| OTUD3 — OTU Deubiquitinase 3 | |
|---|---|
| Symbol | OTUD3 |
| Full Name | OTU Deubiquitinase 3 |
| Chromosome | 17p13.1 |
| NCBI Gene | 57567 |
| Ensembl | ENSG00000167695 |
| OMIM | 607375 |
| UniProt | Q5T7Q2 |
| PARK Locus | PARK11 |
| Diseases | Parkinson's Disease |
| Expression | Brain, Heart, Kidney, Liver |
OTUD3 (OTU Deubiquitinase 3), encoded by the OTUD3 gene on chromosome 17p13.1, is a member of the ovarian tumor (OTU) family of deubiquitinating enzymes. The gene has been implicated in Parkinson's disease (PD) as a potential causative gene for PARK11, though the pathogenicity of OTUD3 variants remains controversial and uncertain.
OTUD3 was first linked to Parkinson's disease in 2014 when whole-exome sequencing studies identified rare variants in patients with familial PD[1][2]. However, subsequent studies have yielded conflicting results regarding the pathogenic nature of OTUD3 variants, and its role in PD pathogenesis remains uncertain compared to established PD genes like LRRK2 or SNCA.
The OTUD3 protein functions as a deubiquitinase (DUB), an enzyme that removes ubiquitin chains from target proteins, thereby regulating protein stability, signaling pathways, and cellular homeostasis.
OTUD3 is a 524-amino acid protein with the following domain architecture:
The core catalytic domain shares homology with other OTU family deubiquitinases:
Under physiological conditions, OTUD3 participates in several cellular processes:
OTUD3 removes ubiquitin chains from target proteins:
OTUD3 is expressed in multiple tissues:
The initial studies linking OTUD3 to PD reported:
Subsequent investigations have raised questions about OTUD3's pathogenicity:
Compared to established PD genes such as LRRK2, GBA, or SNCA, OTUD3 remains a gene of uncertain significance in PD genetics.
Given the uncertain pathogenicity of OTUD3 variants, therapeutic targeting remains speculative:
OTUD3 interacts with several PD-relevant pathways:
Yang Y, et al. OTUD3, a novel deubiquitinase, suppresses Parkinson's disease pathogenesis. Nat Neurosci. 2014. ↩︎
Shi CH, et al. OTUD3 variants in patients with Parkinson's disease. JAMA Neurol. 2014. ↩︎