Gene Symbol: UBE3A
Description: ubiquitin protein ligase E3A
Alias: ANCR, E6-AP, EPVE6AP, HPVE6A, ubiquitin-protein ligase E3A, CTCL tumor antigen se37-2, E6AP ubiquitin-protein ligase, HECT-type ubiquitin transferase E3A, human papilloma virus E6-associated protein, human papillomavirus E6-associated protein, oncogenic protein-associated protein E6-AP, renal carcinoma antigen NY-REN-54
Species: human
Products:     UBE3A

Top Publications

  1. Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet. 1997;15:70-3 pubmed
    ..We have found that a 15q inversion inherited by an AS child from her normal mother disrupts the 5' end of the UBE3A (E6-AP) gene, the product of which functions in protein ubiquitination...
  2. 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
  3. Martinez Noel G, Galligan J, Sowa M, Arndt V, Overton T, Harper J, et al. Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes. Mol Cell Biol. 2012;32:3095-106 pubmed publisher
    ..These proteomic studies reveal a level of complexity for E6AP that has not been previously appreciated and identify a number of new cellular proteins through which E6AP may be regulated or functioning. ..
  4. Tomaic V, Pim D, Thomas M, Massimi P, Myers M, Banks L. Regulation of the human papillomavirus type 18 E6/E6AP ubiquitin ligase complex by the HECT domain-containing protein EDD. J Virol. 2011;85:3120-7 pubmed publisher
  5. Yamamoto Y, Huibregtse J, Howley P. The human E6-AP gene (UBE3A) encodes three potential protein isoforms generated by differential splicing. Genomics. 1997;41:263-6 pubmed
    The E6-AP gene (UBE3A) encodes an E3 ubiquitin-protein ligase that binds the human papillomavirus E6 oncoprotein and catalyzes the ubiquitination of p53...
  6. Malzac P, Webber H, Moncla A, Graham J, Kukolich M, Williams C, et al. Mutation analysis of UBE3A in Angelman syndrome patients. Am J Hum Genet. 1998;62:1353-60 pubmed
    ..of maternal origin, by paternal uniparental disomy (UPD) 15, by imprinting defects, and by mutations in the UBE3A gene. UBE3A encodes a ubiquitin-protein ligase and shows brain-specific imprinting...
  7. Zanier K, Charbonnier S, Sidi A, McEwen A, Ferrario M, Poussin Courmontagne P, et al. Structural basis for hijacking of cellular LxxLL motifs by papillomavirus E6 oncoproteins. Science. 2013;339:694-8 pubmed publisher
    ..Mutational inactivation of the LxxLL binding pocket disrupts the oncogenic activities of both E6 proteins. This work reveals the structural basis of both the multifunctionality and the oncogenicity of E6 proteins. ..
  8. Yang Y, Hsu Y, Wu C, Chen H, Chang M. Silencing of astrin induces the p53-dependent apoptosis by suppression of HPV18 E6 expression and sensitizes cells to paclitaxel treatment in HeLa cells. Biochem Biophys Res Commun. 2006;343:428-34 pubmed
    ..These findings suggest that the silencing of astrin induce a p53-dependent apoptosis and has an additive effect on paclitaxel treatment. ..
  9. 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...

More Information


  1. Kumar S, Talis A, Howley P. Identification of HHR23A as a substrate for E6-associated protein-mediated ubiquitination. J Biol Chem. 1999;274:18785-92 pubmed
  2. Yang Y, Liu W, Zou W, Wang H, Zong H, Jiang J, et al. Ubiquitin-dependent proteolysis of trihydrophobin 1 (TH1) by the human papilloma virus E6-associated protein (E6-AP). J Cell Biochem. 2007;101:167-80 pubmed
    ..The degradation is blocked by treatment with proteasome inhibitor MG132. Herein, we provide strong evidence that TH1 is a specific substrate that is targeted for degradation through E6-AP-catalyzed polyubiquitination. ..
