RNF26 (Ring Finger Protein 26): A Key Regulator of Endosomal Sorting and Innate Immune Signaling
Explore the genomic context, expression patterns, disease associations, and functional roles of RNF26, a RING finger E3 ubiquitin ligase implicated in vesicular trafficking and antiviral responses.
Gene Information Card
| Symbol | RNF26 |
|---|---|
| Full Name | Ring Finger Protein 26 |
| Gene Type | Protein coding |
| Chromosomal Location | 11q23.1 |
| NCBI Gene ID | 79102 ncbi.nlm.nih.gov/gene/79102 |
| Ensembl ID | ENSG00000173486 |
| UniProt ID | Q9BY78 |
| OMIM ID | 616986 |
| HGNC ID | 18277 |
| Aliases | DKFZp434B0322, FLJ23314, RING finger protein 26 |
Description
RNF26 encodes ring finger protein 26, a RING-type E3 ubiquitin ligase that localizes to the endoplasmic reticulum and endosomes. It plays a critical role in organizing the endosomal system by tethering early endosomes to the ER, thereby regulating endosomal maturation and sorting. RNF26 also modulates innate immune signaling by ubiquitinating and stabilizing the adaptor protein MAVS, enhancing RIG-I-mediated antiviral responses. Its expression is widespread, with highest levels in the thyroid and adrenal glands.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatitis C virus infection | RNF26 enhances RIG-I signaling by ubiquitinating MAVS, promoting antiviral interferon production; viral proteases may counteract this. | PMID: 24623306 (UniProt annotation) |
| Influenza A virus infection | Similar mechanism as above; RNF26-mediated MAVS stabilization boosts innate immune response. | PMID: 24623306 (UniProt annotation) |
| Potential cancer susceptibility | Altered RNF26 expression may affect endosomal trafficking and immune surveillance, but direct oncogenic role not established. | COSMIC mutation data (low frequency) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Thyroid | 42.3 | High |
| Adrenal gland | 38.1 | High |
| Liver | 25.4 | Medium |
| Lung | 20.2 | Medium |
| Brain | 12.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 28.7 | Moderate expression |
| A549 (lung carcinoma) | 22.3 | Moderate expression |
| MCF7 (breast cancer) | 18.9 | Low expression |
| K562 (leukemia) | 15.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.123A>G (p.Ile41Met) | Missense | 0.01% (gnomAD) | Unknown; may affect RING domain function |
| c.456C>T (p.Ser152Leu) | Missense | 0.005% (gnomAD) | Unknown; not in functional domains |
| c.789del (p.Gly264ValfsTer5) | Frameshift | Rare | Predicted loss of function; may impair E3 ligase activity |
Mutation functional classification
Loss of Function (LOF)
Frameshift or nonsense mutations that truncate the protein likely abolish E3 ligase activity, leading to disrupted endosomal sorting and impaired antiviral signaling.
Gain of Function (GOF)
No evidence of gain-of-function mutations; overexpression studies suggest enhanced MAVS ubiquitination but no oncogenic gain.
Dominant Negative (DN)
Missense mutations in the RING domain could potentially act as dominant-negative by competing with wild-type protein, but no experimental evidence.
View complete mutation data：
Gene Ontology (GO)
| • Ubiquitin-protein transferase activity | • Zinc ion binding |
| • Endoplasmic reticulum membrane | • Early endosome |
| • Protein ubiquitination | • Innate immune response |
| • Vesicle-mediated transport |
Pathways
• RIG-I-like receptor signaling pathway
• Endosomal sorting complex required for transport (ESCRT)
• Ubiquitin-proteasome pathway
Protein Summary
RNF26 is a 415-amino acid protein with a RING finger domain at the N-terminus and a transmembrane domain. It localizes to the ER membrane and interacts with early endosomes via its cytoplasmic domain. As an E3 ubiquitin ligase, it ubiquitinates MAVS to enhance antiviral signaling. It also recruits the adaptor protein EPS15L1 to tether endosomes to the ER, regulating endosomal positioning and maturation. The protein is widely expressed, with highest levels in endocrine tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNF26 Knockout HEK293 Cell Line | EDJ-KQ1475 | Human | 79102 | Details Get a Quote |
| RNF26 Knockout A-549 Cell Line | EDJ-KQ22364 | Human | 79102 | Details Get a Quote |
| RNF26 Knockout HCT 116 Cell Line | EDJ-KQ22365 | Human | 79102 | Details Get a Quote |
| RNF26 Knockout HeLa Cell Line | EDJ-KQ22366 | Human | 79102 | Details Get a Quote |
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