Biological Background and Significance of Hamartin (TSC1)

Hamartin, encoded by the TSC1 gene located on chromosome 9q34, is a 130 kDa cytoplasmic scaffold protein that functions as a critical tumor suppressor. Its primary mechanism of action involves forming a stable heterodimeric complex with Tuberin (encoded by TSC2). Together, the TSC1-TSC2 complex acts as a GTPase-activating protein (GAP) toward the small GTPase Rheb, converting active Rheb-GTP to inactive Rheb-GDP, thereby suppressing the mechanistic target of rapamycin complex 1 (mTORC1) activity.

Dysregulation of this pathway leads to uncontrolled mTORC1 activation, driving excessive cell growth, proliferation, and survival — hallmarks of tumor formation. Loss-of-function mutations in either TSC1 or TSC2 are causally linked to Tuberous Sclerosis Complex (TSC), a rare autosomal dominant multisystem disorder characterized by benign hamartomas in the brain, kidneys, skin, lungs, and heart, with significant neurological morbidity including epilepsy and intellectual disability.

Beyond TSC, hamartin is implicated in broader cancer biology, autophagy regulation, and cellular energy sensing, making it a high-value research target across oncology, neurology, and cell biology disciplines.

Protein Characteristics and Product Specifications

Recombinant Human Hamartin Protein (SKU: rp365374; Supplier Ref: absea#PP-937) is produced using recombinant expression technology to provide researchers with a well-characterized, consistent source of TSC1 protein for in vitro biochemical and cell-based assays.

Key protein characteristics include:

• Gene: TSC1
• Species: Human (Homo sapiens)
• Alternative Names: Hamartin, TSC1, Tuberous Sclerosis 1 Protein
• Molecular Weight: The full-length human hamartin protein has a predicted molecular weight of approximately 130 kDa; the apparent molecular weight on SDS-PAGE may differ due to post-translational modifications and anomalous migration.
• Formulation: Specific buffer composition and additives should be confirmed from the Certificate of Analysis (CoA) supplied with each lot.
• Purity: Researchers should verify purity grade from the product CoA or by contacting Aladdin Scientific technical support.

Note: Detailed specifications including exact purity percentage, host expression system, tag information, and concentration are subject to lot-specific CoA. Please request the CoA for your specific lot prior to experimental use.

Recommended Handling, Storage, and Reconstitution

Proper handling of Recombinant Human Hamartin Protein is essential to maintain biological activity and experimental reproducibility. The following general guidelines apply to recombinant proteins of this class; always cross-reference with the product-specific CoA:

• Short-term storage (≤1 week): Store at 4 °C in the supplied buffer.
• Long-term storage: Aliquot and store at -80 °C immediately upon receipt. Avoid repeated freeze-thaw cycles, as these can cause protein aggregation and loss of activity.
• Reconstitution: If supplied lyophilized, reconstitute in the recommended volume of sterile, ultrapure water or buffer as specified on the CoA. Allow to dissolve gently without vigorous vortexing.
• Carrier protein: For highly dilute working solutions, addition of 0.1% BSA (bovine serum albumin) to the diluent is recommended to prevent adsorption to tube surfaces and maintain protein stability.
• Avoid: Repeated freeze-thaw cycles, prolonged exposure to room temperature, and highly alkaline or acidic pH conditions outside the recommended range.

All handling should be performed on ice where feasible. Use low-protein-binding microcentrifuge tubes to minimize protein loss during preparation.

Research Applications

Recombinant Human Hamartin Protein supports a wide range of biochemical and cell biology research applications. Validated and suggested uses include:

• Protein-protein interaction studies: Investigating the TSC1-TSC2 (hamartin-tuberin) complex formation, binding domains, and interaction with regulatory partners such as Rheb, FKBP38, and ERK.
• mTOR pathway biochemical assays: Reconstitution of TSC complex GAP activity toward Rheb-GTP in cell-free systems to study upstream regulation of mTORC1.
• Antibody validation: Use as a positive control antigen for Western blot, ELISA, and immunoprecipitation antibody validation experiments.
• Structural biology: Supplying purified protein for crystallography, cryo-EM, or hydrogen-deuterium exchange mass spectrometry (HDX-MS) studies of hamartin domain architecture.
• Drug discovery screening: Identification and validation of small-molecule modulators of TSC1 interactions or stability in biochemical binding assays.
• Functional rescue experiments: In vitro complementation assays to study functional consequences of TSC1 mutations identified in TSC patients.

Note: Optimal working concentrations for each application should be determined empirically by the end user. Please consult the CoA and Aladdin Scientific technical support for application-specific guidance.

Quality Assurance and Regulatory Considerations

Aladdin Scientific is committed to supplying research-grade recombinant proteins that meet consistent quality standards. For Recombinant Human Hamartin Protein (rp365374), the following quality considerations apply:

• Certificate of Analysis (CoA): Each lot is accompanied by a CoA detailing purity, concentration, biological activity (where applicable), endotoxin levels, and recommended storage conditions. Request the lot-specific CoA before use.
• Endotoxin testing: For cell-based applications, ensure endotoxin levels are within acceptable limits as stated on the CoA. High endotoxin levels can confound cellular assays.
• Research use only (RUO): This product is intended exclusively for research purposes and is NOT approved for diagnostic, therapeutic, or clinical use in humans or animals.
• Lot-to-lot consistency: While Aladdin Scientific maintains rigorous production standards, researchers performing longitudinal studies are advised to reserve sufficient quantity from a single validated lot to ensure experimental consistency.
• Safety: Handle according to standard laboratory biosafety practices. Consult the Safety Data Sheet (SDS) for complete hazard information and disposal guidelines.