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FLASH GENE

Symbol

MAGEA4

contributors: mct/npt - updated : 04-06-2020

HGNC name	melanoma antigen family A, 4
HGNC id	6802

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	Xq28      Physical location : 151.081.360 - 151.093.640
Synonym name	cancer/testis antigen family 1, member 4
	MAGE-X2 antigen
	MAGE-41 antigen
Synonym symbol(s)	MAGE4, MAGE4A, MAGEA4B, MAGE-41, MAGE-X2, MGC21336, CT1.4

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
STRUCTURE	12.28 kb     3 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Binding site
motif
text structure	Ets binding motifs

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	eight alternatively spliced first exons, followed by two invariant exons (the first encoding) (de Flaen) the four described variants encode the same protein

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001011548 3 - 1724 NP_001011548 34 317 - 2017 28744588 having the 5'-most exon compared to variants 2-4 NM_002362 3 - 1727 NP_002353 34.9 317 - 2017 28744588 differing in the 5' UTR compared to variant 1 NM_001011549 3 - 1721 NP_001011549 34 317 - 2017 28744588 differing in the 5' UTR compared to variant 1 NM_001011550 3 - 1712 NP_001011550 34 317 - 2017 28744588 differing in the 5' UTR compared to variant 1

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive intestine small intestine     specific   liver       moderately   stomach       moderately Reproductive female system placenta         female system uterus     moderately   male system testis     highly

cells

System Cell Pubmed Species Stage Rna symbol Reproductive spermatocyte Reproductive spermatogonia

cell lineage
cell lines	Reed-Sternberg cells, many tumors cell lines (melanoma, lung, breast)
fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a MAGE domain
	a C-terminal fragment with pro-apoptotic activity

HOMOLOGY

interspecies	homolog to C.elegans c10g11.7
	homolog to murine Magea9

intraspecies

homolog to MAGEA3/MAGEA1

Homologene

FAMILY

MAGE family

CATEGORY

antigen

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus
text	identified in the nucleus and cytoplasm of spermatogonia and in primary spermatocytes but not in spermatids or Sertoli cells (Takahashi 1995)
	MAGEA3, MAGEA4, MAGEA6,MAGEA8, are expressed in the undifferentiated human embryonic stem (hES) cells and early differentiated embryoid bodies (EBs) cells while only one gene of MAGEA family was expressed in the later differentiated cell derivatives of hES cells, MAGEA4 in the neuroectodermal progenitors

basic FUNCTION	may play a role in embryonal development and tumor transformation or aspects of tumor progression
	normal tissue antigen compartmmentalized in particular testicular cells playing an important role in the early phase of the spermatogenesis (Takahashi 1995)
	inducing apoptosis via a C-terminal fragment with pro-apoptotic activity generated from full-length MAGE-A4 after genotoxic stress
	its expression may promote tumor cell death, sensitize malignancies to apoptotic stimuli , such as chemotherapeutic agents, and therefore may represent a tumor suppressor protein (Peikert 2006)
	MAGEA4 inhibits growth arrest of cells in the G1 phase of the cell cycle

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	PSMD10
	ZBTB17
	CTCFL positively regulates MAGEA2, MAGEA3, MAGEA4 by binding and inducing a shift to a more open chromatin conformation with promoter demethylation for MAGEA3 or independent of promoter demethylation in case of MAGEA2 and MAGEA4
	CTCFL binding to the promoters of MAGEA2, MAGEA3, and MAGEA4, is associated with their transcriptional activation in lung cancer
	MAGEA4 promotes growth by preventing cell cycle arrest and by inhibiting apoptosis mediated by the TP53 transcriptional targets
	indirect binding of TWIST1 to the E-boxes of MAGEA4 promoter sequence and a novel regulatory role of TWIST1 in MAGEA4 upregulation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in non-small cell lung carcinomas (Peikert 2006) tumoral     --over   in primary breast cancer tumoral     --over   in a variety of malignancies in significant correlation with tumor cell invasiveness and aggressiveness tumoral     --over   in patients with synovial sarcoma tumoral     --other   MAGEA4 immunohistochemical expressionis associated with decreased disease free and overall survival in patients with high-grade endometrial cancer

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	potential utility of MAGEA4 as an ancillary diagnostic marker for synovial sarcoma combined with CTAG1B
	CTAG1B and MAGEA4 may be useful for the diagnosis of synovial sarcoma
Therapy target

ANIMAL & CELL MODELS