Gene Symbol: Ube3a
Description: ubiquitin protein ligase E3A
Alias: 4732496B02, 5830462N02Rik, A130086L21Rik, Hpve6a, ubiquitin-protein ligase E3A, E6-AP ubiquitin protein ligase, HECT-type ubiquitin transferase E3A, oncogenic protein-associated protein E6-AP, ubiquitin conjugating enzyme E3A
Species: mouse
Products:     Ube3a

Top Publications

  1. Mishra A, Godavarthi S, Jana N. UBE3A/E6-AP regulates cell proliferation by promoting proteasomal degradation of p27. Neurobiol Dis. 2009;36:26-34 pubmed publisher
    The UBE3A/E6-AP is known to function both as an E3 ubiquitin ligase of the ubiquitin proteasome system and as a transcriptional coactivator...
  2. Huang H, Burns A, Nonneman R, Baker L, Riddick N, Nikolova V, et al. Behavioral deficits in an Angelman syndrome model: effects of genetic background and age. Behav Brain Res. 2013;243:79-90 pubmed publisher
    ..AS) is a severe neurodevelopmental disorder associated with disruption of maternally inherited UBE3A (ubiquitin protein ligase E3A) expression. At the present time, there is no effective treatment for AS...
  3. Daily J, Nash K, Jinwal U, Golde T, Rogers J, Peters M, et al. Adeno-associated virus-mediated rescue of the cognitive defects in a mouse model for Angelman syndrome. PLoS ONE. 2011;6:e27221 pubmed publisher
    ..The gene responsible for AS was discovered to be UBE3A and encodes for E6-AP, an ubiquitin ligase...
  4. Yamasaki K, Joh K, Ohta T, Masuzaki H, Ishimaru T, Mukai T, et al. Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a. Hum Mol Genet. 2003;12:837-47 pubmed
    The human UBE3A gene shows brain-specific partial imprinting, and lack of a maternally inherited allele causes Angelman syndrome (AS), which is characterized by neurobehavioral anomalies...
  5. Miura K, Kishino T, Li E, Webber H, Dikkes P, Holmes G, et al. Neurobehavioral and electroencephalographic abnormalities in Ube3a maternal-deficient mice. Neurobiol Dis. 2002;9:149-59 pubmed
    ..and seizures, is caused by several genetic etiologies involving chromosome 15q11-q13, including mutations of the UBE3A gene...
  6. Greer P, Hanayama R, Bloodgood B, Mardinly A, Lipton D, Flavell S, et al. The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell. 2010;140:704-16 pubmed publisher
    Angelman Syndrome is a debilitating neurological disorder caused by mutation of the E3 ubiquitin ligase Ube3A, a gene whose mutation has also recently been associated with autism spectrum disorders (ASDs)...
  7. Chamberlain S, Brannan C. The Prader-Willi syndrome imprinting center activates the paternally expressed murine Ube3a antisense transcript but represses paternal Ube3a. Genomics. 2001;73:316-22 pubmed
    The imprinted UBE3A gene exhibits maternal-only expression in specific cell types in the brain, but exhibits biallelic expression in other cell types...
  8. van Woerden G, Harris K, Hojjati M, Gustin R, Qiu S, de Avila Freire R, et al. Rescue of neurological deficits in a mouse model for Angelman syndrome by reduction of alphaCaMKII inhibitory phosphorylation. Nat Neurosci. 2007;10:280-2 pubmed
    ..Moreover, these double mutants no longer show the behavioral deficits seen in AS mice, suggesting that these deficits are the direct result of increased inhibitory phosphorylation of alphaCaMKII. ..
  9. Dindot S, Antalffy B, Bhattacharjee M, Beaudet A. The Angelman syndrome ubiquitin ligase localizes to the synapse and nucleus, and maternal deficiency results in abnormal dendritic spine morphology. Hum Mol Genet. 2008;17:111-8 pubmed
    Loss of function of the maternally inherited allele for the UBE3A ubiquitin ligase gene causes Angelman syndrome (AS), which is characterized by severe neurological impairment and motor dysfunction...

