TISIDB

Summary
Symbol	UBE3A
Name	ubiquitin protein ligase E3A
Aliases	E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location	15q11.2
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	UBE3A
Name	ubiquitin protein ligase E3A
Aliases	E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location	15q11.2
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

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Literatures describing the relation between UBE3A and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29463595	Prostate Carcinoma	Inhibit immunity	Genetic 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
Symbol	UBE3A
Name	ubiquitin protein ligase E3A
Aliases	E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location	15q11.2
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	UBE3A
Name	ubiquitin protein ligase E3A
Aliases	E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location	15q11.2
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.31	0.253
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.869	0.652
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.099	0.945
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.049	0.904
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.214	0.925
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.386	0.897
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.14	0.728
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.217	0.91
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.1	0.961
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.291	0.828
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.676	0.738
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.009	0.857

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	2.7	4.7	0.294
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	3.4	4	0.587
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	UBE3A
Name	ubiquitin protein ligase E3A
Aliases	E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location	15q11.2
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 [ TOP ]

Summary
Symbol	UBE3A
Name	ubiquitin protein ligase E3A
Aliases	E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location	15q11.2
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	UBE3A
Name	ubiquitin protein ligase E3A
Aliases	E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location	15q11.2
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	UBE3A
Name	ubiquitin protein ligase E3A
Aliases	E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location	15q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of UBE3A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	UBE3A
Name	ubiquitin protein ligase E3A
Aliases	E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location	15q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between UBE3A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	UBE3A
Name	ubiquitin protein ligase E3A
Aliases	E6-AP; FLJ26981; Angelman syndrome; EPVE6AP; HPVE6A; human papilloma virus E6-associated protein; CTCL tumor ......
Chromosomal Location	15q11.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting UBE3A collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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