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FLASH GENE
Symbol MPL contributors: mct - updated : 10-12-2015
HGNC name myeloproliferative leukemia virus oncogene
HGNC id 7217
Corresponding disease
CAMT congenital amegakaryocytic thrombocytopenia
Location 1p34.2      Physical location : 43.803.474 - 43.820.134
Synonym name
  • thrombopoietin receptor
  • CD110 antigen
    • Synonym symbol(s) TPOR, CD110, MPLV, CAMT, c-MPL
    DNA
    TYPE functioning gene
    STRUCTURE 16.66 kb     12 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    text three alternatively spliced isoforms
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - - 3700 - 365 hematopoietic cells 1992 1608974
    - splicing 1800 - 579 hematopoietic cells 1992 1608974
  • also called MPL-K
  • last exon made of exon 10 and part of intron 10
    • - splicing - - - secreted -
  • also called MPL-S
  • lacking exons 9, 10
    • 12 - 3645 - 635 - 2000 10880227
    also called isoform DEL
    EXPRESSION
    Type
    constitutive of
       expressed in (based on citations)
    organ(s)
    cell lineage hematopoietic cells
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two intracellular cytokine receptor box motifs containing cysteine residues receptor, transducing exclusive signals in embryonic and fetal hematopoietic cells; within the Mpl-EC domain 1 (Mpl-EC-D1), AAs 102–251 were strongly involved in ligand binding (TPO and NUDC- binding to the AA region from 206 to 251)
  • the WSXWS motif, participating in the interaction between MPL and NUDC, and may play a role in stabilizing the conformation of the receptor during cytokine binding
  • two fibronectin type 3 domains
    • mono polymer dimer
    HOMOLOGY
    intraspecies homolog to virus myeloproliferative leukemia oncogene
    Homologene
    FAMILY
  • type I cytokine receptor family
  • type 1 subfamily
    • CATEGORY protooncogene , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
    text type 1 membrane protein
    basic FUNCTION
  • may be a regulatory molecule specific for TPOR dependent immune responses
  • playing a specific role in early embryonic or fetal hematopoietic progenitors and stem cells
  • positive-selection marker for the isolation of cancer stem cells in some case of T-caute lymphoblastic leukemia (Yamazaki 2009)
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • protein constituent of transmembrane
    • INTERACTION
    DNA
    RNA
    small molecule
    protein . regulated by RUNX1, both positively and negatively by changing the binding partner according to cell types
  • receptor of thrombopoietin
  • interacts with NUDC
  • following commitment to megakaryocyte differentiation, the H3K27 demethylase KDM6B up-regulation influences both ITGA2B and MPL expression
  • CLASP2-mediated stabilization of microtubules is required for proper attachment, homing, and maintenance of hematopoietic stem cells, and this is necessary to sustain MPL transcription
  • association between ATP5F1D and the Aa98-113 domain of MPL (the dissociation of ATP5F1D from MPL after TPO stimulation suggests that ATP5F1D may be a new component of TPO signaling
  • RBM15 which associates with HDAC3 and the histone methyltransferase, SETD1B, binds to both MPL RNA and chromatin and regulates H4 acetylation and H3K4me3 marks
  • DLGAP1 is a novel, potent factor in MPL signaling, affecting megakaryocytic growth and differentiation
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) CAMT
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in polycythemia vera and idiopathic myelofibrosis
    tumoral     --over  
    in B precursor leukemia cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS