MAGEA2

Summary

MAGEA2 (MAGE family member A2, HGNC:6800) is a protein-coding gene on chromosome Xq28, encoding Melanoma-associated antigen 2 (P43356). Reduces p53/TP53 transactivation function through recruitment of HDAC3 to p53/TP53 transcription sites.

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. This gene has two identical copies at different loci. Alternatively spliced transcript variants encoding the same protein have been identified for this gene.

Source: NCBI Gene 4101 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001386130

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6800
Approved symbol	MAGEA2
Name	MAGE family member A2
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	MAGEA2A, CT1.2
Ensembl gene	ENSG00000268606
Ensembl biotype	protein_coding
OMIM	300173
Entrez	4101

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 41 protein_coding

ENST00000595583, ENST00000598543, ENST00000611557, ENST00000611674, ENST00000617505, ENST00000617846, ENST00000620710, ENST00000623438, ENST00000623806, ENST00000684311, ENST00000911624, ENST00000911625, ENST00000911626, ENST00000911627, ENST00000911628, ENST00000911629, ENST00000911630, ENST00000911631, ENST00000911632, ENST00000911633, ENST00000911634, ENST00000911635, ENST00000911636, ENST00000911637, ENST00000911638, ENST00000911639, ENST00000911640, ENST00000911641, ENST00000911642, ENST00000911643, ENST00000911644, ENST00000911645, ENST00000911646, ENST00000911647, ENST00000911648, ENST00000911649, ENST00000911650, ENST00000911651, ENST00000911652, ENST00000911653, ENST00000911654

RefSeq mRNA: 8 — MANE Select: NM_001386130 NM_001282501, NM_001282502, NM_001282504, NM_001282505, NM_001386130, NM_005361, NM_175742, NM_175743

CCDS: CCDS76049

Canonical transcript exons

ENST00000684311 — 5 exons

Exon	Start	End
ENSE00002985422	152751509	152751574
ENSE00003160695	152752394	152752513
ENSE00003721239	152753313	152753391
ENSE00003736331	152753788	152753842
ENSE00003826032	152749863	152751428

Expression profiles

Bgee: expression breadth broad, 20 present calls, max score 80.81.

Top tissues by expression

110 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.63	gold quality
right testis	UBERON:0004534	68.00	gold quality
testis	UBERON:0000473	65.37	gold quality
left testis	UBERON:0004533	63.96	gold quality
sural nerve	UBERON:0015488	42.23	silver quality
colonic epithelium	UBERON:0000397	41.39	gold quality
placenta	UBERON:0001987	41.32	gold quality
lower esophagus mucosa	UBERON:0035834	37.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	36.52	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
prefrontal cortex	UBERON:0000451	36.01	gold quality
superior frontal gyrus	UBERON:0002661	35.75	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	34.79	gold quality
lymph node	UBERON:0000029	32.47	gold quality
muscle tissue	UBERON:0002385	32.09	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
frontal cortex	UBERON:0001870	31.44	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	30.97	silver quality
liver	UBERON:0002107	30.78	gold quality
endometrium	UBERON:0001295	30.52	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
cortex of kidney	UBERON:0001225	29.49	gold quality
cerebral cortex	UBERON:0000956	29.45	silver quality
putamen	UBERON:0001874	28.88	gold quality
urinary bladder	UBERON:0001255	28.71	gold quality
muscle of leg	UBERON:0001383	28.59	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	87.20
E-CURD-53	no	50.48
E-ANND-3	no	0.16

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting MAGEA2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-6509-3P	98.32	67.33	1343
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-96-3P	97.47	68.03	839
HSA-MIR-6750-3P	96.79	67.50	740
HSA-MIR-6857-3P	96.70	65.43	915
HSA-MIR-151A-3P	95.52	65.29	516
HSA-MIR-5195-5P	90.84	65.09	287

Literature-anchored findings (GeneRIF, showing 16)

