TISIDB

Summary
Symbol	MAGEA3
Name	melanoma antigen family A3
Aliases	HYPD; HIP8; MGC14613; CT1.3; melanoma-associated antigen 3; antigen MZ2-D; MAGE-3 antigen; cancer/testis ant ......
Chromosomal Location	Xq28
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	-
Domain	PF01454 MAGE family PF12440 Melanoma associated antigen family N terminal
Function	Proposed to enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. May enhance ubiquitin ligase activity of TRIM28 and stimulate p53/TP53 ubiquitination by TRIM28. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. May play a role in embryonal development and tumor transformation or aspects of tumor progression. In vitro promotes cell viability in melanoma cell lines. Antigen recognized on a melanoma by autologous cytolytic T-lymphocytes.

> Gene Ontology [ TOP ]
Biological Process	GO:0010466 negative regulation of peptidase activity GO:0010951 negative regulation of endopeptidase activity GO:0010955 negative regulation of protein processing GO:0016485 protein processing GO:0034976 response to endoplasmic reticulum stress GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0045861 negative regulation of proteolysis GO:0051346 negative regulation of hydrolase activity GO:0051604 protein maturation GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0070613 regulation of protein processing GO:0097193 intrinsic apoptotic signaling pathway GO:1902235 regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1902532 negative regulation of intracellular signal transduction GO:1903317 regulation of protein maturation GO:1903318 negative regulation of protein maturation GO:1903573 negative regulation of response to endoplasmic reticulum stress GO:2000116 regulation of cysteine-type endopeptidase activity GO:2000117 negative regulation of cysteine-type endopeptidase activity GO:2001233 regulation of apoptotic signaling pathway GO:2001234 negative regulation of apoptotic signaling pathway GO:2001242 regulation of intrinsic apoptotic signaling pathway GO:2001243 negative regulation of intrinsic apoptotic signaling pathway
Molecular Function	GO:0002020 protease binding GO:0089720 caspase binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	-

Summary
Symbol	MAGEA3
Name	melanoma antigen family A3
Aliases	HYPD; HIP8; MGC14613; CT1.3; melanoma-associated antigen 3; antigen MZ2-D; MAGE-3 antigen; cancer/testis ant ......
Chromosomal Location	Xq28
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MAGEA3 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 MAGEA3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
24671426	Melanoma	Promote immunity (T cell function); essential for immunotherapy	MAGE-A3 with cell-penetrating domain as an efficient therapeutic cancer vaccine. To determine whether generating melanoma antigen family A, 3 (MAGE-A3), a tumor-specific cancer-testis antigen, as a fusion protein with CPD will enhance the cytosolic bioavailability of MAGE-A3. Enhanced cytosolic bioavailability of tumor-specific antigens improves access to human leukocyte antigen (HLA) class I molecules for more efficient cytotoxic T lymphocyte generation.
24520093	Plasma Cell Myeloma	Promote immunity (T/NK cell function); essential for immunotherapy	Combination immunotherapy after ASCT for multiple myeloma using MAGE-A3/Poly-ICLC immunizations followed by adoptive transfer of vaccine-primed and costimulated autologous T cells. A high frequency of vaccine-specific T-cell responses were generated after transplant by combining costimulated autologous T cells with a Poly-ICLC/GM-CSF-primed MAGE-A3 vaccine.
23838315	Childhood acute lymphoblastic leukemia	Promote immunity (T cell function); essential for immunotherapy	Peripheral blood mononuclear cells were stimulated with autologous dendritic cells pulsed with complete peptide libraries of WT1, Survivin, MAGE-A3, and PRAME, antigens frequently expressed on ALL blasts. Antigen-specificity was observed in more than 50% of patients after the initial stimulation and increased to more than 90% after three stimulations as assessed in IFN-γ-enzyme-linked immunospot (ELISpot) and (51)Cr-release assays. This study supports the use of immunotherapy with adoptively transferred autologous tumor antigen-specific T cells to prevent relapse and improve the prognosis of patients with high-risk ALL.
19074732	Melanoma	Promote immunity (T cell function)	Three of 10 patients treated with MAGE-A3-GML showed an increase of circulating anti-MAGE-A3 T cells, and developed skin delayed-type hypersensitivity to MAGE-A3. Interestingly, in 2 of these patients, with progressive and measurable tumors at study entry, anti-MAGE-A3 T cells were detected not only in the blood but also within tumors resected after vaccination.
29674449	lung carcinoma	Promote immunity	The ihv-DCs, which are engineered to express MAGEA3 and high levels of 4-1BBL and MICA, induce simultaneous production of both HLA-A2-restricted, MAGEA3-specific CTLs and NK cells from HLA-A2+ donor peripheral blood mononuclear cells.
23904461	Melanoma	Promote immunity (T cell function); essential for immunotherapy	Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic messenger RNA (mRNA) encoding a CD40 ligand, a constitutively active Toll-like receptor 4 and CD70, together with mRNA encoding fusion proteins of a human leukocyte antigen (HLA)-class II targeting signal (DC-LAMP) and a melanoma-associated antigen (MAA); either MAGE-A3, MAGE-C2, tyrosinase or gp100) (TriMixDC-MEL) are superiorly immunogenic.

