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FLASH GENE
Symbol KLF2 contributors: mct/pgu - updated : 22-01-2016
HGNC name Kruppel-like factor 2 (lung)
HGNC id 6347
Location 19p13.11      Physical location : 16.435.650 - 16.438.337
Synonym name lung Kruppel-like zinc finger transcription factor
Synonym symbol(s) LKLF
DNA
TYPE functioning gene
STRUCTURE 2.69 kb     3 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter (TATA box)
cytosine-phosphate-guanine/HTF
Binding site   transcription factor
text structure
  • a GC-rich promoter with multiple SP1-binding sites
  • 2 putative TATA boxes
  • hnRNP-U, hnRNP-D, PCAF, and P-300 bind to the KLF2 promoter, and these proteins are important for regulating KLF2 transcription
  • MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 1655 - 355 - 2005 15718498
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen    
    Cardiovascularheart   moderately
     vessels    
    Endocrinepancreas   highly
    Nervousbrain    
    Reproductivemale systemprostate   
    Respiratorylung   predominantly
    Urinarykidney   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  moderately
    Connectiveadipose  moderately
    Connectivebone   
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    Lymphoid/ImmuneB cell Homo sapiens
    Lymphoid/ImmuneT cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, pregnancy
    Text predominantly, in developing lung, spleen, vascular system
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • putative transactivation, proline-rich N terminal domain
  • a highly conserved 81 AA DNA binding domain
  • three zinc finger of the Cys2-His2 type, required for the suppression of WEE1 expression
  • KLF1 and KLF2 have highly homologous zinc finger DNA-binding domains
  • a nuclear localization signal at the C terminus
  • HOMOLOGY
    interspecies ortholog to rattus Klf2 (88.7pc)
    ortholog to murine Klf2 (88.1pc)
    Homologene
    FAMILY
  • CACCC binding zinc finger family
  • krueppel C2H2-type zinc-finger protein family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    text
  • nuclear transcription factor
  • basic FUNCTION
  • putatively involved in programming the quiescent state of single positive T cells and in maintaining their viability in the peripheral lymphoid organs and blood
  • blood wall morphogenesis
  • transcriptional silencer
  • acting as a negative regulator of monocytic activation
  • differentially regulating key factors involved in maintaining an antithrombotic endothelial surface, and transcriptional regulator of endothelial thrombotic function
  • may act as a novel immediate-early transcriptional factor to maximally prime T cell activation
  • plays a role in the maturation and/or stability of erythroid cells in the yolk sac, and is essential for primitive erythropoiesis and regulates the embryonic beta-like globin genes
  • in T cells, KLF2 controls the exit of thymocytes into the blood by regulating the expression of the chemoattractant receptor S1Pr1
  • plays an important role in differentiation and function in a variety of cell types, including T lymphocytes, monocytes, lung cells, and adipocytes
  • plays crucial and unique roles in the vascular wall by functioning as an important transcriptional integrator of upstream and downstream signaling necessary for blood vessel formation
  • inhibitor of HIF1A expression and function, disrupting the interaction between HIF1A and HSP90
  • critical for normal trafficking of T lymphocytes
  • plays a critical role in dictating normal subset differentiation and functional reactivity of mature B cells
  • critical for normal B-cell tissue localization, subset differentiation, and functional reactivity
  • s crucial for B-cell subset differentiation as well as regulation of B-cell activation and trafficking
  • controls homeostasis of mature B cell subsets in peripheral lymphatic organs and homing of antibody-secreting plasma cells to the bone marrow, presumably by controlling the expression of the adhesion molecule beta7-integrin
  • KLF1 and KLF2 positively regulate the embryonic and fetal beta-globin genes through direct promoter binding
  • distinct yet overlapping mechanistic roles for KLF1 and KLF2 in embryonic red blood cells
  • role for myeloid KLF2 expression in modulating atherosclerosis
  • KLF1, KLF2, and MYC control a regulatory network essential for embryonic erythropoiesis
  • is implicated as a key molecule maintaining endothelial function
  • KLF2 and NFE2L2 are major transcriptional factors that contribute to anti-atherogenic responses under laminar flow
  • link between KLF2-induced hepatic triglyceride accumulation and the expression of CD36
  • is an essential factor that sustains ground state pluripotency
  • KLF1 and KLF2 coordinately regulate embryonic erythroid precursor maturation through the regulation of multiple homeostasis-associated genes
  • is involved in strict repression of TERT expression through binding to the promoter in primary human T cells
  • suppressive functions of KLF2 in pancreatic ductal adenocarcinoma
  • continuous role of KLF2 in stabilizing the vessel wall via co-temporal expression of eNOS and AQP1 both preceding and during the pathogenesis of atherosclerosis
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text histogenesis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding to the CACCC box containing proteins
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • WWP1
  • interacting with HSPA5 (important for regulating KLF2 transcription)
  • negatively regulated WEE1 expression
  • promotes the expression of the selectin SELL which is involved in T cell trafficking
  • SMURF1 interacts with and targets KLF2 for poly-ubiquitination and proteasomal degradation specifically in lung cancer
  • directly activates the promoters of SELL and sphingosine-1-phosphate receptor 1, whose expression is critical for T cell egress from the thymus and homing to the lymph nodes
  • interact with EP300 through the region that is homologous to EKLFTAD2
  • KLF1 and KLF2 bind directly to the promoters of the HBE1 and HBG1, HBG2 genes
  • KLF2 repression has an important role in EZH2 oncogenesis
  • CCL19 stimulation of na
  • ve T cells regulates expression of MAPK7, KLF2, and S1PR1
  • suppression of KLF2 by FOXO1 may be a plausible mechanism of diabetic endothelial dysfunction
  • zinc finger transcription factor Krüppel-like factor 2 (KLF2) is a physiological target of FBXW7 in endothelial cells
  • CD36 is a novel transcriptional target of KLF2
  • KLF2 negatively controls the ability of CD8 T cells to respond to the CXCR3 ligand CXCL10
  • IKBKB regulates endothelial thrombomodulin in a KLF2-dependent manner
  • represses TERT transcription by binding to the putative promoter element
  • interacts with beta-catenin and negatively regulates the beta-catenin/TCF signaling
  • binding of KLF2 to the AQP1 promoter
  • cell & other
    REGULATION
    induced by vascular flow
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    deficiency in Kruppel-like factor (KLF) 2 leads to a massive loss of the peripheral T-cell pool
    tumoral     --low  
    in ovarian tumors
    constitutional     --over  
    during the early stage of T cell activation in primary T cells
    tumoral     --low  
    in nonsmall-cell lung cancer with poor prognosis
    tumoral somatic mutation      
    recurrently mutated in splenic marginal zone lymphoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • decreased KLF2 could be identified as a poor prognostic biomarker in nonsmall-cell lung cancer and regulate cell proliferation and apoptosis
  • Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousvascular 
    may be a target for modulating the angiogenic response in disease states
    immunology  
    therapeutic target for the production of regulatory T cells
    cardiovascularatheroma 
    elevating KLF2 expression may be a novel strategy for prevention and treatment of atherosclerosis
    ANIMAL & CELL MODELS
  • B Cell homeostasis is disturbed in other peripheral lymphatic compartments of KLF2-deficient Mice