Recombinant Human DNA (DNMT3A) Protein (His&Myc)

Name: Recombinant Human DNA (DNMT3A) Protein (His&Myc)
Brand: Beta LifeScience
SKU: BLC-06370P
Availability: InStock

Greater than 90% as determined by SDS-PAGE.

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Product Overview

Description	Recombinant Human DNA (DNMT3A) Protein (His&Myc) is produced by our E.coli expression system. This is a full length protein.
Purity	Greater than 90% as determined by SDS-PAGE.
Uniprotkb	Q9Y6K1
Target Symbol	DNMT3A
Species	Homo sapiens (Human)
Expression System	E.coli
Tag	N-10His&C-Myc
Target Protein Sequence	MPAMPSSGPGDTSSSAAEREEDRKDGEEQEEPRGKEERQEPSTTARKVGRPGRKRKHPPVESGDTPKDPAVISKSPSMAQDSGASELLPNGDLEKRSEPQPEEGSPAGGQKGGAPAEGEGAAETLPEASRAVENGCCTPKEGRGAPAEAGESSAPGAASSGPTSIP
Expression Range	1-166aa
Protein Length	Full Length
Mol. Weight	24.3 kDa
Research Area	Epigenetics And Nuclear Signaling
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target 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. Also has weak auto-methylation activity on Cys-710 in absence of DNA.
Subcellular Location	Nucleus. Chromosome. Cytoplasm.
Protein Families	Class I-like SAM-binding methyltransferase superfamily, C5-methyltransferase family
Database References	HGNC: 2978 OMIM: 602769 KEGG: hsa:1788 STRING: 9606.ENSP00000264709 UniGene: PMID: 29802960 Most had constantly high DNMT3A(mut) transcript levels. PMID: 28643785 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 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 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 Genetic variation in DNMT3A gene is not associated with gastric cancer. PMID: 29956566 concluded that miR-876-5p suppressed hepatocellular carcinoma progression by targeting DNMT3A PMID: 29724530 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 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 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 In univariable analysis, patients carrying mutations in DNMT3A, U2AF1, and EZH2 had worse overall and relapse-free survival. PMID: 29321554 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 HIF1A-AS2 exerted the oncogenic functions in CRC through regulating miR-129-5p/DNMT3A axis. PMID: 29278853 we found that DNMT3A was responsible for the down-regulation of miR-105 in gastric cancer cells PMID: 28829505 Taken together, these data demonstrate that adipose Dnmt3a is a novel epigenetic mediator of insulin resistance in vitro and in vivo. PMID: 29091029 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 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 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 The emodininduced downregulation of UHRF1 led to an increase in the level of DNA methyltransferase 3A. PMID: 28901428 Data suggest that miR-200b-3p may exhibit targeting and suppressive effects on DNA methyltransferase 3A (DNMT3A). PMID: 28345813 Prostaglandin E2 promotes the acquisition of DNMT3A-dependent tolerogenic functions in human myeloid-derived suppressor cells. PMID: 28978469 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 the immunohistochemical expressions of Klotho and DNMT3a in tissues obtained from oral dysplasia and oral squamous cell carcinoma, is reported. PMID: 28303350 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 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 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 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 Silencing DNMT3A inhibits proliferation and invasion in ESCC cells by inducing demethylation of DOK7. PMID: 28343076 Data show that DNA methyltransferase 3A (DNMT3A) mutation was significantly associated with adverse outcome in addition to conventional risk stratification. PMID: 27359055 DNMT3A polymorphisms may be potential predictive markers for acute myelogenous leukemia patients' outcomes in China PMID: 27528035 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 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 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 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 DNMT3 mutation in OCI-AML3 strain enhances leukemic aggressiveness by promoting extramedullary infiltration process, which is partially through upregulating TWIST1. PMID: 27724883 Concurrent STAT3, DNMT3A, and TET2 mutations in T-LGL leukemia with molecularly distinct clonal hematopoiesis of indeterminate potential PMID: 27761930 No evidence for genetic variants in DNMT3A being implicated in cognitive performance decline in individuals with mild cognitive impairment. PMID: 27092400 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 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 Mechanical compression induced miR-9 downregulation by DNMT3A-dependent promoter methylation. PMID: 28252641 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 alterations in DNMT3A and TET2 may be associated with acute myeloid leukemia prognosis PMID: 28992762 Mutation in the DNMT3A gene is associated with acute myeloid leukemia patients with lympho-myeloid clonal hematopoiesis. PMID: 27881874 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 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 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 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 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 The results show that DNMT3A mutations are associated with an unfavourable clinical outcome in our Southeast Asian AML patient cohort. PMID: 28100593 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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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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