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FLASH GENE
Symbol HOXA9 contributors: mct/shn - updated : 09-03-2013
HGNC name homeobox A9
HGNC id 5109
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • helix-turn-helix, DNA binding domain
    • HOMOLOGY
    interspecies ortholog to Hoxa9, Mus musculus
    ortholog to Hoxa9, Rattus norvegicus
    ortholog to HOXA9, pan troglodytes
    intraspecies homolog to hoxd9
    Homologene
    FAMILY
  • Abd-B homeobox family
    • CATEGORY regulatory , DNA associated , transcription factor , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities in the antero-posterior axis
  • activating CYBB transcription in differentiated myeloid cells
  • maintains endothelial cells in a quiescent state by negatively regulating NFKB1 activity
  • important for normal hematopoiesis, modulating MEIS1 through CREB1 targeting
  • overexpression of HOXA9 induces IGF1R expression and subsequently promotes leukemic cell growth
  • acting as an obligate proinflammatory factor by mediating cytokine induction of E-selectin
  • major differentiation factors of the NK-cell lineage, including HOXA9, HOXA10 and ID2, were (de)regulated via polycomb repressor complex 2 (PRC2) which therefore contributes to T-cell leukemogenesis
  • an important regulatory role in cytokine induction of the EC-leukocyte adhesion molecules E-selectin and vascular cell adhesion molecule 1
  • stimulus-dependent methylation of HOXA9 is essential for ELAM expression during the EC inflammatory response
  • HOXA9 and FLT3 signaling are individually important for the generation of lymphoid lineage precursors from multipotent hematopoietic progenitors (MPP) in bone marrow
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text a key regulator of hematopoiesis and embryonic development
    PATHWAY
    metabolism
    signaling
    a component
  • HOXA9/MADH4 in response to TGFB stimulation to repress osteopontin gene transcription
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • PBX2 and MEIS1
  • Smad4
  • CBP
  • PIM1
  • protein arginine methyltransferase 5, PRMT5
  • HOXA9, HOXA10 are direct transcriptional targets of SETBP1
  • DACH1 has a stronger transcription-promoting activity with HOXA9 than does PBX2 with HOXA9
  • CDX4 activates transcription of the HOXA9 and HOXA10 genes, and HOXA10 activates CDX4 transcription
  • SYNCRIP and MSI2 interact indirectly though shared mRNA targets (SYNCRIP maintains HOXA9 translation, and MSI2 or HOXA9 overexpression rescued the effects of SYNCRIP depletion)
    • cell & other
    REGULATION
    inhibited by phosphorylation by PKC, impairing its DNA binding ability and inducing myeloid differentiation
    Other negatively regulated by miR-126 binding to the homeobox
    methylation by PRMT5 is essential for endothelial cell expression of leukocyte adhesion molecules
    stability of HOXA9 controled by CUL-4A ubiquitylation machinery
    ASSOCIATED DISORDERS
    corresponding disease(s) AMLT2
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with NUP98 in translocation t(7;11),in acute myeloid leukemia (see AML2)
    tumoral       gain of function
    coactivated by MEIS1 in acute and chronic myelogenous leukemia and in infant acute lymphoid leukemia
    tumoral     --over  
    in acute monocytic leukemia
    tumoral     --over  
    of NUP98-HOXA9 represses myeloid-specific gene transcription, thereby contributing to differentiation block in leukemogenesis
    constitutional     --over  
    very high expression in haemopoietic cells in adults over sixty
    constitutional     --over  
    inhibits inflammatory cytokine dependent inducible expression of leukocyte adhesion molecules in endothelial cells
    tumoral   translocation    
    t(7;17)(p15;q23) with MSI2 may contribute to disease progression in chronic myeloid leukemia
    tumoral     --other  
    aberrant expression has been shown to be important to the development of leukemia
    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
    Variant & Polymorphism
    Candidate gene hypermethylated target gene in ovarian carcinogenesis
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    is required for survival in human MLL-rearranged acute leukemias and targeting HOXA9 may be a novel therapeutic option
    ANIMAL & CELL MODELS