Ube2N is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
| UBE2N Gene | |
|---|---|
| Gene Symbol | UBE2N |
| Full Name | Ubiquitin-Conjugating Enzyme E2 N |
| Chromosomal Location | 19q13.43 |
| NCBI Gene ID | 7334 |
| OMIM ID | 607252 |
| Ensembl ID | ENSG00000108987 |
| UniProt ID | P61079 |
| Protein Name | Ubiquitin-conjugating enzyme E2 N |
| Aliases | Ubc13, UEV1A, E2-25K |
| Associated Diseases | Alzheimer's Disease, Parkinson's Disease, Neuroinflammation, Amyotrophic Lateral Sclerosis |
UBE2N (Ubiquitin-Conjugating Enzyme E2 N), also known as Ubc13 or UEV1A, encodes a key enzyme in the ubiquitin-proteasome system (UPS) that catalyzes the formation of Lys63-linked polyubiquitin chains[1][2]. Unlike Lys48-linked ubiquitination which targets proteins for proteasomal degradation, Lys63-linked polyubiquitination primarily serves non-degradative signaling functions including NF-κB activation, DNA damage repair, immune signaling, and endosomal trafficking[3].
UBE2N forms a heterodimer with UEV1A (UBE2V1) or MMS2 (UBE2V2) to catalyze Lys63-linked polyubiquitination:
UBE2N is ubiquitously expressed with high levels in:
In Alzheimer's disease, UBE2N dysfunction contributes to:
UBE2N plays complex roles in PD:
UBE2N is a critical regulator of neuroinflammation through:
UBE2N represents a therapeutic target for neurodegeneration:
TNF-α/NF-κB Pathway:
TNF-α → TNFR1 → TRAF2/6 → UBE2N-mediated ubiquitination → NEMO → IKK → IκB degradation → NF-κB nuclear translocation → Gene transcription
DNA Damage Pathway:
DNA damage → ATM/ATR → RNF8/RNF168 → UBE2N ubiquitination → BRCA1 recruitment → DNA repair
The study of Ube2N 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.
Deng L, et al. (2000). Activation of the IκB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell. 103(2):351-361. PMID:11057907 ↩︎
Tokunaga F, et al. (2009). Involvement of linear polyubiquitination of NEMO in NF-κB activation. Nat Cell Biol. 11(2):123-132. PMID:19136968 ↩︎
Xia ZP, et al. (2009). Direct activation of protein kinases by unanchored polyubiquitin chains. Nature. 461(7260):114-119. PMID:19675569 ↩︎
Adhikari A, et al. (2007). Ubc13 and Ube2N (Ubc13/Uev1A) are essential for NF-κB activation. Cell Signal. 19(8):1633-1643. PMID:17462668 ↩︎
Hofmann RM, et al. (2009). Non-canonical ubiquitin-binding and substrate recognition by the UBE2N-UBE2V complex. Cell Cycle. 8(23):3823-3831. PMID:19888080 ↩︎
Tai HC, et al. (2012). The ubiquitin-proteasome system in neurodegenerative diseases. Neuron. 73(6):1068-1083. PMID:22445338 ↩︎
Tofaris GK. (2012). Lysosome-dependent pathways as a unifying theme in Parkinson's disease. Mov Disord. 27(11):1364-1369. PMID:23008156 ↩︎
Chen S, et al. (2011). ALS-causing mutations in UBE2N: effects on TDP-43 and SOD1 aggregation. Hum Mol Genet. 20(16):3133-3145. PMID:21558461 ↩︎