UBQLN2
Ubiquilin 2: A Key Regulator of Protein Degradation Linked to Neurodegeneration
Gene Information Card
| Symbol | UBQLN2 |
|---|---|
| Full Name | Ubiquilin 2 |
| Gene Type | Protein coding |
| Chromosomal Location | Xp11.21 |
| NCBI Gene ID | 29978 ncbi.nlm.nih.gov/gene/29978 |
| Ensembl ID | ENSG00000188021 |
| UniProt ID | Q9UHD9 |
| OMIM ID | 300264 |
| HGNC ID | 12509 |
| Aliases | CHAP1, DSK2, N4BP4, PLIC2, UBQN2 |
Description
UBQLN2 encodes ubiquilin 2, a member of the ubiquilin family that links ubiquitinated proteins to the proteasome for degradation. It plays a critical role in protein homeostasis and is implicated in neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mutations in UBQLN2 cause X-linked dominant ALS/FTD.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Amyotrophic Lateral Sclerosis (ALS) | Mutations in UBQLN2 impair proteasomal degradation and promote aggregation of ubiquitinated proteins, leading to motor neuron death. | OMIM #300264; Deng et al., Nature 2011 |
| Frontotemporal Dementia (FTD) | UBQLN2 mutations cause accumulation of TDP-43 and other proteins, contributing to neurodegeneration in frontal and temporal lobes. | OMIM #300264; Deng et al., Nature 2011 |
| Neurodegeneration with brain iron accumulation (NBIA) | Rare UBQLN2 variants may disrupt protein quality control, leading to iron accumulation and neuronal loss. | ClinVar; limited case reports |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Spinal cord | 15.3 | Medium |
| Heart | 8.2 | Low |
| Liver | 6.1 | Low |
| Skeletal muscle | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.2 | Neuronal model |
| HeLa (cervical carcinoma) | 9.8 | Epithelial |
| HEK 293 (embryonic kidney) | 11.5 | Common expression system |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Pro497Ser | Missense | Rare | Impaired proteasome binding; linked to ALS |
| p.Pro506Ser | Missense | Rare | Disrupts ubiquitin binding; ALS-associated |
| p.Pro509Ser | Missense | Rare | Reduced protein degradation; ALS/FTD |
Mutation functional classification
Loss of Function (LOF)
Some UBQLN2 mutations reduce proteasomal degradation capacity, leading to accumulation of misfolded proteins.
Gain of Function (GOF)
Mutant UBQLN2 forms aggregates that sequester other proteins, contributing to toxicity.
Dominant Negative (DN)
Mutant UBQLN2 may interfere with wild-type ubiquilin function, impairing overall protein quality control.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-dependent protein catabolic process (GO:0006511) | • protein stabilization (GO:0050821) |
| • ubiquitin protein ligase binding (GO:0031625) | • cytoplasm (GO:0005737) |
| • nucleus (GO:0005634) |
Pathways
• Ubiquitin-proteasome system (UPS)
• Autophagy-lysosome pathway
• Protein processing in endoplasmic reticulum
Protein Summary
Ubiquilin 2 is a 624-amino acid protein containing an N-terminal ubiquitin-like (UBL) domain and a C-terminal ubiquitin-associated (UBA) domain. It shuttles ubiquitinated substrates to the proteasome for degradation. Mutations in the UBA domain (e.g., P497S, P506S, P509S) disrupt this function, leading to protein aggregation and neurodegeneration. The protein is widely expressed, with highest levels in the brain and spinal cord.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UBQLN2 Knockout HEK293 Cell Line | EDJ-KQ9116 | Human | 29978 | Details Get a Quote |
| UBQLN2 Knockout A-549 Cell Line | EDJ-KQ35629 | Human | 29978 | Details Get a Quote |
| UBQLN2 Knockout HCT 116 Cell Line | EDJ-KQ35630 | Human | 29978 | Details Get a Quote |
| UBQLN2 Knockout HeLa Cell Line | EDJ-KQ35631 | Human | 29978 | Details Get a Quote |
