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: Heterotetramer composed of 1 DNMT3A homodimer and 2 DNMT3L subunits (DNMT3L-DNMT3A-DNMT3A-DNMT3L). Interacts with UBC9, PIAS1 and PIAS2 (By similarity). Binds the ZNF238 transcriptional repressor. Interacts with SETDB1. Associates with HDAC1 through its ADD domain. Interacts with UHRF1 (By similarity). Interacts with DNMT1 and DNMT3B. Interacts with the PRC2/EED-EZH2 complex. Interacts with MPHOSPH8. Interacts with histone H3 that is not methylated at 'Lys-4' (H3K4). INTERACTION: O75530:EED; NbExp=2; IntAct=EBI-923653, EBI-923794; Q15910:EZH2; NbExp=4; IntAct=EBI-923653, EBI-530054; Q15047:SETDB1; NbExp=7; IntAct=EBI-923653, EBI-79691; SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Accumulates in the major satellite repeats at pericentric heterochromatin (By similarity). TISSUE SPECIFICITY: Highly expressed in fetal tissues, skeletal muscle, heart, peripheral blood mononuclear cells, kidney, and at lower levels in placenta, brain, liver, colon, spleen, small intestine and lung. DOMAIN: The PWWP domain is essential for targeting to pericentric heterochromatin. PTM: Sumoylated; sumoylation disrupts the ability to interact with histone deacetylases (HDAC1 and HDAC2) and repress transcription (By similarity). 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. CAUTION: It is uncertain whether Met-1 or Met-4 is the initiator. SEQUENCE CAUTION: Sequence=AAL57039.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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.
ModBase Predicted Comparative 3D Structure on Q9Y6K1
Front
Top
Side
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.
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:0003886 DNA (cytosine-5-)-methyltransferase activity GO:0005515 protein binding GO:0008168 methyltransferase activity GO:0009008 DNA-methyltransferase activity GO:0016740 transferase activity GO:0042802 identical protein binding GO:0046872 metal ion binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0000278 mitotic cell cycle GO:0006306 DNA methylation GO:0006325 chromatin organization GO:0006346 methylation-dependent chromatin silencing GO:0006349 regulation of gene expression by genetic imprinting GO:0007283 spermatogenesis GO:0007568 aging GO:0009636 response to toxic substance GO:0010212 response to ionizing radiation GO:0010288 response to lead ion GO:0010468 regulation of gene expression GO:0010942 positive regulation of cell death GO:0030182 neuron differentiation GO:0031667 response to nutrient levels GO:0032259 methylation GO:0032355 response to estradiol GO:0032776 DNA methylation on cytosine GO:0033189 response to vitamin A GO:0042220 response to cocaine GO:0042493 response to drug GO:0043045 DNA methylation involved in embryo development GO:0043046 DNA methylation involved in gamete generation GO:0045471 response to ethanol GO:0045814 negative regulation of gene expression, epigenetic GO:0071230 cellular response to amino acid stimulus GO:0071361 cellular response to ethanol GO:0071456 cellular response to hypoxia GO:0090116 C-5 methylation of cytosine GO:0097284 hepatocyte apoptotic process
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
