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FLASH GENE
Symbol KLF5 contributors: mct/pgu - updated : 03-03-2015
HGNC name Kruppel-like factor 5 (intestinal)
HGNC id 6349
Location 13q22.1      Physical location : 73.633.141 - 73.651.675
Synonym name
  • basic transcription element-binding protein 2
  • GC box binding protein 2
  • transcription factor BTEB2
  • colon kruppel-like factor
  • intestinal-enriched kruppel-like factor
  • Synonym symbol(s) CKLF, IKLF, BTEB2
    DNA
    TYPE functioning gene
    STRUCTURE 18.75 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure
  • a GC rich DNA region in the promoter
  • lacking a TATA box
  • deletion or mutations of Sp1 site significantly reduced promoter activity in several epithelial cell lines,
  • Sp1 is a key transcription factor in KLF5 dynamic transcriptional regulation
  • MAPPING cloned Y linked N status confirmed
    Physical map
    LOC390411 13 similar to nucleophosmin 1; nucleolar phosphoprotein B23; numatrin; nucleophosmin/nucleoplasmin family, member 1 OR7E33P 13q22.3 olfactory receptor, family 7, subfamily E, member 33 pseudogene LOC390412 13 hypothetical gene supported by BC050367 KLHL1 13q21 kelch-like 1 (Drosophila) DACH 13q21-q22 dachshund homolog (Drosophila) FLJ22624 13q21.33 FLJ22624 protein DIS3 13q21.33 FLJ22624 protein PIBF1 13q21.33 progesterone-induced blocking factor 1 LOC338091 13q21 proteasome 26S non-ATPase subunit 10 pseudogene KLF5 13q21.33 Kruppel-like factor 5 (intestinal) LOC387934 13 similar to Fatty acid-binding protein, epidermal (E-FABP) (Psoriasis-associated fatty acid-binding protein homolog) (PA-FABP) LOC122134 13q21.33 similar to MAP/microtubule affinity-regulating kinase 3 LOC387935 13 LOC387935 KLF12 13q22 Kruppel-like factor 12 LOC122145 13q21.33 suppressor of bimD6 homolog pseudogene LOC387936 13 hypothetical gene supported by AL133018 LOC387937 13 LOC387937 TBC1D4 13q22 TBC1 domain family, member 4 AK000009  Acrg embryonic lethality (mouse) minimal region ortholog UCHL3 13q22 ubiquitin carboxyl-terminal esterase L3 (ubiquitin thiolesterase) LMO7 13q22 LIM domain only 7 KCTD12 13q21 potassium channel tetramerisation domain containing 12 BTF3L1 13q22 basic transcription factor 3, like 1 LOC341720 13q22.1 similar to immune-responsive gene 1 LOC390413 13 similar to 60S ribosomal protein L7 DHX9P 13q21 DEAH (Asp-Glu-Ala-His) box polypeptide 9 pseudogene CLN5 13q22 ceroid-lipofuscinosis, neuronal 5 FBXL3A 13q22 F-box and leucine-rich repeat protein 3A PAM 5q15 peptidylglycine alpha-amidating monooxygenase SCEL 13q22 sciellin LOC390414 13 similar to chromosome 15 open reading frame 2 FLJ30046 13q22.1 hypothetical protein FLJ30046 EDNRB 13q22 endothelin receptor type B POU4F1 13q21.1-q22 POU domain, class 4, transcription factor 1 C13orf7 13q22.2 chromosome 13 open reading frame 7
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    4 - 3350 - 457 - 2007 17158781
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   highly
    Digestiveintestinelarge intestinecolon  
    Reproductivemale systemprostate   
    Respiratoryrespiratory tractlarynx  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialabsorptive excretorydigestive epithelium (mucosa)  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveenterocyte
    not specificchondrocyte
    Skeletonosteoblast
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES basic
    STRUCTURE
    motifs/domains
  • a N terminal helix-loop-helix (HLH)
  • a highly conserved 81 AA DNA binding domain
  • leucine zipper motifs
  • three C terminal C2H2-type zinc fingers
  • a PY motif in a transactivation domain necessary for interaction with WWP1
  • conjugated ubiquitinated
    HOMOLOGY
    interspecies ortholog to murine Klf5
    Homologene
    FAMILY
  • Sp1-like family of GC box binding transcription factors
  • Krüppel family of C2H2-type zinc finger
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • transcriptional activator, promoting cell proliferation
  • involved in the cellular response to cardiovascular injury
  • plays a key part in the pathogenesis of cardiovascular diseases such as atherosclerosis and cardiac hypertrophy and fibrosis by mediating tissue remodeling in response to external stresses
  • implicated in carcinogenesis
  • playing a key role in mediating tissue remodeling
  • binding and transactivating the TCR-Dbeta 1 promoter
  • is important for induction of PDGF-alpha chain
  • is a key regulator of adipocyte differentiation
  • acts in concert with CEBPB/CEBPD to activate the PPARG promoter
  • having a growth-promoting role in intestinal epithelium
  • regulator of lipid metabolism and its SUMOylation within transcription factor complexes that also contain PPAR- serves as a molecular switch to repress or activate genes involved in lipid catabolism in response to PPAR- ligand and other signals
  • causes cartilage matrix degradation through transcriptional induction of MMP9, providing the first evidence that transcriptional regulation of a proteinase contributes to endochondral ossification and skeletal development
  • may be indispensable for skeletal development only in the perinatal period but be dispensable after birth under physiological and pathological conditions
  • plays a central role in cardiovascular pathologies through direct and specific stimulation of cell growth as well as inhibition of apoptosis
