TRIM21
E3 ubiquitin-protein ligase TRIM21
Also known as: RNF81, RO52, RO52_HUMAN, SSA1
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P19474
- Gene
- TRIM21
- Ensembl
- ENSG00000132109
- Chromosome
- 11
- Canonical length
- 475 aa
- Protein class
- Enzymes, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm
- Quaternary structure
- Homotrimer
OverviewNCBI Gene
This gene encodes a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The encoded protein is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus. RoSSA interacts with autoantigens in patients with Sjogren syndrome and systemic lupus erythematosus. Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
475 residues, UniProt reviewed canonical sequence.
>P19474|TRIM21
1 MASAARLTMM WEEVTCPICL DPFVEPVSIE CGHSFCQECI SQVGKGGGSV CPVCRQRFLL
61 KNLRPNRQLA NMVNNLKEIS QEAREGTQGE RCAVHGERLH LFCEKDGKAL CWVCAQSRKH
121 RDHAMVPLEE AAQEYQEKLQ VALGELRRKQ ELAEKLEVEI AIKRADWKKT VETQKSRIHA
181 EFVQQKNFLV EEEQRQLQEL EKDEREQLRI LGEKEAKLAQ QSQALQELIS ELDRRCHSSA
241 LELLQEVIIV LERSESWNLK DLDITSPELR SVCHVPGLKK MLRTCAVHIT LDPDTANPWL
301 ILSEDRRQVR LGDTQQSIPG NEERFDSYPM VLGAQHFHSG KHYWEVDVTG KEAWDLGVCR
361 DSVRRKGHFL LSSKSGFWTI WLWNKQKYEA GTYPQTPLHL QVPPCQVGIF LDYEAGMVSF
421 YNITDHGSLI YSFSECAFTG PLRPFFSPGF NDGGKNTAPL TLCPLNIGSQ GSTDYLocalizationUniProt · AlphaFold · HPA
Whether an antibody against TRIM21 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.34
- Highest tissue expression
- 31 nTPM
Expression across tissuesHPA
Tissue
- spleen: 31 nTPM
- bone marrow: 26 nTPM
- lymph node: 22 nTPM
- lung: 22 nTPM
- tonsil: 22 nTPM
- ovary: 21 nTPM
Single-cell type
- neutrophils: 36 nCPM
- kupffer cells: 15 nCPM
- monocyte progenitors: 15 nCPM
- extravillous trophoblasts: 13 nCPM
- neutrophil progenitors: 13 nCPM
- cholangiocytes: 13 nCPM
Immune cell
- neutrophil: 355 nTPM
- eosinophil: 313 nTPM
- total PBMC: 175 nTPM
- intermediate monocyte: 140 nTPM
- classical monocyte: 133 nTPM
- non-classical monocyte: 131 nTPM
Brain region
- medulla oblongata: 10 nTPM
- thalamus: 9.6 nTPM
- spinal cord: 9.1 nTPM
- white matter: 8 nTPM
- choroid plexus: 7.8 nTPM
- pons: 7.6 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about TRIM21.
Disease | ImmuneIEDB
Conditions an epitope on TRIM21 was assayed in.
- systemic scleroderma B cell
- systemic lupus erythematosus B cell
- autoimmune disease of skin and connective tissue B cell
- dermatomyositis B cell
- Sjogren's syndrome B cell
- mixed connective tissue disease B cell
- autoimmune disease of musculoskeletal system B cell
- rheumatoid arthritis B cell
- congenital heart block B cell
Disease | AutoantibodyPubMed
Conditions in which antibodies against TRIM21 are reported. Each links to that disease's full target list.
- Lung Diseases, Interstitial 81
- Sjogren's Syndrome 73
- Myositis 72
- Dermatomyositis 52
- Lupus Erythematosus, Systemic 48
- Scleroderma, Systemic 19
- Heart Block 16
- Polymyositis 10
- Neuromyelitis Optica 8
- Liver Cirrhosis, Biliary 6
- Arthritis 5
- Hepatitis, Autoimmune 4
- Lupus Erythematosus, Cutaneous 4
- Mixed Connective Tissue Disease 4
- Muscle Weakness 4
- Pulmonary Fibrosis 4
- Arthritis, Rheumatoid 3
- COVID-19 3
- Hypertension, Pulmonary 3
Showing 19 of 22 — disease pages carrying at least 10 antigens.
