TNFR2 Human
Description
Overview of TNFR2 Human
Tumor Necrosis Factor Receptor 2 (TNFR2), encoded by the TNFRSF1B gene in humans, is a type I transmembrane protein belonging to the TNF receptor superfamily (TNFRSF). Unlike TNFR1, TNFR2 lacks a death domain and primarily signals through the non-canonical NF-κB pathway. It is constitutively expressed on regulatory T-cells (Tregs), myeloid-derived suppressor cells (MDSCs), endothelial cells, and neurons, playing dual roles in immune regulation and tissue repair .
Key Domains and Polymorphisms:
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Genetic Variants: The rs1061622 polymorphism (methionine substitution at position 196) alters TNFR2-TNF binding kinetics and is linked to autoimmune diseases like rheumatoid arthritis and Crohn’s disease .
Functional Roles in Immune Regulation
TNFR2 exhibits context-dependent effects:
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Dual Signaling: TNFR2 activation in Tregs suppresses autoimmunity but may exacerbate inflammation in pathogenic T-cell subsets .
TNFR2 Agonists in Disease Models
Antagonists in Oncology
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TNFR2-blocking mAbs: Reduced tumor-associated Treg activity in ovarian cancer ascites and Sézary syndrome, while sparing peripheral Tregs .
Recombinant TNFR2 (ProSpec Bio)8
| Parameter | Specification |
|---|---|
| Source | Escherichia coli-expressed polypeptide (23-206 aa) with N-terminal His-tag. |
| Molecular Weight | 24.45 kDa |
| Purity | >95% (proprietary chromatography) |
| Formulation | 20 mM Tris-HCl, 5 mM EDTA, 50% glycerol (pH 8.0) |
Challenges and Future Directions
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Tissue-Specific Effects: TNFR2 agonism may worsen hepatitis or tumor progression in certain contexts .
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Human vs. Mouse Models: Species-specific differences in TNFR2 homology complicate translational research .
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Clinical Trials: No TNFR2-targeted therapies are FDA-approved, though phase I trials for agonists (e.g., NewStar2) are anticipated .
Product Specs
Product Science Overview
TNFR2 is a member of the tumor necrosis factor receptor superfamily . The extracellular region of TNFR2 consists of four cysteine-rich domains that facilitate binding to TNFα . Unlike its counterpart, Tumor Necrosis Factor Receptor 1 (TNFR1), TNFR2 lacks a death domain (DD), which means it does not directly induce apoptosis .
When TNFα binds to TNFR2, it leads to the recruitment of anti-apoptotic proteins such as c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity . These proteins are thought to potentiate TNF-induced apoptosis by ubiquitinating and degrading TNF-receptor-associated factor 2 (TRAF2), which mediates anti-apoptotic signals .
TNFR2 plays a significant role in various physiological and pathological processes. It is neuroprotective, partly because it lacks an intracellular death domain . Increased levels of soluble TNFR2 (sTNFR2) have been observed in patients with schizophrenia .
In the context of cancer, TNFR2 is associated with increased tumor cell death and decreased progression of tumor cell growth . Increased expression of TNFR2 has been found in several types of cancer, including breast, cervical, colon, and renal cancers . Targeting TNFR2 in tumor cells has shown potential for therapeutic applications, as it can lead to increased tumor cell death and inhibition of tumor growth .
Recent research has highlighted the potential of TNFR2 as a therapeutic target in cancer therapy . TNFR2 promotes tumor immune escape by stimulating various immune suppressive cell types, such as regulatory T-cells (Tregs) and myeloid-derived suppressor cells (MDSCs) . However, TNFR2 also elicits antitumoral activities by costimulating cytotoxic T-cells .
Both antagonists and agonists targeting TNFR2 have been preclinically evaluated for tumor therapy and have demonstrated anti-tumor activity in preclinical studies . The dual role of TNFR2 in promoting immune suppression and stimulating cytotoxic T-cells makes it a complex but promising target for cancer treatment .
