Browse UBE3A

Summary
SymbolUBE3A
Nameubiquitin protein ligase E3A
Aliases E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location15q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm Nucleus
Domain PF16558 Amino-terminal Zinc-binding domain of ubiquitin ligase E3A
PF00632 HECT-domain (ubiquitin-transferase)
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 (PubMed:10373495, PubMed:16772533, PubMed:19204938, PubMed:19233847, PubMed:19325566, PubMed:19591933, PubMed:22645313, PubMed:24273172, PubMed:24728990). 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 (PubMed:10373495, PubMed:19204938, PubMed:19325566, PubMed:19591933, PubMed:22645313, PubMed:24728990). Additionally, may function as a cellular quality control ubiquitin ligase by helping the degradation of the cytoplasmic misfolded proteins (PubMed:19233847). 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 (PubMed:24728990). Acts as transcriptional coactivator of progesterone receptor PGR upon progesterone hormone activation (PubMed:16772533). Acts as a regulator of synaptic development by mediating ubiquitination and degradation of ARC (By similarity). Synergizes with WBP2 in enhancing PGR activity (PubMed:16772533). ; FUNCTION: (Microbial infection) Catalyzes the high-risk human papilloma virus E6-mediated ubiquitination of p53/TP53, contributing to the neoplastic progression of cells infected by these viruses.

> Gene Ontology
 
Biological Process GO:0000209 protein polyubiquitination
GO:0001541 ovarian follicle development
GO:0001655 urogenital system development
GO:0007338 single fertilization
GO:0007548 sex differentiation
GO:0007623 circadian rhythm
GO:0008406 gonad development
GO:0008585 female gonad development
GO:0009566 fertilization
GO:0009755 hormone-mediated signaling pathway
GO:0009894 regulation of catabolic process
GO:0014065 phosphatidylinositol 3-kinase signaling
GO:0014066 regulation of phosphatidylinositol 3-kinase signaling
GO:0014068 positive regulation of phosphatidylinositol 3-kinase signaling
GO:0022602 ovulation cycle process
GO:0030518 intracellular steroid hormone receptor signaling pathway
GO:0030521 androgen receptor signaling pathway
GO:0030522 intracellular receptor signaling pathway
GO:0030850 prostate gland development
GO:0031329 regulation of cellular catabolic process
GO:0031396 regulation of protein ubiquitination
GO:0031398 positive regulation of protein ubiquitination
GO:0035037 sperm entry
GO:0035265 organ growth
GO:0042176 regulation of protein catabolic process
GO:0042698 ovulation cycle
GO:0042752 regulation of circadian rhythm
GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0043401 steroid hormone mediated signaling pathway
GO:0045137 development of primary sexual characteristics
GO:0046545 development of primary female sexual characteristics
GO:0046660 female sex differentiation
GO:0048015 phosphatidylinositol-mediated signaling
GO:0048017 inositol lipid-mediated signaling
GO:0048511 rhythmic process
GO:0048545 response to steroid hormone
GO:0048608 reproductive structure development
GO:0048732 gland development
GO:0051865 protein autoubiquitination
GO:0060736 prostate gland growth
GO:0061458 reproductive system development
GO:0070936 protein K48-linked ubiquitination
GO:0071383 cellular response to steroid hormone stimulus
GO:0071396 cellular response to lipid
GO:0071407 cellular response to organic cyclic compound
GO:1903050 regulation of proteolysis involved in cellular protein catabolic process
GO:1903320 regulation of protein modification by small protein conjugation or removal
GO:1903322 positive regulation of protein modification by small protein conjugation or removal
GO:1903362 regulation of cellular protein catabolic process
GO:2000058 regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Molecular Function GO:0003713 transcription coactivator activity
GO:0004842 ubiquitin-protein transferase activity
GO:0019787 ubiquitin-like protein transferase activity
GO:0061630 ubiquitin protein ligase activity
GO:0061659 ubiquitin-like protein ligase activity
Cellular Component GO:0000502 proteasome complex
GO:1905368 peptidase complex
GO:1905369 endopeptidase complex
> KEGG and Reactome Pathway
 
KEGG hsa04120 Ubiquitin mediated proteolysis
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-983168: Antigen processing
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-168256: Immune System
Summary
SymbolUBE3A
Nameubiquitin protein ligase E3A
Aliases E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location15q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between UBE3A and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between UBE3A and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
29463595Prostate CarcinomaInhibit immunityGenetic manipulations of E6AP in prostate cancer cells expose a role of E6AP in promoting growth and survival of prostate cancer cells in vitro and in vivo. Concomitant knockdown of E6AP and clusterin supported the contribution of clusterin to the phenotype induced by E6AP.
Summary
SymbolUBE3A
Nameubiquitin protein ligase E3A
Aliases E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location15q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of UBE3A in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolUBE3A
Nameubiquitin protein ligase E3A
Aliases E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location15q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of UBE3A in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.310.253
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.8690.652
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0990.945
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0490.904
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.2140.925
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.3860.897
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.140.728
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2170.91
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.10.961
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2910.828
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.6760.738
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0090.857
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of UBE3A in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.42.74.70.294
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.43.440.587
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolUBE3A
Nameubiquitin protein ligase E3A
Aliases E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location15q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of UBE3A. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolUBE3A
Nameubiquitin protein ligase E3A
Aliases E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location15q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of UBE3A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by UBE3A.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolUBE3A
Nameubiquitin protein ligase E3A
Aliases E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location15q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of UBE3A. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolUBE3A
Nameubiquitin protein ligase E3A
Aliases E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location15q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of UBE3A expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolUBE3A
Nameubiquitin protein ligase E3A
Aliases E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location15q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between UBE3A and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolUBE3A
Nameubiquitin protein ligase E3A
Aliases E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location15q11.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting UBE3A collected from DrugBank database.
> Drugs from DrugBank database
 

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