Recombinant Human DNA (cytosine-5)-methyltransferase 3A(DNMT3A) ,partial

Code CSB-EP897314HU
Size US$1726
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.

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Product Details

Purity Greater than 90% as determined by SDS-PAGE.
Target Names DNMT3A
Uniprot No. Q9Y6K1
Research Area Epigenetics and Nuclear Signaling
Alternative Names DNA (cytosine 5) methyltransferase 3 alpha; DNA (cytosine 5) methyltransferase 3A; DNA (cytosine-5)-methyltransferase 3A; DNA cytosine methyltransferase 3A2; DNA methyltransferase 3 alpha; DNA methyltransferase 3a; DNA methyltransferase HsaIIIA; DNA MTase HsaIIIA; DNM3A_HUMAN; DNMT 3a; DNMT; Dnmt3a; DNMT3A2; M.HsaIIIA; MCMT; OTTHUMP00000201149; TBRS
Species Homo sapiens (Human)
Source E.coli
Expression Region 680-902aa
Target Protein Sequence KIMYVGDVRSVTQKHIQEWGPFDLVIGGSPCNDLSIVNPARKGLYEGTGRLFFEFYRLLHDARPKEGDDRPFFWLFENVVAMGVSDKRDISRFLESNPVMIDAKEVSAAHRARYFWGNLPGMNRPLASTVNDKLELQECLEHGRIAKFSKVRTITTRSNSIKQGKDQHFPVFMNEKEDILWCTEMERVFGFPVHYTDVSNMSRLARQRLLGRSWSVPVIRHLF
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight 29.9kDa
Protein Length Partial
Tag Info N-terminal 6xHis-tagged
Form Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting
and FAQs
Protein FAQs
Storage Condition Store at -20°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Notes Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA Please contact us to get it.

