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target has curated data in GtoImmuPdb
Target id: 2967
Nomenclature: tripartite motif containing 21
Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | - | 475 | 11p15.4 | TRIM21 | tripartite motif containing 21 | |
| Mouse | - | 470 | 7 E3 | Trim21 | tripartite motif-containing 21 | |
| Rat | - | 471 | 1q32 | Trim21 | tripartite motif-containing 21 | |
| Previous and Unofficial Names |
| RNF81 | RO52 | Ro/SSA | Sjogren syndrome antigen A1 | SSA1 |
| Database Links |
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| Alphafold | P19474 (Hs), Q62191 (Mm) |
| BRENDA | 2.3.2.27 |
| Ensembl Gene | ENSG00000132109 (Hs), ENSMUSG00000030966 (Mm), ENSRNOG00000018517 (Rn) |
| Entrez Gene | 6737 (Hs), 20821 (Mm), 308901 (Rn) |
| Human Protein Atlas | ENSG00000132109 (Hs) |
| KEGG Enzyme | 2.3.2.27 |
| KEGG Gene | hsa:6737 (Hs), mmu:20821 (Mm), rno:308901 (Rn) |
| OMIM | 109092 (Hs) |
| Pharos | P19474 (Hs) |
| RefSeq Nucleotide | NM_003141 (Hs), NM_009277 (Mm), NM_001082572 (Rn) |
| RefSeq Protein | NP_003132 (Hs), NP_033303 (Mm), NP_001076041 (Rn) |
| UniProtKB | P19474 (Hs), Q62191 (Mm) |
| Wikipedia | TRIM21 (Hs) |
| Selected 3D Structures |
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| Enzyme Reaction |
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| Immunopharmacology Comments |
| Tripartite motif-containing (TRIM) superfamily proteins are critical in a variety of biological processes in innate immunity and are important for eradication of invading pathogens [7-9]. The PRYSPRY domain of TRIM21 interacts with IgG Fc domains [2], and the mode of interaction identifies TRIM21 as a superantigen that may be relevant to the pathogenic accumulation of anti-TRIM21 autoantibody complexes discovered in autoimmune disease [3,6]. In the lymphocyte population, TRIM21 is mainly expressed on T cells, macrophages, and natural killer cells. TRIM21 is a component of the Ro/SSA ribonucleoprotein complex. It is implicated in the pathogensis of autoimmune diseases, including rheumatic diseases, Sjögren syndrome (SS) and systemic lupus erythematosus (SLE). Anti-Ro/SSA antibodies are more prevalent in some autoimmune diseases, including SS, SLE, antiphospholipid syndrome, systemic sclerosis and primary biliary cirrhosis [1,5-6]. A 2017 article by Zhou et al. indicates a role for TRIM21 in protection against intestinal mucosal inflammation (and by inference, inflammatory bowel diseases) via inhibition of Th1/Th17 cell differentiation [10]. |
| Immuno Process Associations | ||
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| General Comments |
| TRIM21 is proposed as a druggable anti-cancer target. In the colorectal cancer setting it ubiquitinates serine/threonine kinase 3 (MST2; STK3) and activates Hippo signaling, which has an inhibitory effect on invasion and metastasis [4]. Pharmacologically stabilising TRIM21-induced MST2 activation (using vilazodone) produces an anti-metastatic effect. |
1. Agmon-Levin N, Dagan A, Peri Y, Anaya JM, Selmi C, Tincani A, Bizzaro N, Stojanovich L, Damoiseaux J, Cohen Tervaert JW et al.. (2017) The interaction between anti-Ro/SSA and anti-La/SSB autoantibodies and anti-infectious antibodies in a wide spectrum of auto-immune diseases: another angle of the autoimmune mosaic. Clin Exp Rheumatol, 35 (6): 929-935. [PMID:28770708]
2. Foss S, Watkinson R, Sandlie I, James LC, Andersen JT. (2015) TRIM21: a cytosolic Fc receptor with broad antibody isotype specificity. Immunol Rev, 268 (1): 328-39. [PMID:26497531]
3. James LC, Keeble AH, Khan Z, Rhodes DA, Trowsdale J. (2007) Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function. Proc Natl Acad Sci USA, 104 (15): 6200-5. [PMID:17400754]
4. Liu YX, Wan S, Yang XQ, Wang Y, Gan WJ, Ye WL, He XS, Chen JJ, Yang Y, Yang XM et al.. (2023) TRIM21 is a druggable target for the treatment of metastatic colorectal cancer through ubiquitination and activation of MST2. Cell Chem Biol, 30 (7): 709-725.e6. [PMID:37354905]
5. Novak GV, Marques M, Balbi V, Gormezano NW, Kozu K, Sakamoto AP, Pereira RM, Terreri MT, Magalhães CS, Guariento A et al.. (2017) Anti-RO/SSA and anti-La/SSB antibodies: Association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus. Autoimmun Rev, 16 (2): 132-135. [PMID:27988434]
6. Oke V, Wahren-Herlenius M. (2012) The immunobiology of Ro52 (TRIM21) in autoimmunity: a critical review. J Autoimmun, 39 (1-2): 77-82. [PMID:22402340]
7. Ozato K, Shin DM, Chang TH, Morse 3rd HC. (2008) TRIM family proteins and their emerging roles in innate immunity. Nat Rev Immunol, 8 (11): 849-60. [PMID:18836477]
8. Rajsbaum R, García-Sastre A, Versteeg GA. (2014) TRIMmunity: the roles of the TRIM E3-ubiquitin ligase family in innate antiviral immunity. J Mol Biol, 426 (6): 1265-84. [PMID:24333484]
9. Versteeg GA, Benke S, García-Sastre A, Rajsbaum R. (2014) InTRIMsic immunity: Positive and negative regulation of immune signaling by tripartite motif proteins. Cytokine Growth Factor Rev, 25 (5): 563-76. [PMID:25172371]
10. Zhou G, Wu W, Yu L, Yu T, Yang W, Wang P, Zhang X, Cong Y, Liu Z. (2018) Tripartite motif-containing (TRIM) 21 negatively regulates intestinal mucosal inflammation through inhibiting TH1/TH17 cell differentiation in patients with inflammatory bowel diseases. J Allergy Clin Immunol, 142 (4): 1218-1228.e12. [PMID:29113905]
2.3.2.27 RING-type E3 ubiquitin transferase: tripartite motif containing 21. Last modified on 21/07/2023. Accessed on 20/01/2025. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2967.
