TRIM21: Tripartite Motif Containing 21 - E3 Ubiquitin Ligase and Autoantigen
Key regulator of innate immunity, antibody-dependent intracellular neutralization, and autoimmunity
Gene Information Card
| Symbol | TRIM21 |
|---|---|
| Full Name | Tripartite Motif Containing 21 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.4 |
| NCBI Gene ID | 6737 ncbi.nlm.nih.gov/gene/6737 |
| Ensembl ID | ENSG00000132155 |
| UniProt ID | P19474 |
| OMIM ID | 109092 |
| HGNC ID | 11312 |
| Aliases | Ro52, RNF81, SSA1, Sjögren syndrome antigen A1 |
Description
TRIM21 (tripartite motif containing 21), also known as Ro52, is a member of the TRIM protein family. It functions as an E3 ubiquitin ligase, playing a critical role in innate immunity by mediating ubiquitination of interferon regulatory factors (IRFs) and other substrates. TRIM21 is also a major autoantigen in Sjögren syndrome and systemic lupus erythematosus. It participates in antibody-dependent intracellular neutralization (ADIN) by binding to antibody-coated viruses and targeting them for proteasomal degradation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sjögren Syndrome | Autoantibodies against TRIM21 (anti-Ro52) are a serological hallmark; TRIM21 dysfunction may contribute to immune dysregulation and tissue damage. | OMIM #270150; ClinVar |
| Systemic Lupus Erythematosus | Anti-Ro52 autoantibodies are frequently detected; TRIM21 variants may influence disease susceptibility. | OMIM #152700; ClinVar |
| Neonatal Lupus Erythematosus | Maternal anti-Ro52 antibodies cross the placenta and can cause fetal heart block and skin lesions. | OMIM #234000; ClinVar |
| Primary Biliary Cholangitis | Anti-Ro52 antibodies are present in a subset of patients, associated with more severe disease. | PubMed; ClinVar |
| Viral Infections | TRIM21 restricts infection by multiple viruses (e.g., adenovirus, influenza) via antibody-dependent neutralization. | PubMed; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 28.5 | High |
| Spleen | 25.3 | High |
| Bone marrow | 22.1 | High |
| Lung | 18.7 | Medium |
| Kidney | 15.4 | Medium |
| Liver | 12.8 | Medium |
| Heart | 9.2 | Low |
| Brain | 6.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 32.4 | High expression in embryonic kidney cells |
| HeLa | 28.9 | High expression in cervical cancer cells |
| Jurkat | 35.2 | High expression in T-cell leukemia line |
| THP-1 | 30.1 | High expression in monocytic leukemia line |
| MCF7 | 18.3 | Moderate expression in breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.862C>T (p.Arg288Trp) | Missense | Rare | May alter E3 ligase activity; reported in Sjögren syndrome |
| c.1045G>A (p.Glu349Lys) | Missense | Rare | Potential impact on autoantibody binding |
| c.1333C>T (p.Arg445Cys) | Missense | Rare | Associated with SLE in some studies |
| c.1567_1569del (p.Lys523del) | In-frame deletion | Rare | May affect protein stability |
Mutation functional classification
Loss of Function (LOF)
Mutations disrupting the RING finger domain or ubiquitin ligase activity impair TRIM21-mediated IRF degradation and antiviral responses.
Gain of Function (GOF)
Not well characterized; some variants may enhance autoantigenicity or alter substrate specificity.
Dominant Negative (DN)
Truncating or missense mutations in the coiled-coil domain may interfere with TRIM21 dimerization and function.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004842 - ubiquitin-protein transferase activity | • GO:0005515 - protein binding |
| • GO:0005634 - nucleus | • GO:0005737 - cytoplasm |
| • GO:0005829 - cytosol | • GO:0016567 - protein ubiquitination |
| • GO:0045087 - innate immune response | • GO:0061630 - ubiquitin protein ligase activity |
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• RIG-I-like receptor signaling pathway (KEGG: hsa04622)
• Cytosolic DNA-sensing pathway (KEGG: hsa04623)
• Interferon signaling (Reactome: R-HSA-913531)
Protein Summary
TRIM21 is a 475-amino acid protein with an N-terminal RING finger domain, B-box, coiled-coil region, and a C-terminal PRY/SPRY domain. It functions as an E3 ubiquitin ligase, targeting substrates such as IRF3, IRF5, IRF8, and DDX41 for ubiquitination and proteasomal degradation. TRIM21 also acts as a cytosolic antibody receptor, binding to the Fc region of IgG antibodies and mediating intracellular neutralization of antibody-coated pathogens. Its autoantigenic properties are central to the pathogenesis of Sjögren syndrome and systemic lupus erythematosus.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRIM21 Knockout HEK293 Cell Line | EDC07925 | Human | 6737 | Details Get a Quote |
| TRIM21 Knockout A-549 Cell Line | EDC07660 | Human | 6737 | Details Get a Quote |
| TRIM21 Knockout HCT 116 Cell Line | EDJ-KQ20141 | Human | 6737 | Details Get a Quote |
| TRIM21 Knockout HeLa Cell Line | EDC90404 | Human | 6737 | Details Get a Quote |
| TRIM21 Knockout U2OS Cell Line | EDC90510 | Human | 6737 | Details Get a Quote |
| TRIM21 Knockout H4 Cell Line | EDC90129 | Human | 6737 | Details Get a Quote |
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