ReferencesPubMed · IEDB
Publications for TRIM21 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
344 publications
- Clinical Characteristics of Anti-Synthetase Syndrome: Analysis From the Classification Criteria for Anti-Synthetase Syndrome Project.
2025 · Arthritis Rheumatol · RCR 13.2 · 34 citations - Association of anti-Ro52 autoantibody with interstitial lung disease in autoimmune diseases: a systematic review and meta-analysis.
2023 · BMJ Open Respir Res · RCR 12.4 · 67 citations - Identification of Three Different Phenotypes in Anti-Melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis Patients: Implications for Prediction of Rapidly Progressive Interstitial Lung Disease.
2023 · Arthritis Rheumatol · RCR 10.5 · 79 citations - Coexistence of Anti-Ro52 Antibodies in Anti-MDA5 Antibody-Positive Dermatomyositis Is Highly Associated With Rapidly Progressive Interstitial Lung Disease and Mortality Risk.
2023 · J Rheumatol · RCR 8.5 · 48 citations - Prognostic values of anti-Ro52 antibodies in anti-MDA5-positive clinically amyopathic dermatomyositis associated with interstitial lung disease.
2021 · Rheumatology (Oxford) · RCR 7.5 · 89 citations
Show 20 more of 344 total
- Rapidly progressive interstitial lung disease risk prediction in anti-MDA5 positive dermatomyositis: the CROSS model.
2024 · Front Immunol · RCR 7.5 · 29 citations - Anti-Ro52 antibodies are associated with the prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease.
2022 · Rheumatology (Oxford) · RCR 7.2 · 61 citations - Short-term and long-term outcome of anti-Jo1-positive patients with anti-Ro52 antibody.
2012 · Semin Arthritis Rheum · RCR 6.8 · 178 citations - Anti-Ro52 autoantibodies are associated with interstitial lung disease and more severe disease in patients with juvenile myositis.
2019 · Ann Rheum Dis · RCR 6.7 · 125 citations - Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function.
2007 · Proc Natl Acad Sci U S A · RCR 6.1 · 321 citations - An updated review of anti-Ro52 (TRIM21) antibodies impact in connective tissue diseases clinical management.
2022 · Autoimmun Rev · RCR 5.8 · 59 citations - Rituximab in the Treatment of Jo1 Antibody-associated Antisynthetase Syndrome: Anti-Ro52 Positivity as a Marker for Severity and Treatment Response.
2016 · J Rheumatol · RCR 5.3 · 113 citations - Latest update on the Ro/SS-A autoantibody system.
2009 · Autoimmun Rev · RCR 5.1 · 181 citations - Anti-Ro52 antibodies frequently co-occur with anti-Jo-1 antibodies in sera from patients with idiopathic inflammatory myopathy.
1997 · Clin Exp Immunol · RCR 4.7 · 168 citations - Anti-Ro52 antibody is an independent risk factor for interstitial lung disease in dermatomyositis.
2020 · Respir Med · RCR 4.5 · 63 citations - Anti-Ro52 Autoantibody Is Common in Systemic Autoimmune Rheumatic Diseases and Correlating with Worse Outcome when Associated with interstitial lung disease in Systemic Sclerosis and Autoimmune Myositis.
2022 · Clin Rev Allergy Immunol · RCR 4.4 · 39 citations - Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE.
2007 · Clin Immunol · RCR 4.3 · 193 citations - Prevalence of anti-Ro52-kDa/SSA (TRIM21) antibodies and associated clinical phenotype in systemic sclerosis: Data from a French cohort, a systematic review and meta-analysis.
2024 · Autoimmun Rev · RCR 4.3 · 19 citations - Diagnostic Utility of Separate Anti-Ro60 and Anti-Ro52/TRIM21 Antibody Detection in Autoimmune Diseases.
2019 · Front Immunol · RCR 4.2 · 76 citations - Progression and mortality of interstitial lung disease in mixed connective tissue disease: a long-term observational nationwide cohort study.
2018 · Rheumatology (Oxford) · RCR 4.1 · 77 citations - Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis.
2012 · Arthritis Res Ther · RCR 4.1 · 117 citations - The immunobiology of Ro52 (TRIM21) in autoimmunity: a critical review.
2012 · J Autoimmun · RCR 4 · 150 citations - Management and outcomes of interstitial lung disease associated with anti-synthetase syndrome: a systematic literature review.