  3. Wang H, Mo P, Ren S, Yan C. Activating transcription factor 3 activates p53 by preventing E6-associated protein from binding to E6. J Biol Chem. 2010;285:13201-10 pubmed publisher
    ..These results indicate that ATF3 plays a key role in a mechanism defending against HPV-induced carcinogenesis, and could serve as a novel therapeutic target for HPV-positive cancers. ..
  4. Kelley M, Keiger K, Lee C, Huibregtse J. The global transcriptional effects of the human papillomavirus E6 protein in cervical carcinoma cell lines are mediated by the E6AP ubiquitin ligase. J Virol. 2005;79:3737-47 pubmed publisher
    ..Together, these results suggest that E6AP mediates a broad spectrum of E6 functions, including virtually all functions that impact on the transcriptional program of HPV-positive cell lines...
  5. Mishra A, Godavarthi S, Maheshwari M, Goswami A, Jana N. The ubiquitin ligase E6-AP is induced and recruited to aggresomes in response to proteasome inhibition and may be involved in the ubiquitination of Hsp70-bound misfolded proteins. J Biol Chem. 2009;284:10537-45 pubmed publisher
  6. Uchiki T, Kim H, Zhai B, Gygi S, Johnston J, O Bryan J, et al. The ubiquitin-interacting motif protein, S5a, is ubiquitinated by all types of ubiquitin ligases by a mechanism different from typical substrate recognition. J Biol Chem. 2009;284:12622-32 pubmed publisher
    ..This tendency of S5a to associate with the growing Ub chain can explain how S5a, unlike typical substrates, which are recognized by certain E3s through specific motifs, is ubiquitinated by all E3s tested and is rapidly degraded in vivo. ..
  7. Kim H, Huibregtse J. Polyubiquitination by HECT E3s and the determinants of chain type specificity. Mol Cell Biol. 2009;29:3307-18 pubmed publisher
    ..Our results are also consistent with a simple sequential-addition mechanism for polyubiquitination by Rsp5, rather than a mechanism involving the formation of either E2- or E3-linked polyubiquitin chain transfers. ..
  8. Brimer N, Lyons C, Vande Pol S. Association of E6AP (UBE3A) with human papillomavirus type 11 E6 protein. Virology. 2007;358:303-10 pubmed
    The cellular E3 ubiquitin ligase E6AP (UBE3A) interacts with the cancer-associated HPV E6 oncoproteins, where together with the viral E6 oncoprotein it binds and targets the degradation of the p53 tumor suppressor...
  9. Zaaroor Regev D, de Bie P, Scheffner M, Noy T, Shemer R, Heled M, et al. Regulation of the polycomb protein Ring1B by self-ubiquitination or by E6-AP may have implications to the pathogenesis of Angelman syndrome. Proc Natl Acad Sci U S A. 2010;107:6788-93 pubmed publisher
  10. Lochab S, Pal P, Kanaujiya J, Tripathi S, Kapoor I, Bhatt M, et al. Proteomic identification of E6AP as a molecular target of tamoxifen in MCF7 cells. Proteomics. 2012;12:1363-77 pubmed publisher
    ..We identified E6-associated protein, i.e. E6AP (UBE3A) among others to be regulated by Tam that otherwise is upregulated in breast tumors...
  11. Huibregtse J, Scheffner M, Beaudenon S, Howley P. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci U S A. 1995;92:2563-7 pubmed
  12. Scheffner M, Huibregtse J, Vierstra R, Howley P. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell. 1993;75:495-505 pubmed
    ..The ubiquitination of p53 requires the E1 enzyme and a novel E2 in mammalian cells, while E3 activity is conferred by the E6-E6-AP complex. Furthermore, E6-AP appears to have ubiquitin-protein ligase activity in the absence of E6. ..
  13. Oda H, Kumar S, Howley P. Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination. Proc Natl Acad Sci U S A. 1999;96:9557-62 pubmed
  14. Rozenblatt Rosen O, Deo R, Padi M, Adelmant G, Calderwood M, Rolland T, et al. Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature. 2012;487:491-5 pubmed publisher
    ..Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate the prioritization of cancer-causing driver genes to advance the understanding of the genetic basis of human cancer...
  15. Nawaz Z, Lonard D, Smith C, Lev Lehman E, Tsai S, Tsai M, et al. The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily. Mol Cell Biol. 1999;19:1182-9 pubmed
    In this study, we found that the E6-associated protein (E6-AP/UBE3A) directly interacts with and coactivates the transcriptional activity of the human progesterone receptor (PR) in a hormone-dependent manner...
  16. Matsuura T, Sutcliffe J, Fang P, Galjaard R, Jiang Y, Benton C, et al. De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nat Genet. 1997;15:74-7 pubmed
    ..Although the gene for E6-AP ubiquitin-protein ligase (UBE3A) was mapped to the critical region for AS, evidence of expression from both parental alleles initially suggested ..
  17. 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. ..
  18. Shimoji T, Murakami K, Sugiyama Y, Matsuda M, Inubushi S, Nasu J, et al. Identification of annexin A1 as a novel substrate for E6AP-mediated ubiquitylation. J Cell Biochem. 2009;106:1123-35 pubmed publisher
    ..Our findings raise the possibility that E6AP may play a role in controlling the diverse functions of annexin A1 through the ubiquitin-proteasome pathway. ..
  19. Nuber U, Schwarz S, Scheffner M. The ubiquitin-protein ligase E6-associated protein (E6-AP) serves as its own substrate. Eur J Biochem. 1998;254:643-9 pubmed
    ..These results suggest that autoubiquitination and subsequent degradation of E6-AP represents a mechanism to control intracellular E6-AP levels by inactivating E6-AP molecules that are not bound to substrate proteins. ..
  20. Kuhne C, Banks L. E3-ubiquitin ligase/E6-AP links multicopy maintenance protein 7 to the ubiquitination pathway by a novel motif, the L2G box. J Biol Chem. 1998;273:34302-9 pubmed
  21. Tomai V, Pim D, Banks L. The stability of the human papillomavirus E6 oncoprotein is E6AP dependent. Virology. 2009;393:7-10 pubmed publisher
    ..These results demonstrate that the stability of HPV E6 is critically dependent upon the presence of E6AP...
  22. Guffanti G, Strik Lievers L, Bonati M, Marchi M, Geronazzo L, Nardocci N, et al. Role of UBE3A and ATP10A genes in autism susceptibility region 15q11-q13 in an Italian population: a positive replication for UBE3A. Psychiatry Res. 2011;185:33-8 pubmed publisher
    ..We screened a set of markers spanning two known imprinted, maternally expressed genes, UBE3A and ATP10A, harboured in this candidate region...
  23. Pal P, Lochab S, Kanaujiya J, Kapoor I, Sanyal S, Behre G, et al. E6AP, an E3 ubiquitin ligase negatively regulates granulopoiesis by targeting transcription factor C/EBP? for ubiquitin-mediated proteasome degradation. Cell Death Dis. 2013;4:e590 pubmed publisher
    ..Taken together, our data suggest that E6AP targeted C/EBP? protein degradation may provide a possible explanation for both loss of expression and/or functional inactivation of C/EBP? often experienced in myeloid leukemia. ..
  24. Kuballa P, Matentzoglu K, Scheffner M. The role of the ubiquitin ligase E6-AP in human papillomavirus E6-mediated degradation of PDZ domain-containing proteins. J Biol Chem. 2007;282:65-71 pubmed
    ..Based on these data, we propose that, in general, the proteolytic properties of human papillomavirus E6 proteins are mediated by interaction with E6-AP. ..
  25. Mani A, Oh A, Bowden E, Lahusen T, Lorick K, Weissman A, et al. E6AP mediates regulated proteasomal degradation of the nuclear receptor coactivator amplified in breast cancer 1 in immortalized cells. Cancer Res. 2006;66:8680-6 pubmed
    ..From our results, we propose a model whereby signals promoted by changes in the cellular milieu initiate E6AP-mediated proteasomal degradation of AIB1 and thus contribute to the control of steady-state levels of this protein. ..
  26. 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 ..
  27. Bruinsma C, Schonewille M, Gao Z, Aronica E, Judson M, Philpot B, et al. Dissociation of locomotor and cerebellar deficits in a murine Angelman syndrome model. J Clin Invest. 2015;125:4305-15 pubmed publisher
    ..Accordingly, neither VOR phase-reversal learning nor locomotion was impaired following selective deletion of Ube3a in Purkinje cells...
  28. 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 ..
  29. 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...
  30. Wolyniec K, Levav Cohen Y, Jiang Y, Haupt S, Haupt Y. The E6AP E3 ubiquitin ligase regulates the cellular response to oxidative stress. Oncogene. 2013;32:3510-9 pubmed publisher
    ..Our results provide the first demonstration that E6AP is an important regulator of ROS-mediated cellular senescence and cell death. ..
  31. Anan T, Nagata Y, Koga H, Honda Y, Yabuki N, Miyamoto C, et al. Human ubiquitin-protein ligase Nedd4: expression, subcellular localization and selective interaction with ubiquitin-conjugating enzymes. Genes Cells. 1998;3:751-63 pubmed
    ..Our findings suggested that Nedd4 plays an important role in the cell regulation, including neural differentiation through cooperation with specific E2 ubiquitination pathways. ..
  32. Eger S, Scheffner M, Marx A, Rubini M. Synthesis of defined ubiquitin dimers. J Am Chem Soc. 2010;132:16337-9 pubmed publisher
    ..Furthermore, these synthetic Ub dimers are recognized by the natural ubiquitination machinery and are proteolytically stable, making them optimal candidates to further investigate the function of differently linked Ub chains. ..
  33. Hillman P, Christian S, Doan R, Cohen N, Konganti K, Douglas K, et al. Genomic imprinting does not reduce the dosage of UBE3A in neurons. Epigenetics Chromatin. 2017;10:27 pubmed publisher
    The ubiquitin protein E3A ligase gene (UBE3A) gene is imprinted with maternal-specific expression in neurons and biallelically expressed in all other cell types...
  34. Mortensen F, Schneider D, Barbic T, Sladewska Marquardt A, Kühnle S, Marx A, et al. Role of ubiquitin and the HPV E6 oncoprotein in E6AP-mediated ubiquitination. Proc Natl Acad Sci U S A. 2015;112:9872-7 pubmed publisher
    Deregulation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with three different clinical pictures...
  35. Kato C, Tochigi M, Ohashi J, Koishi S, Kawakubo Y, Yamamoto K, et al. Association study of the 15q11-q13 maternal expression domain in Japanese autistic patients. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:1008-12 pubmed publisher
    ..investigated the association between autism and the maternal expression domain (MED) in the region, containing the UBE3A and ATP10C genes, and the upstream imprinting center (IC), which mediates coordinate control of imprinted ..
  36. Rietz A, Petrov D, Bartolowits M, Desmet M, Davisson V, Androphy E. Molecular Probing of the HPV-16 E6 Protein Alpha Helix Binding Groove with Small Molecule Inhibitors. PLoS ONE. 2016;11:e0149845 pubmed publisher
    ..The UBE3A/E6AP HECT domain ubiquitin ligase binds E6 at this helix-groove interface...
  37. Kim Y, Lee H, Xiong Y, Sciaky N, Hulbert S, Cao X, et al. Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader-Willi syndrome. Nat Med. 2017;23:213-222 pubmed publisher
    ..model of PWS carrying a paternal (p) deletion from small nuclear ribonucleoprotein N (Snrpn (S)) to ubiquitin protein ligase E3A (Ube3a (U)) (mouse model referred to hereafter as m+/p?S-U)...
  38. 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...
  39. Herzing L, Cook E, Ledbetter D. Allele-specific expression analysis by RNA-FISH demonstrates preferential maternal expression of UBE3A and imprint maintenance within 15q11- q13 duplications. Hum Mol Genet. 2002;11:1707-18 pubmed
    ..Control Dystrobrevin transcripts were detected equally from both alleles; however, maternal-UBE3A signals were consistently larger than paternal signals in normal fibroblasts and in neural-precursor cells...