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Target Data

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 ZBTB18. Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. Can actively repress transcription through the recruitment of HDAC activity.
Gene References into Functions
  1. Multiple evidences suggested that PRMT5 repressed transcription of tumor suppressor IRX1 via recruitment of DNMT3A on promoter. PMID: 29802960
  2. Most had constantly high DNMT3A(mut) transcript levels. PMID: 28643785
  3. Together findings presented here recognize an inherent role of MTA1 as a modifier of DNMT3a and IGFBP3 expression, and consequently, the role of MTA1-DNMT3a-IGFBP3 axis in breast cancer progression. PMID: 28393842
  4. we developed a modular dCas9-SunTag (dC9Sun-D3A) system that can recruit multiple DNMT3A catalytic domains to a target site for editing DNA methylation. dC9Sun-D3A is tunable, specific, and exhibits much higher induction of DNA methylation at target sites than the dC9-D3A direct fusion protein. PMID: 29907613
  5. Results indicate that DNMT3A mutations alone do not affect the clinical outcomes of AML patients undergoing allogeneic HSCT, but when accompanied by FLT3-ITD mutations, the OS was significantly reduced (5-year OS 0% for DNMT3A R882mut/FLT3-ITDpos patients vs. 62% DNMT3A R882wt/FLT3-ITDneg, p=0.025) and the relapse rate increased. PMID: 29786546
  6. Genetic variation in DNMT3A gene is not associated with gastric cancer. PMID: 29956566
  7. concluded that miR-876-5p suppressed hepatocellular carcinoma progression by targeting DNMT3A PMID: 29724530
  8. These findings indicated a novel mechanism by which EID3, a p300 acetyltransferase inhibitor, could directly affect DNMT3A, this enzyme possesses dual methylation and demethylation abilities. PMID: 28074931
  9. DNMT3A R882 mutation plays an important role in CN-AML patients' prognosis and clinical outcomes in the presence and absence of NPM1 and FLT3 mutations. PMID: 29079128
  10. a feedback loop between miR-145 and DNMT3A is a potent signature for the Warburg effect in ovarian cancer, promising a potential target for improved anticancer treatment. PMID: 29993160
  11. In univariable analysis, patients carrying mutations in DNMT3A, U2AF1, and EZH2 had worse overall and relapse-free survival. PMID: 29321554
  12. Elastic Network Models, information theory, Protein Structure Network, and sequence evolution analysis were used to investigate intrinsic dynamics and allosteric properties of DNMT3A resolved in autoinhibitory and active states. The conformational transition between 2 states shows global motions. The dimer interface has a major role in defining the quaternary structure dynamics and establishing interdomain communication. PMID: 29674125
  13. HIF1A-AS2 exerted the oncogenic functions in CRC through regulating miR-129-5p/DNMT3A axis. PMID: 29278853
  14. we found that DNMT3A was responsible for the down-regulation of miR-105 in gastric cancer cells PMID: 28829505
  15. Taken together, these data demonstrate that adipose Dnmt3a is a novel epigenetic mediator of insulin resistance in vitro and in vivo. PMID: 29091029
  16. Low frequency of DNMT3A mutations in pediatric T-ALL is in striking contrast to adult T-ALL and renders the necessity for the search of other candidate prognostic markers. Combined Sanger sequencing-HRM approach offers a cost-effective option for genotyping DNMT3A coding sequence, with potential clinical application in other hematological malignancies. PMID: 28905428
  17. 2.65-angstrom crystal structure of the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides, with the target sites separated by 14 base pairs within the same DNA duplex; mechanistic basis for DNMT3A-mediated DNA methylation and establishment of its aetiological link to human disease PMID: 29414941
  18. based on the investigation of previously reported variants in patients with Tatton-Brown-Rahman syndrome , we found overlap in the spectrum of DNMT3A variants observed in this disorder and somatic variants in hematological malignancies PMID: 28941052
  19. The emodininduced downregulation of UHRF1 led to an increase in the level of DNA methyltransferase 3A. PMID: 28901428
  20. Data suggest that miR-200b-3p may exhibit targeting and suppressive effects on DNA methyltransferase 3A (DNMT3A). PMID: 28345813
  21. Prostaglandin E2 promotes the acquisition of DNMT3A-dependent tolerogenic functions in human myeloid-derived suppressor cells. PMID: 28978469
  22. human mammary epithelial cells reprogramming is dependent on gene silencing by the DNA methyltransferase DNMT3A and loss of histone transcriptional marks following downregulation of the methyltransferase DOT1L. PMID: 28781076
  23. the immunohistochemical expressions of Klotho and DNMT3a in tissues obtained from oral dysplasia and oral squamous cell carcinoma, is reported. PMID: 28303350
  24. this epigenetic antagonism precedes malignant transformation and can be observed in preleukemic LSK cells from Idh2(R140Q) or Dnmt3a(R882H) single-mutant and Idh2(R140Q)/Dnmt3a(R882H) double-mutant mice. IDH/DNMT3A double-mutant acute myeloid leukemia (AML)manifested upregulation of a RAS signaling signature and displayed unique sensitivity to MEK inhibition ex vivo as compared with AMLs with either single mutation. PMID: 28408400
  25. The current findings confirmed that downregulation of DNMT3A protein expression and the ensuing disturbance of the maintenance DNA methylation may serve an important role in the pathogenesis of early embryo growth arrest. PMID: 28560437