More Information


  1. Albrecht U, Sutcliffe J, Cattanach B, Beechey C, Armstrong D, Eichele G, et al. Imprinted expression of the murine Angelman syndrome gene, Ube3a, in hippocampal and Purkinje neurons. Nat Genet. 1997;17:75-8 pubmed
    ..Imprinting mutations and loss of function mutations of E6-associated-protein (E6-AP) ubiquitin-protein ligase (UBE3A). All of these abnormalities are associated with loss of maternal expression of UBE3A...
  2. Louria Hayon I, Alsheich Bartok O, Levav Cohen Y, Silberman I, Berger M, Grossman T, et al. E6AP promotes the degradation of the PML tumor suppressor. Cell Death Differ. 2009;16:1156-66 pubmed publisher
    ..This PML elevation is enhanced in response to DNA damage. Our results identify E6AP as an important regulator of PML and PML-NBs. ..
  3. Yashiro K, Riday T, Condon K, Roberts A, Bernardo D, Prakash R, et al. Ube3a is required for experience-dependent maturation of the neocortex. Nat Neurosci. 2009;12:777-83 pubmed publisher
    ..We tested whether experience-dependent neocortical modifications require Ube3a, an E3 ubiquitin ligase whose dysregulation has been implicated in autism and Angelman syndrome...
  4. Landers M, Bancescu D, Le Meur E, Rougeulle C, Glatt Deeley H, Brannan C, et al. Regulation of the large (approximately 1000 kb) imprinted murine Ube3a antisense transcript by alternative exons upstream of Snurf/Snrpn. Nucleic Acids Res. 2004;32:3480-92 pubmed
    Most cases of Angelman syndrome (AS) result from loss or inactivation of ubiquitin protein ligase 3A (UBE3A), a gene displaying maternal-specific expression in brain...
  5. Heck D, Zhao Y, Roy S, Ledoux M, Reiter L. Analysis of cerebellar function in Ube3a-deficient mice reveals novel genotype-specific behaviors. Hum Mol Genet. 2008;17:2181-9 pubmed publisher
    ..Most cases of AS are caused by mutations which disrupt expression of maternal UBE3A. Although some progress has been made in understanding hippocampal-related memory and learning aspects of the ..
  6. Samaco R, Hogart A, LaSalle J. Epigenetic overlap in autism-spectrum neurodevelopmental disorders: MECP2 deficiency causes reduced expression of UBE3A and GABRB3. Hum Mol Genet. 2005;14:483-92 pubmed
    ..disorder caused by MECP2 mutations, and Angelman syndrome, an imprinted disorder caused by maternal 15q11-q13 or UBE3A deficiency, have phenotypic and genetic overlap with autism...
  7. Cheron G, Servais L, Wagstaff J, Dan B. Fast cerebellar oscillation associated with ataxia in a mouse model of Angelman syndrome. Neuroscience. 2005;130:631-7 pubmed
    ..in vivo cerebellar activity in a mouse model of Angelman syndrome produced by null mutation of the maternal Ube3a gene...
  8. Meng L, Person R, Huang W, Zhu P, Costa Mattioli M, Beaudet A. Truncation of Ube3a-ATS unsilences paternal Ube3a and ameliorates behavioral defects in the Angelman syndrome mouse model. PLoS Genet. 2013;9:e1004039 pubmed publisher
    Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by maternal deficiency of the imprinted gene UBE3A. Individuals with AS suffer from intellectual disability, speech impairment, and motor dysfunction...
  9. Dhar M, Webb L, Smith L, Hauser L, Johnson D, West D. A novel ATPase on mouse chromosome 7 is a candidate gene for increased body fat. Physiol Genomics. 2000;4:93-100 pubmed
    ..We have physically mapped the 1-Mb critical region, which lies between the Gabrb3 and Ube3a/Ipw genes, and DNA sequencing has localized a new member of the third subfamily of P-type ATPases to the minimal ..
