Recombinant Mouse Ubiquitin-Protein Ligase E3A (UBE3A) Protein (His)

Name: Recombinant Mouse Ubiquitin-Protein Ligase E3A (UBE3A) Protein (His)
Brand: Beta LifeScience
SKU: BLC-09348P
Availability: InStock

Greater than 90% as determined by SDS-PAGE.

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Product Overview

Description	Recombinant Mouse Ubiquitin-Protein Ligase E3A (UBE3A) Protein (His) is produced by our E.coli expression system. This is a protein fragment.
Purity	Greater than 90% as determined by SDS-PAGE.
Uniprotkb	O08759
Target Symbol	UBE3A
Synonyms	Ube3a; Ubiquitin-protein ligase E3A; EC 2.3.2.26; HECT-type ubiquitin transferase E3A; Oncogenic protein-associated protein E6-AP
Species	Mus musculus (Mouse)
Expression System	E.coli
Tag	N-6His
Target Protein Sequence	NPADLKKQLYVEFEGEQGVDEGGVSKEFFQLVVEEIFNPDIGMFTYDEATKLFWFNPSSFETEGQFTLIGIVLGLAIYNNCILDVHFPMVVYRKLMGKKGTFRDLGDSHPVLYQSLKDLLEYEGSVEDDMMITFQISQTDLFGNPMMYDLKENGDKIPITNENRKEFVNLYSDYILNKSVEKQFKAFRRGFHMVTNESPLKYLFRPEEIELLICGSRNLDFQALEETTEYDGGYTRESVVIREFWEIVHSFTDEQKRLFLQFTTGTDRAPVGGLGKLKMIIAKNGPDTERLPTSHTCFNVLLLPEYSSKEKLKERLLKAITYAKGFGML
Expression Range	542-870aa
Protein Length	Partial
Mol. Weight	41.9kDa
Research Area	Epigenetics And Nuclear Signaling
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target Function	E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates. Several substrates have been identified including the ARNTL/BMAL1, ARC, RAD23A and RAD23B, MCM7 (which is involved in DNA replication), annexin A1, the PML tumor suppressor, and the cell cycle regulator CDKN1B. Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins. Finally, UBE3A also promotes its own degradation in vivo. Plays an important role in the regulation of the circadian clock: involved in the ubiquitination of the core clock component ARNTL/BMAL1, leading to its proteasomal degradation. Acts as a regulator of synaptic development by mediating ubiquitination and degradation of ARC. Synergizes with WBP2 in enhancing PGR activity.
Subcellular Location	Cytoplasm. Nucleus.
Database References	KEGG: mmu:22215 STRING: 10090.ENSMUSP00000103161 UniGene: PMID: 27306933 Using in vivo patch-clamp electrophysiology, study measured the visually evoked responses to square-wave drifting gratings in L2/3 regular-spiking (RS) neurons in control mice, Ube3a-deficient mice (Angelman syndrome model), and mice in which Ube3a was conditionally reinstated in GABAergic neurons; found that Ube3a-deficient mice exhibited enhanced pyramidal neuron excitability in vivo as well as weaker orientation tuning PMID: 28468997 Findings show neuronal overexpression of Ube3a isoform 2 causes phenotypes translatable to neurodevelopmental disorders. PMID: 29016856 Findings suggest that aberrant function of Ube3a could influence the progression of AD and restoring normal level of Ube3a might be beneficial for AD. PMID: 29016862 Encephalomyocarditis virus (EMCV) 3C protease accumulates to higher levels in EMCV-infected E6AP knockdown cells than in control cells, indicating a role for E6AP in in vivo 3C protease concentration regulation. PMID: 29054411 The expression of three tumor suppressor genes encoded in the INK4/ARF locus (p15(INK4b), p16(INK4a), and p19(ARF)) was decreased in E6AP(-/-) embryo fibroblasts. PMID: 28074012 Maternal loss of Ube3a affects nociception via a central, but not peripheral mechanism. PMID: 28931574 Our findings suggest that UBE3A may act locally to regulate individual synapses while also mediating global, neuronwide influences through the regulation of gene transcription PMID: 27339004 We report that mice with maternally-inherited deletions of Ube3a that models Angelman syndrome show an increased social preference/interaction. PMID: 28411125 increasing UBE3A in the nucleus downregulates the glutamatergic synapse organizer Cbln1, which is needed for sociability in mice PMID: 28297715 Based on our findings, we propose that imprinting of UBE3A does not function to reduce the dosage of UBE3A in neurons but rather to regulate some other, as yet unknown, aspect of gene expression or protein function PMID: 28515788 the role of UBE3A is investigated in neurite contact guidance during neuronal development, is reported. PMID: 26845073 Results substantiate GABAergic Ube3a loss as the principal cause of circuit hyperexcitability in Angelman syndrome mice, lending insight into ictogenic mechanisms in AS. PMID: 27021170 Loss of Ube3a from tyrosine hydroxylase-expressing neurons impairs mesoaccumbal, non-canonical GABA co-release and enhances reward-seeking behaviour measured by optical self-stimulation. PMID: 26869263 Results suggest that the phenotypes observed in Angelman syndrome mice may be modulated by factors independent of Ube3a genotype PMID: 26028516 UBE3A dampens ERK pathway signalling in HPV E6 transformed HeLa cells PMID: 25815718 The normal window of development in Angelman syndrome patients is supported by an incompletely silenced paternal allele in developing neurons, resulting in a relative preservation of Ube3a expression during this crucial epoch of early development. PMID: 25894543 Inactivation of Ube3a expression elevates BMAL1 levels in brain regions that control circadian behavior of AS-model mice, indicating an important role for Ube3a in modulating BMAL1 turnover. PMID: 25660546 This study demonstrated that abnormal sleep patterns arise from a deficit in accumulation of sleep drive, uncovering the Ube3a gene