  26. Our results provided novel insight into the role of the DNMT3A R882H mutation in AML pathogenesis and suggested that targeting the cellular GSH synthetic pathway could enhance the current therapy for AML patients with the DNMT3A R882H mutation. PMID: 28418922
  27. data confirm MLL-PTD and, to a lesser extent, FLT3-ITD as common events in +11 AML.6, 7, 8 However, the high mutation frequencies of U2AF1 and genes involved in methylation (DNMT3A, IDH2) have hitherto not been reported in +11 AML PMID: 27435003
  28. Silencing DNMT3A inhibits proliferation and invasion in ESCC cells by inducing demethylation of DOK7. PMID: 28343076
  29. Data show that DNA methyltransferase 3A (DNMT3A) mutation was significantly associated with adverse outcome in addition to conventional risk stratification. PMID: 27359055
  30. DNMT3A polymorphisms may be potential predictive markers for acute myelogenous leukemia patients' outcomes in China PMID: 27528035
  31. this study shows that DNMT3A mutations are present in a significant proportion of SF3B1mut patients with RARS and its presence has a clearly negative impact on outcomes, determining a higher RBC transfusion dependency, higher risk of progression to AML, and lower OS. PMID: 27771989
  32. DNMT3A is a de novo DNA methyltransferase that has recently gained relevance because of its frequent mutation in a large variety of immature and mature hematologic neoplasms. DNMT3A mutations are early events during cancer development and seem to confer poor prognosis to acute myeloid leukemia patients making this gene an attractive target for new therapies. [review] PMID: 28003281
  33. the present cohort study demonstrated that FLT3-ITD and DNMT3A R882 double mutation predicts poor prognosis in Chinese AML patients receiving chemotherapy or allo-HSCT treatment. PMID: 28616699
  34. propose a model of the DNMT3A PWWP domain-H3K36me3 complex and build a model of DNMT3A (PWWP-ADD-CD) in a nucleosomal context PMID: 26993463
  35. DNMT3 mutation in OCI-AML3 strain enhances leukemic aggressiveness by promoting extramedullary infiltration process, which is partially through upregulating TWIST1. PMID: 27724883
  36. Concurrent STAT3, DNMT3A, and TET2 mutations in T-LGL leukemia with molecularly distinct clonal hematopoiesis of indeterminate potential PMID: 27761930
  37. No evidence for genetic variants in DNMT3A being implicated in cognitive performance decline in individuals with mild cognitive impairment. PMID: 27092400
  38. A Methylated DNA Quantification Kit was used to quantify global DNA methylation, and single nucleotide polymorphisms (SNPs) in DNMT3A (rs36012910, rs1550117, and R882) and DNMT3B (rs1569686, rs2424909, and rs2424913) were identified using the restriction fragment length polymorphism method PMID: 28945286
  39. DNMT3A1 and DNMT3A2V were detected in newly diagnosed acute myeloid leukemia (AML) patients and controls, with DNMT3A2V significantly up-regulated in AML patients. The main transcript switched from DNMT3A1 to DNMT3A2V in some patients, especially the low risk group based on the NCCN 2016 guidelines. These findings suggest that DNMT3A1 and DNMT3A2V are the main variants in AML. PMID: 29024628
  40. Mechanical compression induced miR-9 downregulation by DNMT3A-dependent promoter methylation. PMID: 28252641
  41. TP(thymidine phosphorylase ) curbed the expression of three proteins-IRF8, RUNX2, and osterix. This downregulation was epigenetically driven: High levels of 2DDR, a product of TP secreted by myeloma cells, activated PI3K/AKT signaling and increased the methyltransferase DNMT3A's expression. PMID: 27658717
  42. alterations in DNMT3A and TET2 may be associated with acute myeloid leukemia prognosis PMID: 28992762
  43. Mutation in the DNMT3A gene is associated with acute myeloid leukemia patients with lympho-myeloid clonal hematopoiesis. PMID: 27881874
  44. These data demonstrate that haploinsufficiency for Dnmt3a alters hematopoiesis and predisposes mice (and probably humans) to myeloid malignancies by a mechanism that is not yet clear. PMID: 28872462
  45. This report represents the first documentation of the same variant (DNMT3A p.Arg882His) as both the constitutional mutation associated with TBRS and the somatic mutation hotspot of AML. PMID: 27991732
  46. Mutations in genes associated with epigenetic regulations such as DNMT3A and ASXL1 seem to play an important role in the pathogenesis of CML progression and TKI-resistance independent of ABL1 KD mutations PMID: 28667884
  47. Dnmt3a2 is at the core of memory processes and represents a novel target for cognition-enhancing therapies to ameliorate anxiety and fear disorders and boost memory consolidation. PMID: 26598069
  48. Data indicate that DNMT3A allele G of rs1550117 was associated with an increased risk of non-small cell lung cancer (NSCLC) susceptibility and binding affinity of transcription repressor SP1. PMID: 28423585
  49. The results show that DNMT3A mutations are associated with an unfavourable clinical outcome in our Southeast Asian AML patient cohort. PMID: 28100593
  50. DNMT3A mutations were rare in Chinese children with acute myeloid leukemia (AML). The mutation positions were different from the hotspots reported in adult AML. DNMT3A mutations may have adverse impact on prognosis of children with AML. PMID: 28767575

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Involvement in disease Tatton-Brown-Rahman syndrome (TBRS)
Subcellular Location Nucleus, Cytoplasm
Protein Families Class I-like SAM-binding methyltransferase superfamily, C5-methyltransferase family
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.
Database Links

HGNC: 2978

OMIM: 602769

KEGG: hsa:1788

STRING: 9606.ENSP00000264709

UniGene: Hs.515840

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