tripartite motif containing 21

Target id: 2967

Nomenclature: tripartite motif containing 21

Family: 2.3.2.27 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

   GtoImmuPdb view: OFF :     tripartite motif containing 21 has curated GtoImmuPdb data

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
BRENDA
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
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.
PDB Id:  2IWG
Resolution:  2.35Å
Species:  Human
References:  3
Enzyme Reaction
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 [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
Immuno Process ID:  1
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  positive regulation of viral entry into host cell (GO:0046598) IEA
References: 
Immuno Process:  Inflammation
Immuno Process ID:  2
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  response to interferon-gamma (GO:0034341) IDA
innate immune response (GO:0045087) IDA
interferon-gamma-mediated signaling pathway (GO:0060333) TAS
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  regulation of type I interferon production (GO:0032479) TAS
response to interferon-gamma (GO:0034341) IDA
interferon-gamma-mediated signaling pathway (GO:0060333) TAS
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  regulation of type I interferon production (GO:0032479) TAS
response to interferon-gamma (GO:0034341) IDA
interferon-gamma-mediated signaling pathway (GO:0060333) TAS
References: 
Immuno Process:  Cellular signalling
Immuno Process ID:  11
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  protein polyubiquitination (GO:0000209) IDA
ubiquitin-protein transferase activity (GO:0004842) IDA
protein monoubiquitination (GO:0006513) IDA
protein ubiquitination (GO:0016567) IDA
protein autoubiquitination (GO:0051865) IDA
References: 

References

Show »

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.,  [Epub ahead of print]. [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 Rev16 (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. (2017) TRIM21 negatively regulates intestinal mucosal inflammation through inhibiting Th1/Th17 cell differentiation in inflammatory bowel diseases. J. Allergy Clin. Immunol.,  [Epub ahead of print]. [PMID:29113905]

How to cite this page

2.3.2.27 RING-type E3 ubiquitin transferase: tripartite motif containing 21. Last modified on 13/11/2017. Accessed on 13/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2967.