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FLASH GENE
Symbol MEIS1 contributors: mct - updated : 14-10-2015
HGNC name Meis homeobox 1
HGNC id 7000
Location 2p14      Physical location : 66.662.531 - 66.799.890
Synonym name
  • MEIS1 homeo box protein
  • myeloid ecotropic integration site 1
  • Meis1, myeloid ecotropic viral integration site 1 homolog (mouse)
  • leukemogenic homolog protein
  • Synonym symbol(s) EVI8, MGC43380, WUGSC:H_NH0444B04.1
    DNA
    TYPE functioning gene
    STRUCTURE 137.36 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure
  • . promoter sequence revealed multiple GFI1B consensus binding motifs
  • MAPPING cloned Y linked N status confirmed
    Physical map
    PELI1 2p13.3 pellino homolog 1 (Drosophila) LOC130773 2p15 similar to 60S ribosomal protein L23a HSPC159 2p15 HSPC159 protein FLJ20080 2p15 hypothetical protein FLJ20080 TRIP-Br2 2p15 transcriptional regulator interacting with the PHS-bromodomain 2 SLC1A4 2p13.3 solute carrier family 1 (glutamate/neutral amino acid transporter), member 4 LOC200731 2p14 hypothetical LOC200731 KIAA0582 2p14 hypothetical LOC200731 RAB1A 2p14 RAB1A, member RAS oncogene family LOC150984 2p14 similar to voltage-dependent anion channel isoform 2 ACTR2 2p14 ARP2 actin-related protein 2 homolog (yeast) SPRED2 2p14 sprouty-related, EVH1 domain containing 2 LOC388956 2 LOC388956 LOC391379 2 similar to DnaJ homolog subfamily B member 12 LOC391380 2 similar to Keratin, type I cytoskeletal 18 (Cytokeratin 18) (K18) (CK 18) MEIS1 2p14-p13 Meis1, myeloid ecotropic viral integration site 1 homolog (mouse) LOC391381 2 similar to DNA cytosine methyltransferase 3 alpha isoform a; DNA methyltransferase HsaIIIA; DNA MTase HsaIIIA; DNA cytosine methyltransferase 3A2 ETAA16 2p13-p15 ETAA16 protein LOC391382 2 similar to F-box/LRR-repeat protein 12 (F-box and leucine-rich repeat protein 12) C1D 2p13-p12 similar to F-box/LRR-repeat protein 12 (F-box and leucine-rich repeat protein 12) LOC116143 2p13.3 hypothetical protein BC014022 LOC56902 2p13.3 putatative 28 kDa protein PPP3R1 2p16-p15 protein phosphatase 3 (formerly 2B), regulatory subunit B, 19kDa, alpha isoform (calcineurin B, type I) DKFZP566K1924 2p13.3 DKFZP566K1924 protein PLEK 2p14 pleckstrin LOC391383 2 similar to WD repeat domain 4 protein; WD repeat-containing protein 4 MGC47799 LOC391384 2 similar to KIAA0779 protein GPR73 2p14-p13.1 G protein-coupled receptor 73
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 3198 - 390 - 2009 19126776
    13 - - - 377 - 2009 19126776
    exon 1b
    11 - 2373 - 246 - 2009 19126776
    lacks exons 1 and 2
    12 - - - 252 - 2009 19126776
    skips exon 8 and prematurely truncates the protein to 252 amino acid by using a STOP codon located in exon 9
    14 - 4613 - 378 - 2009 19126776
    includes the entire unspliced sequence from intron 11, and prematurely truncates the protein to 378 amino acid
    13 - - - - - 2009 19126776
  • includes an additional 81 bp from the 5' end of intron 10, and is predicted to add a 27 amino acid in-frame segment near the C-terminus of the protein, with a putative PKG phosphorylation site
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainhindbraincerebellum highly
    Reproductivefemale systemovary  highly
     female systemuterus  highly
    Respiratoryrespiratory tractlarynx  highly
     respiratory tracttrachea  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneB cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text mainly during embryonal development, liver
    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)
  • MEIS1 regulates FOXN4 expression during retinal progenitor cell differentiation
  • is a direct and prominent target of GFI1B (direct yet differential regulation of MEIS1 transcription by GFI1B in distinct hematopoietic lineages)
  • 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