tripartite motif containing 21 | RING-type E3 ubiquitin transferase | IUPHAR Guide to IMMUNOPHARMACOLOGY

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tripartite motif containing 21

  Target has curated data in GtoImmuPdb

Target id: 2967

Nomenclature: tripartite motif containing 21

Family: RING-type E3 ubiquitin transferase

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 475 11p15.5-p15.3 TRIM21 tripartite motif containing 21
Mouse - 462 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
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  X-ray structure of the PRYSPRY domain of TRIM21 and IgG Fc domain.
Resolution:  2.35Å
Species:  Human
References:  3
Enzyme Reaction
EC Number:
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 [6-8]. 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 [3,5].

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 [1,4-5]. 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 [9].
Immuno Process Associations
Immuno Process:  Barrier integrity
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0046598 positive regulation of viral entry into host cell IEA
Immuno Process:  Inflammation
GO Annotations:  Associated to 3 GO processes
GO:0034341 response to interferon-gamma IDA
GO:0045087 innate immune response IDA
GO:0060333 interferon-gamma-mediated signaling pathway TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes
GO:0032479 regulation of type I interferon production TAS
GO:0034341 response to interferon-gamma IDA
GO:0060333 interferon-gamma-mediated signaling pathway TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 5 GO processes
GO:0000209 protein polyubiquitination IDA
GO:0004842 ubiquitin-protein transferase activity IDA
GO:0006513 protein monoubiquitination IDA
GO:0016567 protein ubiquitination IDA
GO:0051865 protein autoubiquitination IDA


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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. U.S.A., 104 (15): 6200-5. [PMID:17400754]

4. 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]

5. 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]

6. 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]

7. 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]

8. 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]

9. 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 RING-type E3 ubiquitin transferase: tripartite motif containing 21. Last modified on 13/11/2017. Accessed on 11/08/2020. IUPHAR/BPS Guide to PHARMACOLOGY,