| 2005 |
Uev1A (UBE2V1) and Mms2 differentially modulate the length of Ubc13-mediated Lys63-linked polyubiquitin chains; Ubc13-Uev1A is specifically required for NF-κB activation but not DNA damage repair, whereas Ubc13-Mms2 is required for DNA damage repair but not NF-κB activation, demonstrating that different Uev partners direct Ubc13 to distinct cellular processes through physical interaction. |
In vitro polyubiquitination assays, functional complementation, RNA interference knockdown, NF-κB reporter assays, DNA damage survival assays |
The Journal of cell biology |
High |
16129784
|
| 2003 |
TNF-induced activation of GCKR and the SAPK/JNK pathway requires the E2 complex Ubc13/Uev1A and the E3 TRAF2; TNF signaling leads to TRAF2 polyubiquitination and oligomerization and to GCKR ubiquitination and activation, all sensitive to disruption of Ubc13 function. |
Dominant-negative interference with Ubc13, siRNA knockdown of Ubc13, immunoprecipitation, kinase activity assays, co-immunoprecipitation of TRAF2 and GCKR |
The Journal of biological chemistry |
High |
12591926
|
| 2007 |
In an in vitro reconstituted system, UEV1A presents Lys63 of ubiquitin to suppress direct substrate modification while enabling Lys63-linked ubiquitin chain synthesis; protein modification with K63-linked chains occurs through a UEV1A-independent substrate modification step and a UEV1A-dependent chain-elongation mechanism. |
In vitro ubiquitination reconstitution assay with UBC13-UEV1A and TRAF6 |
The Journal of biological chemistry |
High |
17709375
|
| 2006 |
NMR structure of hUev1a determined; hUev1a interacts with ubiquitin and hUbc13; a structural model of the Ub-hUev1a-hUbc13-Ub tetramer proposes that a hydrogen-bond network involving hUbc13-Asp81 and Ub-Glu64 positions Ub-Lys63 proximal to the active site for K63-linked chain synthesis. |
NMR spectroscopy, structural modeling, restrained molecular dynamics simulations |
Biochemistry |
High |
16893187
|
| 1998 |
UEV-1 (UBE2V1/CROC-1) proteins lack the catalytic cysteine of E2 enzymes and are catalytically inactive in vitro (cannot conjugate or transfer ubiquitin to substrates); constitutive expression of UEV in HT-29-M6 cells inhibited differentiation upon confluence, caused G2-M accumulation, and inhibited the mitotic kinase Cdk1. |
In vitro ubiquitin conjugation/transfer assay, sequence analysis, cell cycle analysis by flow cytometry, constitutive overexpression in HT-29-M6 cells |
Molecular and cellular biology |
High |
9418904
|
| 2012 |
The small-molecule NSC697923 inhibits the Ubc13-Uev1A E2 complex by blocking formation of the Ubc13-ubiquitin thioester conjugate, thereby suppressing constitutive NF-κB activity and inhibiting proliferation and survival of DLBCL cells; Ubc13 knockdown similarly inhibited DLBCL cell survival. |
Small-molecule inhibitor screen, thioester conjugate formation assay, NF-κB reporter assay, siRNA knockdown, cell proliferation/survival assays |
Blood |
High |
22791293
|
| 2018 |
Ube2v1 promotes Ubc13-mediated ubiquitination and proteasomal degradation of Sirt1, leading to inhibition of histone H4 lysine 16 acetylation and epigenetic suppression of autophagy gene expression, which promotes EMT and metastasis in colorectal cancer. |
Quantitative mass spectrometry, immunoprecipitation, ubiquitination assay, Western blotting, immunofluorescence, in vivo xenograft model |
Journal of hematology & oncology |
Medium |
30016968
|
| 2014 |
Uev1A-Ubc13 complex promotes breast cancer cell invasion and metastasis through NF-κB activation and upregulation of MMP1; this process requires functional Ubc13 (physical interaction with Uev1A is necessary), and depletion of UEV1 reduces MMP1 expression and prevents tumor formation/metastasis in xenograft mice. |
Overexpression and siRNA knockdown in MDA-MB-231 cells, NF-κB reporter assay, invasion/migration assays, xenograft mouse model, MMP1 rescue experiment |
Breast cancer research : BCR |
