SETD2 Antibodies

Structure of SETD2

The histone methyltransferase encoded by the SETD2 gene is a large molecular weight protein complex, with a molecular weight of approximately 250-280 kDa. The specific molecular weight varies among different species and isoforms, mainly due to the variable splicing of gene transcription and the diversity of post-translational modifications.

This protein contains several highly conserved domains, such as the SET domain for catalytic activity, the WW domain for chromatin interaction, and the AWS domain for RNA binding. The core three-dimensional structure of this protein is centered around the SET domain, forming a specific substrate binding channel that can precisely recognize the lysine at position 36 of histone H3 and catalyze its trimethylation. The adjacent aspartic acid and tyrosine residues are crucial for maintaining the conformation and activity of the catalytic center. This combination of multiple domains enables it to integrate transcriptional signals and precisely regulate chromatin state and gene expression.

Fig. 1 The main domains of SETD2.¹

Key structural properties of SETD2:

• Containing a conservative catalytic activity SET domain
• Contains the WW domain that interacts with proteins
• Containing an AWS domain that binds RNA
• Form a specific substrate binding channel
• Dependent on key aspartic and tyrosine residues to maintain catalytic center conformation

Functions of SETD2

The core function of the SETD2 protein is to act as a histone methyltransferase, catalyzing the trimethylation of lysine at position 36 of histone H3. However, this modification is also widely involved in a variety of crucial cellular biological processes.

Unlike the widespread distribution of some histone modifications, the distribution of H3K36me3 modification on the genome is highly specific, mainly enriched in the genomic regions of actively transcribed genes. This reflects the high precision of its function and its direct regulatory role in the transcription process.

Applications of SETD2 and SETD2 Antibody in Literature

1. He, Jiahui, et al. "SETD2-H3K36ME3: an important bridge between the environment and tumors." Frontiers in Genetics 14 (2023): 1204463. https://doi.org/10.3389/fgene.2023.1204463

The article indicates that SETD2 catalyzes the H3K36me3 modification, and plays a crucial role in epigenetic regulation, transcription elongation, and mismatch repair. Its mutations are closely related to the occurrence and development of various tumors such as renal cancer, gastric cancer, and lung cancer, serving as an important bridge connecting the environment and tumors, and providing important targets for clinical diagnosis and treatment.

2. Xue, Wei, et al. "Knockdown of SETD2 promotes erastin-induced ferroptosis in ccRCC." Cell Death & Disease 14.8 (2023): 539. https://doi.org/10.1038/s41419-023-06057-8

The article indicates that in renal clear cell carcinoma, low expression of histone methyltransferase SETD2 predicts a poor prognosis. SETD2 regulates the transcription of iron chelase through catalyzing the H3K36me3 modification. Its absence can enhance the sensitivity of tumor cells to iron death inducers, providing a new target for the treatment of renal cancer.

3. Molenaar, Thom M., and Fred van Leeuwen. "SETD2: from chromatin modifier to multipronged regulator of the genome and beyond." Cellular and Molecular Life Sciences 79.6 (2022): 346. https://doi.org/10.1007/s00018-022-04352-9

The research has found that SETD2 not only participates in transcriptional regulation and chromatin stability by catalyzing H3K36me3, but also methylates non-histone substrates such as α-tubulin. It is often inactivated in cancer and possesses both epigenetic and non-epigenetic functions. A comprehensive understanding of its pleiotropic effects is necessary to deeply comprehend its tumor-suppressing mechanism.

4. Ding, Zhaoyun, et al. "Setd2 supports GATA3+ ST2+ thymic-derived Treg cells and suppresses intestinal inflammation." Nature Communications 13.1 (2022): 7468. https://doi.org/10.1038/s41467-022-35250-0

The study found that the histone methyltransferase Setd2 regulates the expression of GATA3 and ST2, maintaining the survival and inhibitory function of intestinal Treg cells, thereby controlling the intestinal immune balance. Its expression is upregulated in human colorectal cancer Treg cells, suggesting its crucial role in mucosal immunity and the tumor microenvironment.

5. Lee, Sunwoo, et al. "Epigenotype–genotype–phenotype correlations in SETD1A and SETD2 chromatin disorders." Human Molecular Genetics 32.22 (2023): 3123-3134. https://doi.org/10.1093/hmg/ddad079

The study found that germline mutations in the SETD2 gene are associated with neurodevelopmental disorders. The truncation mutations and missense mutations (such as the arginine mutation at position 1740) exhibit different methylation epigenetic characteristics and clinical phenotypes, revealing specific associations between epigenetic, genotypic and phenotypic factors, and suggesting that missense mutations may have functional gain-of-function mechanisms.

Creative Biolabs: SETD2 Antibodies for Research

Creative Biolabs specializes in the production of high-quality SETD2 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom SETD2 Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our SETD2 antibodies, custom preparations, or technical support, contact us at email.