UBA6 Antibody
Description
Introduction to UBA6 and Its Antibody
UBA6 (UniProt ID: A0AVT1) is an E1 ubiquitin-activating enzyme that initiates ubiquitination by transferring ubiquitin or ubiquitin-like proteins (e.g., FAT10) to downstream targets, marking them for proteasomal degradation . Unlike other E1 enzymes, UBA6 operates independently and is highly expressed in vertebrates, particularly in the testis and brain . The UBA6 antibody enables detection and functional analysis of this enzyme in experimental settings, aiding studies on its roles in cancer, neurodegeneration, and immune regulation.
Mechanistic Insights
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Ubiquitination and Autophagy: UBA6 partners with BIRC6 to monoubiquitinate LC3B, a key autophagy protein, targeting it for proteasomal degradation. Knockout studies show increased autophagic flux and reduced protein aggregates in neuronal cells .
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Immune Regulation: UBA6 suppresses IFN-γ production in T cells by stabilizing IκBα, thereby inhibiting NF-κB activation. UBA6-deficient T cells exacerbate multi-organ inflammation in murine models .
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Cancer Biology: UBA6 depletion enhances tumor immunogenicity, improving responses to immune checkpoint blockade (ICB) in melanoma and breast cancer models. Low UBA6 levels correlate with favorable ICB outcomes in humans .
Disease Associations
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Neurodegeneration: UBA6/BIRC6 inhibition reduces α-synuclein aggregates in neurons, suggesting therapeutic potential for Parkinson’s disease .
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Autoimmunity: Lupus patients exhibit reduced UBA6 levels in T cells, inversely correlating with IFN-γ production .
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Breast Cancer: UBA6 knockdown disrupts mammary acinar morphogenesis, promoting tumor-like cell aggregation .
Applications of UBA6 Antibodies in Research
UBA6 antibodies are widely used in:
Clinical and Therapeutic Implications
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Cancer Immunotherapy: Targeting UBA6 could enhance ICB efficacy by increasing tumor immunogenicity .
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Neurodegenerative Therapies: Inhibiting UBA6/BIRC6 may boost autophagy to clear pathogenic protein aggregates .
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Autoimmune Disease: Modulating UBA6 in T cells could mitigate IFN-γ-driven inflammation in lupus .
Validation and Considerations
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Specificity: Antibodies like 13211-1-AP recognize full-length UBA6 and a truncated isoform (60–70 kDa) .
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Functional Rescue: Overexpression of UBA6 cDNA reverses phenotypic effects of shRNA knockdown, confirming antibody specificity .
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Limitations: Overexpression systems (e.g., CMV-driven LC3B) may mask UBA6-dependent effects, necessitating endogenous protein studies .
Product Specs
Target Background
- Polyubiquitination and proteasomal degradation of ezrin and CUGBP1 rely on Uba6, but not Uba1. This suggests that Uba6 is involved in the control of ezrin localization and epithelial morphogenesis. These findings indicate distinct substrate pools for Uba1 and Uba6, reflecting non-redundant biological roles for Uba6. PMID: 28134249
- Research has unveiled a novel function of LMO2 within the regulatory hierarchy of the UBA6-USE1-FAT10ylation pathway by targeting the E1 enzyme UBA6. PMID: 27569286
- Interstitial microdeletions encompassing the chromosome band 4q13.2 and the UBA6 gene are considered potential causes of intellectual disability and behavior disorder. PMID: 26284580
- The diminished ubiquitylation phenotype observed in enteropathogenic Escherichia coli infected cells corresponds to a significant reduction in the abundance of both Ube1 and Uba6. PMID: 22999844
- Data suggest a potential role for cytokine-induced FAT10 expression in regulating Uba6 pathways. PMID: 22427669
- UBE1L2 is identified as a novel E1 enzyme with specificity for ubiquitin. PMID: 17580310
- Human Uba6 and Ube1 exhibit distinct preferences for E2 charging in vitro. This specificity partially relies on their C-terminal ubiquitin-fold domains, which recruit E2s. PMID: 17597759
- The discovery of an E1-like protein, termed E1-L2, which activates both ubiquitin and another ubiquitin-like protein, FAT10, has been reported. PMID: 17889673
- Ubiquitin-like modifier activating enzyme 6 activates not only ubiquitin but also the ubiquitin-like modifier FAT10. PMID: 18353650
