TOPORS (TOP1 Binding Arginine/Serine Rich Protein, E3 Ubiquitin Ligase)
A dual-function E3 ubiquitin ligase and SUMO E3 ligase implicated in retinal degeneration and cancer.
Gene Information Card
| Symbol | TOPORS |
|---|---|
| Full Name | TOP1 binding arginine/serine rich protein, E3 ubiquitin ligase |
| Gene Type | Protein coding |
| Chromosomal Location | 9p21.1 |
| NCBI Gene ID | 10210 ncbi.nlm.nih.gov/gene/10210 |
| Ensembl ID | ENSG00000197579 |
| UniProt ID | Q9NS56 |
| OMIM ID | 609507 |
| HGNC ID | 21654 |
| Aliases | TP53BPL, LUN, FLJ10529 |
Description
TOPORS encodes a protein with dual E3 ubiquitin ligase and SUMO E3 ligase activities. It interacts with topoisomerase I and p53, playing roles in DNA damage response, cell cycle regulation, and apoptosis. Mutations in TOPORS are associated with autosomal dominant retinitis pigmentosa (adRP), and altered expression is observed in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Retinitis pigmentosa (autosomal dominant) | Missense mutations in the RING finger domain impair ubiquitin ligase activity, leading to photoreceptor degeneration. | ClinVar, OMIM |
| Cancer (various types) | Dysregulation of TOPORS expression affects p53 stability and genomic stability, contributing to tumorigenesis. | COSMIC, PubMed (via NCBI) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.3 | Medium |
| Retina | 8.5 | Low |
| Brain | 6.2 | Low |
| Lung | 4.1 | Low |
| Liver | 3.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line; high expression |
| A549 | 8.7 | Lung carcinoma; moderate expression |
| MCF7 | 6.5 | Breast cancer; moderate expression |
| HEK293 | 5.8 | Embryonic kidney; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2558G>A (p.Arg853His) | Missense | Rare (adRP) | Impairs ubiquitin ligase activity; associated with retinitis pigmentosa |
| c.1A>G (p.Met1Val) | Missense | Rare (adRP) | Affects protein initiation; likely loss of function |
| c.2542C>T (p.Arg848Cys) | Missense | Rare (adRP) | Disrupts RING finger domain; reduces E3 activity |
| c.2543G>A (p.Arg848His) | Missense | Rare (adRP) | Similar to Arg848Cys; pathogenic |
| c.2545C>T (p.Arg849Cys) | Missense | Rare (adRP) | RING finger mutation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most adRP-associated missense mutations in the RING finger domain reduce or abolish E3 ubiquitin ligase activity, leading to loss of function.
Gain of Function (GOF)
No clear gain-of-function mutations reported; some variants may exert dominant-negative effects.
Dominant Negative (DN)
Mutant TOPORS may interfere with wild-type protein function in heterozygous state, contributing to autosomal dominant inheritance.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity | • SUMO transferase activity |
| • zinc ion binding | • protein binding |
| • nucleus | • cytoplasm |
| • ubiquitin-dependent protein catabolic process | • protein sumoylation |
| • DNA damage response | • apoptotic process |
Pathways
• p53 signaling pathway
• Ubiquitin-mediated proteolysis
• SUMOylation pathway
• DNA damage response
Protein Summary
TOPORS is a 1045-amino acid protein containing a RING finger domain, a coiled-coil domain, and an arginine/serine-rich region. It functions as an E3 ubiquitin ligase for p53 and topoisomerase I, and also possesses SUMO E3 ligase activity. It localizes to the nucleus and is involved in DNA damage response, cell cycle control, and apoptosis. Its dual enzymatic activities are critical for maintaining genomic stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TOPORS Knockout HEK293 Cell Line | EDJ-KQ6950 | Human | 10210 | Details Get a Quote |
| TOPORS Knockout HeLa Cell Line | EDJ-KQ30241 | Human | 10210 | Details Get a Quote |
| TOPORS Knockout A-549 Cell Line | EDJ-KQ31616 | Human | 10210 | Details Get a Quote |
| TOPORS Knockout HCT 116 Cell Line | EDJ-KQ31617 | Human | 10210 | Details Get a Quote |
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