TET2 Antibody (Rabbit mAb) [B6D15]

Application: Reactivity: Mouse

Usage Information

Dilution
WB1:1000 IP1:50 IF1:400 - 1:1600 FCM1:100

Application
WB, IP, IF, FCM

Reactivity
Mouse

Source
Rabbit Monoclonal Antibody

Storage Buffer
PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage (from the date of receipt)
-20°C (avoid freeze-thaw cycles), 2 years

Predicted MW
212 kDa

Positive Control	C2C12 cells; NIH/3T3 cells
Negative Control	mES cells; F9 cells

Datasheet & SDS

Biological Description

Specificity
TET2 Antibody (Rabbit mAb) [B6D15] detects endogenous levels of total TET2 protein.

Clone
B6D15

Synonym(s)
Ayu17-44; Ayu17-449; E130014J05Rik; Kiaa1546; Methylcytosine dioxygenase TET2; MGC37385; mKIAA1546; tet oncogene 2; tet oncogene family member 2; Tet2

Background
TET2 belongs to the ten-eleven translocation family of Fe(II)- and alpha-ketoglutarate-dependent dioxygenases, alongside TET1 and TET3, and catalyzes the stepwise oxidation of 5-methylcytosine on DNA, first generating 5-hydroxymethylcytosine and then further oxidizing this intermediate to 5-formylcytosine and 5-carboxylcytosine. Catalysis proceeds through molecular oxygen acting as a cosubstrate for the oxidative decarboxylation of alpha-ketoglutarate, generating a reactive enzyme-bound Fe(IV)-oxo intermediate that then drives hydroxylation of the methylated cytosine base, coupling TET2 activity directly to cellular metabolic state through its dependence on oxygen, alpha-ketoglutarate, and ascorbic acid, the last of which enhances the reaction. The oxidized cytosine derivatives generated by TET2, specifically 5-formylcytosine and 5-carboxylcytosine, are directly recognized and excised by thymine DNA glycosylase, linking TET2-catalyzed oxidation to the base excision repair pathway and completing a route to active, replication-independent DNA demethylation rather than passive dilution of the methyl mark during cell division. TET2 is the most highly expressed TET family member in hematopoietic tissue, particularly within hematopoietic stem cells, where it promotes regulated demethylation of promoter, enhancer, and silencer elements, a process required for the transcriptional control that governs cell lineage commitment, proliferation, and survival, and for maintaining genomic fidelity as hematopoietic stem cells age. Beyond its DNA-oxidizing catalytic function, TET2 recruits the enzyme O-linked beta-N-acetylglucosamine transferase to chromatin, coupling TET2 activity to histone post-translational modification and providing a mechanism through which TET2 influences gene expression independently of its core dioxygenase chemistry. Restoring catalytically active TET2, but not a catalytically dead mutant, into TET2-deficient hematopoietic stem and progenitor cells reverses the increased self-renewal and skewed myeloid differentiation characteristic of TET2 loss, directly establishing that the dioxygenase activity itself, rather than a scaffolding function of the protein, is required for TET2's role in suppressing myeloid malignancy. Loss-of-function TET2 mutations, together with mutations in the metabolic enzyme IDH1/2 that indirectly inhibit TET2 catalysis by generating the oncometabolite 2-hydroxyglutarate, are among the most frequent lesions found in clonal hematopoiesis and in myelodysplastic syndrome, myeloproliferative neoplasm, acute myeloid leukemia, and chronic myelomonocytic leukemia, producing regional DNA hypermethylation, a block in normal differentiation, and a proliferative advantage in hematopoietic stem and progenitor cells that together drive clonal expansion.

Background

TET2 belongs to the ten-eleven translocation family of Fe(II)- and alpha-ketoglutarate-dependent dioxygenases, alongside TET1 and TET3, and catalyzes the stepwise oxidation of 5-methylcytosine on DNA, first generating 5-hydroxymethylcytosine and then further oxidizing this intermediate to 5-formylcytosine and 5-carboxylcytosine. Catalysis proceeds through molecular oxygen acting as a cosubstrate for the oxidative decarboxylation of alpha-ketoglutarate, generating a reactive enzyme-bound Fe(IV)-oxo intermediate that then drives hydroxylation of the methylated cytosine base, coupling TET2 activity directly to cellular metabolic state through its dependence on oxygen, alpha-ketoglutarate, and ascorbic acid, the last of which enhances the reaction. The oxidized cytosine derivatives generated by TET2, specifically 5-formylcytosine and 5-carboxylcytosine, are directly recognized and excised by thymine DNA glycosylase, linking TET2-catalyzed oxidation to the base excision repair pathway and completing a route to active, replication-independent DNA demethylation rather than passive dilution of the methyl mark during cell division. TET2 is the most highly expressed TET family member in hematopoietic tissue, particularly within hematopoietic stem cells, where it promotes regulated demethylation of promoter, enhancer, and silencer elements, a process required for the transcriptional control that governs cell lineage commitment, proliferation, and survival, and for maintaining genomic fidelity as hematopoietic stem cells age. Beyond its DNA-oxidizing catalytic function, TET2 recruits the enzyme O-linked beta-N-acetylglucosamine transferase to chromatin, coupling TET2 activity to histone post-translational modification and providing a mechanism through which TET2 influences gene expression independently of its core dioxygenase chemistry. Restoring catalytically active TET2, but not a catalytically dead mutant, into TET2-deficient hematopoietic stem and progenitor cells reverses the increased self-renewal and skewed myeloid differentiation characteristic of TET2 loss, directly establishing that the dioxygenase activity itself, rather than a scaffolding function of the protein, is required for TET2's role in suppressing myeloid malignancy. Loss-of-function TET2 mutations, together with mutations in the metabolic enzyme IDH1/2 that indirectly inhibit TET2 catalysis by generating the oncometabolite 2-hydroxyglutarate, are among the most frequent lesions found in clonal hematopoiesis and in myelodysplastic syndrome, myeloproliferative neoplasm, acute myeloid leukemia, and chronic myelomonocytic leukemia, producing regional DNA hypermethylation, a block in normal differentiation, and a proliferative advantage in hematopoietic stem and progenitor cells that together drive clonal expansion.

References
https://pubmed.ncbi.nlm.nih.gov/24220273/ https://pubmed.ncbi.nlm.nih.gov/27003514/

Protein Size (kDa)	PVDF Transfer Membrane Pore Size (μm)
< 10	0.22
10-20	0.22
20-30	0.45
30-45	0.45
45-70	0.45
80-100	0.45
100-140	0.45
> 140	0.45

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Protein Size (kDa)	Separating Gel Percentage
4-40	20%
12-45	15%
10-70	12.5%
15-100	10%
25-100	8%
60-210	5%