Ask about this productRelated genes to: UBE2A antibody
- Gene:
- UBE2A NIH gene
- Name:
- ubiquitin conjugating enzyme E2 A
- Previous symbol:
- -
- Synonyms:
- UBC2, HHR6A, RAD6A
- Chromosome:
- Xq24
- Locus Type:
- gene with protein product
- Date approved:
- 1992-12-02
- Date modifiied:
- 2016-03-14
Related products to: UBE2A antibody
Related articles to: UBE2A antibody
- Cells are continuously exposed to mechanical stimuli arising from the extracellular matrix, neighboring cells, and tissue architecture. Through mechanotransduction, these physical cues are converted into intracellular signaling events that regulate cellular behavior and fate. In our previous study, we showed that UBE2A/B localize predominantly in the cytosol when cells are cultured on soft substrates or at high density but translocate to the nucleus on stiff substrates or at low density. This mechanosensitive translocation promotes H2B monoubiquitination and regulates the expression of genes involved in cell growth. However, the mechanism underlying UBE2A/B nuclear localization remains unclear. In the present study, we used mutagenesis to identify regulatory post-translational modifications and define a putative nuclear localization signal (NLS) within UBE2A/B. The phospho-mimetic mutant S120D enhanced UBE2A nuclear localization, whereas substitution of three arginine residues within the predicted NLS (3RA) reduced nuclear localization under low-density conditions. Pharmacological inhibition of cyclin-dependent kinases (CDKs), which are known to phosphorylate S120, suppressed both exogenous and endogenous UBE2A/B nuclear localization and decreased H2B monoubiquitination. Using pull-down assays, we demonstrated that XPO4, a bidirectional nuclear transport receptor, interacts with S120D UBE2A/B but not with wild-type UBE2A/B. Structural modeling suggested that XPO4 interacts with the N-terminal basic helix and phosphorylated S120 residue of UBE2A/B, consistent with our mutational analyses. Moreover, the 3RA mutation abolished the enhanced nuclear localization conferred by S120D. Analysis of public RNA-seq data identified extensive mechanosensitive regulatory programs controlling CDK activity, which align with the nuclear translocation dynamics of UBE2A/B. Together, these findings demonstrate that UBE2A/B nuclear localization is governed by coordinated regulation of its N-terminal basic helix and S120 phosphorylation and identify XPO4 as a potential mediator of its nuclear import. - Source: PubMed
Publication date: 2026/09/16
Feng MingweiNakamura Fumihiko - Ubiquitin‑conjugating enzyme E2A (UBE2A), a member of the ubiquitin‑conjugating E2 enzyme family, has been implicated in tumor development; however, its role across human cancer types remains incompletely understood. The present study aimed to systematically characterize the expression pattern, prognostic importance and immune relevance of UBE2A in a pan‑cancer context. Public datasets, including The Cancer Genome Atlas, Gene Expression Omnibus and Genotype‑Tissue Expression, were integrated to evaluate UBE2A expression, clinical importance, molecular characteristics, immune associations and biological functions across cancer types. Single‑cell RNA sequencing data were analyzed to investigate the cellular distribution of UBE2A. Functional validation was performed through UBE2A knockdown in breast cancer cell lines. Results indicated that UBE2A was significantly upregulated in a number of cancer types and was associated with unfavorable overall and progression‑free survival. UBE2A expression exhibited significant correlations with immune cell infiltration and immune checkpoint‑associated genes across cancer types. Functional enrichment analyses indicated that UBE2A was primarily involved in cell cycle regulation and proliferative processes. Single‑cell analysis revealed preferential UBE2A expression in proliferative T‑cell populations. Furthermore, experiments demonstrated that UBE2A knockdown significantly suppressed breast cancer cell proliferation, migration and invasion. Overall, UBE2A was shown to be a promising prognostic biomarker associated with tumor progression, cell cycle activity and immune‑associated characteristics across cancer types. Its preferential expression in proliferative T‑cell populations and oncogenic role in breast cancer suggest that UBE2A may serve as a potential therapeutic target and a candidate biomarker for evaluating tumor prognosis and the tumor immune microenvironment. - Source: PubMed
