| 1997 |
Ubc6p (yeast ortholog of UBE2J2) is a membrane-bound ER ubiquitin-conjugating enzyme that works together with Cue1p-assembled Ubc7p to ubiquitinate ERAD substrates; ubiquitination by this pair is a prerequisite for retrograde transport of lumenal substrates out of the ER. |
Genetic (deletion mutants), biochemical fractionation, ERAD substrate degradation assays in yeast |
Science |
High |
9388185
|
| 2000 |
Ubc6p/Ubc7p ubiquitin-conjugating enzyme pair recognizes cytosolic degradation signals containing a patch of bulky hydrophobic residues and positively charged residues; ubiquitination of these substrates occurs on the cytosolic face of the ER without prior transfer to the ER lumen, independently of Hrd1p/Der3p and Sec61p retrograde transport. |
Genetic analysis with deletion mutants (hrd1/der3Δ, sec61-2), fusion protein degradation assays, mutational analysis of degron sequences in yeast |
Molecular and cellular biology |
High |
10982838
|
| 2001 |
The tail-anchored ER membrane protein Ubc6p undergoes self-ubiquitination-dependent degradation that requires its own catalytic site cysteine and Cue1p-assembled Ubc7p, but is independent of Ubc1p, Hrd1p/Der3p, Hrd3p, Der1p, and the Sec61p translocon; a membrane-bound degradation intermediate accumulates in proteasome mutants. |
Genetic deletion mutants, sec61 mutants, pulse-chase degradation assays, proteasome mutant analysis in yeast |
The EMBO journal |
High |
11406589
|
| 2001 |
Murine UBE2J2 (MmUbc6) is an integral membrane protein anchored via its hydrophobic C-terminal tail to the endoplasmic reticulum; overexpression of catalytically inactive MmUbc7 (not MmUbc6 dominant-negative) significantly delayed ERAD of T cell receptor alpha and CD3-delta subunits, implicating these ER-localized E2s in mammalian ERAD. |
Immunofluorescence colocalization, dominant-negative overexpression, pulse-chase degradation assays in mammalian cells |
The Journal of biological chemistry |
Medium |
11278356
|
| 2002 |
Two families of mammalian Ubc6p-related proteins (including UBE2J2/NCUBE2) are localized to the ER membrane with the same cytoplasmic-face topology as yeast Ubc6p; expression of wild-type and dominant-negative alleles specifically affects ERAD of TCR-alpha and mutant CFTR, and elevated Ubc6p levels in yeast also affect ERAD, indicating highly conserved function. |
Subcellular fractionation, topology assays, dominant-negative overexpression, ERAD substrate degradation assays in mammalian cells and yeast |
Journal of cell science |
High |
12082160
|
| 2006 |
Human UBE2J2 (hsUbc6) possesses tail-anchored protein motifs, is localized to the ER, is a functional ubiquitin-conjugating enzyme as shown by in vitro thiol-ester assay, and its expression is induced by the unfolded protein response. |
In vitro ubiquitin thiol-ester assay, subcellular localization, UPR induction experiments |
The Journal of biological chemistry |
Medium |
16720581
|
| 2009 |
UBE2J2 is the primary cellular E2 recruited by the viral E3 ligase mK3 for ERAD; the UBE2J2-mK3 pair preferentially ubiquitinates hydroxylated amino acids (serine/threonine) on ERAD substrates via ester bonds even when lysine residues are present, establishing that noncanonical ubiquitination of hydroxylated residues is physiologically relevant. |
E2 identification by co-immunoprecipitation/pulldown, in vitro ubiquitination assay with lysine-less substrate mutants, mass spectrometry of ubiquitin linkages |
The Journal of cell biology |
High |
19951915
|
| 2014 |
UBE2J2 is essential for US11-mediated ERAD of HLA class I molecules; TMEM129 (an E3 ligase) together with UBE2J2 (as its cognate E2) is responsible for ubiquitination, dislocation, and degradation of US11-associated MHC-I via a Derlin-1-dependent ERAD complex. |
Genome-wide shRNA screen, CRISPR forward genetic screen in near-haploid cells, Co-IP, functional degradation assays |
Nature communications / PNAS |
High |
24807418 25030448
|
| 2014 |
UBE2J2 is itself an unstable protein subject to proteasomal degradation; proteasomal inhibitors increase its steady-state levels. This effect requires both catalytic activity and ER localization (disruption of either stabilizes the enzyme), suggesting auto-ubiquitination-linked turnover. |
Proteasome inhibitor treatment, catalytic mutants, truncation mutants, immunoblot in transfected mammalian cells |
Biochemical and biophysical research communications |
Medium |
25083800
|
| 2017 |