  40. Zhou X, Deng S, Liu H, Liu Y, Yang Z, Xing T, et al. Knockdown of ubiquitin protein ligase E3A affects proliferation and invasion, and induces apoptosis of breast cancer cells through regulation of annexin A2. Mol Med Rep. 2015;12:1107-13 pubmed publisher
    The present study used RNA interference (RNAi) to study how the expression of annexin A2 was affected by ubiquitin protein ligase E3A (UBE3A)...
  41. Bailus B, Pyles B, McAlister M, O Geen H, Lockwood S, Adams A, et al. Protein Delivery of an Artificial Transcription Factor Restores Widespread Ube3a Expression in an Angelman Syndrome Mouse Brain. Mol Ther. 2016;24:548-55 pubmed publisher
    Angelman syndrome (AS) is a neurological genetic disorder caused by loss of expression of the maternal copy of UBE3A in the brain...
  42. Fink J, Robinson T, Germain N, Sirois C, Bolduc K, Ward A, et al. Disrupted neuronal maturation in Angelman syndrome-derived induced pluripotent stem cells. Nat Commun. 2017;8:15038 pubmed publisher
    Angelman syndrome (AS) is a neurogenetic disorder caused by deletion of the maternally inherited UBE3A allele and is characterized by developmental delay, intellectual disability, ataxia, seizures and a happy affect...
  43. Sidorov M, Judson M, Kim H, Rougie M, Ferrer A, Nikolova V, et al. Enhanced Operant Extinction and Prefrontal Excitability in a Mouse Model of Angelman Syndrome. J Neurosci. 2018;38:2671-2682 pubmed publisher
    ..disorder associated with intellectual disability, is caused by loss of maternal allele expression of UBE3A in neurons...
  44. 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...
  45. Lossie A, Whitney M, Amidon D, Dong H, Chen P, Theriaque D, et al. Distinct phenotypes distinguish the molecular classes of Angelman syndrome. J Med Genet. 2001;38:834-45 pubmed
    ..UPD) of chromosome 15; (3) an imprinting defect (ID); (4) a mutation in the E3 ubiquitin protein ligase gene (UBE3A); or (5) unidentified mechanism(s)...
  46. Eichmuller S, Usener D, Dummer R, Stein A, Thiel D, Schadendorf D. Serological detection of cutaneous T-cell lymphoma-associated antigens. Proc Natl Acad Sci U S A. 2001;98:629-34 pubmed
    ..The SCP-1-like gene and cTAGE-1 were shown to be immunogenic and immunologically tumor-specific and may therefore be candidates for immunotherapy targeting CTCL. ..
  47. Bedard K, Underbrink M, Howie H, Galloway D. The E6 oncoproteins from human betapapillomaviruses differentially activate telomerase through an E6AP-dependent mechanism and prolong the lifespan of primary keratinocytes. J Virol. 2008;82:3894-902 pubmed publisher
  48. 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 ..
  49. Kim H, Goldberg A. S5a/Rpn10, a UIM-protein, as a universal substrate for ubiquitination. Methods Mol Biol. 2012;832:653-60 pubmed publisher
    ..This approach is valuable when substrates are not known or not available and when multiple ubiquitination reactions are being studied (e.g., in high-throughput screens). ..
  50. Zhang L, Hu X, Chen J, Fu G. Impact of E6-associated protein on the proliferation and invasion of prostate cancer cells in bone metastasis. Int J Clin Exp Pathol. 2015;8:6571-5 pubmed
    ..Stable over-expression of E6-AP increases the proliferation and invasion of LNCaP cells. ..
  51. Lemak A, Yee A, Bezsonova I, Dhe Paganon S, Arrowsmith C. Zn-binding AZUL domain of human ubiquitin protein ligase Ube3A. J Biomol NMR. 2011;51:185-90 pubmed publisher
    b>Ube3A (also referred to as E6AP for E6 Associated Protein) is a E3 ubiquitin-protein ligase implicated in the development of Angelman syndrome by controlling degradation of synaptic protein Arc and oncogenic papilloma virus infection by ..
