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FLASH GENE
Symbol PKNOX1 contributors: mct - updated : 16-01-2020
HGNC name PBX/knotted 1 homeobox 1
HGNC id 9022
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
11 - 4997 - 436 - 1998 9479508
10 - 5180 - 319 - 1998 9479508
11 - 5297 - 435 - 1998 9479508
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrain    
Reproductivemale systemprostate   
Respiratorylung    
Urinarykidney    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal  
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticmegakaryocyte
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • helix-turn-helix,DNA binding domain
  • TALE (three AA loop extension between helices) subfamily and an atypical homeo domain
  • a putative binding motif for EIF4E2
  • a novel motif, flanking the homeodomain (HD) at the C-terminus, is required for cooperativity with PBX1
  • HOMOLOGY
    intraspecies homolog to PBX1
    homolog to MEIS1
    Homologene
    FAMILY three-amino-acid loop extension (TALE) class homeodomain proteins family
    CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • PBX regulating protein,involved in growth and morphogenesis
  • is required for a correct and complete hematopoiesis
  • nonredundant roles for this homeodomain protein during different stages of T cell development
  • controls insulin sensitivity through the MYBBP1A-SLC2A44 pathway
  • has a novel cytoplasmic, EIF4E2-dependent, function in the regulation of translation
  • important transcription factor that regulates PF4 gene expression such as MEIS1,through activation of its promoter
  • silencer of insulin signal, and is a transcriptional target of PKNOX1
  • homeodomain transcription factor that is essential in embryonic development and functions in the adult as a tumor suppressor
  • involved in maintaining genomic stability and preventing neoplastic transformation
  • tumor suppressor role of PKNOX1 is associated with the maintenance of genomic stability
  • involvement of PBX1, MEIS1, PKNOX1 during the early development in mammals
  • is a regulator of oxidative phosphorylation components via direct and indirect mechanisms
  • play a critical role in embryonic hematopoiesis, as its insufficiency caused late embryonic lethality associated with defective hematopoiesis and angiogenesis
  • PKNOX1 and PBX1 are homeodomain (HD) transcription factors that play crucial roles in embryonic development
  • prevents premature adipogenesis of mesenchymal progenitors (pMID: 29138456)
  • required for adult spermatogenesis in a germ cell-intrinsic manner
  • PKNOX1-tumor suppressor protects the late-replicating DNA by controlling its replication timing and symmetry
  • is essential for embryogenesis, but in the adult it also acts as a tumor suppressor
  • is required for normal adult mammary gland development, in particular at its branching morphogenesis step
  • is likely a potential regulator of the adipo-osteogenic differentiation of mesenchymal stromal cells
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding cooperatively with the heterodimer E2A/myogenic transcription factors
    RNA
    small molecule
    protein
  • PKNOX1- EIF4E2 interaction might bridge the 3prime UTR of HOXB4 mRNA to the 5prime cap structure
  • in liver, transcriptional activation of PTPN6 gene by PKNOX1 attenuates insulin signal transduction and reduces glucose storage
  • interaction with MEIS1 (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)
  • PKNOX1 posttranslationally controls the level of MEIS1, decreasing its stability by sequestering PBX1
  • PKNOX1 may likely control hepatic insulin sensitivity by targeting FOXO1 nuclear stability
  • PKNOX1 is a critical regulator of maintenance and subsequent differentiation of the KIT+ stage of spermatogonia in the adult testes
  • by binding SNAI2, PKNOX1 protects it from the proteasomal degradation
  • MN1 participates in transcriptional regulation of target genes through interaction with the transcription factors PBX1, PKNOX1, and ZBTB24
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    silencing reduces inflammatory response and increases insulin sensitivity in adipose tissue
    constitutional     --low  
    down-regulation affects DNA replication rate, increases the number of simultaneously firing origins and the asymmetry of DNA replication, leading to DNA damage
    constitutional       loss of function
    results in the accumulation of lineage-committed progenitors, increased monocyte/macrophage differentiation and arrested erythroid maturation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS