| 1998 |
UBE2G2 was identified as the human homologue of yeast Ubc7p, confirmed to be ubiquitously expressed, and mapped to chromosome 21q22.3. It encodes a 165-amino-acid protein with significant similarity to other UBC family members involved in proteasome-dependent degradation. |
cDNA cloning, sequence analysis, chromosomal mapping |
Genomics |
Medium |
9693041
|
| 2005 |
Recombinant His-tagged UBE2G2 expressed in E. coli adopts the typical alpha/beta secondary structure of class I E2 enzymes and is enzymatically active, capable of binding ubiquitin molecules when exposed to HeLa cell extract in an in vitro ubiquitin-binding assay. |
Recombinant protein expression, nickel-affinity purification, circular dichroism, in vitro ubiquitin-binding assay |
Protein expression and purification |
Medium |
16214370
|
| 2006 |
Crystal structure of human UBE2G2 solved at 2.56 Å resolution; the structure comprises an antiparallel beta-sheet with four strands, five alpha-helices, and two 3(10)-helices. Structural comparison with yeast Ubc7 and UbcH7 suggested that two loop regions of UBE2G2 interact with RING domains, with an extra loop potentially conferring binding specificity. |
X-ray crystallography |
Acta crystallographica. Section F |
High |
16582478
|
| 2009 |
gp78 forms oligomers via a hydrophobic segment in its cytosolic domain; a gp78 oligomer can simultaneously associate with multiple Ube2g2 molecules via a novel Ube2g2 surface distinct from the predicted RING binding site. This heterooligomeric assembly brings multiple Ube2g2 molecules into proximity, enabling transfer of ubiquitin moieties between neighboring Ube2g2s to form Lys-48-linked active site-linked polyubiquitin chains on the Ube2g2 catalytic cysteine prior to substrate transfer. |
Biochemical oligomerization assays, site-directed mutagenesis, in vitro ubiquitination assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
19223579
|
| 2010 |
Solution NMR structure of Ube2g2 revealed that two catalytically important loops flanking the active site cysteine (residues 95-107 and 130-135) are highly dynamic. 15N spin relaxation and residual dipolar coupling analysis showed these loops require binding partners (E3, acceptor ubiquitin, or thiolester-linked donor ubiquitin) to adopt a catalytically relevant conformation. His94 was identified as a potential general base activated by carboxylate side-chains of Asp98 or Asp99. |
NMR spectroscopy, 15N spin relaxation, residual dipolar coupling analysis |
Proteins |
High |
20014027
|
| 2010 |
AUP1 localizes to lipid droplets in a monotopic fashion with both termini facing the cytosol, and binds Ube2g2 via its C-terminal G2BR domain. Deletion or mutation of the G2BR domain abolishes Ube2g2 binding without affecting AUP1's LD localization. The AUP1-Ube2g2 complex at lipid droplets provides a direct molecular link between lipid droplets and the cellular ubiquitination machinery. |
Co-immunoprecipitation, domain deletion/mutation analysis, fluorescence microscopy, subcellular fractionation |
The Journal of biological chemistry |
High |
21127063
|
| 2010 |
Ube2g2 binds ubiquitin with ~90 μM affinity in two orientations rotated 180°. It binds Lys-48-linked and Lys-63-linked diubiquitin primarily through the distal ubiquitin subunit (containing the free Lys-48 or Lys-63). For Lys-48-linked diubiquitin, there is ~3-fold preference for the distal subunit, attributed to partial steric occlusion of the proximal subunit's Lys-48, suggesting Lys-48-linked chains are designed to position the terminal ubiquitin's reactive Lys-48 for chain elongation. |
NMR chemical shift perturbation, paramagnetic relaxation enhancement, RosettaDock computational modeling |
The Journal of biological chemistry |
Medium |
21098018
|
| 2014 |
Ube2g2 in complex with E3 ligase gp78 mediates polyubiquitylation of HERP, targeting it for proteasomal degradation during ER stress recovery. The polyubiquitylation of HERP in vitro depends on a physical interaction between the CUE domain of gp78 and the ubiquitin-like (UBL) domain of HERP, and this interaction is essential for HERP degradation in vivo. |
In vitro ubiquitylation assay, co-immunoprecipitation, domain mapping, cell-based degradation assays |
Journal of cell science |
High |
24496447
|
| 2017 |
NMR conformational dynamics analysis showed that the G2BR domain of gp78 increases the affinity between the RING domain and Ube2g2 by 50-fold via allostery. Binding of G2BR and RING to two distant regions of Ube2g2 sequentially progresses toward ubiquitin transfer through redistribution of ground and excited conformational state populations. The RING domain binding triggers departure of G2BR in an allosteric fashion. |
