DNMT3A
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Official Full Name
DNA (cytosine-5-)-methyltransferase 3 alpha
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Overview
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 that is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008] -
Synonyms
DNMT3A; DNA (cytosine-5-)-methyltransferase 3 alpha; DNMT3A2; M.HsaIIIA; DNA (cytosine-5)-methyltransferase 3A; DNA MTase HsaIIIA; DNA cytosine methyltransferase 3A2;
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What is Dnmt3a protein?
Dnmt3a protein, also known as DNA (cytosine-5)-methyltransferase 3A, is an enzyme that plays a crucial role in DNA methylation. It is involved in the addition of a methyl group to the 5th carbon of cytosine residues in DNA, leading to the formation of 5-methylcytosine. DNA methylation is an epigenetic modification that regulates gene expression and is essential for normal development and cellular function.
What is the function of Dnmt3a protein?
Dnmt3a primarily functions during early embryonic development and is responsible for establishing the DNA methylation patterns in the genome. It is also involved in maintaining DNA methylation patterns throughout life by ensuring faithful replication and inheritance of methylation marks during cell division.
Dnmt3a mutations have been implicated in several diseases, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), where abnormal DNA methylation patterns contribute to the development of these malignancies.
Dnmt3a related signaling pathway
Dnmt3a plays a crucial role in epigenetic regulation by controlling gene expression through DNA methylation. Dysregulation of Dnmt3a has been associated with various diseases, including cancer. In particular, mutations in Dnmt3a have been identified in acute myeloid leukemia (AML) patients.
The exact signaling pathway involving Dnmt3a is still being investigated. However, it is known that Dnmt3a interacts with other proteins and factors involved in DNA methylation, chromatin remodeling, and gene expression regulation. These include Dnmt3L (Dnmt3a cofactor), histone modifying enzymes, transcription factors, and chromatin remodeling complexes.
Dnmt3a Related Diseases
- Acute Myeloid Leukemia (AML): Dnmt3a mutations are frequently found in patients with AML, particularly in cases with normal cytogenetics. These mutations contribute to abnormal DNA methylation patterns and impaired differentiation of hematopoietic stem cells.
- Myelodysplastic Syndromes (MDS): Dnmt3a mutations are also observed in patients with MDS, a heterogeneous group of bone marrow disorders characterized by ineffective blood cell production. Dnmt3a mutations are associated with dysregulated DNA methylation and altered hematopoietic stem cell function.
- Solid Tumors: Dnmt3a mutations have been reported in various solid tumors, although their prevalence in these cancers is relatively low compared to hematological malignancies.
- Cancer research and therapy: Dnmt3a mutations are frequently found in various cancers, including acute myeloid leukemia (AML). Understanding the role of Dnmt3a mutations in cancer development and progression can help in the development of targeted therapies. Inhibitors targeting Dnmt3a activity are also being investigated as potential cancer treatments.
- Biomarker discovery: Dnmt3a mutations or altered expression levels have been identified as potential biomarkers for several diseases, including cancer. Detection of these biomarkers can assist in disease diagnosis, prognosis, and monitoring treatment response.
Biomedical Application of Dnmt3a Protein
- Cancer research and therapy: Dnmt3a mutations are frequently found in various cancers, including acute myeloid leukemia (AML). Understanding the role of Dnmt3a mutations in cancer development and progression can help in the development of targeted therapies. Inhibitors targeting Dnmt3a activity are also being investigated as potential cancer treatments.
- Epigenetic research: Studying the function and regulation of Dnmt3a contributes to understanding epigenetic modifications and their impact on gene expression and cellular processes. This knowledge can aid in deciphering the mechanisms underlying various diseases and developing new therapeutic strategies.
- Reprogramming of stem cells: Dnmt3a plays a crucial role in the establishment and maintenance of DNA methylation patterns during embryonic development. Manipulating Dnmt3a expression or activity can influence the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), allowing for the generation of patient-specific stem cells for disease modeling and regenerative medicine.
- Reprogramming of stem cells: Dnmt3a plays a crucial role in the establishment and maintenance of DNA methylation patterns during embryonic development. Manipulating Dnmt3a expression or activity can influence the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), allowing for the generation of patient-specific stem cells for disease modeling and regenerative medicine.
High Purity
Fig1. SDS-PAGE (DNMT3A-2790H)
High Bioactivity & Detection Sensitivity
Fig2. DNMT3A activity verified in a biochemical assay: DNMT3A (DNA (cytosine-5-)-methyltransferase 3 alpha) is a DNA methyltransferase that is thought to function in de novo methylation, rather than maintenance methylation. It modifies DNA in a non-processive manner and also methylates non-CpG sites. Varying concentrations of DNMT3A were added to a microplate containing a bound methyltransferase substrate. After incubation, the resulting methylated DNA residues were detected immunologically and a colorimetric signal was generated and measured.