• MAGE-A2 targets p53 transactivation function through histone deacetylase recruitment (PMID:16847267)
• These data show, for the first time, the involvement of methyl-CpG binding domain proteins in the regulation of the MAGE-A genes. (PMID:17634428)
• Multiple simultaneous detection of MAGE-A [subtypes] more specific and sensitive than detection of single MAGE-A antigen for the diagnostic and prognostic evaluation of oral squamous cell carcinoma (PMID:18197853)
• These data suggest that MAGEA2 is differentially expressed in HNSCC and functions, in part, through the p53 pathway by increasing cellular proliferation and abrogating cell cycle arrest. (PMID:21422315)
• MageA2 interferes with p53 acetylation at PML-nuclear bodies (NBs) and with PMLIV-dependent activation of p53. (PMID:22117195)
• Report MAGEA1-A6 expression in sputum suggests presence of lung cancer cells or precancerous cells. (PMID:22134685)
• Consistent with increased cell death, the induced loss of MAGEA2 expression correlated with increased caspase 3/7 activity, BCL2/BAX ratio and TUNEL signal. (PMID:24481586)
• MAGEA2 has a critical role in the development of tamoxifen-resistant breast cancer (PMID:24662835)
• We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. (PMID:26001071)
• Immunohistochemistry using D2-40 monoclonal antibody (MAGE2) and anti-MITF1 increased detection of lymphovascular invasion in primary cutaneous melanoma. (PMID:26675354)
• Data indicate that melanoma-associated antigen A2 (MAGEA2)is significantly overexpressed in triple-negative breast cancer (TNBC) tissues and is important for progression of TNBC and may serve as a novel molecular therapeutic target. (PMID:28415749)
• suppression of MAGEA2 in lung cancer cells significantly reduced the growth/survival of cancer cells. High-MAGEA2 was identified as an independent prognostic factor in lung adenocarcinoma. Specific inhibition of MAGEA2 may be a promising therapeutic strategy for patients with lung cancer. (PMID:28498455)
• high MAGEA2 expression is an independent prognostic factor for glioma patient poor overall survival (PMID:30064232)
• Reduced cytoplasmic expression of MAGE-A2 predicts tumor aggressiveness and survival: an immunohistochemical analysis. (PMID:32772147)
• Overexpression of melanoma-associated antigen A2 has a clinical significance in embryonal carcinoma and is associated with tumor progression. (PMID:34837545)
• hMAGEA2 Accelerates the Progression of Prostate Cancer via the EFNA3-Erk1/2 Signaling Pathway. (PMID:38925815)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndnl2	ENSDARG00000058212
mus_musculus	Magea13	ENSMUSG00000046180
rattus_norvegicus	Magea13	ENSRNOG00000003532
drosophila_melanogaster	MAGE	FBGN0037481

Paralogs (37): MAGEC2 (ENSG00000046774), TRO (ENSG00000067445), MAGEB2 (ENSG00000099399), MAGED2 (ENSG00000102316), MAGEB4 (ENSG00000120289), MAGEA9 (ENSG00000123584), MAGEA10 (ENSG00000124260), MAGEA4 (ENSG00000147381), MAGED4 (ENSG00000154545), MAGEC1 (ENSG00000155495), MAGEA8 (ENSG00000156009), MAGEC3 (ENSG00000165509), MAGEB6 (ENSG00000176746), MAGEB18 (ENSG00000176774), MAGEF1 (ENSG00000177383), MAGEB10 (ENSG00000177689), MAGED1 (ENSG00000179222), NDN (ENSG00000182636), MAGEB17 (ENSG00000182798), MAGEA2B (ENSG00000183305), NSMCE3 (ENSG00000185115), MAGEA11 (ENSG00000185247), MAGEE2 (ENSG00000186675), MAGED4B (ENSG00000187243), MAGEH1 (ENSG00000187601), MAGEB5 (ENSG00000188408), MAGEB16 (ENSG00000189023), MAGEA6 (ENSG00000197172), MAGEA1 (ENSG00000198681), MAGEB3 (ENSG00000198798), MAGEE1 (ENSG00000198934), MAGEA12 (ENSG00000213401), MAGEB1 (ENSG00000214107), MAGEA3 (ENSG00000221867), MAGEB6B (ENSG00000232030), MAGEL2 (ENSG00000254585), MAGEA9B (ENSG00000267978)

Protein

Protein identifiers

Melanoma-associated antigen 2 — P43356 (reviewed: P43356)

