Mouse,Mus musculus,Oncogenic protein-associated protein E6-AP,Ube3a,Ubiquitin-protein ligase E3A
- Known as:
- Mouse,Mus musculus,Oncogenic protein-associated protein E6-AP,Ube3a,Ubiquitin-protein ligase E3A
- Catalog number:
- EIAAB44916
- Category:
- -
- Supplier:
- EIAab
- Gene target:
- Mouse Mus musculus Oncogenic protein-associated protein E6- Ube3a Ubiquitin-protein ligase E3A
Related genes to: Mouse,Mus musculus,Oncogenic protein-associated protein E6-AP,Ube3a,Ubiquitin-protein ligase E3A
- Gene:
- UBE3A NIH gene
- Name:
- ubiquitin protein ligase E3A
- Previous symbol:
- EPVE6AP, HPVE6A
- Synonyms:
- AS, ANCR, E6-AP, FLJ26981
- Chromosome:
- 15q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1993-10-21
- Date modifiied:
- 2019-04-23
Related products to: Mouse,Mus musculus,Oncogenic protein-associated protein E6-AP,Ube3a,Ubiquitin-protein ligase E3A
Related articles to: Mouse,Mus musculus,Oncogenic protein-associated protein E6-AP,Ube3a,Ubiquitin-protein ligase E3A
- Down syndrome (DS) is the most common form of inherited intellectual disability caused by trisomy of chromosome 21, presenting with intellectual impairment, craniofacial abnormalities, cardiac defects, and gastrointestinal disorders. The Ts65Dn mouse model replicates many abnormalities of DS. We hypothesized that investigation of the cerebral cortex of fluoxetine-treated trisomic mice may provide proteomic signatures that identify therapeutic targets for DS. Subcellular fractionation of synaptosomes from cerebral cortices of age- and brain-area-matched samples from fluoxetine-treated vs. water-treated trisomic and euploid male mice were subjected to HPLC-tandem mass spectrometry. Analysis of the data revealed enrichment of trisomic risk genes that participate in regulation of synaptic vesicular traffic, pre-synaptic and post-synaptic development, and mitochondrial energy pathways during early brain development. Proteomic analysis of trisomic synaptic fractions revealed significant downregulation of proteins involved in synaptic vesicular traffic, including vesicular endocytosis (CLTA, CLTB, CLTC), synaptic assembly and maturation (EXOC1, EXOC3, EXOC8), anterograde axonal transport (EXOC1), neurotransmitter transport to PSD (SACM1L), endosomal-lysosomal acidification (ROGDI, DMXL2), and synaptic signaling (NRXN1, HIP1, ITSN1, YWHAG). Additionally, trisomic proteomes revealed upregulation of several trafficking proteins, involved in vesicular exocytosis (Rab5B), synapse elimination (UBE3A), scission of endocytosis (DBN1), transport of ER in dendritic spines (MYO5A), presynaptic activity-dependent bulk endocytosis (FMR1), and NMDA receptor activity (GRIN2A). Chronic fluoxetine treatment of Ts65Dn mice rescued synaptic vesicular abnormalities and prevented abnormal proteomic changes in adult Ts65Dn mice, pointing to therapeutic targets for potential treatment of DS. - Source: PubMed
Publication date: 2024/04/03
Fatemi S HosseinOtte Elysabeth DFolsom Timothy DEschenlauer Arthur CRoper Randall JAman Justin WThuras Paul D - E6AP dysfunction is associated with Angelman syndrome and Autism spectrum disorder. Additionally, the host E6AP is hijacked by the high-risk HPV E6 to aberrantly ubiquitinate the tumor suppressor p53, which is linked with development of multiple types of cancer, including most cervical cancers. Here we show that E6AP and the E6AP/E6 complex exist, respectively, as a monomer and a dimer of the E6AP/E6 protomer. The short α1-helix of E6AP transforms into a longer helical structure when in complex with E6. The extended α1-helices of the dimer intersect symmetrically and contribute to the dimerization. The two protomers sway around the crossed region of the two α1-helices to promote the attachment and detachment of substrates to the catalytic C-lobe of E6AP, thus facilitating ubiquitin transfer. These findings, complemented by mutagenesis analysis, suggest that the α1-helix, through conformational transformations, controls the transition between the inactive monomer and the active dimer of E6AP. - Source: PubMed
Publication date: 2024/04/26
