Ube2I — Sumo Conjugating Enzyme is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| Gene Symbol | UBE2I |
| Full Name | Ubiquitin-Conjugating Enzyme E2 I |
| Chromosome | 16p13.3 |
| NCBI Gene ID | 7332 |
| OMIM | 601231 |
| Ensembl ID | ENSG00000184254 |
| UniProt ID | P63279 |
| Associated Diseases | Alzheimer's Disease, Huntington's Disease |
UBE2I (Ubiquitin-Conjugating Enzyme E2 I), also known as UBC9, is the sole E2 conjugating enzyme responsible for SUMOylation—the post-translational modification of proteins by Small Ubiquitin-like Modifier (SUMO) proteins. Located on chromosome 16p13.3, UBE2I plays a critical role in cellular proteostasis by catalyzing the covalent attachment of SUMO to target proteins, thereby modulating their localization, stability, activity, and protein-protein interactions [1][2].
The SUMOylation pathway is essential for normal neuronal function, regulating synaptic plasticity, transcription, DNA repair, autophagy, and stress responses. In the context of neurodegenerative diseases, dysregulation of UBE2I and the SUMOylation machinery has been implicated in the pathogenesis of Alzheimer's disease, Huntington's disease, and Parkinson's disease [3][4]. Understanding the role of UBE2I in neuronal proteostasis provides insights into potential therapeutic strategies targeting protein aggregation and cellular clearance mechanisms.
This page explores the molecular function of UBE2I, its expression pattern in the brain, and its relevance to neurodegenerative disease mechanisms.
UBE2I encodes the SUMO-conjugating enzyme (also known as UBC9), which is essential for SUMOylation—the post-translational modification of proteins by SUMO (Small Ubiquitin-like Modifier). UBE2I catalyzes the formation of an isopeptide bond between the C-terminal glycine of SUMO and lysine residues in target proteins. This enzyme is the sole E2 conjugating enzyme for SUMOylation.
In neurons, SUMOylation regulates various processes including synaptic plasticity, transcription, DNA repair, and protein quality control. Dysregulation of SUMOylation has been implicated in neurodegenerative diseases.
Widely expressed in the brain with high levels in hippocampus, cortex, and basal ganglia. UBE2I localizes to both nuclear and cytoplasmic compartments.
| Disease | Mechanism |
|---|---|
| Alzheimer's Disease | Altered SUMOylation of tau, APP |
| Huntington's Disease | Dysregulated SUMOylation of mutant huntingtin |
The study of Ube2I — Sumo Conjugating Enzyme has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.