TRIM21 Antibodies

Background

The TRIM21 gene encodes a protein with a trimeric domain, which is mainly distributed in various tissue cells of mammals. This protein participates in recognizing and binding to antibody-coated pathogens that enter the cytoplasm, thereby mediating the ubiquitination degradation of the targets and activating the innate immune response. Its uniqueness lies in its ability to act as an intracellular antibody receptor, directly eliminating invading substances such as viruses marked by antibodies. Therefore, it is regarded as a key bridge connecting adaptive immunity and intracellular defense. Since its discovery in the 1990s, the structure and functional mechanism of TRIM21 have been gradually revealed. The antibody-dependent intracellular neutralization mediated by it provides important directions for the research on antiviral immunity, autoimmune diseases, and protein degradation systems.

Structure Function Application Advantage Our Products

Structure of TRIM21

TRIM21 is a protein with a molecular weight of approximately 54 kDa. This molecular weight is relatively conserved among different mammalian species, but the exact value may vary slightly due to post-translational modifications or subtypes.

Species	Human	Mouse	Rat
Molecular Weight (kDa)	About 54	About 54	About 54
Primary Structural Differences	Containing RING, B-Box, coiled-coil and PRY/SPRY domains	The composition of the domain is highly homologous	It has a high sequence similarity to human TRIM21

TRIM21 is composed of approximately 475 amino acids and its primary structure presents as a linear sequence containing multiple characteristic domains. Its three-dimensional structure is composed of an N-terminal RING domain (mediating E3 ligase activity), two B-Box zinc finger domains, a coiled-coil region (responsible for forming homodimers), and a C-terminal PRY/SPRY domain (responsible for specifically recognizing and binding to the Fc fragment of antibodies). This unique structural combination enables it to act as an intracellular antibody receptor, bridging adaptive immunity and innate immune responses.

Fig. 1 The domains of tripartite motif 21 (TRIM21) protein. Fig. 1 The domains of tripartite motif 21 (TRIM21) protein.¹

Key structural properties of TRIM21:

Multidomain assembly
Dimerization interface
Antibody recognition module

Functions of TRIM21

The main function of TRIM21 is to act as an intracellular antibody receptor and E3 ubiquitin ligase, mediating the innate immune response against pathogen markers. Additionally, it is also widely involved in physiological and pathological processes such as cell cycle regulation, signal transduction, and autoimmunity.

Function	Description
Antibody-dependent cellular neutralization	Specifically recognizes and binds to the virus or bacteria coated with antibodies (IgG) that have entered the cytoplasm, targeting and degrading the pathogen.
Activation of the Ubiquitin-Proteasome Pathway	By its E3 ligase activity in the RING domain, it catalyzes the ubiquitination modification of the target protein, guiding its degradation by the proteasome.
Innate Immune Signal Regulation	It can participate in regulating the interferon signaling pathway and other innate immune responses, influencing the state of antiviral defense.
Autoimmune Disease Association	As an autoantigen, it is related to the pathogenesis of autoimmune diseases such as Sjögren's syndrome.
Cell Cycle and Apoptosis Effects	By degrading specific substrates, it participates in the regulation of cell cycle checkpoints and the apoptotic process.

Unlike most E3 ligases that specifically recognize a single substrate, TRIM21, through its PRY/SPRY domain, is capable of broadly recognizing the Fc fragments of various IgG subtypes, making it a key hub molecule connecting humoral immunity with intracellular defense.

Applications of TRIM21 and TRIM21 Antibody in Literature

1. Gong, Xiangmei, Shukang He, and Pengcheng Cai. "Roles of TRIM21/Ro52 in connective tissue disease-associated interstitial lung diseases." Frontiers in Immunology 15 (2024): 1435525. https://doi.org/10.3389/fimmu.2024.1435525

Research has found that TRIM21 and its autoantibodies play a significant role in the pathogenesis of connective tissue disease-related interstitial lung disease (CTD-ILD), and are of great value for disease diagnosis, prognosis assessment and potential therapeutic targets.

2. Li, Jun-Yan, et al. "TRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models." Nature Communications 14.1 (2023): 865. https://doi.org/10.1038/s41467-023-36523-y

Research has found that TRIM21 degrades mitochondrial protein VDAC2 through ubiquitination, inhibits the release of mtDNA and the activation of the cGAS/STING pathway after radiotherapy, thereby weakening the radiotherapy-induced CD8⁺ T cell anti-tumor immunity of nasopharyngeal carcinoma, which is associated with a poor prognosis for patients.

3. Li, Aizhuo, Jiannan Wang, and Yi Qu. "TRIM21: a multifaceted regulator in cancer." Frontiers in cell and developmental biology 13 (2025): 1637451. https://doi.org/10.3389/fcell.2025.1637451

Research has found that TRIM21, as an E3 ubiquitin ligase, participates in key processes such as tumorigenesis, autophagy, immune escape and metabolic reprogramming by regulating substrate protein ubiquitination. A thorough understanding of its mechanism of action in different tumors is conducive to the development of novel therapeutic strategies targeting TRIM21.

4. Liu, Ri-Xu, et al. "Trim21 depletion alleviates bone loss in osteoporosis via activation of YAP1/β-catenin signaling." Bone Research 11.1 (2023): 56. https://doi.org/10.1038/s41413-023-00296-3

Research has found that TRIM21 inhibits osteogenic differentiation of bone marrow mesenchymal stem cells and promotes osteoclast formation through the YAP1/β-catenin signaling pathway, thereby exacerbating osteoporosis. Targeting TRIM21 may offer a new strategy for treating bone metabolic diseases.

5. Chen, Xintian, et al. "TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability." Journal of Experimental & Clinical Cancer Research 42.1 (2023): 34. https://doi.org/10.1186/s13046-022-02583-z

Research has found that TRIM21 inhibits adipogenesis and fatty acid dependence in renal cell carcinoma (RCC) cells by ubiquitinating and degrading the transcription factor SREBF1. The TRIM21-SREBF1 axis can serve as a potential biomarker for the prognosis diagnosis and targeted metabolic therapy of RCC.

Creative Biolabs: TRIM21 Antibodies for Research

Creative Biolabs specializes in the production of high-quality TRIM21 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom TRIM21 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 TRIM21 antibodies, custom preparations, or technical support, contact us at email.

Reference

Li, Aizhuo, Jiannan Wang, and Yi Qu. "TRIM21: a multifaceted regulator in cancer." Frontiers in cell and developmental biology 13 (2025): 1637451. https://doi.org/10.3389/fcell.2025.1637451