ARIH1
Ariadne RBR E3 Ubiquitin Protein Ligase 1
Gene Information Card
| Symbol | ARIH1 |
|---|---|
| Full Name | Ariadne RBR E3 Ubiquitin Protein Ligase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q24.1 |
| NCBI Gene ID | 25820 ncbi.nlm.nih.gov/gene/25820 |
| Ensembl ID | ENSG00000137822 |
| UniProt ID | Q9Y4X5 |
| OMIM ID | 605624 |
| HGNC ID | 689 |
| Aliases | ARI-1, HHARI, UBC7BP, UBCH7BP |
Description
ARIH1 encodes a RING-between-RING (RBR) E3 ubiquitin ligase that functions in ubiquitination and proteasomal degradation. It acts as a hybrid E3, cooperating with UBE2L3 (UbcH7) to transfer ubiquitin directly to substrates. ARIH1 is involved in cell cycle regulation, DNA repair, and immune signaling. Dysregulation is linked to cancer and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Altered ARIH1 expression affects ubiquitination of BRCA1 and other tumor suppressors, promoting genomic instability. | PMID: 25609812 |
| Colorectal cancer | ARIH1 overexpression correlates with poor prognosis; modulates β-catenin signaling. | PMID: 30530647 |
| Parkinson disease | ARIH1 interacts with parkin (PARK2) and may influence mitophagy pathways. | PMID: 21874021 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.3 | Medium |
| Heart | 6.1 | Low |
| Liver | 4.7 | Low |
| Kidney | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | High expression |
| HeLa | 8.9 | Moderate expression |
| MCF7 | 7.5 | Moderate expression |
| HepG2 | 5.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | <0.01% | Unknown functional impact |
| c.457G>A (p.Glu153Lys) | Missense | <0.01% | Reported in cancer samples; potential loss of ligase activity |
Mutation functional classification
Loss of Function (LOF)
Missense mutations in the RBR domain (e.g., Cys357Ser) impair ubiquitin transfer and substrate degradation.
Gain of Function (GOF)
Not well characterized; overexpression in some cancers suggests possible oncogenic gain-of-function.
Dominant Negative (DN)
Mutant ARIH1 lacking RING2 domain can inhibit wild-type ligase activity in vitro.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• Protein processing in endoplasmic reticulum (KEGG: hsa04141)
• Parkin-ubiquitin proteasomal system (Reactome: R-HSA-983168)
Protein Summary
ARIH1 is a 557-amino acid RBR E3 ubiquitin ligase with three zinc-binding domains: RING1, IBR (in-between-RING), and RING2. It forms a complex with UBE2L3 to catalyze ubiquitin transfer. The protein is localized to the nucleus and cytosol, and its activity is regulated by autoinhibition and phosphorylation. Structural studies reveal a compact architecture where RING1 binds E2, and RING2 contains the active site cysteine.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| No Data | ||||
