MAGEA3
Melanoma-associated antigen 3
Also known as: CT1.3, HIP8, HYPD, MAGA3_HUMAN, MAGE3, MGC14613
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P43357
- Gene
- MAGEA3
- Ensembl
- ENSG00000221867
- Chromosome
- X
- Canonical length
- 314 aa
- Protein class
- Cancer-related genes, Predicted intracellular proteins
OverviewNCBI Gene
This gene is a member of the MAGEA gene family. The members of this family encode proteins with 50 to 80% sequence identity to each other. The promoters and first exons of the MAGEA genes show considerable variability, suggesting that the existence of this gene family enables the same function to be expressed under different transcriptional controls. The MAGEA genes are clustered at chromosomal location Xq28. They have been implicated in some hereditary disorders, such as dyskeratosis congenita. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
Canonical amino-acid sequenceUniProt
314 residues, UniProt reviewed canonical sequence.
>P43357|MAGEA3
1 MPLEQRSQHC KPEEGLEARG EALGLVGAQA PATEEQEAAS SSSTLVEVTL GEVPAAESPD
61 PPQSPQGASS LPTTMNYPLW SQSYEDSSNQ EEEGPSTFPD LESEFQAALS RKVAELVHFL
121 LLKYRAREPV TKAEMLGSVV GNWQYFFPVI FSKASSSLQL VFGIELMEVD PIGHLYIFAT
181 CLGLSYDGLL GDNQIMPKAG LLIIVLAIIA REGDCAPEEK IWEELSVLEV FEGREDSILG
241 DPKKLLTQHF VQENYLEYRQ VPGSDPACYE FLWGPRALVE TSYVKVLHHM VKISGGPHIS
301 YPPLHEWVLR EGEELocalizationUniProt · AlphaFold · HPA
Whether an antibody against MAGEA3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.45
- Highest tissue expression
- 7.6 nTPM
Expression across tissuesHPA
Tissue
- testis: 7.6 nTPM
- placenta: 0.3 nTPM
- adipose tissue: 0.2 nTPM
- adrenal gland: 0 nTPM
- amygdala: 0 nTPM
- appendix: 0 nTPM
Single-cell type
- early primary spermatocytes: 55 nCPM
- differentiating spermatogonia: 43 nCPM
- undifferentiated spermatogonia: 33 nCPM
- oocytes: 4.6 nCPM
- late primary spermatocytes: 3.9 nCPM
- late spermatids: 1.2 nCPM
Immune cell
- basophil: 0 nTPM
- classical monocyte: 0 nTPM
- eosinophil: 0 nTPM
- gdT-cell: 0 nTPM
- intermediate monocyte: 0 nTPM
- MAIT T-cell: 0 nTPM
Brain region
- amygdala: 0 nTPM
- basal ganglia: 0 nTPM
- cerebellum: 0 nTPM
- cerebral cortex: 0 nTPM
- choroid plexus: 0 nTPM
- hippocampal formation: 0 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about MAGEA3.
Disease | ImmuneIEDB
Conditions an epitope on MAGEA3 was assayed in.
- skin melanoma B and T cell
- melanoma T cell
- hepatocellular carcinoma T cell
- lung cancer T cell
- lung non-small cell carcinoma T cell
- testis seminoma T cell
- pancreatic adenocarcinoma T cell
- stomach cancer B cell
- gastrointestinal system disease B cell
- cholangiocarcinoma T cell
- multiple myeloma T cell
- anaplastic oligodendroglioma T cell
- hepatitis C T cell
- ovarian cancer T cell
- liver cirrhosis T cell
- testicular germ cell cancer T cell
- smoldering myeloma T cell
- lung adenocarcinoma T cell
- brain glioblastoma multiforme T cell
- castration-resistant prostate carcinoma T cell
ReferencesPubMed · IEDB
Publications for MAGEA3 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
2 publications
- Diagnostic performance of anti-MAGEA family protein autoantibodies in esophageal squamous cell carcinoma.
2023 · Int Immunopharmacol · RCR 0.5 · 4 citations - Serum cancer testis antigen MAGEA3-IgG serves as a diagnostic biomarker in lung adenocarcinoma.
2026 · Clin Transl Oncol
Reference: B cellIEDB
2 publications
- Vaccination with Melanoma Helper Peptides Induces Antibody Responses Associated with Improved Overall Survival.
2015 · Clin Cancer Res · RCR 1 · 39 citations - Novel immunodominant epitopes derived from MAGE-A3 and its significance in serological diagnosis of gastric cancer.
