TSC2 Antibodies

Background

The TSC2 gene encodes a large protein called tuberin, which plays a crucial negative regulatory role in the mammalian target of rapamycin (mTOR) signaling pathway. Its encoded products form the TSC1/TSC2 protein complex, integrating intracellular and extracellular growth and energy signals, thereby inhibiting the excessive activation of the mTORC1 pathway and regulating the processes of cell growth, proliferation and autophagy. Pathogenic mutations in this gene can lead to an autosomal dominant genetic disorder - tuberous sclerosis, in which patients are prone to benign tumors involving multiple organ systems. Since its successful cloning in 1993, the TSC2 gene, as an important tumor suppressor, has deepened our understanding of the cell growth regulatory network through research on its molecular mechanism and provided a theoretical basis for the development of related targeted drugs.

Structure Function Application Advantage Our Products

Structure of TSC2

TSC2 is a large protein with a molecular weight of approximately 200 kDa, and its precise molecular weight varies among different species. The following table shows the molecular characteristics of TSC2 proteins in different mammals:

Species	Human	Mouse	Rat	Bovine
Molecular Weight (kDa)	200.7	199.2	198.8	201.1
Primary Structural Differences	Contains 1807 amino acids, with functions of multiple domains	GAP structure domain highly conservative	There are differences in the coiled spiral area at the N-end	The C-end has a relatively high degree of homology with humans

This protein is composed of 1,807 amino acids, and its structure includes a coiled helical region at the N-terminal and a GAP domain at the C-terminal. TSC2 exerts the function of a GTP-activating protein by forming a stable heterodimer with TSC1, catalyzes the hydrolysis of Rheb-GTP through its GAP domain, and thereby inhibits the activity of the mTORC1 signaling pathway. This molecular mechanism plays a core role in the regulation of cell growth.

Fig. 1 Structure of TSC2 and inhibitory phosphorylation sites with ERK2, AKT MK2, AMPK and RSK1.¹

Key structural properties of TSC2:

Contains multiple linear function structure domain protein sequences
N-terminal coiling helix mediates heterodimerization with TSC1
The C-terminal GAP domain catalyzes the GTP hydrolysis of Rheb

Functions of TSC2

The core function of the TSC2 gene is to serve as a negative regulatory hub for the mTOR signaling pathway. However, its biological effects have expanded to the integrated regulation of various cellular processes, as follows:

Function	Description
Cell growth inhibition	The hydrolysis of Rheb-GTP is catalyzed through the GAP domain to inhibit the activity of mTORC1 and prevent excessive cell growth.
Maintenance of energy steady state	Sense the energy state of cells (AMP/ATP ratio) and inhibit anabolism under low-energy conditions.
Autophagy regulation	By inhibiting mTORC1, the inhibitory effect on the initiation of autophagy is relieved, promoting the self-renewal of cells under stress.
Regulation of protein synthesis	Negatively regulate ribosome biosynthesis and the activity of translation initiation factors to control the rate of protein synthesis.
Tumor suppressive function	Loss-of-function mutations lead to the continuous activation of mTOR signaling, causing tuberous sclerosis and related tumor lesions.

TSC2 exerts a "molecular braking" effect on the mTOR pathway through its GAP activity, which has a similar physiological regulatory logic to the oxygen buffering function of myoglobin - both maintain the dynamic balance of life systems in different states through precise regulation at the molecular level.

Applications of TSC2 and TSC2 Antibody in Literature

1. Patel, Chirag H., et al. "TSC2 S1365A mutation potently regulates CD8+ T cell function and differentiation and improves adoptive cellular cancer therapy." JCI insight 8.21 (2023): e167829. https://doi.org/10.1172/jci.insight.167829

The article indicates that the TSC2 S1365A mutation can enhance the mTORC1 signal upon activation, enabling CD8+ T cells to acquire strong effector functions while retaining the ability to form long-term memory, thereby improving their anti-tumor efficacy.

2. Wang, Xinyue, et al. "Rescue RM/CS-AKI by blocking strategy with one-dose anti-myoglobin RabMAb." Nature Communications 16.1 (2025): 1044. https://doi.org/10.1126/sciadv.abi9533

The article indicates that TSC1/TSC2 gene mutations can serve as novel biomarkers for non-small cell lung cancer, used to identify subtypes of patients with a "inflamed" tumor microenvironment that are more likely to benefit from immunotherapy.

3. Kashii, Hirofumi, et al. "Tsc2 mutation rather than Tsc1 mutation dominantly causes a social deficit in a mouse model of tuberous sclerosis complex." Human Genomics 17.1 (2023): 4. https://doi.org/10.1186/s40246-023-00450-2

Studies have shown that mutations in the TSC1 and TSC2 genes have a synergistic effect in causing neurological symptoms such as autism, and their co-action pattern is similar to that of TSC2 mutations, which provides a new perspective for understanding the genotype-phenotype association of TSC.

4. Brazill, Jennifer M., et al. "Knockout of TSC2 in Nav1. 8+ neurons predisposes to the onset of normal weight obesity." Molecular Metabolism 68 (2023): 101664. https://doi.org/10.1016/j.molmet.2022.101664

Studies have shown that specifically activating the mTOR signal in mouse Nav1.8+ neurons (by knocking out TSC2) can cause chronic itching, anxiety, and alter fat distribution, leading to metabolic abnormalities and bone loss even without weight gain.

5. He, Xin, et al. "Eosinophilic solid and cystic renal cell carcinoma with TSC2 mutation: a case report and literature review." Diagnostic Pathology 18.1 (2023): 53. https://doi.org/10.1186/s13000-023-01341-9

Studies have shown that eosinophilic cystic solid renal cell carcinoma (ESC-RCC) is a new type of renal cell carcinoma with a unique CK20+/CK7- immunophenotype and TSC2 gene mutation. Understanding its characteristics is helpful to avoid misdiagnosis.

Creative Biolabs: TSC2 Antibodies for Research

Creative Biolabs specializes in the production of high-quality TSC2 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom TSC2 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 TSC2 antibodies, custom preparations, or technical support, contact us at email.

Reference

Wang, Shuang, et al. "Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate." Stem Cell Research & Therapy 16.1 (2025): 38. https://doi.org/10.1186/s13287-025-04170-3

Anti-TSC2 antibodies

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Mouse Anti-TSC2 Recombinant Antibody (6I3) (CBMAB-BR477LY)

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Target: TSC2

Host: Mouse

Antibody Isotype: IgG2b

Specificity: Human

Clone: 6I3

Application*: FC, IHC-P, WB