Alternative names: Cancer/testis antigen 1.2, MAGE-2 antigen

All UniProt accessions (3): A0A087WZT8, P43356, E7ENJ0

UniProt curated annotations — full annotation on UniProt →

Function. Reduces p53/TP53 transactivation function through recruitment of HDAC3 to p53/TP53 transcription sites. Also represses p73/TP73 activity. Proposed to enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. In vitro enhances ubiquitin ligase activity of TRIM28 and stimulates p53/TP53 ubiquitination by TRIM28 potentially in presence of Ubl-conjugating enzyme UBE2H. 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. Negatively regulates acetylation and sumoylation of PML and represses PML-induced p53/TP53 acetylation and activation.

Subunit / interactions. Interacts with TRIM28 and UBE2H. Interacts with HDAC3. Interacts with PML (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5).

Subcellular location. Nucleus. PML body.

Tissue specificity. Expressed in many tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma, but not in normal tissues except for testes.

RefSeq proteins (8): NP_001269430, NP_001269431, NP_001269433, NP_001269434, NP_001373059, NP_005352, NP_786884, NP_786885 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002190	MHD_dom	Domain
IPR021072	MAGE_N	Domain
IPR037445	MAGE	Family
IPR041898	MAGE_WH1	Homologous_superfamily
IPR041899	MAGE_WH2	Homologous_superfamily

Pfam: PF01454, PF12440

UniProt features (7 total): compositionally biased region 2, chain 1, domain 1, region of interest 1, modified residue 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43356-F1	71.63	0.43

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 64

Mutagenesis-validated functional residues (1):

Position	Phenotype
170	improves ability to bind to hla-a1.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 69 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, MODULE_52, GOBP_REGULATION_OF_PROTEIN_SUMOYLATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_CELLULAR_SENESCENCE, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_PEPTIDYL_LYSINE_MODIFICATION, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_PROTEIN_ACETYLATION, GOBP_PROTEIN_SUMOYLATION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_PROTEIN_ACETYLATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), protein catabolic process (GO:0030163), negative regulation of protein sumoylation (GO:0033234), positive regulation of ubiquitin-protein transferase activity (GO:0051443), signal transduction by p53 class mediator (GO:0072331), cellular senescence (GO:0090398), negative regulation of protein acetylation (GO:1901984)

GO Molecular Function (4): ubiquitin protein ligase binding (GO:0031625), histone deacetylase binding (GO:0042826), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), PML body (GO:0016605)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
macromolecule catabolic process	1
protein metabolic process	1
protein sumoylation	1
regulation of protein sumoylation	1
negative regulation of protein modification by small protein conjugation or removal	1
ubiquitin-protein transferase activity	1
positive regulation of protein ubiquitination	1
positive regulation of catalytic activity	1
regulation of ubiquitin-protein transferase activity	1
intracellular signal transduction	1
cellular process	1
cellular response to stress	1
protein acetylation	1
negative regulation of protein modification process	1
regulation of protein acetylation	1
ubiquitin-like protein ligase binding	1
enzyme binding	1
transcription factor binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear body	1

Protein interactions and networks

STRING

444 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAGEA2	CTAG1A	P78358	812
MAGEA2	CTAG2	O75638	787
MAGEA2	CSAG2	Q9Y5P2	670
MAGEA2	GAGE4	P0DSO3	662
MAGEA2	PMEL	P40967	605
MAGEA2	TRIM28	Q13263	598
MAGEA2	TP53	P04637	589
MAGEA2	CSAG1	Q6PB30	542
MAGEA2	DDX43	Q9NXZ2	538
MAGEA2	TYR	P14679	522
MAGEA2	GAGE2A	Q6NT46	507
MAGEA2	A0A1W2PQG5	A0A1W2PQG5	506
MAGEA2	ESR1	P03372	489
MAGEA2	XAGE1B	Q9HD64	473
MAGEA2	MAGEF1	Q9HAY2	455

IntAct

111 interactions, top by confidence:

A	B	Type	Score
TP53	MAGEA2	psi-mi:“MI:0915”(physical association)	0.730
MAGEA2	TP53	psi-mi:“MI:0915”(physical association)	0.730
TP53	MAGEA2	psi-mi:“MI:0407”(direct interaction)	0.730
SEPTIN5	MAGEA2	psi-mi:“MI:0915”(physical association)	0.670
MAGEA2	P4HA3	psi-mi:“MI:0915”(physical association)	0.670
TRIM28	MAGEA2	psi-mi:“MI:0915”(physical association)	0.670
MAGEA2	TRIM28	psi-mi:“MI:0403”(colocalization)	0.670
MAGEA2	HDAC3	psi-mi:“MI:0407”(direct interaction)	0.590
MAGEA2	HDAC3	psi-mi:“MI:0914”(association)	0.590
MAGEA2	HDAC3	psi-mi:“MI:0915”(physical association)	0.590
MAGEA2	GCD7	psi-mi:“MI:0915”(physical association)	0.560
TIM10	MAGEA2	psi-mi:“MI:0915”(physical association)	0.560
CSN9	MAGEA2	psi-mi:“MI:0915”(physical association)	0.560
MAGEA2	TIM10	psi-mi:“MI:0915”(physical association)	0.560
MAGEA2	CEP57	psi-mi:“MI:0915”(physical association)	0.560
MAGEA2	SMARCD1	psi-mi:“MI:0915”(physical association)	0.560
MAGEA2	PSMC1	psi-mi:“MI:0915”(physical association)	0.560
MAGEA2	ANKRD45	psi-mi:“MI:0915”(physical association)	0.560
MAGEA2	COQ4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (74): MAGEA2B (Two-hybrid), MAGEA2B (Two-hybrid), MAGEA2B (Two-hybrid), MAGEA2B (Two-hybrid), MAGEA2B (Two-hybrid), P4HA3 (Two-hybrid), CEP57L1 (Two-hybrid), ANKRD45 (Two-hybrid), MDM2 (Reconstituted Complex), MDM2 (Affinity Capture-Western), MAGEA2 (Affinity Capture-Western), MDM2 (Protein-peptide), MAGEA2 (Reconstituted Complex), MAGEA2B (Two-hybrid), CEP57 (Two-hybrid)

ESM2 similar proteins: A0A0J9YX57, A1A5P9, A2A368, A2A9R3, A8MXT2, B2KFW1, O15479, O15480, O15481, O15553, P0C6Y7, P10073, P17040, P25233, P43355, P43356, P43357, P43358, P43360, P43362, P43363, P43364, P43366, Q13342, Q16666, Q4R998, Q5PPP4, Q5RD14, Q6AY37, Q6PCZ4, Q8BQR7, Q8IWY8, Q8IX06, Q8N660, Q8N7X4, Q8TD90, Q96DU7, Q96LZ2, Q96M61, Q99608

Diamond homologs: A0A0J9YX57, A1A5P9, A2A368, A2A9R3, A6NCF6, A6QLI5, A8MXT2, O15479, O15480, O15481, O60732, P25233, P43355, P43356, P43357, P43358, P43360, P43361, P43362, P43363, P43364, P43365, P43366, Q12816, Q4R998, Q5PPP4, Q5RFC2, Q6AY37, Q6ITT4, Q6PCZ4, Q8BQR7, Q8N7X4, Q8TD90, Q8TD91, Q96JG8, Q96LZ2, Q96M61, Q96MG7, Q99608, Q9BE18

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1158360324 (X:152755653 T>G), RS1164302235 (X:152755515 G>A), RS1169145433 (X:152755234 A>G), RS1171897735 (X:152719042 A>G), RS1174396920 (X:152755823 A>G), RS1174701234 (X:152755802 C>A), RS1176853966 (X:152755207 G>A), RS1181515099 (X:152755535 T>C), RS1184605133 (X:152755390 A>G), RS1189185891 (X:152755842 A>C,T), RS1191015603 (X:152755249 T>C), RS1195481679 (X:152755413 T>C), RS1197493201 (X:152755690 G>A), RS1202788089 (X:152755885 T>G), RS1204705199 (X:152755271 T>A,C)

Disease associations

OMIM: gene MIM:300173 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
manganese chloride	decreases expression, increases abundance	1
cupric chloride	increases expression	1
Fluorouracil	decreases expression, affects response to substance	1
Manganese	decreases expression, increases abundance	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.