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FLASH GENE
Symbol FLT3 contributors: mct/npt/pgu - updated : 08-02-2016
HGNC name fms-related tyrosine kinase 3
HGNC id 3765
Location 13q12.2      Physical location : 28.577.411 - 28.674.729
Synonym name
  • CD135 antigen
  • stem cell tyrosine kinase 1
  • fetal liver kinase 2
  • FLT3 receptor tyrosine kinase
  • growth factor receptor tyrosine kinase type III
    • Synonym symbol(s) FLK2, STK1, CD135, FLK-2
    EC.number 2.7.1.112, 2.7.10.1
    DNA
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    text linked in a head to tail configuration with FLT1 and separated by about 150 kb
    STRUCTURE 97.32 kb     24 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence cytosine-phosphate-guanine/HTF
    text structure one CpG island
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    24 - 3848 - 993 - 2007 18031378
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunethymus    
    Urinarybladder    
     kidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow    Homo sapiens
    Connectivebone   
    Epithelialbarrier/lining   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticprogenitor cell Homo sapiens
    Cardiovascularendothelial cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text liver
    PROTEIN
    PHYSICAL PROPERTIES Hydrophilic
    STRUCTURE
    motifs/domains
  • five immunoglobulin-like C2-type domains in the extracellular region
  • a signal peptide domain
  • a catalytic domain interrupted in two part by a specific hydrophilic "interkinase" sequence
  • a juxtamembrane domain (in ETV6/FLT3 fusion protein is critical for cell proliferation and PIM1 up-regulation that might be independent of a requirement for signaling through STAT5, MAPK, and AKT pathways)
    • conjugated GlycoP , PhosphoP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to murine Flt3
    homolog to C.elegans F59F3.5
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • CSF-1/PDGF receptor subfamily
    • CATEGORY enzyme , protooncogene , receptor membrane tyrosine kinase
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text type I membrane protein, localized primarily at the cell surface (
    basic FUNCTION
  • receptor for the FL cytokine
  • having tyrosine-protein kinase activity
  • involved in proliferative events of hematopoietic stem cells
  • activated at the late stages of liver regeneration and participates in the proliferation response that is observed during progenitor-dependent liver regeneration
  • plays a critical role in maintenance of hematopoietic homeostasis
  • FLT3 signaling might play an important role in cell survival, especially at stem and progenitor cells that are critical cellular targets for acute myelogenous leukemia transformation
  • FLT3-mediated MAPK14 activation participates in the control of megakaryopoiesis in primary myelofibrosis
  • HOXA9 and FLT3 signaling are individually important for the generation of lymphoid lineage precursors from multipotent hematopoietic progenitors (MPP) in bone marrow
  • FLT3 signaling plays a crucial role in regulating the survival and differentiation of lymphoid progenitors into B cell precursors (BCPs) in bone marrow
  • regulates the proliferation, survival, and maintenance of developmental stage-specific hematopoietic progenitors that give rise to BCPs
  • FYN cooperates with oncogenic FLT3-ITD (internal tandem duplication) in cellular transformation by selective activation of the STAT5 pathway
    • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text positive control of cell proliferation
    PATHWAY
    metabolism
    signaling
    FLT3 signaling regulates the proliferation, survival, and maintenance of multipotent hematopoietic progenitors that generate B cell precursors
    a component
    INTERACTION
    DNA
    RNA
    small molecule nucleotide,
  • ATP
    • protein
  • binding to the FL cytokine
  • PTPRJ is negatively regulating FLT3 signaling activity and its loss may contribute to but is not sufficient for leukemogenic cell transformation
  • SOCS6 negatively regulates FLT3 activation, the downstream Erk signaling pathway, and cell proliferation
  • FLT3-mediated inhibition of hematopoiesis in KMT2A-AFF1-expressing hESCs, which is associated with large transcriptional changes and downregulation of genes involved in hematopoietic system development and function
  • SOCS2 negatively regulates FLT3 signaling by blocking activation of Erk 1/2 and STAT5
  • direct interaction of PTPRJ with the hematopoietic receptor-tyrosine kinase Fms-like tyrosine kinase-3 (FLT3), and interaction occurs mainly via an enzyme-substrate complex formation triggered by FLT3 ligand stimulation
  • BCL11A is required for expression of I7 receptor (IL7RA) and FLT3 in early hematopoietic progenitor cells
  • promotes FLT3 receptor activation in acute myeloid leukemia cells
  • CBFB is essential for the development of FLT3(+) macrophage-dendritic cell (DC) progenitors in the bone marrow and all DC subsets in the periphery
  • HES1 directly bound to the promoter region of the FMS-like tyrosine kinase 3 (FLT3) gene and downregulated the promoter activity
  • ITD-FLT3 increases cell migration toward CXCL12 by antagonizing the down-regulation of ROCK1 expression
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in childhood acute myeloid leukemia
    tumoral somatic mutation      
    duplication mutations within the juxtamembrane domain in adult de novo acute myeloid leukemia
    tumoral somatic mutation      
    in high hyperdiploid childhood acute lymphoblastic leukemia
    tumoral somatic mutation      
    an internal tandem duplication (FLT3/ITD) is associated with poor prognosis in acute myeloid leukemia (AML), interaction with NPM1 mutations identify 3 prognostic groups: good (FLT3/ITD(-)NPM1(+)), intermediate (FLT3/ITD(-)NPM1(-) or FLT3/ITD(+)NPM1(+)), and poor (FLT3/ITD(+)NPM1(-))
    constitutional       gain of function
    activating mutations in FLT3 induce ligand-independent downstream signaling that promotes oncogenesis through pathways involved in proliferation, differentiation, and survival
      fusion translocation    
    ETV6/FLT3 (EF) fusion proteins in a patient with myeloproliferative disorder (MPD) and a t(12;13)(p13;q12) translocation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    activated FLT3 is a promising molecular target for AML therapies
    ANIMAL & CELL MODELS
    model of APL-like disease in mice