Medium |
25022892
|
| 2017 |
Uev1A-Ubc13 complex interacts with RHBDF2 and, upon TNFα stimulation cooperates with the E3 CHIP to promote K63-linked ubiquitination of RHBDF2, enhancing TACE maturation and subsequent shedding of the TNFα receptor to attenuate NF-κB signaling. |
Co-immunoprecipitation, K63-linked ubiquitination assay, TACE maturation assay, UEV1A overexpression and inhibition experiments |
Cellular signalling |
Medium |
29069608
|
| 2017 |
Uev1A promotes osteosarcoma differentiation by collaborating with the E3 ligase Smurf1 to promote ubiquitination and degradation of Smad1 (a BMP signaling effector), and this process occurs in a Ubc13-independent manner. |
Co-immunoprecipitation, ubiquitination assay, Western blotting, UEV1A overexpression and knockdown, Smad1 as downstream effector readout |
Cell death & disease |
Medium |
28771228
|
| 2020 |
Ube2v1 positively regulates K63-linked ubiquitination to promote protein aggregate formation in cardiomyocytes; Ube2v1 knockdown improves ubiquitin proteasome system performance and promotes degradation of insoluble ubiquitinated proteins without altering autophagic flux; cardiomyocyte-specific Ube2v1 knockout alleviates CryABR120G-induced protein aggregation, improves cardiac function, and prolongs lifespan in vivo. |
Adenoviral overexpression/knockdown in neonatal rat ventricular cardiomyocytes, UPS reporter assay, AAV9-CRISPR cardiomyocyte-specific knockout in mice, echocardiography, autophagic flux assay |
Circulation research |
High |
32081062
|
| 2020 |
The N-terminal extension of Uev1A (absent in Mms2) stimulates polyubiquitin chain assembly, weakens the Uev-Ubc13 interaction affinity, and is specifically required for NF-κB activation; a chimeric protein with the Uev1A N-terminus fused to Mms2 functionally resembles Uev1A, whereas truncated Uev1A lacking the N-terminal extension behaves like Mms2. |
In vitro polyubiquitination assay, thermodynamic binding measurements (ITC or equivalent), chimeric and truncation mutant functional assays, NF-κB reporter assay |
Cellular signalling |
High |
32659264
|
| 2006 |
Constitutive high-level expression of UEV1A alone in human cells is sufficient to increase NF-κB activity, upregulate the anti-apoptotic protein Bcl-2, confer prolonged cell survival under serum deprivation, and protect against apoptosis from diverse stressing agents; all effects are reversible upon RNAi-mediated suppression of UEV1. |
Stable overexpression of UEV1A, NF-κB luciferase reporter assay, Western blotting, RNAi knockdown, cell survival/apoptosis assays |
Apoptosis : an international journal on programmed cell death |
Medium |
17041755
|
| 2018 |
Uev1A-Ubc13 promotes colorectal cancer metastasis through NF-κB activation and upregulation of CXCL1; UEV1A overexpression depends on its physical interaction with Ubc13 to promote invasion, and depletion of UEV1 reduces CXCL1 expression and prevents tumor growth in a xenograft model. |
Overexpression and siRNA knockdown in HCT116 cells, NF-κB reporter, invasion assay, xenograft mouse model, IHC of human samples |
Oncotarget |
Medium |
29662619
|
| 2019 |
UEV1A promotes breast cancer cell survival under serum starvation and chemoresistance through activation of the AKT signaling pathway that in turn inhibits FOXO1 and BIM expression; depletion of UEV1 inhibits AKT signaling and promotes FOXO1/BIM expression, reducing cell survival and enhancing chemosensitivity. |
Overexpression and siRNA knockdown of UEV1A in MDA-MB-231 and MCF7 cells, Western blotting for AKT/FOXO1/BIM, cell viability and chemosensitivity assays |
Cancer cell international |
Medium |
31827405
|
| 2010 |
C. elegans UEV-1 (ortholog of UBE2V1) regulates trafficking of the AMPA-type glutamate receptor GLR-1; loss of uev-1 causes GLR-1 accumulation in RAB-10-containing endosomes in neuron cell bodies and along neurites, independent of clathrin-mediated endocytosis; ubc-13 mutants phenocopy uev-1 mutants, and UEV-1 can physically interact with C. elegans UBC-13. |
