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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
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
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 1724 34 317 - 2017 28744588
    having the 5'-most exon compared to variants 2-4
    3 - 1727 34.9 317 - 2017 28744588
    differing in the 5' UTR compared to variant 1
    3 - 1721 34 317 - 2017 28744588
    differing in the 5' UTR compared to variant 1
    3 - 1712 34 317 - 2017 28744588
    differing in the 5' UTR compared to variant 1
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  specific
     liver   moderately
     stomach   moderately
    Reproductivefemale systemplacenta   
     female systemuterus  moderately
     male systemtestis  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Reproductivespermatocyte
    Reproductivespermatogonia
    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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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