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tripartite motif containing 21

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2967

Nomenclature: tripartite motif containing 21

Family: 2.3.2.27 RING-type E3 ubiquitin transferase

Gene and Protein Information Click here for help
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 Click here for help
RNF81 | RO52 | Ro/SSA | Sjogren syndrome antigen A1 | SSA1
Database Links Click here for help
Alphafold
BRENDA
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  X-ray structure of the PRYSPRY domain of TRIM21 and IgG Fc domain.
PDB Id:  2IWG
Resolution:  2.35Å
Species:  Human
References:  3
Enzyme Reaction Click here for help
EC Number: 2.3.2.27
Description Reaction Reference
Direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to acceptor protein. S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine <=> [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine
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
Immuno Process:  Barrier integrity
Immuno Process:  Inflammation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
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.

References

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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]

How to cite this page

2.3.2.27 RING-type E3 ubiquitin transferase: tripartite motif containing 21. Last modified on 21/07/2023. Accessed on 21/05/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2967.