Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

UBE3A (ubiquitin protein ligase E3A)

Written2008-11Konstantin Matentzoglu, Martin Scheffner
Laboratory of cellular biochemistry, Department of biology, Box 642, University of Konstanz, D-78457 Konstanz, Germany

(Note : for Links provided by Atlas : click)


HGNC Alias symbAS
HGNC Alias nameAngelman syndrome
HGNC Previous nameEPVE6AP
HGNC Previous namehuman papilloma virus E6-associated protein
LocusID (NCBI) 7337
Atlas_Id 42756
Location 15q11.2  [Link to chromosome band 15q11]
Location_base_pair Starts at 25333728 and ends at 25439024 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping UBE3A.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
UBE3A (15q11.2)::CYP19A1 (15q21.2)


Description The UBE3A gene is located on Chr. 15 (23133489-23235221); 13 exons.
Transcription 3 Isoforms through alternative splicing; mRNA Isoform 1: 4491 bp, ORF: 2556 bp; mRNA Isoform 2: 4516 bp, ORF: 2625 bp; mRNA Isoform 3: 5164 bp, ORF: 2616 bp.


Description The UBE3A gene product is commonly referred to as E6AP (E6 associated protein).
Isoform 1: 852 amino acids, Isoform 2: 875 amino acids, Isoform 3: 872 amino acids. Migration in SDS-PAGE with an approximate molecular mass of 100 kDa.
HECT (Homologous to the E6AP C terminus) domain: amino acids 500-852; Active cysteine residue at position 820 (amino acid positions refer to Isoform 1).
Posttranslational modifications: ubiquitylation.
Binding partners and interaction sites on E6AP: Human papillomavirus (HPV) E6 oncoprotein: amino acids 378-395; Herc2 (unpublished): amino acids 150-200; Steroid hormone receptors (AR, ER, PR): amino acids 386-390 and 638-642 (LxxLL motif); Hepatitis C virus core protein: amino acids 395-494 (amino acid positions refer to Isoform 1).
Expression Monoallelically expressed (maternal allele) in Purkinje neurons, a subset of hippocampal neurons, and neurons of the olfactory bulb. Biallelically expressed in most other tissues.
Localisation Predominantly cytoplasmic.
Function Ubiquitin-protein ligase. In complex with the E6 oncoprotein of cervical cancer-associated HPVs, E6AP targets p53 and other cellular proteins (e.g. hDLG, Scribble, E6TP1, NFX1-91) for ubiquitylation and proteasomal degradation. E6-independent substrates include HHR23A and HHR23B, BLK, BAK, MCM7, and AIB1. Loss-of-function results in Angelman Syndrome.
Coactivator of the nuclear hormone receptor superfamily. This function appears to be independent of the ubiquitin ligase function and its role in human disease remains unknown.
Homology E6AP shares homology from fly to man and is highly conserved in vertebrates.


Note All known disease-associated mutations (maternal allele) result in an inactivation of the ubiquitin ligase function and have been etiologically associated with the Angelman Syndrome. Mutations in the UBE3A gene have not been associated with cancer development.

Implicated in

Entity Cervical Cancer
Oncogenesis The E6 oncoprotein of so-called high risk HPVs that have been etiologically associated with malignant lesion of the anogenital tract (most notably, cervical cancer) have the ability to bind to E6AP. The E6/E6AP complex binds to the p53 tumor suppressor, thereby targeting p53 for ubiquitylation and proteasomal degradation. It is commonly assumed that this (p53 degradation and, thus, inactivation) represents a critical step in the development of cervical cancer. Although additional targets of the E6/E6AP complex have been described (see above), the relevance of these interactions for cervical carcinogenesis is currently unclear. Furthermore, E6AP itself is a target for E6-dependent autoubiquitylation and degradation. However, if this contributes to HPV-induced cervical carcinogenesis is currently unknown.
Entity Angelman Syndrome
Disease Angelman Syndrome is a severe neurological disorder, genetically linked to UBE3A. Almost 95 % of all known mutations hit the maternal UBE3A allele or its relevant imprinting center, resulting in inactivation of the ubiquitin ligase function of E6AP.


