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FLASH GENE
Symbol HOXA9 contributors: mct/shn - updated : 09-03-2013
HGNC name homeobox A9
HGNC id 5109
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinecolon highly
Reproductivefemale systemuterus  highly
Urinarykidney   highly
cell lineage primitive hematopoietic cells
cell lines
fluid/secretion
at STAGE
Text expressed throughout the forelimb bud at early stages
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