ArticleHuman molecular genetics2020
Conserved UBE3A subcellular distribution between human and mice is facilitated by non-homologous isoforms.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 26 citations in OpenAlex.
- UBE3A isoform-selective and non-selective contributions to Angelman syndrome phenotypes.Molecular psychiatry · 2026Article
- Article
- UBE3A promotes foam cell formation and counters remyelination by targeting ABCA1 for proteasomal degradation.Nature communications · 2025Article
- Localization of human UBE3A isoform 3 is highly sensitive to amino acid substitutions at p.Met21 position.Human molecular genetics · 2025Article
- A human Angelman Syndrome class II pluripotent stem cell line with fluorescent paternalFrontiers in cell and developmental biology · 2025Article
- Neuronal UBE3A substrates hold therapeutic potential for Angelman syndrome.Current opinion in neurobiology · 2024Review
- High-throughput assay exploiting disorder-to-order conformational switches: application to the proteasomal Rpn10:E6AP complex.Chemical science · 2024Article
- The Hippocampal Response to Acute Corticosterone Elevation Is Altered in a Mouse Model for Angelman Syndrome.International journal of molecular sciences · 2022Article
- Identification of Novel Genes for Cell Fusion during Osteoclast Formation.International journal of molecular sciences · 2022Article
- Dual-isoform hUBE3A gene transfer improves behavioral and seizure outcomes in Angelman syndrome model mice.JCI insight · 2021Article
- Secreted retrovirus-like GAG-domain-containing protein PEG10 is regulated by UBE3A and is involved in Angelman syndrome pathophysiology.Cell reports. Medicine · 2021Article
- UBE3A reinstatement as a disease-modifying therapy for Angelman syndrome.Developmental medicine and child neurology · 2021Review
- Loss of nuclear UBE3A activity is the predominant cause of Angelman syndrome in individuals carrying UBE3A missense mutations.Human molecular genetics · 2021Article
- Evaluation of UBE3A antibodies in mice and human cerebral organoids.Scientific reports · 2021Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
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Abstract
The human UBE3A gene, which is essential for normal neurodevelopment, encodes three Ubiquitin E3 ligase A (UBE3A) protein isoforms. However, the subcellular localization and relative abundance of these human UBE3A isoforms are unknown. We found, as previously reported in mice, that UBE3A is predominantly nuclear in human neurons. However, this conserved subcellular distribution is achieved by strikingly distinct cis-acting mechanisms. A single amino-acid deletion in the N-terminus of human hUBE3A-Iso3, which is homologous to cytosolic mouse mUBE3A-Iso2, results in its translocation to the nucleus. This singe amino-acid deletion is shared with apes and Old World monkeys and was preceded by the appearance of the cytosolic hUBE3A-Iso2 isoform. This hUBE3A-Iso2 isoform arose after the lineage of New World monkeys and Old World monkeys separated from the Tarsiers (Tarsiidae). Due to the loss of a single nucleotide in a non-coding exon, this exon became in frame with the remainder of the UBE3A protein. RNA-seq analysis of human brain samples showed that the human UBE3A isoforms arise by alternative splicing. Consistent with the predominant nuclear enrichment of UBE3A in human neurons, the two nuclear-localized isoforms, hUBE3A-Iso1 and -Iso3, are the most abundantly expressed isoforms of UBE3A, while hUBE3A-Iso2 maintains a small pool of cytosolic UBE3A. Our findings provide new insight into UBE3A localization and evolution and may have important implications for gene therapy approaches in Angelman syndrome.
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