2013 · J Cancer Res Clin Oncol · RCR 0.3 · 8 citations
Reference: T cellIEDB
58 publications
- Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma.
2013 · Blood · RCR 24.2 · 975 citations - Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma.
2021 · Nat Med · RCR 21.4 · 429 citations - Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells.
2013 · Sci Transl Med · RCR 14 · 592 citations - High-throughput discovery of MHC class I- and II-restricted T cell epitopes using synthetic cellular circuits.
2025 · Nat Biotechnol · RCR 9.7 · 32 citations - SARS-CoV-2-specific CD8+ T cell responses in convalescent COVID-19 individuals.
2021 · J Clin Invest · RCR 9.6 · 209 citations
Show 20 more of 58 total
- Tuning T cell receptor sensitivity through catch bond engineering.
2022 · Science · RCR 7.6 · 128 citations - Prediction of neo-epitope immunogenicity reveals TCR recognition determinants and provides insight into immunoediting.
2021 · Cell Rep Med · RCR 6.3 · 131 citations - T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes.
2019 · Cell · RCR 5.8 · 198 citations - Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma.
2021 · Immunity · RCR 5.3 · 114 citations - Neoantigen-specific CD8 T cells with high structural avidity preferentially reside in and eliminate tumors.
2023 · Nat Commun · RCR 3.9 · 55 citations - 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.
2014 · Clin Cancer Res · RCR 2.8 · 103 citations - Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA.
2020 · J Clin Invest · RCR 2.7 · 71 citations - Direct molecular mimicry enables off-target cardiovascular toxicity by an enhanced affinity TCR designed for cancer immunotherapy.
2016 · Sci Rep · RCR 2.7 · 96 citations - VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens.
2024 · Front Immunol · RCR 2.4 · 8 citations - A randomized phase II trial of multiepitope vaccination with melanoma peptides for cytotoxic T cells and helper T cells for patients with metastatic melanoma (E1602).
2013 · Clin Cancer Res · RCR 2.3 · 92 citations - Vγ9Vδ2 T Cells Concurrently Kill Cancer Cells and Cross-Present Tumor Antigens.
2021 · Front Immunol · RCR 2.3 · 45 citations - Vaccination with LAG-3Ig (IMP321) and Peptides Induces Specific CD4 and CD8 T-Cell Responses in Metastatic Melanoma Patients--Report of a Phase I/IIa Clinical Trial.
2016 · Clin Cancer Res · RCR 2.3 · 81 citations - Dendritic cell-based vaccination in metastatic melanoma patients: phase II clinical trial.
2012 · Oncol Rep · RCR 2.2 · 88 citations - Structural features of peptide analogs of human histocompatibility leukocyte antigen class I epitopes that are more potent and immunogenic than wild-type peptide.
2001 · J Exp Med · RCR 2.1 · 121 citations - Analysis of the T cell response to tumor and viral peptide antigens by an IFNgamma-ELISPOT assay.
1997 · Int J Cancer · RCR 2 · 100 citations - T cell receptor specificity landscape revealed through de novo peptide design.
2025 · Proc Natl Acad Sci U S A · RCR 1.9 · 8 citations - A New Plasmacytoid Dendritic Cell-Based Vaccine in Combination with Anti-PD-1 Expands the Tumor-Specific CD8+ T Cells of Lung Cancer Patients.
2023 · Int J Mol Sci · RCR 1.8 · 20 citations - α-type-1 polarized dendritic cell-based vaccination in recurrent high-grade glioma: a phase I clinical trial.
2012 · BMC Cancer · RCR 1.8 · 71 citations - Global analysis of HLA-A2 restricted MAGE-A3 tumor antigen epitopes and corresponding TCRs in non-small cell lung cancer.
2023 · Theranostics · RCR 1.8 · 17 citations - A multiepitope of XBP1, CD138 and CS1 peptides induces myeloma-specific cytotoxic T lymphocytes in T cells of smoldering myeloma patients.
2015 · Leukemia · RCR 1.6 · 56 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD missense Z
- -2.34
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- negative regulation of autophagy
- negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway
- negative regulation of protein processing
- negative regulation of transcription by RNA polymerase II
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of MAGEA3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads MAGEA3 as an antibody target. Whether an autoantibody or antibody against MAGEA3 could matter depends on whether native MAGEA3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
MAGEA3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label MAGEA3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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