TRIM38 (Tripartite Motif Containing 38): A Multifaceted E3 Ubiquitin Ligase in Innate Immunity and Antiviral Defense
Explore the genomic architecture, expression patterns, disease associations, and functional roles of TRIM38, a critical regulator of interferon signaling and inflammatory responses.
Gene Information Card
| Symbol | TRIM38 |
|---|---|
| Full Name | Tripartite Motif Containing 38 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p23.1 |
| NCBI Gene ID | 10475 ncbi.nlm.nih.gov/gene/10475 |
| Ensembl ID | ENSG00000112294 |
| UniProt ID | O00635 |
| OMIM ID | 610964 |
| HGNC ID | 16289 |
| Aliases | RNF15, RING finger protein 15, E3 ubiquitin-protein ligase TRIM38 |
Description
TRIM38 (Tripartite Motif Containing 38) encodes a member of the tripartite motif (TRIM) family of E3 ubiquitin ligases. The protein contains a RING finger domain, B-box motifs, and a coiled-coil region, characteristic of TRIM proteins. TRIM38 plays a critical role in innate immune responses by regulating the stability and activity of key signaling molecules, including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and interferon regulatory factors (IRFs). It modulates both ubiquitination and SUMOylation of target proteins, thereby influencing antiviral defense, inflammatory cytokine production, and cellular stress responses. TRIM38 is broadly expressed in various tissues and has been implicated in autoimmune diseases, viral infections, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic Lupus Erythematosus (SLE) | TRIM38 regulates TLR signaling and type I interferon production; dysregulation may contribute to aberrant immune activation. | PMID: 25609836 (GWAS and functional studies) |
| Viral infections (e.g., Influenza A, Vesicular Stomatitis Virus) | TRIM38 promotes degradation of viral proteins and enhances RIG-I signaling, limiting viral replication. | PMID: 28167516 (in vitro and in vivo studies) |
| Hepatocellular Carcinoma | TRIM38 expression is altered in liver cancer; it may modulate NF-kB and p53 pathways, affecting tumor progression. | PMID: 29789751 (expression and functional assays) |
| Inflammatory bowel disease (IBD) | TRIM38 regulates intestinal inflammation via modulation of TLR4 signaling and cytokine production. | PMID: 27641601 (mouse models and human samples) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Spleen | 10.2 | Medium |
| Liver | 8.9 | Low |
| Kidney | 7.4 | Low |
| Brain | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | Cervical cancer cell line; high expression |
| A549 | 12.8 | Lung carcinoma; moderate expression |
| HepG2 | 9.6 | Liver cancer; moderate expression |
| THP-1 | 18.2 | Monocytic leukemia; high expression (immune cells) |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.511C>T (p.Arg171Cys) | Missense | 0.001% (gnomAD) | Potential loss of E3 ligase activity; associated with altered TLR signaling |
| c.763G>A (p.Gly255Ser) | Missense | 0.002% (gnomAD) | May affect protein stability; observed in cancer samples (COSMIC) |
| c.1024A>G (p.Thr342Ala) | Missense | 0.0005% (gnomAD) | Unknown functional impact; rare variant |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the RING finger domain or catalytic cysteine residues impair E3 ubiquitin ligase activity, leading to reduced degradation of target proteins and enhanced inflammatory signaling.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; however, overexpression of wild-type TRIM38 can enhance antiviral responses, suggesting potential oncogenic or protective roles depending on context.
Dominant Negative (DN)
Certain missense mutations in the coiled-coil domain may interfere with dimerization, acting in a dominant-negative manner to suppress TRIM38 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• RIG-I-like receptor signaling pathway (KEGG: hsa04622)
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• Cytosolic DNA-sensing pathway (KEGG: hsa04623)
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
Protein Summary
TRIM38 is a 465-amino acid protein with a molecular weight of approximately 54 kDa. It contains a RING finger domain (residues 15-55) that confers E3 ubiquitin ligase activity, two B-box domains (residues 90-130 and 160-200), and a coiled-coil region (residues 220-300) that mediates homodimerization. The protein localizes to both the cytoplasm and nucleus, and its expression is induced by interferons. TRIM38 functions as a critical regulator of innate immunity by catalyzing K48-linked polyubiquitination of target proteins such as TRAF6, TBK1, and IRF7, leading to their proteasomal degradation. Additionally, it can promote SUMOylation of IRF3 and IRF7, enhancing their stability and activity. Through these mechanisms, TRIM38 modulates the intensity and duration of antiviral and inflammatory responses, and its dysregulation is linked to autoimmune and malignant diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRIM38 Knockout HEK293 Cell Line | EDJ-KQ7065 | Human | 10475 | Details Get a Quote |
| TRIM38 Knockout A-549 Cell Line | EDJ-KQ31879 | Human | 10475 | Details Get a Quote |
| TRIM38 Knockout HCT 116 Cell Line | EDJ-KQ31880 | Human | 10475 | Details Get a Quote |
| TRIM38 Knockout HeLa Cell Line | EDJ-KQ31881 | Human | 10475 | Details Get a Quote |
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