  10. Sutcliffe J, Jiang Y, Galijaard R, Matsuura T, Fang P, Kubota T, et al. The E6-Ap ubiquitin-protein ligase (UBE3A) gene is localized within a narrowed Angelman syndrome critical region. Genome Res. 1997;7:368-77 pubmed
    ..Mapping data indicate that the entire transcriptional unit of the E6-AP ubiquitin-protein ligase (UBE3A) gene lies within the AS region...
  11. Kohama C, Kato H, Numata K, Hirose M, Takemasa T, Ogura A, et al. ES cell differentiation system recapitulates the establishment of imprinted gene expression in a cell-type-specific manner. Hum Mol Genet. 2012;21:1391-401 pubmed publisher
    ..In neurons, the gene Ube3a is expressed from the maternal allele only, and a paternally expressed non-coding, antisense RNA has been ..
  12. Gustin R, Bichell T, Bubser M, Daily J, Filonova I, Mrelashvili D, et al. Tissue-specific variation of Ube3a protein expression in rodents and in a mouse model of Angelman syndrome. Neurobiol Dis. 2010;39:283-91 pubmed publisher
    Angelman syndrome (AS) is a neurogenetic disorder caused by loss of maternal UBE3A expression or mutation-induced dysfunction of its protein product, the E3 ubiquitin-protein ligase, UBE3A...
  13. Wallace M, Burette A, Weinberg R, Philpot B. Maternal loss of Ube3a produces an excitatory/inhibitory imbalance through neuron type-specific synaptic defects. Neuron. 2012;74:793-800 pubmed publisher
    Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of the maternally inherited allele of UBE3A. AS model mice, which carry a maternal Ube3a null mutation (Ube3a(m-/p+)), recapitulate major features of AS in humans, ..
  14. Tsai T, Jiang Y, Bressler J, Armstrong D, Beaudet A. Paternal deletion from Snrpn to Ube3a in the mouse causes hypotonia, growth retardation and partial lethality and provides evidence for a gene contributing to Prader-Willi syndrome. Hum Mol Genet. 1999;8:1357-64 pubmed
    ..a portion of a small, upstream open reading frame (ORF); (ii) mice with double targeting for Snrpn exon 2 and Ube3a; (iii) mice deleted from Snrpn to Ube3a, removing coding exons for both loci and intervening genes...
  15. Meng L, Person R, Beaudet A. Ube3a-ATS is an atypical RNA polymerase II transcript that represses the paternal expression of Ube3a. Hum Mol Genet. 2012;21:3001-12 pubmed publisher
    The Angelman syndrome gene, UBE3A, is subject to genomic imprinting controlled by mechanisms that are only partially understood. Its antisense transcript, UBE3A-ATS, is also imprinted and hypothesized to suppress UBE3A in cis...
  16. Jiang Y, Armstrong D, Albrecht U, Atkins C, Noebels J, Eichele G, et al. Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation. Neuron. 1998;21:799-811 pubmed
    The E6-AP ubiquitin ligase (human/mouse gene UBE3A/Ube3a) promotes the degradation of p53 in association with papilloma E6 protein, and maternal deficiency causes human Angelman syndrome (AS)...
  17. Jiang Y, Pan Y, Zhu L, Landa L, Yoo J, Spencer C, et al. Altered ultrasonic vocalization and impaired learning and memory in Angelman syndrome mouse model with a large maternal deletion from Ube3a to Gabrb3. PLoS ONE. 2010;5:e12278 pubmed publisher
    ..disomy (UPD) of chromosome 15 (5%), imprinting mutations (rare), and mutations in the E6-AP ubiquitin ligase gene UBE3A (15%)...
  18. Su H, Fan W, Coskun P, Vesa J, Gold J, Jiang Y, et al. Mitochondrial dysfunction in CA1 hippocampal neurons of the UBE3A deficient mouse model for Angelman syndrome. Neurosci Lett. 2011;487:129-33 pubmed publisher
    Angelman syndrome (AS) is a severe neurological disorder caused by a deficiency of ubiquitin protein ligase E3A (UBE3A), but the pathophysiology of the disease remains unknown...
