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FLASH GENE
Symbol MECOM contributors: mct/npt/pgu - updated : 28-10-2009
HGNC name MDS1 and EVI1 complex locus
HGNC id 3498
Corresponding disease
EVI1 myelodysplastic syndrome
Location 3q26.2      Physical location : 168.801.286 - 169.381.563
Synonym name
  • zinc finger protein Evi1
  • AML1-EVI-1 fusion protein
  • ecotropic viral integration site 1
  • oncogene EVI1
  • myelodysplasia syndrome-associated protein 1
  • ecotropic virus integration site 1 protein homolog
    • Synonym symbol(s) PRDM3, MDS1-EVI1, MGC163392, EVI1, AML1-EVI-1, MDS1
    DNA
    TYPE functioning gene
    STRUCTURE 62.78 kb     17 Exon(s)
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    text some rearrangements result in MDS1/EVI1 fusion transcript. EVI1 is consistently expressed as principal transcript in 3q26 rearrangements associated with hematological malignancies ;
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 splicing 4900 - 1116 - 2006 17014970
  • coding the longest isoform
  • exons 1 & 2 are in the 5'UTR
    • 16 - 4891 - 1051 - 2006 17014970
    - - 4811 - 1043 - 2005 16014322
    - - 5740 - 1042 - 2005 16014322
    3 - 5533 - 1239 - 2005 16014322
    MDS1/EVI1
    - - 4835 - 1051 - 2005 16014322
    variants 2 and 3 encode the same isoform
    EXPRESSION
    Type ubiquitous
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
    Nervousbrain    
    Reproductivefemale systemovary   
    Respiratoryrespiratory tracttrachea   
    Urinarykidney    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    Reproductiveoocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • ten zinc finger motifs organised in two domains (ZF1 & ZF2)
  • the PR domain, GTPase SH3
  • 8th zinc finger motif is an oligomerization domain involved not only in interaction of AME (AML1/EVI1)with itself but also in interactions with the parental proteins
  • a two-third PR domain, completed when fused with MDS1 in a 5'-MDS1/EVI1-3', chimeric protein
    • HOMOLOGY
    interspecies homolog to murine Evi1 (93.02 pc)
    homolog to rattus Evi1_predicted (92.24 pc)
    Homologene
    FAMILY
    CATEGORY transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • oncogene inappropriately expressed in the bone marrow (BM) of approximately 10p100 of myelodysplastic syndrome
  • has a role in prolonging the self-renewal potential of the cells and that this ability of MECOM is limited and modulated by inherent characteristics of the cells
  • common and critical regulator essential for proliferation of embryonic/adult hematopoietic stem cells and transformed leukemic cells
  • involved in megakaryocytic differentiation
  • involved in regulating cell proliferation and diferentiation of haemopoietic & neuronal origin cells
  • contributing to the progression of leukaemia
  • upregulating cell proliferation, impairing cell differentiation, and inducing cell transformation
  • may regulate expression of the calreticulin gene during cardiac development
  • essential for proliferation of hematopoietic stem cells and implicated in the development of myeloid disorders
    • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
  • binding
    • RNA
    small molecule
  • Zn2+
    • protein
  • may interact with CTBP1
  • interacting with RUNX1
  • directly interacts with SUV39H1 and the proteins form an active complex with methyltransferase activity
  • interaction with GATA1 blocks proper erythropoiesis
  • interacts with SPI1 and represses the SPI1-dependent activation of a myeloid promoter
  • with GATA6, are new regulators of the calreticulin gene (antagonistic role between both GATA6 and MECOM)
  • binds to several polycomb group proteins and recruits polycomb repressive complexes for PTEN down-regulation
  • activates PI3K/AKT/MTOR via interactions with polycomb proteins
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) EVI1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   translocation    
    myeloid malignancies: acute myeloid leukemia (AML),chronic myeloid leukemia in blast crisis (CML BC) and myelodysplastic syndromes(MDS)
    tumoral   inversion    
    myeloid malignancies: acute myeloid leukemia (AML),chronic myeloid leukemia in blast crisis (CML BC) and myelodysplastic syndromes(MDS)
    tumoral fusion      
    with MDS1 in t(3;21)(q26;q22) in acute myeloid leukemia
    tumoral     --over  
    in Fanconi anemia-derived in childhood acute myeloid leukemia with biallelic FANCD1/BRCA2 disruption
    tumoral     --other  
    inappropriate expression could contribute to hematopoietic transformation in part by a new mechanism that involves EVI1 association with key hematopoietic regulators, leading to their functional impairment
    tumoral   translocation    
    in acute myeloid leukemia with t(3;8)(q26;q24) resulting in deregulated EVI1 expression, similar to other balanced or unbalanced chromosomal translocations involving chromosome 3q26
    tumoral       gain of function
    one of the targets of MLL oncoproteins and is selectively activated in hematopoietic stem cell-derived MLL leukemic cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    constitutive expression of EVI1 in the BM led to fatal anemia and myeloid dysplasia in mouse