TRIM5 Gene - TRIM5α/RING-Type E3 Ubiquitin Transferase
Key Restriction Factor in Retroviral Defense and Innate Immunity
Gene Information Card
| Symbol | TRIM5 |
|---|---|
| Full Name | Tripartite Motif Containing 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.4 |
| NCBI Gene ID | 85363 ncbi.nlm.nih.gov/gene/85363 |
| Ensembl ID | ENSG00000132256 |
| UniProt ID | Q9C035 |
| OMIM ID | 608487 |
| HGNC ID | 16276 |
| Aliases | RNF88, TRIM5alpha |
Description
The TRIM5 gene encodes a member of the tripartite motif (TRIM) family, characterized by a RING finger, B-box, and coiled-coil domains. TRIM5α, the major isoform, functions as a retroviral restriction factor, particularly against HIV-1 in certain primate species. It recognizes viral capsids and mediates their premature uncoating, thereby blocking viral replication. Additionally, TRIM5α acts as an E3 ubiquitin ligase and participates in innate immune signaling pathways, including NF-κB activation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| HIV-1 Infection (Resistance) | TRIM5α binds to the HIV-1 capsid and promotes its degradation, restricting viral replication. Polymorphisms affect susceptibility. | Multiple studies; ClinVar and literature (e.g., Stremlau et al., 2004; Nakayama et al., 2005). |
| Retrovirus-Associated Diseases (e.g., HTLV-1) | TRIM5α can restrict other retroviruses; variations may influence HTLV-1 infection outcomes. | Evidence from functional assays; OMIM and NCBI. |
| Cancer (Potential) | TRIM5α modulates innate immune responses and may influence tumor microenvironment; somatic mutations have been observed in some cancers. | COSMIC database; limited functional evidence. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | 5.2 | Medium |
| Spleen | 4.8 | Medium |
| Lymph Node | 4.5 | Medium |
| Bone Marrow | 3.9 | Low |
| Lung | 2.1 | Low |
| Liver | 1.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (Monocyte) | 6.5 | High expression; relevant for innate immunity |
| K-562 (Lymphoblast) | 4.2 | Moderate expression |
| HeLa (Cervical) | 2.8 | Low expression |
| A549 (Lung) | 1.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R136Q | Missense | ~5% in some populations | Alters capsid binding specificity; may affect HIV-1 restriction |
| H43Y | Missense | Rare | Impairs E3 ligase activity and antiviral function |
| C15A | Missense (artificial) | Not observed in population | Disrupts RING domain; loss of ubiquitination |
| G249D | Missense | Rare | Affects coiled-coil domain; reduces multimerization |
Mutation functional classification
Loss of Function (LOF)
Mutations such as H43Y and C15A disrupt the RING domain, impairing E3 ubiquitin ligase activity and reducing retroviral restriction.
Gain of Function (GOF)
Certain variants (e.g., R136Q) may enhance capsid binding and broaden restriction specificity, potentially increasing antiviral activity.
Dominant Negative (DN)
Truncated isoforms or mutations affecting multimerization (e.g., G249D) can interfere with wild-type TRIM5α function, acting in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • zinc ion binding |
| • ubiquitin-protein transferase activity | • identical protein binding |
| • innate immune response | • defense response to virus |
| • negative regulation of viral genome replication | • cytoplasm |
| • cytosol | • cytoplasmic vesicle |
Pathways
• Innate Immune System
• Antiviral mechanism by IFN-stimulated genes
• Ubiquitin-Proteasome Dependent Proteolysis
Protein Summary
TRIM5α is a 493-amino acid protein with a RING finger domain (E3 ubiquitin ligase), B-box, coiled-coil, and a C-terminal B30.2/SPRY domain that mediates capsid recognition. It forms trimers and higher-order assemblies that bind retroviral capsids, promoting premature uncoating and proteasomal degradation. It also activates innate immune signaling via TAK1 and NF-κB, contributing to antiviral responses.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TRIM56 Knockout HEK293 Cell Line | EDJ-KQ2107 | Human | 81844 | Details Get a Quote |
| TRIM54 Knockout HEK293 Cell Line | EDJ-KQ3006 | Human | 57159 | Details Get a Quote |
| TRIM55 Knockout HEK293 Cell Line | EDJ-KQ3810 | Human | 84675 | Details Get a Quote |
| TRIM5 Knockout HEK293 Cell Line | EDJ-KQ3941 | Human | 85363 | Details Get a Quote |
| TRIM58 Knockout HEK293 Cell Line | EDJ-KQ8285 | Human | 25893 | Details Get a Quote |
| TRIM50 Knockout HEK293 Cell Line | EDJ-KQ9367 | Human | 135892 | Details Get a Quote |
| TRIM51 Knockout HEK293 Cell Line | EDJ-KQ10193 | Human | 84767 | Details Get a Quote |
| TRIM52 Knockout HEK293 Cell Line | EDJ-KQ10219 | Human | 84851 | Details Get a Quote |
| TRIM59 Knockout HEK293 Cell Line | EDJ-KQ15124 | Human | 286827 | Details Get a Quote |
| TRIM51G Knockout HEK293 Cell Line | EDJ-KQ17192 | Human | 120824 | Details Get a Quote |
| TRIM56 Knockout HeLa Cell Line | EDJ-KQ20935 | Human | 81844 | Details Get a Quote |
| TRIM5 Knockout A-549 Cell Line | EDJ-KQ26189 | Human | 85363 | Details Get a Quote |
| TRIM5 Knockout HCT 116 Cell Line | EDJ-KQ26190 | Human | 85363 | Details Get a Quote |
| TRIM5 Knockout HeLa Cell Line | EDJ-KQ26191 | Human | 85363 | Details Get a Quote |
| TRIM59 Knockout A-549 Cell Line | EDJ-KQ46929 | Human | 286827 | Details Get a Quote |
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