  19. Margolis S, Salogiannis J, Lipton D, Mandel Brehm C, Wills Z, Mardinly A, et al. EphB-mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation. Cell. 2010;143:442-55 pubmed publisher
    ..The degradation of Ephexin5 promotes EphB-dependent excitatory synapse development and is mediated by Ube3A, a ubiquitin ligase that is mutated in the human cognitive disorder Angelman syndrome and duplicated in some forms ..
  20. Mulherkar S, Jana N. Loss of dopaminergic neurons and resulting behavioural deficits in mouse model of Angelman syndrome. Neurobiol Dis. 2010;40:586-92 pubmed publisher
    E6 associated protein is an E3 ubiquitin ligase encoded by the gene Ube3a. Deletion or loss of function of the maternally inherited allele of Ube3a leads to Angelman syndrome...
  21. Cattanach B, Barr J, Beechey C, Martin J, Noebels J, Jones J. A candidate model for Angelman syndrome in the mouse. Mamm Genome. 1997;8:472-8 pubmed
    ..A mouse model of AS is, therefore, strongly indicated. ..
  22. Cao C, Rioult Pedotti M, Migani P, Yu C, Tiwari R, Parang K, et al. Impairment of TrkB-PSD-95 signaling in Angelman syndrome. PLoS Biol. 2013;11:e1001478 pubmed publisher
    ..AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, ..
  23. Kühnle S, Kogel U, Glockzin S, Marquardt A, Ciechanover A, Matentzoglu K, et al. Physical and functional interaction of the HECT ubiquitin-protein ligases E6AP and HERC2. J Biol Chem. 2011;286:19410-6 pubmed publisher
    ..Thus, the data obtained indicate that HERC2 acts as a regulator of E6AP. ..
  24. Khan O, Fu G, Ismail A, Srinivasan S, Cao X, Tu Y, et al. Multifunction steroid receptor coactivator, E6-associated protein, is involved in development of the prostate gland. Mol Endocrinol. 2006;20:544-59 pubmed
    ..Collectively, our data suggest that E6-AP deletion attenuates the growth and development of the prostate gland by interfering with AR function as well as by stimulating p53-mediated apoptosis. ..
  25. Grieco J, Ciarlone S, Gieron Korthals M, Schoenberg M, Smith A, Philpot R, et al. An open-label pilot trial of minocycline in children as a treatment for Angelman syndrome. BMC Neurol. 2014;14:232 pubmed publisher
    ..NCT01531582 - clinicaltrials.gov. ..
  26. Grier M, Carson R, Lagrange A. Of mothers and myelin: Aberrant myelination phenotypes in mouse model of Angelman syndrome are dependent on maternal and dietary influences. Behav Brain Res. 2015;291:260-267 pubmed publisher
    ..AS results from the loss of UBE3A (an imprinted gene) expressed from the maternal chromosome in neurons...
  27. Krishnan V, Stoppel D, Nong Y, Johnson M, Nadler M, Ozkaynak E, et al. Autism gene Ube3a and seizures impair sociability by repressing VTA Cbln1. Nature. 2017;543:507-512 pubmed publisher
    ..chromosomal triplications cause a frequent and highly penetrant type of autism linked to increased gene dosages of UBE3A, which encodes a ubiquitin ligase with transcriptional co-regulatory functions...
  28. Hatakeyama S, Jensen J, Weissman A. Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases. J Biol Chem. 1997;272:15085-92 pubmed
    ..Furthermore, the presence of two E2 binding sites within Nedd-4 suggests models for ubiquitination involving multiple E2 enzymes associated with E3s. ..
  29. Levav Cohen Y, Wolyniec K, Alsheich Bartok O, Chan A, Woods S, Jiang Y, et al. E6AP is required for replicative and oncogene-induced senescence in mouse embryo fibroblasts. Oncogene. 2012;31:2199-209 pubmed publisher
    ..Overall, 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. ..
