RNF125: E3 Ubiquitin-Protein Ligase and Immune Regulator
Comprehensive genomic and functional analysis of RNF125, a key modulator of ubiquitination and antiviral signaling.
Gene Information Card
| Symbol | RNF125 |
|---|---|
| Full Name | Ring Finger Protein 125 |
| Gene Type | Protein coding |
| Chromosomal Location | 18q12.1 |
| NCBI Gene ID | 54941 ncbi.nlm.nih.gov/gene/54941 |
| Ensembl ID | ENSG00000101695 |
| UniProt ID | Q96EQ8 |
| OMIM ID | 610432 |
| HGNC ID | 21149 |
| Aliases | TRAC-1, hRNF125, RIG-I E3 ligase |
Description
RNF125 (Ring Finger Protein 125) encodes an E3 ubiquitin-protein ligase that mediates ubiquitination and proteasomal degradation of target proteins, including key components of the antiviral innate immune response such as RIG-I, MDA5, and MAVS. It also ubiquitinates itself, leading to autoregulation. RNF125 plays a role in T-cell receptor signaling and is implicated in susceptibility to viral infections and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency 84 (IMD84) | Loss-of-function mutations impair ubiquitination of RIG-I/MDA5, leading to dysregulated interferon response | ClinVar, OMIM |
| Prostate cancer | Overexpression may promote tumor growth by degrading tumor suppressors | COSMIC, NCBI |
| Hepatocellular carcinoma | Altered expression linked to poor prognosis | NCBI, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | Medium |
| Lymph node | 10.2 | Medium |
| Bone marrow | 8.9 | Low |
| Liver | 6.3 | Low |
| Testis | 15.1 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.8 | High expression |
| HeLa | 9.5 | Moderate expression |
| Jurkat | 11.2 | High expression |
| HepG2 | 7.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.226C>T (p.Arg76Trp) | Missense | <0.01% | Impaired E3 ligase activity |
| c.487G>A (p.Glu163Lys) | Missense | <0.01% | Reduced ubiquitination of RIG-I |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the RING finger domain or catalytic activity, leading to impaired ubiquitination and dysregulated immune signaling (e.g., p.Arg76Trp).
Gain of Function (GOF)
Not well characterized; overexpression in some cancers may confer gain-of-function by enhancing degradation of tumor suppressors.
Dominant Negative (DN)
Not reported for RNF125.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity (GO:0004842) | • zinc ion binding (GO:0008270) |
| • protein ubiquitination (GO:0016567) | • innate immune response (GO:0045087) |
| • positive regulation of NF-kappaB transcription factor activity (GO:0051092) |
Pathways
• RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
• Ubiquitin mediated proteolysis (KEGG hsa04120)
• Innate immune system (Reactome R-HSA-168249)
Protein Summary
RNF125 is a 232-amino acid protein containing a RING finger domain (residues 18-57) that confers E3 ubiquitin ligase activity. It ubiquitinates RIG-I, MDA5, and MAVS, targeting them for proteasomal degradation, thereby negatively regulating antiviral interferon responses. RNF125 also undergoes autoubiquitination. The protein is localized to the cytoplasm and nucleus. Structural studies indicate that the RING domain coordinates two zinc ions essential for catalytic function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNF125 Knockout HEK293 Cell Line | EDJ-KQ148 | Human | 54941 | Details Get a Quote |
| RNF125 Knockout HCT 116 Cell Line | EDJ-KQ45680 | Human | 54941 | Details Get a Quote |
| RNF125 Knockout HeLa Cell Line | EDJ-KQ56506 | Human | 54941 | Details Get a Quote |
| RNF125 Knockout A-549 Cell Line | EDJ-KQ64998 | Human | 54941 | Details Get a Quote |
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