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FLASH GENE
Symbol MEIS1 contributors: mct - updated : 14-10-2015
HGNC name Meis homeobox 1
HGNC id 7000
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • helix-turn-helix, DNA binding domain
  • TALE (three AA loop extension between helices) subfamily
    • HOMOLOGY
    interspecies ortholog to murine Meis1 (myeloid ecotropic viral integration site 1)
    Homologene
    FAMILY
  • TALE/MEIS homeobox family
  • three-amino-acid loop extension (TALE) class homeodomain proteins family
    • CATEGORY DNA associated , transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    text
  • KAT6A localizes to the MEIS1 locus in pre-B-cells and maintains MEIS1 expression
    • basic FUNCTION
  • normal embryonic neuroblast development
  • causative role in neuroblastoma pathogenesis
  • playing an important role in megakaryocytic gene expression
  • critical downstream effector within an essential homeoprotein network that serving a rate-limiting regulatory role in MLL leukemogenesis
  • maintain retinal progenitor cells in a rapidly proliferating state and control the expression of some ocular-determination genes and components of the cell cycle machinery
  • Hox cofactor known for its role in development and is strongly linked to normal and leukemic hematopoiesis
  • up-regulating with PBX1 the expression of SOX3 gene (Mojsin 2010)
  • potentially involved in regulation of genes acting in DNA replication and in cell-cycle entry (CDK2, CDK6, CDKN3, CDC7, cyclin D3, and others)
  • works as a transcription factor for mitochondrial genes in pancreatic cancer cells
  • regulated the expression of mitochondrial genes by direct binding to the H-strand mitochondrial promoter region
  • involvement of PBX1, MEIS1, PKNOX1 during the early development in mammals
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimeric or heterotrimeric complex with PBX and HOX proteins to augment the affinity and specificity of DNA binding by HOX proteins
    • INTERACTION
    DNA binding cooperatively with the heterodimer E2A/myogenic transcription factors
    RNA
    small molecule
    protein
  • HOXA7 and HOXA9, coactivating in acute myeloid leukemia
  • PBX1, PBX2, PBX3 DNA-binding partner
  • collaboration between IRF8 deficiency and MEIS1/MEIS3 in the acceleration of chronic myeloid leukemia-like disease
  • co-operation between TLX1 and MEIS1, MEIS2 proteins may have a significant role in T-cell leukemogenesis
  • binding of MEIS1 to the mitochondrial promoter region
  • interaction with PKNOX1 (C-terminal domain of MEIS1 confers to PKNOX1 an ectopic transactivating function that promotes leukemogenesis by regulating expression of genes involved in chromatin accessibility and cell cycle progression)
  • is a direct and prominent target of GFI1B (direct yet differential regulation of MEIS1 transcription by GFI1B in distinct hematopoietic lineages)
  • MEIS1 regulates FOXN4 expression during retinal progenitor cell differentiation
  • PKNOX1 posttranslationally controls the level of MEIS1, decreasing its stability by sequestering PBX1
  • HOXA2 operates as a tissue-specific cofactor, enhancing MEIS1 binding to specific sites that provide the IIBA with its anatomical identity
  • crucial role for RING1-dependent repression of MEIS2 and likely also MEIS1 for distal specification
    • cell & other
    REGULATION
    Other positively regulated by HOXA9 through CREB1 targeting
    reulated by ETS transcription factor ELF1 which is an important positive regulator of MEIS1 expression
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    coactivated by HOXA9 in myeloid leukemias, in infant acute lymphoblastic leukemia
    tumoral       gain of function
    in neuroblastoma cell lines and with HOXB3 in acute myeloid leukemia
    tumoral   amplification    
    or overexpressed in neuroblastoma, erythroleukemia or medulloblastoma
    tumoral     --over  
    represses myeloid-specific gene transcription, thereby contributing to differentiation block in leukemogenesis
    tumoral     --over  
    extensively expressed in ovarian carcinomas and may play a role in ovarian carcinogenesis
    constitutional       loss of function
    results in cardiac anomalies that resemble those caused by PBX mutations
    tumoral     --over  
    of HOXA9 and HOXA10 and their essential cofactor MEIS1 in cells with the t(4;11) chromosome translocation and MLL-AF4 in acute leukemia
    Susceptibility to restless legs (RLS)
    Variant & Polymorphism other Decreased expression possibly through intronic cis-regulatory element(s), predisposes to RLS
    Candidate gene combinatorial expression of Meis family proteins might be a candidate mechanism for the differential regulation of eye growth among vertebrate species
    Marker
    Therapy target
    ANIMAL & CELL MODELS