Forward genetic screen in C. elegans, fluorescence imaging of GLR-1::GFP, behavioral reversal assay, genetic epistasis with ubc-13, co-immunoprecipitation of UEV-1 and UBC-13, K63-ubiquitin immunostaining |
PloS one |
Medium |
21179194
|
| 2021 |
UEV1A overexpression induces CT45A family gene expression in breast cancer cells and promotes cell migration and EMT signaling through the AKT pathway (independently of NF-κB); depletion of CT45A abolishes these effects, identifying CT45A as a critical downstream effector of Uev1A in AKT-dependent migration. |
UEV1A and CT45A overexpression/knockdown in breast cancer cells, gene expression profiling, cell migration assay, Western blotting for AKT and NF-κB pathway components |
BMC cancer |
Medium |
34503444
|
| 2020 |
Drosophila Uev1a forms a stable heterodimer with Bendless (Drosophila Ubc13 ortholog); Uev1a-F15E mutation abolishes this interaction, and Uev1a-F15Y severely reduces it; dUev1a functionally rescues yeast mms2 null mutants in a Bendless-dependent manner, and heterozygous dUev1a mutant flies show increased sensitivity to DNA-damaging agents and reduced mobility consistent with neurological defects. |
Co-immunoprecipitation, site-directed mutagenesis (F15E, F15Y), yeast functional complementation, DNA damage sensitivity assay, Drosophila mutant behavioral analysis |
Cellular signalling |
Medium |
32702441
|
| 2025 |
UBE2V1 competes with HIF-1α for binding to the β-domain of VHL protein and, in complex with UBE2S, catalyzes K11/K48-linked ubiquitination of VHL at K196, leading to VHL proteasomal degradation, reduced HIF-1α ubiquitination, and sustained HIF-1α stabilization, creating a positive feedback loop in hepatocellular carcinoma. |
Co-immunoprecipitation, ubiquitination assay (K11/K48-specific), UBE2V1 overexpression/knockdown, HIF-1α reporter assay, VHL degradation assay, in vivo xenograft |
Research (Washington, D.C.) |
Medium |
41446875
|
| 1998 |
Human UEV-1A cDNA fully complements the UV and MMS sensitivity of a yeast YGL087c deletion mutant, demonstrating functional conservation of UEV proteins in DNA damage tolerance across species. |
Yeast deletion mutant complementation assay, DNA damage sensitivity assay (UV and MMS) |
FEBS letters |
Medium |
9580084
|
| 1998 |
Human UEV (CROC-1/hMMS2) genes complement yeast mms2 defects in DNA damage sensitivity and spontaneous mutagenesis, and both MMS2 and hMMS2 transactivate a c-fos-CAT reporter gene in mammalian cells, demonstrating functional conservation across species in both DNA repair and transcriptional activation. |
Yeast mms2 mutant complementation assay, transient co-transfection with c-fos-CAT reporter in Rat-1 cells |
Nucleic acids research |
Medium |
9705497
|
| 2025 |
UBE2V1 positively regulates ubiquitinated protein aggregate formation in mouse oocytes; UBE2V1 expression increases with maternal aging and correlates with aggresome formation; restoring UBE2V1 expression in aged oocytes/embryos alleviates aggresome formation and partly ameliorates age-related defects in oocyte maturation and embryo development. |
Mouse model of advanced maternal age, UBE2V1 overexpression/knockdown in oocytes, immunofluorescence for ubiquitinated aggregates/aggresomes, oocyte maturation and embryo development assessment |
Communications biology |
Medium |
40394227
|
| 2025 |
Uev1A collaborates with the E3 APC/C complex to mediate proteasomal degradation of Cyclin A in Drosophila, representing a non-canonical (proteolytic) function; this protects polyploid nurse cells from oncogenic Ras-induced aberrant division stress; human UBE2V1 and UBE2V2 similarly counteract oncogenic Ras-driven tumorigenesis in vivo. |
Genome-wide genetic screen in Drosophila, genetic epistasis, Cyclin A degradation assay, xenograft tumor model in nude mice with human UBE2V1/UBE2V2 overexpression |
eLife |
Medium |
41879050
|