  30. Smith S, Zhou Y, Zhang G, Jin Z, Stoppel D, Anderson M. Increased gene dosage of Ube3a results in autism traits and decreased glutamate synaptic transmission in mice. Sci Transl Med. 2011;3:103ra97 pubmed publisher
    ..To test this, we tripled the dosage of one of these genes, the ubiquitin protein ligase Ube3a, which is expressed solely from the maternal allele in mature neurons, and reconstituted the three core autism ..
  31. Mandel Brehm C, Salogiannis J, Dhamne S, Rotenberg A, Greenberg M. Seizure-like activity in a juvenile Angelman syndrome mouse model is attenuated by reducing Arc expression. Proc Natl Acad Sci U S A. 2015;112:5129-34 pubmed publisher
    ..is a neurodevelopmental disorder arising from loss-of-function mutations in the maternally inherited copy of the UBE3A gene, and is characterized by an absence of speech, excessive laughter, cognitive delay, motor deficits, and ..
  32. Carmody M, Notarianni T, Sambel L, Walsh S, Burke J, Armstrong J, et al. E6AP/UBE3A catalyzes encephalomyocarditis virus 3C protease polyubiquitylation and promotes its concentration reduction in virus-infected cells. Biochem Biophys Res Commun. 2017;494:63-69 pubmed publisher
    ..Here we report that the ubiquitin-conjugating enzyme UbcH7/UBE2L3 and the ubiquitin-protein ligase E6AP/UBE3A are components of a previously unknown EMCV 3Cpro-polyubiquitylating pathway...
  33. Cummings C, Reinstein E, Sun Y, Antalffy B, Jiang Y, Ciechanover A, et al. Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice. Neuron. 1999;24:879-92 pubmed
    ..Taken together, NIs are not necessary to induce neurodegeneration, but impaired proteasomal degradation of mutant ataxin-1 may contribute to SCA1 pathogenesis. ..
  34. Landers M, Calciano M, Colosi D, Glatt Deeley H, Wagstaff J, Lalande M. Maternal disruption of Ube3a leads to increased expression of Ube3a-ATS in trans. Nucleic Acids Res. 2005;33:3976-84 pubmed
    ..Individuals with AS fail to inherit a normal active maternal copy of the gene encoding ubiquitin protein ligase E3A (UBE3A)...
  35. Berrios J, Stamatakis A, Kantak P, McElligott Z, Judson M, Aita M, et al. Loss of UBE3A from TH-expressing neurons suppresses GABA co-release and enhances VTA-NAc optical self-stimulation. Nat Commun. 2016;7:10702 pubmed publisher
    ..Here we demonstrate that loss of the E3-ubiquitin ligase, UBE3A, from tyrosine hydroxylase-expressing neurons impairs mesoaccumbal, non-canonical GABA co-release and enhances ..
  36. Dhar M, Johnson D. A microsatellite map of the pink-eyed dilution (p) deletion complex in mouse chromosome 7. Mamm Genome. 1997;8:143-5 pubmed
  37. Godavarthi S, Dey P, Sharma A, Jana N. Impaired adult hippocampal neurogenesis and its partial reversal by chronic treatment of fluoxetine in a mouse model of Angelman syndrome. Biochem Biophys Res Commun. 2015;464:1196-1201 pubmed publisher
    ..characterized by severe cognitive and motor deficits, caused by the loss of function of maternally inherited Ube3a. Ube3a-maternal deficient mice (AS model mice) recapitulate many essential features of AS, but how the deficiency ..
  38. Fiorenza M, Mukhopadhyay M, Westphal H. Expression screening for Lhx3 downstream genes identifies Thg-1pit as a novel mouse gene involved in pituitary development. Gene. 2001;278:125-30 pubmed
    ..No expression is observed in the pituitary rudiment of mutants that lack Lhx3 function. A possible role is thus suggested for Lhx3 activities in the regulation of Thg-1pit function during early steps of pituitary organogenesis. ..
