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FLASH GENE
Symbol KLF15 contributors: mct - updated : 18-05-2016
HGNC name Kruppel-like factor 15
HGNC id 14536
Location 3q21.3      Physical location : 126.061.477 - 126.076.236
Synonym name kidney-enriched Kruppel-like factor
Synonym symbol(s) KKLF, DKFZp779M1320
DNA
TYPE functioning gene
STRUCTURE 14.76 kb     4 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Binding site
MAPPING cloned Y linked N status provisional
Physical map
SLC12A8 3q21 solute carrier family 12 (potassium/chloride transporters), member 8 ZNF148 3q21 zinc finger protein 148 (pHZ-52) SNX4 3q21.1-q21.3 sorting nexin 4 OSBPL11 3q21 oxysterol binding protein-like 11 LOC389144 3 similar to seven transmembrane helix receptor OR7E93P 3q13.33 olfactory receptor, family 7, subfamily E, member 93 pseudogene OR7E53P 3q13.33 olfactory receptor, family 7, subfamily E, member 53 pseudogene OR7E97P 3q13.33 olfactory receptor, family 7, subfamily E, member 97 pseudogene LOC344729 3q21.2 similar to chromosome 11 open reading frame2; chromosome  11 open reading frame2 LOC389145 3 LOC389145 LOC165622 3q21.2 similar to Alkaline sphingomyelinase LOC200810 3q21.2 similar to asparagine-linked glycosylation 1 homolog (yeast, beta-1,4-mannosyltransferase); beta-1,4 mannosyltransferase LOC152015 3q21.2 similar to AKAP-binding sperm protein ropporin FLJ20473 FTHFD 3q21.2 formyltetrahydrofolate dehydrogenase KLF15 3q13-q21 Kruppel-like factor 15 FLJ40083 3q21.3 hypothetical protein FLJ40083 FLJ20123 3q21.3 hypothetical protein FLJ20123 MGC11349 3q21.3 hypothetical protein MGC11349 FLJ31300 3q21.3 hypothetical protein FLJ31300 CHST13 3q21.3 carbohydrate (chondroitin 4) sulfotransferase 13 MGC34728 3q21.3 hypothetical protein MGC34728 TXNRD3 3p13-q13.33 thioredoxin reductase 3 LOC255330 3q21.3 hypothetical protein LOC255330 LOC391571 3 similar to Splicing factor 3A subunit 2 (Spliceosome associated protein 62) (SAP 62) (SF3a66) MGC13016 DKFZp564A176 3q21.3 hypothetical protein DKFZp564A176 LOC285311 3q21.3 hypothetical gene supported by AK097460
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
3 - 2539 - 416 - 2005 15963234
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Digestivelivervesselsinusoid highly Homo sapiens
Endocrinepancreas   highly Homo sapiens
Nervousbrain    
Reproductivefemale systemuteruscervix  
Urinarykidney   highly Homo sapiens
Visualeyeretina   
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectiveadiposebrown   Homo sapiens
Connectiveadiposewhite   Homo sapiens
Muscularstriatumskeletal highly Homo sapiens
Muscularstriatumcardiacmyocardiumhighly Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Muscularmyoblast Homo sapiens
not specificadipocyte Homo sapiens
Urinarymesangial cell Homo sapiens
Urinarymesenchymal cell Homo sapiens
Urinarypodocyte Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal serine rich streches
  • a highly conserved 81 AA DNA binding domain
  • a central proline rich segment
  • three zinc finger motifs of the C2H2 type, forming a DNA-binding domain at the C terminus
  • HOMOLOGY
    interspecies homolog to murine Klf15
    Homologene
    FAMILY
  • Sp1 C2H2-type zinc-finger protein family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • may help to regulate the strict tissue and nephron segment-specific expression of CLCNKA and CLCNKB channel genes
  • transcriptional repressor of the rhodopsin and IRBP promoters and, in the retina, is a possible participant in repression of photoreceptor-specific gene expression in nonphotoreceptor cells
  • regulated by insulin and contributing to the regulation of PCK2 gene expression in the liver
  • playing an essential role in adipogenesis in cells through its regulation of PPARG expression
  • acting as an essential regulator of cardiac remodeling under stress
  • negative regulator of CTGF expression and cardiac fibrosis
  • implicated in the regulation of adrenomedullin expression in adipose tissu
  • plays a key role in adipocyte differentiation and glucose transport in adipocytes through activation of its target genes
  • having a potential role in the regulation of female testosterone production and fat stores may play a central role in the pathogenesis of polycystic ovary syndrome
  • regulates BMPER in endothelial cells
  • plays an important role in the transcriptional regulation of genes during adipogenesis
  • robustly inhibits myocardin, a potent transcriptional activator
  • acts a transcriptional repressor of pathological cardiac hypertrophy
  • acting as a potent competitive inhibitor of myocardin, thereby preventing transcription of SRF target genes
  • KLF11 and KLF15 enhanced UCP1 expression level during brown adipocyte differentiation through their direct interaction with specific binding domains of the UCP1 promoter
  • play an important role in the regulation of gluconeogenesis
  • serves as a molecular link between myogenic factors and the activity of the D4Z4 enhancer, and it thus contributes to the overexpression of the DUX4L9 and FRG2 genes during normal myogenic differentiation and in FSHMD1A
  • required to activate the D4Z4 enhancer in proliferating myoblasts
  • controls FRG2 expression without affecting myogenic differentiation
  • possible role of KLF15 in D4Z4 enhancer activation during myogenic differentiation
  • directly regulates a broad transcriptional program spanning all major segments of the lipid-flux pathway in muscle
  • is a direct transcriptional regulator of the lipid-flux pathway
  • kidney-enriched nuclear transcription factor, that has been previously shown to mediate cell differentiation
  • critical role of KLF15 in mediating podocyte differentiation and in protecting podocytes against injury
