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FLASH GENE
Symbol KLF6 contributors: mct - updated : 10-01-2015
HGNC name kruppel-like factor 6
HGNC id 2235
Location 10p15.2      Physical location : 3.818.188 - 3.827.473
Synonym name
  • core promoter element binding protein
  • B cell derived protooncogene
  • tumor suppressor gene(s),chromosome 10
  • prostate adenocarcinoma-1
  • suppression of tumorigenicity 12 (prostate)
  • GC-rich binding factor
  • kruppel-like zinc finger protein Zf9
  • protooncogene B-cell derived 1
  • Synonym symbol(s) CPBP, BCD1, GBF, ZF9, COPEB, PMC1, ST12, TSG10C, PAC1, DKFZp686N0199, GBM
    DNA
    TYPE functioning gene
    STRUCTURE 9.29 kb     4 Exon(s)
    regulatory sequence Promoter (CAAT box)
    Binding site
    text structure
  • a minimal promoter region lacking a TATA-box yet containing an initiator
  • a transcription start site at the first nucleotide downstream of the initiator element
  • two strong activating sequences located between positions -407/-344 and -307/-207, where the latter contained Sp1 and CAAT-box sites
  • MAPPING cloned Y linked   status confirmed
    Map pter - [D10S249 - D10S558 - D10S594 - D10S559 - D10S1435 ] - D10S533 - D10S602 - D10S591 - D10S552 - D10S1713 - D10S189 - D10S1691 - D10S1779 - D10S226 - D10S527 - D10S547 - D10S585 - D10S1705 - D10S223 - D10S1664 - D10S172 - D10S191 - D10S548 - D10S211 - D10S582 - D10S89 - D10S111 - D10S193 - D10S199 - cen
    Text [LOH in glioma]
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 splicing 4679 31 283 - 1998 9685731
  • isoform A
  • 3 - 4555 - 237 - 1998 9685731
    isoform C, Sv3
    4 - 4553 - 241 higher in primary hepatocarcinoma (PHC) tissues and hepatoma cell strains 1998 9685731
  • isoform B, SV2
  • - splicing - - - - 2012 22535637
  • major splice variant of KLF6
  • SV1 binds directly to KLF6 and accelerates its degradation
  • splice variant KLF6-SV1 increases in nonalcoholic fatty liver disease (NAFLD) hepatocytes and inversely correlates with glucokinase regulatory protein, which negatively regulates GCK activity
  • KLF6-SV1 is an important regulator of the growth, migration, invasion, and survival of gastric cancer cells
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
     pharynx   highly
    Nervousnerve   highly
    Reproductivefemale systemplacenta  highly Homo sapiens
     male systemprostate   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneB cell
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    physiological period fetal, pregnancy
    Text brain, spleen, thymus, placenta
    PROTEIN
    PHYSICAL PROPERTIES acid
    STRUCTURE
    motifs/domains
  • a N terminal acidic region
  • a highly conserved 81 AA DNA binding domain
  • a serine/threonine rich central region
  • three C terminal zinc finger domains (C2H2 type)
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to rattus Klf6 (93.99 pc)
    homolog to murine Klf6 (95.05 pc)
    intraspecies homolog to KLF7
    Homologene
    FAMILY
  • krueppel C2H2-type zinc-finger protein family
  • CATEGORY regulatory , transcription factor , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text perinuclear space
    basic FUNCTION
  • core promoter element binding protein
  • acting as an inhibitor of cell proliferation by counteracting the function of the c-Jun proto-oncoprotein involving enhanced c-Jun degradation by the proteasome-dependent pathway, and further reinforces KLF6 as a potential tumor suppressor gene product
  • having a role as a multifunctional transcriptional regulator capable of mediating adipocyte differentiation through gene repression
  • involved in differentiation and development, growth-related signal transduction, cell proliferation, apoptosis, and angiogenesis
  • playing an important role in the development or progression of sporadic gastric cancers
  • inducing cell death by apoptosis via BCL2L1 induction and p53 repression
  • transcription factor involved in the regulation of ASAH1 gene expression