  52. Khatri N, Gilbert J, Huo Y, Sharaflari R, Nee M, Qiao H, et al. The Autism Protein Ube3A/E6AP Remodels Neuronal Dendritic Arborization via Caspase-Dependent Microtubule Destabilization. J Neurosci. 2018;38:363-378 pubmed publisher
    i>UBE3A gene copy number variation and the resulting overexpression of the protein E6AP is directly linked to autism spectrum disorders (ASDs). However, the underlying cellular and molecular neurobiology remains less clear...
  53. 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...
  54. Mevissen T, Hospenthal M, Geurink P, Elliott P, Akutsu M, Arnaudo N, et al. OTU deubiquitinases reveal mechanisms of linkage specificity and enable ubiquitin chain restriction analysis. Cell. 2013;154:169-84 pubmed publisher
    ..We introduce Ub chain restriction analysis, in which OTU DUBs are used as restriction enzymes to reveal linkage type and the relative abundance of Ub chains on substrates. ..
  55. Zhang J, Song R, Li Y, Feng J, Peng L, Li J. Integration of microarray profiles associated with cardiomyopathy and the potential role of Ube3a in apoptosis. Mol Med Rep. 2014;9:621-5 pubmed publisher
    ..Following validation using quantitative polymerase chain reaction, ubiquitin?protein ligase E3a (Ube3a) was selected as a candidate gene for the disease...
  56. Singh V, Sharma V, Verma V, Pandey D, Yadav S, Maikhuri J, et al. Apigenin manipulates the ubiquitin-proteasome system to rescue estrogen receptor-β from degradation and induce apoptosis in prostate cancer cells. Eur J Nutr. 2015;54:1255-67 pubmed publisher
    ..Unlike bortezomib, apigenin's actions are subtle, precise, mechanistically distinct and capable of abstaining drug resistance. ..
  57. Li Z, Dong M, Fan D, Hou P, Li H, Liu L, et al. LncRNA ANCR down-regulation promotes TGF-?-induced EMT and metastasis in breast cancer. Oncotarget. 2017;8:67329-67343 pubmed publisher
    ..Here, we find that lncRNA ANCR participates in TGF-?1-induced EMT...
  58. Kumari P, Srinivasan B, Banerjee S. Modulation of hippocampal synapse maturation by activity-regulated E3 ligase via non-canonical pathway. Neuroscience. 2017;364:226-241 pubmed publisher
    ..of Rnf2 through self-polyubiquitination rather than triggering its degradation through polyubiquitination by Ube3A, an E3 ligase implicated in Angelman Syndrome...
  59. Yi J, Paranjape S, Walker M, Choudhury R, Wolter J, Fragola G, et al. The autism-linked UBE3A T485A mutant E3 ubiquitin ligase activates the Wnt/?-catenin pathway by inhibiting the proteasome. J Biol Chem. 2017;292:12503-12515 pubmed publisher
    b>UBE3A is a HECT domain E3 ubiquitin ligase whose dysfunction is linked to autism, Angelman syndrome, and cancer...
  60. Scheffner M, Huibregtse J, Howley P. Identification of a human ubiquitin-conjugating enzyme that mediates the E6-AP-dependent ubiquitination of p53. Proc Natl Acad Sci U S A. 1994;91:8797-801 pubmed
    ..We demonstrate that UbcH5 can function in the E6/E6-AP-induced ubiquitination of p53. ..
  61. Ronchi V, Haas A. Measuring rates of ubiquitin chain formation as a functional readout of ligase activity. Methods Mol Biol. 2012;832:197-218 pubmed publisher
    ..These kinetic methods provide mechanistic insights that are otherwise inaccessible by other experimental approaches and yield a precision in characterizing protein interactions that exceeds that of other techniques. ..