2025 · Rheumatology (Oxford) · RCR 3.8 · 10 citations - Predictive Features and Clinical Presentation of Interstitial Lung Disease in Inflammatory Myositis.
2021 · Clin Rev Allergy Immunol · RCR 3.7 · 43 citations - Analysis of the clinical features of antisynthetase syndrome: a retrospective cohort study in China.
2023 · Clin Rheumatol · RCR 3.6 · 20 citations
Reference: B cellIEDB
8 publications
- Ro/SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block.
2005 · J Exp Med · RCR 2.8 · 128 citations - Computational analysis of high-density peptide microarray data with application from systemic sclerosis to multiple sclerosis.
2012 · Autoimmun Rev · RCR 1 · 35 citations - Serological epitope profile of anti-Ro52-positive patients with systemic autoimmune rheumatic diseases.
2015 · Arthritis Res Ther · RCR 0.5 · 15 citations - Cloning and characterization of two human Ro52-specific monoclonal autoantibodies directed towards a domain associated with congenital heart block.
2004 · J Autoimmun · RCR 0.5 · 20 citations - Structurally derived mutations define congenital heart block-related epitopes within the 200-239 amino acid stretch of the Ro52 protein.
2005 · Scand J Immunol · RCR 0.4 · 17 citations
Show 3 more
- Autoantibodies reactive to PEP08 are clinically related with morbidity and severity of interstitial lung disease in connective tissue diseases.
2018 · Eur J Immunol · RCR 0.3 · 6 citations - Autoantibody to the leucine zipper region of 52 kDa Ro/SSA binds native 60 kDa Ro/SSA: identification of a tertiary epitope with components from 60 kDa Ro/SSA and 52 kDa Ro/SSA.
2001 · Scand J Immunol · RCR 0.3 · 11 citations - Identification of discrete epitopes of Ro52p200 and association with fetal cardiac conduction system manifestations in a rodent model.
2016 · Clin Exp Immunol · RCR 0.2 · 4 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.12
- gnomAD pLI
- 0
- gnomAD missense Z
- -0.29
- DepMap mean gene effect
- 0.12
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- antiviral innate immune response
- cellular response to chemical stress
- innate immune response
- negative regulation of innate immune response
- negative regulation of NF-kappaB transcription factor activity
- negative regulation of protein deubiquitination
- negative regulation of viral transcription
- positive regulation of autophagy
- positive regulation of cell cycle
- positive regulation of non-canonical NF-kappaB signal transduction
- positive regulation of protein binding
- positive regulation of viral entry into host cell
- proteasomal protein catabolic process
- protein autoubiquitination
- protein destabilization
- protein K27-linked ubiquitination
- protein K48-linked ubiquitination
- protein K6-linked ubiquitination
- protein K63-linked ubiquitination
- protein monoubiquitination
- protein polyubiquitination
- protein ubiquitination
- pyroptotic inflammatory response
- regulation of gene expression
- regulation of type I interferon production
- response to type II interferon
- stress granule disassembly
- suppression of viral release by host
Molecular functions
- DNA binding
- identical protein binding
- RNA binding
- transcription coactivator activity
- ubiquitin protein ligase activity
- ubiquitin-protein transferase activity
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- B-box-type zinc finger
- Zinc finger, RING-type
- B30.2/SPRY domain
- U-box domain
- SPRY domain
- Butyrophylin-like, SPRY domain
- SPRY-associated
- Zinc finger, RING/FYVE/PHD-type
- Concanavalin A-like lectin/glucanase domain superfamily
- Zinc finger, RING-type, conserved site
- Zinc finger, C3HC4 RING-type
- Zinc finger, B-box, chordata
- B30.2/SPRY domain superfamily
- Tripartite motif-containing
- Zinc finger, C3HC4 type (RING finger)
- SPRY domain
- B-box zinc finger
- SPRY-associated domain
- TRIM21, PRY/SPRY domain
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of TRIM21 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads TRIM21 as an antibody target. Whether an autoantibody or antibody against TRIM21 could matter depends on whether native TRIM21 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
TRIM21 is annotated at the cell surface, where native TRIM21 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Source-annotated serology context
The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.
- RoSSA interacts with autoantigens in patients with Sjogren syndrome and systemic lupus erythematosus.
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