  • playing an important role of tumour suppressor gene in gastric cancer development and progression
  • tumor suppressor activity by down-regulating PTTG1 oncogene
  • KLF6 regulation of GCK contributes to the development of hepatic insulin resistance
  • is frequently inactivated in human cancer and has significant roles in cellular proliferation, apoptosis, differentiation and development
  • is a novel regulator of hepatic glucose and lipid metabolism in fatty liver
  • is a novel transcriptional regulator of macrophage polarization
  • having function in response to malignant transformation, suggesting the relevance of KLF6 in controlling cell proliferation and hindering tumorigenesis
  • is a relevant participant in cytotrophoblast fusion
  • CELLULAR PROCESS cell life, differentiation
    cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text transcriptional activator, B cell differentiation
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • regulation and maintenance of the basal expression of TATA box-less genes
  • binding to the GC rich binding sites of the HIV-1 promoter
  • repressor of the proto-oncogene Delta-like 1 (DLK1), a gene encoding a transmembrane protein that inhibits adipocyte differentiation
  • interaction with HDAC3 (potential mechanism underlying adipogenesis)
  • downregulates the alpha1-proteinase inhibitor gene in corneal epithelial cells and may thereby be involved in keratoconus
  • interacting with CDH1 (transcriptional target of the KLF6 tumor suppressor)
  • E2F1 and KLF6 show cooperation in activating the DAPK2 promoter
  • interacting with ATF3 (ATF3 is a key mediator of KLF6-induced apoptosis in prostate cancer cells)
  • interaction between the C-terminal domain of LCOR and the transcription factor KLF6, a putative tumor suppressor in prostate cancer
  • KLF6 could directly bind and repress PTTG1 expression (down-regulation of the oncogene PTTG1 via the KLF6 tumor suppressor during induction of myeloid differentiation)
  • essential co-activator of NFKB1, suggesting new insight into the molecular regulation of RELA-dependent gene expression
  • cell & other
    REGULATION
    Phosphorylated by GSK3B (GSK3B directly phosphorylates KLF6, which augments its induction of CDKN1A and resultant growth suppression)
    Other regulation of the gene transcription is under control of a TATA-box independent initiation mechanism together with an evolutionary conserved array of positive cis-acting elements
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in primary prostate and astrocytic glioma
    tumoral somatic mutation      
    in nasopharyngeal carcinoma
    tumoral   LOH    
    in gastric cancer
    constitutional     --over  
    during hepatic fibrosis
    tumoral       loss of function
    inactivated in solid tumors
    tumoral   deletion    
    in high grade astrocytomas in progression to glioblastoma multiform, ependymoma, prostate carcinoma, renal, anaplastic or atypical meningioma, primary sarcomas with metastases
    tumoral   LOH    
    represents a clinically-relevant biomarker predicting patient survival and tumor recurrence and that dysregulation of KLF6 function plays an important role in head and neck squamous cell carcinomaprogression
    tumoral     --over  
    n breast cancer
    Susceptibility to hepatocellular carcinoma (minor role)
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurologyacquired 
    manipulating KLF6 or multiple KLF genes may be a useful strategy to add to existing approaches to increase the intrinsic regenerative capacity of mature CNS neurons damaged by injury or disease
    cancerhemopathy 
    drugs that increase the KLF6 inhibition of PTTG1 may have a therapeutic application in acute myeloid leukemia (AML) treatment strategies
    cancerdigestivestomach
    downregulation of KLF6-SV1 by siRNA may offer a new potential gene therapy approach for gastric cancer
    ANIMAL & CELL MODELS
  • in mice, an increased SV1/Klf6 ratio, generated either by increasing SV1, decreasing Klf6, or both, accelerates hepatic carcinogenesis