  • regulates both apoptosis in the early phase and proliferation in the late phase, thus indicating that this factor acts as a bimodal and likely central regulator of proliferative cardiovascular pathologies
  • mediates the signaling functions in cell proliferation, cell cycle, apoptosis, migration, differentiation, and stemness by regulating gene expression in response to environment stimuli
  • may promote breast cancer cell proliferation at least partially through directly activating the FGFBP1 mRNA transcription
  • not only essential for MYC transcription in proliferating epithelial cells but also mediates the inhibitory effect of TGFbeta on MYC transcription
  • mportant transcription factor regulating cell proliferation, cell cycle, survival, migration, differentiation, angiogenesis, and stem cell self-renewal
  • multifunctional transcription factor involved in cell proliferation, differentiation and carcinogenesis
  • required for formation and differentiation of the bladder urothelium
  • promoted cancer cell proliferation, migration and invasiveness in a manner dependent partly on TNFRSF11A expression
  • KLF5 and TNFRSF11A promote cervical cancer cell proliferation, migration and invasiveness
  • CELLULAR PROCESS cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component part of KLF5-FGFBP1-pERK-DUSP1 signaling axis, that may provide new therapeutic targets for invasive breast cancer
    INTERACTION
    DNA binding to epidermal growth factor response element, GC boxes and CAAT/GT boxes
    RNA
    small molecule metal binding, cofactor, other,
  • zinc Zn2+
  • essential cofactor for TGFbeta signaling
  • basic transcription factor binding to GC boxes at a number of gene promoters and regulating their transcription
  • KLF5 activates NOS2 gene transcription and is involved in vascular inflammatory injury and remodeling)
  • protein
  • binding RAR
  • target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells
  • physically associating with PPARD
  • interact with EP300 through the region that is homologous to EKLFTAD2
  • binds directly to the 5' regulatory region of EGFR (regulates MEK/ERK signaling via EGFR and is also downstream of MAPK signaling, providing a novel mechanism for signal amplification or suppression and control of proliferation in basal cells)
  • directly bound to the promoter and up-regulated gene expression of CCND1, as well as showing specific transactivation of cyclins and cyclin-dependent kinase inhibitors in cardiovascular cells
  • interacts with the novel histone chaperone acidic nuclear phosphoprotein 32B (ANP32B), leading to transcriptional repression of a KLF5-downstream gene
  • FBXW7 inhibits breast cell proliferation at least partially through targeting KLF5 for proteolysis
  • WWP1 E3 ligase targets KLF5 for ubiquitin-mediated degradation
  • essential co-factor for the TGFbeta (transforming growth factor B) tumour suppressor
  • transactivates NOTCH1 in the context of TP53 mutation or loss
  • SMURF2, an E3 ubiquitin ligase, is an interacting protein of KLF5
  • interacting with WWTR1 (promotes breast cell growth partially through protecting KLF5 from WWP1-mediated degradation and enhancing KLF5 activities)
  • TNFRSF11A is a direct binding target of KLF5, in tumour cell proliferation and invasiveness
  • cell & other
    REGULATION
    induced by angiotensin 2
    CEBPB and CEBPD
    inhibited by rapidly degraded through the proteasome after ubiquitination by E3 ubiquitin ligases, such as WWP1 and FBXW7
    oestrogen that causes the degradation of KLF5 protein by inducing the expression of TRIM25 in ER-positive breast cancer cells
    repressed by HDAC1 through direct interaction
    Other controlled directly by its protein
    tightly regulated by the ubiquitin-proteasome pathway
    SUMOylation of KLF5 functions as a molecular switch for fatty acid oxidation programs involving PPAR- and various co-regulators
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    frequent hemizygous deletion or loss of expression in breast cancer
    tumoral     --low  
    an LOH and loss of function in prostate cancer
    tumoral     --low  
    in intestinal tumors
    tumoral        
    silenced by hypermethylation in acute myeloid leukemia
    tumoral     --low  
    was lost concurrently with NOTCH1 in squamous cell cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene may be a tumor suppressor gene in prostate cancer
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductivebreast
    FBXW7 tumor suppressor targeting KLF5 for ubiquitin-mediated degradation and suppression of breast cell proliferation, is a therapeutic target for breast cancer and other cancers
    cardiovascular  
    potential diagnostic biomarker and therapeutic target for cardiovascular diseases
    cancerdigestiveoesophagus
    KLF5 may be a useful diagnostic and therapeutic target in esophageal squamous carcinomas and possibly more generally in other cancers associated with TP53 loss of function
    ANIMAL & CELL MODELS
  • Klf5 knockout mice, homozygous mutant died before embryonic day 8.5
  • Klf5 +/- mice showed diminished levels of arterial wall thickening angiogenesis, cardiac hypertrophy and intestinal fibrosis in response to external stress
  • Klf5 null mice were markedly deficient in white adipose tissue development