Antisense targeting of E6AP elevates p53 in HPV-infected cells but not in normal cells.
Beer-Romero P, Glass S, Rolfe M.
Oncogene. 1997 Feb 6;14(5):595-602.
PMID 9053858
Growth suppression induced by downregulation of E6-AP expression in human papillomavirus-positive cancer cell lines depends on p53.
Hengstermann A, D'silva MA, Kuballa P, Butz K, Hoppe-Seyler F, Scheffner M.
J Virol. 2005 Jul;79(14):9296-300.
PMID 15994823
Localization of the E6-AP regions that direct human papillomavirus E6 binding, association with p53, and ubiquitination of associated proteins.
Huibregtse JM, Scheffner M, Howley PM.
Mol Cell Biol. 1993 Aug;13(8):4918-27.
PMID 8393140
Human papillomavirus type 16 E6 induces self-ubiquitination of the E6AP ubiquitin-protein ligase.
Kao WH, Beaudenon SL, Talis AL, Huibregtse JM, Howley PM.
J Virol. 2000 Jul;74(14):6408-17.
PMID 10864652
The global transcriptional effects of the human papillomavirus E6 protein in cervical carcinoma cell lines are mediated by the E6AP ubiquitin ligase.
Kelley ML, Keiger KE, Lee CJ, Huibregtse JM.
J Virol. 2005 Mar;79(6):3737-47.
PMID 15731267
UBE3A/E6-AP mutations cause Angelman syndrome.
Kishino T, Lalande M, Wagstaff J.
Nat Genet. 1997 Jan;15(1):70-3.
PMID 8988171
The human papillomavirus E6 protein and its contribution to malignant progression.
Mantovani F, Banks L.
Oncogene. 2001 Nov 26;20(54):7874-87. (REVIEW)
PMID 11753670
Ubiquitin ligase E6-AP and its role in human disease.
Matentzoglu K, Scheffner M.
Biochem Soc Trans. 2008 Oct;36(Pt 5):797-801.
PMID 18793139
De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome.
Matsuura T, Sutcliffe JS, Fang P, Galjaard RJ, Jiang YH, Benton CS, Rommens JM, Beaudet AL.
Nat Genet. 1997 Jan;15(1):74-7.
PMID 8988172
The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily.
Nawaz Z, Lonard DM, Smith CL, Lev-Lehman E, Tsai SY, Tsai MJ, O'Malley BW.
Mol Cell Biol. 1999 Feb;19(2):1182-9.
PMID 9891052
Human papillomavirus-induced carcinogenesis and the ubiquitin-proteasome system.
Scheffner M, Whitaker NJ.
Semin Cancer Biol. 2003 Feb;13(1):59-67.
PMID 12507557
The human E6-AP gene (UBE3A) encodes three potential protein isoforms generated by differential splicing.
Yamamoto Y, Huibregtse JM, Howley PM.
Genomics. 1997 Apr 15;41(2):263-6.
PMID 9143503
Papillomaviruses and cancer: from basic studies to clinical application.
zur Hausen H.
Nat Rev Cancer. 2002 May;2(5):342-50. (REVIEW)
PMID 12044010


This paper should be referenced as such :
Matentzoglu, K ; Scheffner, M
UBE3A (ubiquitin protein ligase E3A)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(10):737-738.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)UBE3A   12496
LRG (Locus Reference Genomic)LRG_15
Atlas Explorer : (Salamanque)UBE3A
Entrez_Gene (NCBI)UBE3A    ubiquitin protein ligase E3A
AliasesANCR; AS; E6-AP; EPVE6AP; 
GeneCards (Weizmann)UBE3A
Ensembl hg19 (Hinxton)ENSG00000114062 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000114062 [Gene_View]  ENSG00000114062 [Sequence]  chr15:25333728-25439024 [Contig_View]  UBE3A [Vega]
ICGC DataPortalENSG00000114062
TCGA cBioPortalUBE3A
Genatlas (Paris)UBE3A
SOURCE (Princeton)UBE3A
Genetics Home Reference (NIH)UBE3A
Genomic and cartography
GoldenPath hg38 (UCSC)UBE3A  -     chr15:25333728-25439024 -  15q11.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)UBE3A  -     15q11.2   [Description]    (hg19-Feb_2009)
GoldenPathUBE3A - 15q11.2 [CytoView hg19]  UBE3A - 15q11.2 [CytoView hg38]
Genome Data Viewer NCBIUBE3A [Mapview hg19]  
OMIM105830   601623   
Gene and transcription
Genbank (Entrez)AA745240 AB194232 AB194232 AF002224 AF002225
RefSeq transcript (Entrez)NM_000462 NM_001354505 NM_001354506 NM_001354507 NM_001354508 NM_001354509 NM_001354511 NM_001354512 NM_001354513 NM_001354523 NM_001354526 NM_001354538 NM_001354539 NM_001354540 NM_001354541 NM_001354542 NM_001354543 NM_001354544 NM_001354545 NM_001354546 NM_001354547 NM_001354548 NM_001354549 NM_001354550 NM_001354551 NM_001374461 NM_130838 NM_130839
Consensus coding sequences : CCDS (NCBI)UBE3A
Gene ExpressionUBE3A [ NCBI-GEO ]   UBE3A [ EBI - ARRAY_EXPRESS ]   UBE3A [ SEEK ]   UBE3A [ MEM ]
Gene Expression Viewer (FireBrowse)UBE3A [ Firebrowse - Broad ]
GenevisibleExpression of UBE3A in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)7337
GTEX Portal (Tissue expression)UBE3A
Human Protein AtlasENSG00000114062-UBE3A [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)UBE3A
Human Protein Atlas [tissue]ENSG00000114062-UBE3A [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed332 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Jan 20 14:19:54 CET 2022

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us