  39. Riday T, Dankoski E, Krouse M, Fish E, Walsh P, Han J, et al. Pathway-specific dopaminergic deficits in a mouse model of Angelman syndrome. J Clin Invest. 2012;122:4544-54 pubmed publisher
    ..AS) is a neurodevelopmental disorder caused by maternal deletions or mutations of the ubiquitin ligase E3A (UBE3A) allele and characterized by minimal verbal communication, seizures, and disorders of voluntary movement...
  40. Jones K, Han J, Debruyne J, Philpot B. Persistent neuronal Ube3a expression in the suprachiasmatic nucleus of Angelman syndrome model mice. Sci Rep. 2016;6:28238 pubmed publisher
    Mutations or deletions of the maternal allele of the UBE3A gene cause Angelman syndrome (AS), a severe neurodevelopmental disorder...
  41. Smith C, DeVera D, Lamb D, Nawaz Z, Jiang Y, Beaudet A, et al. Genetic ablation of the steroid receptor coactivator-ubiquitin ligase, E6-AP, results in tissue-selective steroid hormone resistance and defects in reproduction. Mol Cell Biol. 2002;22:525-35 pubmed
  42. Mardirossian S, Rampon C, Salvert D, Fort P, Sarda N. Impaired hippocampal plasticity and altered neurogenesis in adult Ube3a maternal deficient mouse model for Angelman syndrome. Exp Neurol. 2009;220:341-8 pubmed publisher
    ..It results from lack of the functional maternal allele of UBE3A gene...
  43. Bhat K, Yan S, Wang C, Li S, Li X. Differential ubiquitination and degradation of huntingtin fragments modulated by ubiquitin-protein ligase E3A. Proc Natl Acad Sci U S A. 2014;111:5706-11 pubmed publisher
    ..The association of Htt with the K48-specific E3 ligase, Ube3a, is decreased in aged mouse brain...
  44. Mishra A, Maheshwari M, Chhangani D, Fujimori Tonou N, Endo F, Joshi A, et al. E6-AP association promotes SOD1 aggresomes degradation and suppresses toxicity. Neurobiol Aging. 2013;34:1310.e11-23 pubmed publisher
    ..These data suggest that enhancing the activity of E6-AP ubiquitin ligase might be a viable therapeutic strategy to eliminate mutant SOD1-mediated toxicity in ALS. ..
  45. Pignatelli M, Piccinin S, Molinaro G, Di Menna L, Riozzi B, Cannella M, et al. Changes in mGlu5 receptor-dependent synaptic plasticity and coupling to homer proteins in the hippocampus of Ube3A hemizygous mice modeling angelman syndrome. J Neurosci. 2014;34:4558-66 pubmed publisher
    Angelman syndrome (AS) is caused by the loss of Ube3A, an ubiquitin ligase that commits specific proteins to proteasomal degradation. How this defect causes autism and other pathological phenotypes associated with AS is unknown...
  46. Judson M, Sosa Pagán J, Del Cid W, Han J, Philpot B. Allelic specificity of Ube3a expression in the mouse brain during postnatal development. J Comp Neurol. 2014;522:1874-96 pubmed publisher
    Genetic alterations of the maternal UBE3A allele result in Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, lack of speech, and difficulty with movement and balance...
  47. Ehlen J, Jones K, Pinckney L, Gray C, Burette S, Weinberg R, et al. Maternal Ube3a Loss Disrupts Sleep Homeostasis But Leaves Circadian Rhythmicity Largely Intact. J Neurosci. 2015;35:13587-98 pubmed publisher
    ..Here, we explored the mechanistic basis for these sleep disorders in a mouse model of Angelman syndrome (Ube3a(m-/p+) mice)...