Wang ZhenFan FengyingLi ZhihaiYe FeiWang QingxiaGao RongchaoQiu JiaxuanLv YixinLin MinXu WenwenLuo ChengYu Xuekui - The 15q11-q13 region is a genetic locus with genes subject to genomic imprinting, significantly influencing neurodevelopment. Genomic imprinting is an epigenetic phenomenon that causes differential gene expression based on the parent of origin. In most diploid organisms, gene expression typically involves an equal contribution from both maternal and paternal alleles, shaping the phenotype. Nevertheless, in mammals, including humans, mice, and marsupials, the functional equivalence of parental alleles is not universally maintained. Notably, during male and female gametogenesis, parental alleles may undergo differential marking or imprinting, thereby modifying gene expression without altering the underlying DNA sequence. Neurodevelopmental disorders, such as Prader-Willi syndrome (PWS) (resulting from the absence of paternally expressed genes in this region), Angelman syndrome (AS) (associated with the absence of the maternally expressed UBE3A gene), and 15q11-q13 duplication syndrome (resulting from the two common forms of duplications-either an extra isodicentric 15 chromosome or an interstitial 15 duplication), are the outcomes of genetic variations in this imprinting region. - Source: PubMed
Mim Rabeya AkterSoorajkumar AnjanaKosaji NoorRahman Muhammad MizanurSarker ShaoliKaruvantevida NoushadEshaque Tamannyat BinteRahaman Md AtikurIslam AmirulChowdhury Mohammod Shah JahanShams NusratUddin K M FurkanAkter HosnearaUddin Mohammed - Human cell line models, including the neuronal precursor line LUHMES, are important for investigating developmental transcriptional dynamics within imprinted regions, particularly the 15q11-q13 Angelman (AS) and Prader-Willi (PWS) syndrome locus. AS results from loss of maternal UBE3A in neurons, where the paternal allele is silenced by a convergent antisense transcript UBE3A-ATS, a lncRNA that normally terminates at PWAR1 in non-neurons. qRTPCR analysis confirmed the exclusive and progressive increase in UBE3A-ATS in differentiating LUHMES neurons, validating their use for studying UBE3A silencing. Genome-wide transcriptome analyses revealed changes to 11,834 genes during neuronal differentiation, including the upregulation of most genes within the 15q11-q13 locus. To identify dynamic changes in chromatin loops linked to transcriptional activity, we performed a HiChIP validated by 4C, which identified two neuron-specific CTCF loops between MAGEL2-SNRPN and PWAR1-UBE3A. To determine if allele-specific differentially methylated regions (DMR) may be associated with CTCF loop anchors, whole genome long-read nanopore sequencing was performed. We identified a paternally hypomethylated DMR near the SNRPN upstream loop anchor exclusive to neurons and a paternally hypermethylated DMR near the PWAR1 CTCF anchor exclusive to undifferentiated cells, consistent with increases in neuronal transcription. Additionally, DMRs near CTCF loop anchors were observed in both cell types, indicative of allele-specific differences in chromatin loops regulating imprinted transcription. These results provide an integrated view of the 15q11-q13 epigenetic landscape during LUHMES neuronal differentiation, underscoring the complex interplay of transcription, chromatin looping, and DNA methylation. They also provide insights for future therapeutic approaches for AS and PWS. - Source: PubMed
Publication date: 2024/03/29
Fugon Orangel J GutierrezSharifi OsmanHeath Nicholas GSoto Daniela CGomez J AntonioYasui Dag HMendiola Aron Judd PO'Geen HenrietteBeitnere UlrikaTomkova MarketaHaghani ViktoriaDillon GregSegal David JLaSalle Janine - Angelman syndrome (AS) is a neurodevelopmental disorder caused by abnormal expression of the maternal ubiquitin protein ligase E3A gene (UBE3A). As one of the most challenging symptoms and important focuses of new treatment, sleep disturbance is reported to occur in 70-80% of patients with AS and has a serious impact on the lives of patients and their families. Although clinical studies and animal model studies have provided some clues, recent research into sleep disorders in the context of AS is still very limited. It is generally accepted that there is an interaction between neurodevelopment and sleep; however, there is no recognized mechanism for sleep disorders in AS patients. Accordingly, there are no aetiologically specific clinical treatments for AS-related sleep disorders. The most common approaches involve ameliorating symptoms through methods such as behavioural therapy and symptomatic pharmacotherapy. In recent years, preclinical and clinical studies on the targeted treatment of AS have emerged. Although precision therapy for restoring the UBE3A level and the function of its signalling pathways is inevitably hindered by many remaining obstacles, this approach has the potential to address AS-related sleep disturbance. - Source: PubMed
Publication date: 2024/04/05
Qu SongWang JunyiGuan XingyingSong CuiWang Yanyan