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FLASH GENE
Symbol KLF8 contributors: mct - updated : 22-02-2012
HGNC name Kruppel-like factor 8
HGNC id 6351
Location Xp11.21      Physical location : 56.258.821 - 56.314.320
Synonym name
  • basic Kruppel-like factor3
  • zinc finger protein 741
    • Synonym symbol(s) DXS741, ZNF741, BKLF3, MGC138314, DKFZp686O08126
    DNA
    TYPE functioning gene
    STRUCTURE 55.50 kb     6 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   hormone
    text structure
  • a SP1 binding site
    • MAPPING cloned Y linked N status provisional
    Map pter - ALAS2 - DXS991 - DXS1302 - DXS741 - KLF8 - DXS759 - DXS580 - DXS429 - MTHFD1P1 - cen
    Authors LOSSI (02)
    RNA
    TRANSCRIPTS type messenger
    text exon 2 alternatively spliced
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 4821 - 257 - 2000 10756197
    6 - 5434 39.2 359 - 2000 10756197
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestivepharynx   predominantly
    Endocrineadrenal gland   moderately
    Nervousnerve   moderately
    Reproductivefemale systembreastmammary gland moderately
    Respiratoryrespiratory tractlarynx  highly
    Urinarykidney   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a PVDLS motif required for contact with GTBP1
  • two nuclear localization signals, one surrounding S165 and K171 and the other being two tandem ZFs, which are critical for the regulation of KLF8 nuclear localization and its cellular functions
  • a valine-rich hydrophobic stretch
  • an activation domain located between AAs 101-260 where the well-conserved Q118 and Q248 are essential for recruiting EP300 and KAT2B to activate target gene transcription
  • three highly conserved C2H2 zinc fingers on the C terminus, which can bind to the GT-box (CACCC) promoter sequence
    • conjugated sumoylated
    HOMOLOGY
    interspecies homolog to murine Klf8 (83.7 pc)
    Homologene
    FAMILY
  • Sp1 C2H2-type zinc-finger protein family
    • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • acting as a transcriptional silencer
  • being important in the regulation of the cell cycle
  • playing a critical role in oncogenic transformation and epithelial to mesenchymal transition
  • mediates cell cycle progression downstream of focal adhesion kinase (PTK2) by upregulating cyclin D1
  • required for v-Src-induced transformation and may play a role in tumor progression of cancer
  • regulates critical cellular processes including cell cycle progression, transformation, epithelial-to-mesenchymal transition, migration and invasion by either repressing or activating target gene promoters
  • critical inducer of epithelial to mesenchymal transition and invasion
  • its overexpression induced a strong increase in MMP9 expression and activity
  • regulates critical gene transcription and cellular events associated with cancer
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
  • binding to CACCC-boxes and GC boxes promoter elements
    • RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • associating with C terminal binding proteins (CTBPs)and through the PVDLS motif
  • interacting with corepressor CtBP2
  • interacted with importin-beta and this interaction required the ZF motif
  • KLF8 activation domain located between AAs 101-260 where the well-conserved Q118 and Q248 are essential for recruiting EP300 and KAT2B to activate target gene transcription
  • interacting with MMP9 (KLF8 activation of MMP9 is a novel and critical signaling mechanism underlying human breast cancer invasion and metastasis)
  • PARP1 1s a novel KLF8-interacting protein and interaction is critical for maintaining the proper subcellular localization, transcription-regulating function, and protein stability of KLF8 in the nucleus
  • KLF8 promoted the EPSTI1 expression by directly acting on the EPSTI1 gene promoter
    • cell & other
    REGULATION
    induced by PTK2 in human ovarian cancer cells
    repressed by KLF3
    Other cellular function of KLF8 is regulated by post-translational sumoylation and acetylation
    sumoylation of KLF8 negatively regulates its transcriptional activity and cellular functions
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   translocation --low  
    in a core of non syndromic mental retardation with translocation t(X;21)(p11.2;q22.3)
    tumoral        
    playing an important role in human breast cancer invasion and metastasis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    co-targeting PARP1 and KLF8 (or other potential PARP1-interacting KLFs) as a novel anti-cancer therapeutic strategy
    ANIMAL & CELL MODELS