Surface Plasmon Ressonance (SPR)
(Rachel Deplus, 2014)
Fig3. Orthophosphate labeling of Dnmt3a-overexpressing cells. U2OS cells were transiently transfected with Myc-Dnmt3a (lane 2) or empty vector (lane 1) and incubated with 32Pi for 4 hr prior to immunoprecipitation (IP) with Myc antibody. A representative experiment is shown, which was successfully repeated three times.
(Chao-Cheng Cho, 2023)
Fig4. Expression and purification of the catalytic domains of human DNMT1, DNMT3A-3L, and DNMT3B-3L. (B) Elution profiles of DNMT1, DNMT3A-3L, and DNMT3B-3L via size-exclusion chromatography (HiLoad 16/60 Superdex 200, GE Healthcare). (C) SDS-PAGE analysis of purified DNMT1, DNMT3A-3L, and DNMT3B-3L reveals high homogeneity for each recombinant protein. M, molecular weight marker.
DNMT3A involved in several pathways and played different roles in them. We selected most pathways DNMT3A participated on our site, such as Chromatin modifying enzymes, Chromatin organization, Cysteine and methionine metabolism, which may be useful for your reference. Also, other proteins which involved in the same pathway with DNMT3A were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.
| Pathway Name | Pathway Related Protein |
|---|---|
| Chromatin modifying enzymes | EED;ACTL6A;KAT7A;KIAA1267;ARID2;GATAD2B;PHF8;PRDM16;KANSL2 |
| Chromatin organization | SMARCB1B;KDM5A;PADI2;KANSL2;KIAA1267;RBBP7;MBD3A;PAX3A;ARID1A |
| Cysteine and methionine metabolism | BHMT;LDHBB;MPST;CBSA;DNMT3AB;APIP;DNMT3A;AHCYL2;LDHBA |
| DNA methylation | DNMT1;DNMT3L;DNMT3B;DNMT3A;UHRF1 |
| Epigenetic regulation of gene expression | SAP130;RRP8;MTF2;AEBP2;TET2;DNMT3B;JARID2;TAF1B;SIN3B |
| Gene Expression | NR2F6A;HNRNPF;ZFP473;NFIC;NR5A1;ESR2A;PTRF;PPARAA;ZNF777 |
| Metabolic pathways | FUT9;ATP5J;SDSL;POLR3K;ATP6V1F;ATP5G3;CYP21A2;HYAL3;BDH1 |
| MicroRNAs in cancer | CCNE1;MCL1;BMI1;PTGS2;ABCB1A;HNRNPK;PLCG1;TRP63;ZFPM2 |
DNMT3A has several biochemical functions, for example, DNA (cytosine-5-)-methyltransferase activity, DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates, DNA binding. Some of the functions are cooperated with other proteins, some of the functions could acted by DNMT3A itself. We selected most functions DNMT3A had, and list some proteins which have the same functions with DNMT3A. You can find most of the proteins on our site.
| Function | Related Protein |
|---|---|
| DNA (cytosine-5-)-methyltransferase activity | DNMT3A;TRDMT1;DNMT3B;DNMT1 |
| DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates | DNMT3B;DNMT3A |
| DNA binding | DNASE2;SOX21;SIX3A;POLR2EB;SMARCA5;ZFAND5B;ZNF398;RNF11;ZBTB17 |
| DNA-methyltransferase activity | DIMT1;METTL7B;DNMT1;METTL21A;PRDM13;NDUFAF5;METTL23;FBLL1;METTL21D |
| chromatin binding | KLHDC3;PAF1;RDBP;TRP63;EED;NUP62;JUN;NSD1;PRDM13 |
| identical protein binding | TRIM5;P2RX2;SCUBE1;PSMD4;DHX8;SEPT7;KHDRBS1;SDF4;TRIP10 |
| metal ion binding | GLI2B;GUCA1E;HENMT1;GALNT4;CSK;RNF145B;ADH1;ZNF367;ZSCAN16 |
| protein binding | TLR1;FGB;KIF1B;HSF2;POU2F1;CCDC103;NR1D2;TEX19.1;NPRL2 |
| unmethylated CpG binding | DNMT3B;KDM2A;MLL1;CXXC1;DNMT3A |
DNMT3A has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with DNMT3A here. Most of them are supplied by our site. Hope this information will be useful for your research of DNMT3A.
EZH2; H3F3A; SETDB1
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Q&As (5)
Ask a questionDNMT3A mutations can serve as biomarkers for certain cancers, aiding in the diagnosis and classification of hematologic malignancies.
DNMT3A is essential for normal DNA methylation patterns during development and differentiation, influencing gene expression and cellular function.
Like many targeted therapies, DNMT3A-targeted treatments may have off-target effects, and their specificity is an area of active research.
Yes, molecular diagnostic tests, such as DNA sequencing, can identify DNMT3A mutations in cancer cells.
DNMT3A mutations lead to abnormal DNA methylation patterns, contributing to altered gene expression and promoting cancer development.
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