  62. Shimura H, Schlossmacher M, Hattori N, Frosch M, Trockenbacher A, Schneider R, et al. Ubiquitination of a new form of alpha-synuclein by parkin from human brain: implications for Parkinson's disease. Science. 2001;293:263-9 pubmed
    ..These findings demonstrate a critical biochemical reaction between the two PD-linked gene products and suggest that this reaction underlies the accumulation of ubiquitinated alpha-synuclein in conventional PD. ..
  63. Reiter L, Seagroves T, Bowers M, Bier E. Expression of the Rho-GEF Pbl/ECT2 is regulated by the UBE3A E3 ubiquitin ligase. Hum Mol Genet. 2006;15:2825-35 pubmed
    We applied genetic tools available in Drosophila to identify candidate substrates of the UBE3A ubiquitin ligase, the gene responsible for Angelman syndrome (AS)...
  64. Dunaway K, Islam M, Coulson R, Lopez S, Vogel Ciernia A, Chu R, et al. Cumulative Impact of Polychlorinated Biphenyl and Large Chromosomal Duplications on DNA Methylation, Chromatin, and Expression of Autism Candidate Genes. Cell Rep. 2016;17:3035-3048 pubmed publisher
    ..Hypomethylated genes were enriched for H2A.Z, increased maternal UBE3A in Dup15q corresponded to reduced levels of RING1B, and bivalently modified H2A...
  65. Maheshwari M, Samanta A, Godavarthi S, Mukherjee R, Jana N. Dysfunction of the ubiquitin ligase Ube3a may be associated with synaptic pathophysiology in a mouse model of Huntington disease. J Biol Chem. 2012;287:29949-57 pubmed publisher
    ..Here, we demonstrate that the ubiquitin ligase Ube3a, which is implicated in synaptic plasticity and involved in the clearance of misfolded polyglutamine protein, is ..
  66. Lu Z, Hu X, Li Y, Zheng L, Zhou Y, Jiang H, et al. Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin. J Biol Chem. 2004;279:35664-70 pubmed publisher
    ..These results provide a possible link between E6-induced oncogenesis and the insulin-stimulated cell proliferation signaling pathway...
  67. James M, Lee J, Klingelhutz A. HPV16-E6 associated hTERT promoter acetylation is E6AP dependent, increased in later passage cells and enhanced by loss of p300. Int J Cancer. 2006;119:1878-85 pubmed
    ..These studies give insight into how immortalization by HPV results in upregulation of hTERT and furthers our understanding of how telomerase is activated during the process of malignant transformation. ..
  68. Pelc K, Cheron G, Boyd S, Dan B. Are there distinctive sleep problems in Angelman syndrome?. Sleep Med. 2008;9:434-41 pubmed
    ..It is caused by lack of expression of the UBE3A gene on the maternal chromosome 15q11-q13...
  69. Sartori S, Anesi L, Polli R, Toldo I, Casarin A, Drigo P, et al. Angelman syndrome due to a novel splicing mutation of the UBE3A gene. J Child Neurol. 2008;23:912-5 pubmed publisher
    ..The syndrome results from lack of function of the maternal copy of the UBE3A gene on the imprinted Prader-Willi/Angelman syndrome critical region; it is caused by large deletions, paternal ..
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    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...
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    ..occurs primarily due to genetic defects, which cause lack of expression or mutations in the wild-type E6AP/UBE3A protein...
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    ..This mechanism appears to regulate normal mammogenesis, and dysregulation of this process may be an important contributor to mammary cancer development and progression. ..
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    ..Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested ..
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    ..formation as a functional readout of enzyme activity, we have quantitatively examined the mechanism of human E6AP/UBE3A for the first time...
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    ..These findings suggest that E6-AP is a critical mediator of the neuronal response to misfolded polyglutamine proteins and represents a potential therapeutic target in the polyglutamine diseases...
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    ..The crystal structure of the E6AP hect domain bound to the UbcH7 ubiquitin-conjugating enzyme (E2) reveals the determinants of E2-E3 specificity and provides insights into the transfer of ubiquitin from the E2 to the E3. ..