UBE2J2, in contrast to UBE2J1, is not essential for recovery from transient ER stress; Ube2j1 (not Ube2j2) is the E2 whose phosphorylation by MAPK signaling mediates ER stress recovery, and c-IAP1 preferentially interacts with phosphorylated Ube2j1. |
Ectopic expression of wild-type and phospho-mutant constructs, cell viability assays, Co-IP in mammalian cells |
Journal of cell communication and signaling |
Medium |
28321712
|
| 2017 |
UBE2J2 counteracts US2-induced ERAD by downregulating TRC8 (RNF139) E3 ligase expression; in contrast, UBE2G2 is the crucial E2 for US2-mediated HLA-I degradation, demonstrating distinct roles for different E2s in HCMV immune evasion. |
Lentiviral CRISPR/Cas9 library screening targeting all human E2 enzymes, functional degradation assays |
Journal of cell science |
Medium |
28743740
|
| 2018 |
UBE2J2 functions as the E2 ubiquitin-conjugating enzyme for the E3 ligase CGRRF1 to ubiquitinate the Wnt cargo receptor Evi/Wls for ERAD in the absence of Wnt ligands, thereby regulating Wnt protein secretion. |
RNAi knockdown, co-immunoprecipitation, ERAD substrate stability assays in mammalian cells |
The EMBO journal |
Medium |
29378775
|
| 2018 |
UBE2J2 is the primary E2 ubiquitin-conjugating enzyme essential for MARCH6-dependent cholesterol-stimulated degradation of squalene monooxygenase (SQLE), but not for sterol-dependent degradation of HMGCR (which requires UBE2G2), revealing substrate-specific E2 usage in ERAD. |
CRISPR/Cas9-based screen for ERAD E2 enzymes, catalytic mutant rescue, cholesterol-stimulated degradation assays in multiple human cell types |
Atherosclerosis |
High |
30658189
|
| 2019 |
US11 recruits Derlin-1, TMEM129, and UBE2J2 to engage FcRn, initiating dislocation of FcRn from the ER to the cytosol and its degradation, thereby inhibiting IgG-FcRn binding and IgG transport. |
Co-immunoprecipitation, ERAD substrate degradation assays, functional IgG transcytosis assays in mammalian cells |
Nature communications |
Medium |
31289263
|
| 2021 |
UBE2J2, together with UBE2K and UBE2N, mediates K11-, K48-, and K63-linked ubiquitylation of EVI/WLS, independently of E3 ligases HRD1 and GP78; ERLIN2 links EVI/WLS to the ubiquitylation machinery. |
RNAi screen, Co-IP, ubiquitin linkage analysis, E3 ligase independence assays in mammalian cells |
Journal of cell science |
Medium |
34406391
|
| 2023 |
Ube2j2 functions cooperatively with Ube2k as E2 ubiquitin-conjugating enzymes with the E3 ligase March5 at the mitochondria; depletion of Ube2j2 sensitizes AML cells to Venetoclax specifically in the presence of March5, and March5 controls Noxa levels to regulate Bax-Mcl1 interactions in the apoptosis pathway. |
Genome-wide CRISPR/Cas9 screens, genetic knockouts, CRISPR epistasis screens in mouse AML cells |
Leukemia |
Medium |
36973350
|
| 2024 |
X-ray crystallography and MD simulations of Ubc6/UBE2J2 revealed a two-layered mechanism for serine ubiquitination: (1) rearrangement of the active site enhances E2-Ub thioester reactivity toward weak nucleophiles; (2) a conserved histidine in Ubc6/UBE2J2 activates substrate serine via general base catalysis. RING-type E3 ligases further increase serine selectivity via an allosteric mechanism requiring specific positioning of the ubiquitin tail at the E2 active site. |
X-ray crystallography, molecular dynamics simulations, in vitro reconstitution ubiquitination assays, active-site mutagenesis |
The EMBO journal |
High |
39533056
|
| 2025 |
UBE2J2 acts as a membrane lipid sensor in ERAD: in loosely packed membranes, its transmembrane domain associates with membrane lipids in a way that impedes ubiquitin loading (rendering it inactive), while tighter lipid packing promotes an active conformation and interaction with E1. This activity directs ubiquitin transfer by multiple E3 ligases (RNF145, MARCHF6, RNF139) targeting themselves and the substrate squalene monooxygenase. |
In vitro reconstitution with purified ERAD factors, lipid-composition modulation of proteoliposomes, ubiquitination assays |
Nature communications |
High |
41068091
|
| 2025 |
UBE2J2 is essential for male meiosis in mice; Ube2j2 knockout male mice are azoospermic with spermatocytes arrested at mid-pachytene stage, exhibiting unstable homologous recombination intermediate complexes that fail to form crossovers, and loss of a broad set of meiosis- and chromosome segregation-associated proteins. |
Knockout mouse model, histology, immunofluorescence of HR markers (e.g., MLH1, RPA), proteomics of spermatocytes |
iScience |
Medium |
40686610
|