Summary
Symbol	MAGEA3
Name	melanoma antigen family A3
Aliases	HYPD; HIP8; MGC14613; CT1.3; melanoma-associated antigen 3; antigen MZ2-D; MAGE-3 antigen; cancer/testis ant ......
Chromosomal Location	Xq28
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 MAGEA3 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	MAGEA3
Name	melanoma antigen family A3
Aliases	HYPD; HIP8; MGC14613; CT1.3; melanoma-associated antigen 3; antigen MZ2-D; MAGE-3 antigen; cancer/testis ant ......
Chromosomal Location	Xq28
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 MAGEA3 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	-0.688	0.309
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.512	0.809
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-1.593	0.425
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-1.593	0.3
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.773	0.395
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.345	0.563
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.615	0.69
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-2.164	0.329
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.909	0.37
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0	1
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	1
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	1.251	0.0433

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MAGEA3 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	0	5.9	-5.9	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	33.3	-33.3	0.231
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	0	2.7	-2.7	1
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	0	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	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	7.7	0	7.7	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	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
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	MAGEA3
Name	melanoma antigen family A3
Aliases	HYPD; HIP8; MGC14613; CT1.3; melanoma-associated antigen 3; antigen MZ2-D; MAGE-3 antigen; cancer/testis ant ......
Chromosomal Location	Xq28
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MAGEA3. 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	MAGEA3
Name	melanoma antigen family A3
Aliases	HYPD; HIP8; MGC14613; CT1.3; melanoma-associated antigen 3; antigen MZ2-D; MAGE-3 antigen; cancer/testis ant ......
Chromosomal Location	Xq28
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MAGEA3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MAGEA3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MAGEA3
Name	melanoma antigen family A3
Aliases	HYPD; HIP8; MGC14613; CT1.3; melanoma-associated antigen 3; antigen MZ2-D; MAGE-3 antigen; cancer/testis ant ......
Chromosomal Location	Xq28
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MAGEA3. 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	MAGEA3
Name	melanoma antigen family A3
Aliases	HYPD; HIP8; MGC14613; CT1.3; melanoma-associated antigen 3; antigen MZ2-D; MAGE-3 antigen; cancer/testis ant ......
Chromosomal Location	Xq28
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MAGEA3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MAGEA3
Name	melanoma antigen family A3
Aliases	HYPD; HIP8; MGC14613; CT1.3; melanoma-associated antigen 3; antigen MZ2-D; MAGE-3 antigen; cancer/testis ant ......
Chromosomal Location	Xq28
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MAGEA3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MAGEA3
Name	melanoma antigen family A3
Aliases	HYPD; HIP8; MGC14613; CT1.3; melanoma-associated antigen 3; antigen MZ2-D; MAGE-3 antigen; cancer/testis ant ......
Chromosomal Location	Xq28
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MAGEA3 collected from DrugBank database.

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

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