NMR spectroscopy, conformational dynamics analysis, binding affinity measurements |
Structure |
High |
28434917
|
| 2017 |
gp78 RING domain binding to Ube2g2 increases the population of the closed (catalytically active) conformation of Ube2g2~Ub conjugates from ~60% to ~82%. Mutations in the hydrophobic patch of the thiolester-linked ubiquitin that abolish closed conformation also abolish catalytic activity. Organization of the active site into a catalytically viable conformation is the rate-limiting step for a single ubiquitin ligation event. |
NMR spectroscopy, single-turnover diubiquitin formation assays, site-directed mutagenesis |
ACS omega |
High |
28884161
|
| 2021 |
The 27-amino acid G2BR domain of AUP1 binds with high specificity and low nanomolar affinity to the backside of UBE2G2. Crystal/structural analysis of the AUP1 G2BR-UBE2G2 complex revealed an interface with salt bridges, hydrogen bonds, and hydrophobic interactions. G2BRAUP1 allosterically activates UBE2G2-mediated ubiquitination in vitro. In cells, AUP1 G2BR binding prevents rapid degradation of UBE2G2, recruits UBE2G2 to the ER membrane, and is required for UBE2G2 activation at the ER membrane for ERAD. |
Co-immunoprecipitation, structural analysis, in vitro ubiquitination assay, cell-based ERAD assays, site-directed mutagenesis, fluorescence microscopy |
PLoS biology |
High |
34879065
|
| 2024 |
UBE2G2 directly binds to LGALS3BP and forms a complex with E3 ubiquitin ligase TRIM38, facilitating ubiquitination-mediated degradation of LGALS3BP at the K104 residue. This suppresses PI3K/AKT signaling and inhibits vasculogenic mimicry and metastasis in uveal melanoma. |
Co-immunoprecipitation, ubiquitination assays, site-directed mutagenesis (K104 site identification), knockdown/overexpression with phenotypic readouts |
Acta pharmaceutica Sinica. B |
Medium |
39807310
|
| 2024 |
UBE2G2 is required for ERAD-mediated degradation of proinsulin and is involved in the generation of the proinsulin B-chain autoantigen PPIB10-18. Screening of E2 ubiquitin conjugating enzymes identified UBE2G2 as specifically involved in this process. |
Gene knockdown screening of E2 enzymes, cell-based ERAD and antigen presentation assays |
PloS one |
Medium |
38787820
|
| 2025 |
AUP1 forms a complex with UBE2G2 that interacts with STING, retaining STING in the ER membrane and preventing its translocation to the Golgi and subsequent signaling. Deficiency of either AUP1 or UBE2G2 causes spontaneous STING activation and enhanced type I interferon expression, demonstrating that the AUP1-UBE2G2 complex is a negative regulator of STING-dependent innate immune signaling. |
Co-immunoprecipitation, genetic knockdown/knockout, cell-based STING signaling assays, in vitro and in vivo viral infection models |
mBio |
Medium |
40237449
|
| 2025 |
A nanobody binding to the backside region of Ube2G2 does not affect ubiquitin loading but differentially inhibits E3-mediated ubiquitination, with order of inhibition HRD1 > CHIP >> TRC8. Occupation of the backside site on Ube2G2 thus differentially affects its interactions with different E3 ligases. G2BR of gp78 enhances Ube2G2 activity when present in cis but its deletion results in similar inhibition as the nanobody. |
Nanobody binding assay, in vitro ubiquitination assays with multiple E3 ligases |
Communications biology |
Medium |
40234692
|
| 2025 |
The m6A reader YTHDF3 directly binds UBE2G2 mRNA in an m6A-dependent manner (confirmed by RIP-qPCR and MeRIP-qPCR), and controls UBE2G2 mRNA stability. Reduced UBE2G2 expression impairs ubiquitination of ACSL4, resulting in ACSL4 stabilization, lipid peroxidation, and ferroptosis. |
RIP-qPCR, MeRIP-qPCR, gene overexpression/knockdown, in vitro ubiquitination assay |
Ecotoxicology and environmental safety |
Medium |
41125048
|
| 2026 |
Inactive (catalytically dead) UBE2G2 induces cell elongation independent of matrix properties, reduces actin stress fibers with dominant cortical ventral fibers aligned along the long axis, redistributes vinculin to ventral stress fibers, and impairs lamellipodia formation. Sequestration of wild-type UBE2G2 by AUP1 to the membrane fraction mimics the elongated phenotype, demonstrating that the cytosolic pool of UBE2G2 is responsible for regulating cell shape and motility. |
Inactive mutant expression, live-cell imaging, actin/vinculin immunostaining, wound healing assay, AUP1-mediated membrane sequestration |
FASEB journal |
Medium |
41989348
|