Ube2V2 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
UBE2V2 (Ubiquitin-Conjugating Enzyme E2 Variant 2), also known as UEV-2 or MMS2, is a ubiquitin-conjugating enzyme variant that plays a critical role in K63-linked polyubiquitination. Unlike canonical E2 enzymes, UBE2V2 lacks catalytic cysteine residues and functions as a scaffold to facilitate ubiquitin chain assembly. This enzyme is involved in critical cellular processes including DNA damage repair, NF-κB signaling, and stress response—all pathways highly relevant to neurodegenerative diseases.
The ubiquitin-proteasome system relies on various E2 enzymes for different types of ubiquitin linkages. K63-linked polyubiquitination, mediated by UBE2V2 in complex with UBE2N, creates non-proteolytic ubiquitin chains that signal for autophagy, DNA repair, and signal transduction.
| Attribute | Value |
|---|---|
| Gene Symbol | UBE2V2 |
| Full Name | Ubiquitin-Conjugating Enzyme E2 Variant 2 |
| Aliases | UEV2, MMS2, DDIT1 |
| Chromosomal Location | 8q24.13 |
| NCBI Gene ID | 7336 |
| OMIM | N/A |
| Ensembl ID | ENSG00000169139 |
| UniProt ID | P61077 |
| Protein Length | 147 amino acids |
| Molecular Weight | ~16 kDa |
UBE2V2 belongs to the ubiquitin-conjugating (E2) enzyme family but functions as an E2 variant (UEV) due to the lack of a catalytic cysteine residue.
UBE2V2 forms a heterodimeric complex with UBE2N (E2 N) to catalyze K63-linked polyubiquitination:
K63-linked ubiquitin chains serve as signaling molecules rather than degradation signals:
| Ubiquitin Linkage | Function | UBE2V2 Involvement |
|---|---|---|
| K63 | Signaling, autophagy, DNA repair | Primary substrate |
| K48 | Proteasomal degradation | Not involved |
| K27 | DNA damage response | May contribute |
| Others | Various | Limited |
UBE2V2-mediated ubiquitination regulates:
DNA Damage Response
NF-κB Signaling
Stress Response
Immune Function
UBE2V2 is expressed throughout the central nervous system:
UBE2V2 expression is regulated by:
UBE2V2 is implicated in AD through multiple mechanisms:
Research findings:
UBE2V2 involvement in PD:
UBE2V2 is a key regulator of inflammatory responses:
Chronic neuroinflammation is a hallmark of:
UBE2V2 represents a potential therapeutic target for:
The study of Ube2V2 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.