Publication date: 2026/07/24
Wen YunLuo Pengfei - Protein ubiquitination regulates diverse cellular processes, and its dysregulation contributes to human disease, including cancer. E2 ubiquitin-conjugating enzymes share a conserved UBC fold in which surface loops fine-tune catalysis and partner interactions, yet the roles of individual loops remain incompletely defined. Here, we identify loop 3-a component of the "backside" β2-β3 hairpin-as a conserved structural and allosteric element in Rad6-family E2s. Structural and bioinformatic analyses of yeast Rad6 and its human homologs (UBE2A/UBE2B) reveal that loop 3 forms an overlapping triple β-turns, with variable first turn and a highly conserved second/third turn that links catalytic regulation to E3 ligase engagement. Systematic mutagenesis of the yeast Rad6 backside β-turn (residues 42-51) shows that this element is required in vivo for Bre1-dependent histone H2B Lys123 monoubiquitination, Rad18-dependent PCNA monoubiquitination, and Ubr1/Ubr2-dependent polyubiquitination and degradation of Sml1 and N-end rule substrates, and related biological processes. Charge-reversal mutations at backside β-turn Glu49 and Asp50 disrupt E3 binding, whereas cancer-relevant substitutions in kink-inducing prolines (Pro43/Pro47) impair mono- and polyubiquitination without abolishing E3 interactions. Certain backside β-turn mutations, including cancer-relevant variants, compromise steady-state levels following DNA damage, revealing them as conditional null or loss-of-function alleles. Nuclear magnetic resonance spectroscopy demonstrates that Pro43/Pro47 mutations induce long-range structural perturbations from backside β-turn into the front-face catalytic pocket, correlating with reduced in vitro ubiquitination activity. Deletion or alanine replacement of the β-turn destabilizes yeast Rad6 and human UBE2A/UBE2B. Together, these findings establish the loop 3/backside β-turn as a critical structural element of Rad6-family enzymes. - Source: PubMed
Shukla Prakash KLeng Andrew MChen Hui-HsuanGanguly RajarshiNewell NicholasChandrasekharan Mahesh B - Aluminum, a ubiquitous environmental neurotoxin, has been implicated in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD). While Aβ deposition is a hallmark of AD progression, the molecular mechanisms underlying aluminum-induced Aβ aggregation remain incompletely understood. This study examines the role of the ciRs-7-miR-7-UBE2A axis in aluminum-induced Aβ deposition. Healthy male SD rats and PC12 cells were stratified into groups based on aluminum maltolate exposure levels to establish an in vivo and in vitro neurotoxicity model. Hippocampal aluminum content, along with the expression levels of ciRs-7, miR-7, UBE2A, and Aβ1-42, were systematically analyzed. The results demonstrated a dose-dependent decrease in ciRs-7 and UBE2A expression with escalating aluminum exposure, accompanied by concurrent upregulation of miR-7 and Aβ1-42 accumulation. Conversely, ciRs-7 overexpression reversed these pathological trends. Mechanistically, aluminum exposure downregulates ciRs-7 in the hippocampus, thereby derepressing miR-7 activity, which suppresses UBE2A expression and ultimately promotes Aβ deposition. These results identify a novel circRNA-dependent mechanism in aluminum neurotoxicity, suggesting therapeutic targets for AD intervention. - Source: PubMed
Publication date: 2025/11/06
Zhang LeiMa YonghaoFang HailunGong YujuanLi ChenyangMeng HuaxingSong JingLu XiaotingZhang HuifangNiu QiaoWang Linping - Endometrial polyps are common, localized overgrowths of endometrial glands and stroma that protrude into the uterine cavity. These tumor-like lesions can cause symptoms like abnormal uterine bleeding and infertility, and they may undergo malignant transformation. The etiology of endometrial polyps remains largely unknown. - Source: PubMed
Publication date: 2025/10/24
Reinikka SiiriMehine Miikavon Nandelstadh PernillaAhvenainen TerhiKhamaiseh SaraNousiainen SusannaJokinen ViljaPasanen AnnukkaBützow RalfSarvilinna NannaPitkänen EsaVahteristo Pia