as a novel genetic regulator of sleep homeostasis PMID: 26446213 The deficiency of Ube3a in Huntington's disease (HD) mice brain also caused significant increase in global aggregates load, and these aggregates were less ubiquitinated when compared with age-matched HD mice. PMID: 25027318 There are distinct neurodevelopmental windows when Ube3a restoration rescues Angelman-syndrome-like phenotypes. Motor deficits are rescued in adolescence. Anxiety, repetitive behavior, and epilepsy are rescued in early development. PMID: 25866966 Mature oligodendrocytes express Ube3a in the cortex and white matter tracts during development. PMID: 24254964 findings provide novel insight into the regulation of Ube3a by synaptic activity and its potential role in kinase regulation PMID: 24434871 These studies demonstrate the feasibility and utility of unsilencing the paternal copy of Ube3a via targeting Ube3a-ATS as a treatment for Angelman syndrome. PMID: 24385930 Activating UBE3A disrupts circadian oscillations in mouse embryonic fibroblasts and rhythms in endogenous mRNA and protein levels of BMAL1. PMID: 24728990 Aging-dependent Ube3a levels result in differential ubiquitination and degradation of Htt fragments, thereby contributing to the age-related neurotoxicity of mutant Htt. PMID: 24706802 This study demonistrated that Changes in mGlu5 receptor-dependent synaptic plasticity and coupling to homer proteins in the hippocampus of Ube3A hemizygous mice. PMID: 24672001 These results demonstrate that UBE3A plays a role in MC1R transcriptional regulation. PMID: 21733131 E6AP may negatively control adipogenesis by inhibiting C/EBPalpha expression. PMID: 23762344 MeCP2 and E6AP play a role in the transcriptional control of common target gene expression. PMID: 23791832 This study described a novel phenotype of severely distended Golgi cisternae in the Angelman syndrome model mouse. PMID: 23447592 The present study is the first to determine that the Ube3a protein ablation seen in the Angelman syndrome mouse model is also characteristic of Angelman syndrome patients PMID: 22560727 findings showed that Ube3a-ATS is an atypical RNAPII transcript that functions to suppress paternal Ube3a expression PMID: 22493002 the loss of function of Ube3a might be associated with the synaptic abnormalities observed in HD. PMID: 22787151 study reports that Ube3a regulates glucocorticoid receptor (GR) transactivation; the GR signaling pathway is disrupted in Ube3a-maternal-deficient mice brain that eventually leads to increased susceptibility to stress and anxiety in these Angelman syndrome mice PMID: 22215440 This study demonistrated that Ube3a deficices mice product produces an excitatory/inhibitory imbalance through neuron type-specific synaptic in visual cortex. PMID: 22681684 our study implicates E6AP as an important regulator of the cellular response to stress, in particular through the regulation of replicative and oncogene-induced senescence. PMID: 21927031 The results suggest that Ube3a gene dosage may contribute to the autism traits of individuals with maternal 15q11-13 duplication and support the idea that increased E3A ubiquitin ligase gene dosage results in reduced excitatory synaptic transmission. PMID: 21974935 In a mouse model of Angelman syndrome, since hippocampal and Purkinje cells have the highest expression of UBE3A in a mouse model of Angelman syndrome, these cells would have the greatest sensitivity to the UBE3A m-\p+ maternal\paternal genotype. PMID: 19563863 HERC2 acts as a regulator of E6AP. PMID: 21493713 The levels of total Akt and phosphorylated Akt (active Akt) are increased in E6-AP overexpressing prostate gland and LNCaP cells suggesting that E6-AP regulates the PI3K-Akt signaling pathway. PMID: 20826237 Data show RNA interference that targets Ube3a in P19 cells caused downregulation of Mc1r and Nr4a2, whereas overexpression of Ube3a results in the upregulation of Mc1r and Nr4a2. PMID: 20571502 Ube3a exhibits brain cell type-specific imprinting, with monoallelic expression from the maternal allele in neurons, but biallelic expression in glial cells. The antisense Ube3a transcript is reciprocally imprinted only in neurons. PMID: 12668607 Ube3a expression is primarily neuronal in all brain regions and present in GABAergic interneurons as well as principal neurons. PMID: 20423730 E6-associated protein is required for human papillomavirus type 16 E6 to cause cervical cancer. PMID: 20530688 polycomb protein Ring1B regulation by self-ubiquitination or by E6-AP may have implications to the pathogenesis of Angelman syndrome PMID: 20351251 As demonstrated by optical imaging, rapid ocular dominance plasticity after brief monocular deprivation was severely impaired during the critical period in the visual cortex of Ube3a maternal-deficient (m-/p+) mice. PMID: 20212164 Disruption of Ube3A function in neurons leads to an increase in Arc expression and a concomitant deregulation in AMPA receptors at synapses; which may contribute to the cognitive dysfunction that occurs in Angelman Syndrome. PMID: 20211139 The imprinted Ube3a antisense transcript is regulated by the U exons rather than Snurf/Snrpn exon 1 (Ube3a antisense RNA). PMID: 15226413 loss of E6AP catalytic activity and improper regulation of E6AP substrate are important in the development of Angelman syndrome PMID: 15263005

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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