  • is a downstream physiological mediator of progesterone cell cycle inhibitory action in the uterine epithelium
  • is a negative regulator of cell proliferation in hormone responsive cell lines, at least in part through its inhibition of MCM2 transcription
  • is an important molecular link between ER stress and insulin action
  • essential mediator of ER stress-induced insulin resistance in the liver
  • plays an important role and may prove to be an antifibrotic factor in renal interstitial fibrosis through regulation of ERK/MAPK and JNK/MAPK signaling pathways
  • is a key regulator of myocardial lipid utilization and is the first to implicate the KLF transcription factor family in cardiac metabolism
  • is a nodal connection between the clock and meaningful rhythmicity in the heart
  • transcription factor family that plays a critical role in regulating renal fibrosis
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • KLF15-FGF19 signalling axis that regulates circadian bile acid production
  • KLF15-dependent pathway that regulates vascular smooth muscle cells (VSMCs) proinflammatory activation
  • a component
    INTERACTION
    DNA CLCNKA promoter
    RNA
    small molecule
    protein
  • MAZ (blocking the activating effect of MAZ)
  • regulates mitochondrial acetyl-CoA synthase expression in skeletal muscle
  • transcriptional regulator of the 17beta-hydroxysteroid dehydrogenase type 5 gene (AKR1C3)
  • very potent inhibitor of myocardin activity
  • bound to GT-boxes of the UCP1 promoter to increase its expression, but the binding was not essential for differentiation
  • inhibits basal and TGFbeta1-mediated induction of the CTGF promoter
  • regulates cardiac gene expression by interfering with Myocardin and MEF2 activity
  • interact with EP300 through the region that is homologous to EKLFTAD2
  • when overexpressed, KLF15 activated the D4Z4 enhancer and led to overexpression of DUX4L9 and FRG2
  • KLF15 directly interacts with the D4Z4 enhancer thereby up-regulating its activity (
  • specific activator of FRG2 (the regulation of FRG2 expression by KLF15 is direct rather than through the action of myogenic factors)
  • is able to bind directly to the promoter of nephrin and podocin and stimulate expression of these two key podocyte differentiation markers
  • mediates the actions of P4E2 in the uterine epithelium through inhibition of the transcription of MCM2, and thereby, of DNA replication licensing
  • KLF15 negatively regulates RNA Pol II binding
  • MCM2 promoter is transcriptionally regulated by E2 and this transcription can be significantly inhibited by KLF15
  • KLF4 stimulates and KLF15 inhibits MCM2 transcription through modulating histone acetylation and methylation, and thereby RNA Pol II binding
  • inhibits mesangial cell proliferation, possibly by regulating the expression of cell cycle regulation proteins through E2F1
  • transcriptional regulator Krüppel-like factor (KLF15) is involved in the regulation of C1QTNF12 expression in adipocytes
  • is the first endogenous negative regulator of circadian FGF15 expression
  • ARID1A positively regulates KLF15 expression with PGR to inhibit epithelial proliferation at peri-implantation
  • JUN can suppress adipocyte differentiation through the down-regulation of KLF15 at the transcriptional level
  • cell & other
    REGULATION
    activated by food deprivation and reduced by feeding
    during myogenic differentiation induced by serum starvation or by overexpression of the myogenic differentiation factor MYOD1
    induced by physiologically important stimuli in humans, and required for normal endurance exercise performance
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    during the differentiation of preadipocytes into adipocytes
    constitutional        
    loss of KLF15 during pathological left ventricular hypertrophy relieves the inhibitory effects on MYOCD and stimulates the expression of serum response factor target genes, such as atrial natriuretic factor
    constitutional     --over  
    in myoblasts, myotubes, and muscle biopsies from FSHD patients as compared with healthy controls
    constitutional   deletion    
    deletion of KLF15 interferes with nuclear control of mitochondrial fission, whereas fusion appears to be unaffected
    constitutional     --low  
    increases the susceptibility of podocytes to injury
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neuromuscularmyopathy 
    modulating KLF15 function might be a fruitful strategy to potentiate the health benefits of exercise and to treat metabolic and myopathic diseases
    cardiovascularaquiredheart failure
    the fact that KLF15 counteracts hypertrophy and is significantly down-regulated in pathological left ventricular hypertrophy suggests that therapeutic interventions aimed at preventing the decrease of KLF15 levels could be beneficial in the prevention of
    diabete  
    might be a potential molecular target for the treatment of diabetic nephropathy
    miscelleaneousurinary 
    potential new target for therapy of kidney diseases with podocyte injury
    ANIMAL & CELL MODELS
  • mice lacking Klf15 have higher base-line expression of ANF and BNP
  • hearts from KLF15-/- mice subjected to aortic banding exhibited increased CTGF levels and fibrosis (
  • Klf15 knock-out mice develop normal skeletal muscles (44) indicating that Klf15 is dispensable for myogenic differentiation of skeletal muscles
  • Klf15-deficient mice have abnormal lipid and energy flux, exaggerated muscle fatigue, and impaired endurance exercise capacity
  • Klf15 (-/-) mice are protected against hepatic insulin resistance and fatty liver under high-fat feeding conditions and in response to pharmacological induction of ER stress