  48. Santini E, Turner K, Ramaraj A, Murphy M, Klann E, Kaphzan H. Mitochondrial Superoxide Contributes to Hippocampal Synaptic Dysfunction and Memory Deficits in Angelman Syndrome Model Mice. J Neurosci. 2015;35:16213-20 pubmed publisher
    ..majority of the patients, AS is caused by the deletion of small portions of maternal chromosome 15 harboring the UBE3A gene. This results in a lack of expression of the UBE3A gene because the paternal allele is genetically imprinted...
  49. Condon K, Ho J, Robinson C, Hanus C, Ehlers M. The Angelman syndrome protein Ube3a/E6AP is required for Golgi acidification and surface protein sialylation. J Neurosci. 2013;33:3799-814 pubmed publisher
    ..caused by neuron-specific loss of the HECT (homologous to E6AP carboxy terminus) domain E3 ubiquitin ligase Ube3a/E6AP...
  50. Miao S, Chen R, Ye J, Tan G, Li S, Zhang J, et al. The Angelman syndrome protein Ube3a is required for polarized dendrite morphogenesis in pyramidal neurons. J Neurosci. 2013;33:327-33 pubmed publisher
    ..Here, we report that the Angelman syndrome (AS) protein ubiquitin-protein ligase E3A (Ube3a) plays an important role in specifying the polarization of pyramidal neuron dendritic arbors in mice...
  51. Burette A, Judson M, Burette S, Phend K, Philpot B, Weinberg R. Subcellular organization of UBE3A in neurons. J Comp Neurol. 2017;525:233-251 pubmed publisher
    ..Loss of the E3 ubiquitin-protein ligase UBE3A causes Angelman syndrome. Despite its clinical importance, the normal role of UBE3A in neurons is still unclear...
  52. Stoppel D, Anderson M. Hypersociability in the Angelman syndrome mouse model. Exp Neurol. 2017;293:137-143 pubmed publisher
    ..Maternally-derived deletions or inactivating mutations of UBE3A, a 15q11-13 gene expressed exclusively from the maternal allele in neurons, cause Angelman syndrome, characterized ..
  53. Wallace M, van Woerden G, Elgersma Y, Smith S, Philpot B. Ube3a loss increases excitability and blunts orientation tuning in the visual cortex of Angelman syndrome model mice. J Neurophysiol. 2017;118:634-646 pubmed publisher
    Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of the maternally inherited allele of UBE3AUbe3aSTOP/p+ mice recapitulate major features of AS in humans and allow conditional reinstatement ..
  54. McCoy E, Taylor Blake B, Aita M, Simon J, Philpot B, Zylka M. Enhanced Nociception in Angelman Syndrome Model Mice. J Neurosci. 2017;37:10230-10239 pubmed publisher
    Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by mutation or deletion of the maternal UBE3A allele...
  55. Mansour M, Haupt S, Chan A, Godde N, Rizzitelli A, Loi S, et al. The E3-ligase E6AP Represses Breast Cancer Metastasis via Regulation of ECT2-Rho Signaling. Cancer Res. 2016;76:4236-48 pubmed publisher
    ..These findings establish E6AP as a novel suppressor of metastasis and provide a compelling rationale for inhibition of ECT2 as a therapeutic approach for patients with metastatic breast cancer. Cancer Res; 76(14); 4236-48. ©2016 AACR. ..
  56. Liu X, Yuan H, Fu B, Disbrow G, Apolinario T, Tomaic V, et al. The E6AP ubiquitin ligase is required for transactivation of the hTERT promoter by the human papillomavirus E6 oncoprotein. J Biol Chem. 2005;280:10807-16 pubmed
  57. Maheshwari M, Shekhar S, Singh B, Jamal I, Vatsa N, Kumar V, et al. Deficiency of Ube3a in Huntington's disease mice brain increases aggregate load and accelerates disease pathology. Hum Mol Genet. 2014;23:6235-45 pubmed publisher
    ..Here, we demonstrate that removal of ubiquitin ligase Ube3a selectively from HD mice brain resulted in accelerated disease phenotype and shorter lifespan in comparison with ..
