UBE2L3

UBE2L3 Full Name

ubiquitin-conjugating enzyme E2L 3

UBE2L3 Introduction

UBE2L3 is a relatively small protein, consisting of 154 amino acids with a molecular weight of approximately 17.9 kDa. Its structure is defined by the presence of a highly conserved Ubiquitin-Conjugating (UBC) catalytic domain, which spans roughly residues 3 to 149. This core domain adopts a characteristic αββββααα topology, a common fold among E2 enzymes, as confirmed by solution NMR spectroscopy. A unique feature of UBE2L3 is that, unlike many other E2 enzymes, it lacks key residues essential for lysine reactivity, specifically an Asp and an Asp residue at positions 88 and 119 are replaced by Pro and His, respectively, which influences its interactions with certain E3 ligases.

Figure 1. Strcuture of UBE2L3.

Mechanism of Action and Enzymatic Function
As a ubiquitin-conjugating enzyme, UBE2L3 plays a central role in the ubiquitin-proteasome system, a critical pathway for targeted protein degradation and regulation. Its primary function is to accept activated ubiquitin from an E1 ubiquitin-activating enzyme, forming a transient thioester bond with the ubiquitin molecule at its active site cysteine. It then transfers this ubiquitin to a substrate protein, a process that is facilitated by an E3 ubiquitin-protein ligase. In vitro studies show that UBE2L3 can catalyze 'Lys-11'-linked polyubiquitination, a specific type of ubiquitin chain that often signals for proteasomal degradation, but it also participates in other linkage types such as K29 and K48-linked chains. It is involved in the selective degradation of short-lived and abnormal proteins and has been shown to regulate signaling pathways like NF-κB, GSK3β/p65, and DSB repair pathways.

Role in Disease and Clinical Significance
Given its central role in protein homeostasis and signaling, dysregulation of UBE2L3 has been linked to a wide range of human diseases. Genetic variants in the UBE2L3 locus have been associated with several immune-mediated inflammatory diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis, psoriasis, inflammatory bowel disease, and celiac disease. The risk haplotype is often linked to increased UBE2L3 expression, which is thought to contribute to disease pathogenesis by modulating pathways like NF-κB, leading to increased inflammation. Furthermore, altered UBE2L3 expression has been observed in various cancers, including hepatocellular carcinoma and gastric cancer, where it can promote apoptosis evasion or cell migration. It is also implicated in neurodegenerative disorders like Parkinson's disease, highlighting its potential as an important therapeutic target.

Alternate Names for UBE2L3

UBE2L3; ubiquitin-conjugating enzyme E2L 3; ubiquitin-conjugating enzyme E2 L3; UBCH7; ubiquitin-protein ligase L3; ubiquitin carrier protein L3; ubiquitin-conjugating enzyme E2-F1; ubiquitin-conjugating enzyme UBCH7; E2-F1; L-UBC; UbcM4;