  58. Srinivasan S, Nawaz Z. E3 ubiquitin protein ligase, E6-associated protein (E6-AP) regulates PI3K-Akt signaling and prostate cell growth. Biochim Biophys Acta. 2011;1809:119-27 pubmed publisher
    ..This article is part of a Special Issue entitled The 26S Proteasome: When degradation is just not enough! ..
  59. Mager J, Montgomery N, de Villena F, Magnuson T. Genome imprinting regulated by the mouse Polycomb group protein Eed. Nat Genet. 2003;33:502-7 pubmed
    ..These data identify Eed as a member of a new class of trans-acting factors that regulate parent-of-origin expression at imprinted loci. ..
  60. Shi S, Bichell T, Ihrie R, Johnson C. Ube3a imprinting impairs circadian robustness in Angelman syndrome models. Curr Biol. 2015;25:537-45 pubmed publisher
    The paternal allele of Ube3a is silenced by imprinting in neurons, and Angelman syndrome (AS) is a disorder arising from a deletion or mutation of the maternal Ube3a allele, which thereby eliminates Ube3a neuronal expression...
  61. Huang H, Allen J, Mabb A, KING I, Miriyala J, Taylor Blake B, et al. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature. 2011;481:185-9 pubmed publisher
    ..is a severe neurodevelopmental disorder caused by deletion or mutation of the maternal allele of the ubiquitin protein ligase E3A (UBE3A)...
  62. Grier M, Carson R, Lagrange A. Toward a Broader View of Ube3a in a Mouse Model of Angelman Syndrome: Expression in Brain, Spinal Cord, Sciatic Nerve and Glial Cells. PLoS ONE. 2015;10:e0124649 pubmed publisher
    ..AS is caused by loss of the Ube3a protein encoded for by the imprinted Ube3a gene...
  63. Judson M, Wallace M, Sidorov M, Burette A, Gu B, van Woerden G, et al. GABAergic Neuron-Specific Loss of Ube3a Causes Angelman Syndrome-Like EEG Abnormalities and Enhances Seizure Susceptibility. Neuron. 2016;90:56-69 pubmed publisher
    Loss of maternal UBE3A causes Angelman syndrome (AS), a neurodevelopmental disorder associated with severe epilepsy...
  64. Meng L, Ward A, Chun S, Bennett C, Beaudet A, Rigo F. Towards a therapy for Angelman syndrome by targeting a long non-coding RNA. Nature. 2015;518:409-12 pubmed publisher
    ..It is caused by maternal deficiency of the imprinted gene UBE3A, encoding an E3 ubiquitin ligase...
  65. Filonova I, Trotter J, Banko J, Weeber E. Activity-dependent changes in MAPK activation in the Angelman Syndrome mouse model. Learn Mem. 2014;21:98-104 pubmed publisher
    Angelman Syndrome (AS) is a devastating neurological disorder caused by disruption of the maternal UBE3A gene. Ube3a protein is identified as an E3 ubiquitin ligase that shows neuron-specific imprinting...
  66. Cooper E, Hudson A, Amos J, Wagstaff J, Howley P. Biochemical analysis of Angelman syndrome-associated mutations in the E3 ubiquitin ligase E6-associated protein. J Biol Chem. 2004;279:41208-17 pubmed
    ..The gene affected in this disorder is UBE3A, the gene encoding the E6-associated protein (E6AP) ubiquitin-protein ligase...
  67. Pal P, Lochab S, Kanaujiya J, Kapoor I, Sanyal S, Behre G, et al. E3 ubiquitin ligase E6AP negatively regulates adipogenesis by downregulating proadipogenic factor C/EBPalpha. PLoS ONE. 2013;8:e65330 pubmed publisher
    ..Taken together, our finding suggests that E6AP may negatively control adipogenesis by inhibiting C/EBP? expression by targeting it to ubiquitin-proteasome pathway for degradation. ..
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    ..Among these, Ubiquitin E3a ligase (UBE3A) has a key role in brain functioning, but its function and how its deficiency results in the neurodevelopmental ..
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