KLF4

This gene encodes a protein that belongs to the Kruppel family of transcription factors. The encoded zinc finger protein is required for normal development of the barrier function of skin. The encoded protein is thought to control the G1-to-S transition of the cell cycle following DNA damage by mediating the tumor suppressor gene p53. Mice lacking this gene have a normal appearance but lose weight rapidly, and die shortly after birth due to fluid evaporation resulting from compromised epidermal barrier function. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

Kruppel Like Factor 4

Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription.

Canonical Wnt signaling pathwayIEA:Ensembl
Cellular response to growth factor stimulusManual Assertion Based On ExperimentIDA:BHF-UCL
Cellular response to laminar fluid shear stressManual Assertion Based On ExperimentIMP:BHF-UCL
Cellular response to leukemia inhibitory factorIEA:Ensembl
Defense response to tumor cellManual Assertion Based On ExperimentIMP:ARUK-UCL
Epidermal cell differentiationIEA:Ensembl
Epidermis morphogenesisIEA:Ensembl
Fat cell differentiationISS:BHF-UCL
Mesodermal cell fate determinationManual Assertion Based On ExperimentTAS:ProtInc
Negative regulation of angiogenesisManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of cell migration involved in sprouting angiogenesisManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of cell population proliferationManual Assertion Based On ExperimentTAS:ProtInc
Negative regulation of chemokine (C-X-C motif) ligand 2 productionManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of G1/S transition of mitotic cell cycleManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of gene expressionManual Assertion Based On ExperimentIGI:BHF-UCL
Negative regulation of heterotypic cell-cell adhesionManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of inflammatory responseManual Assertion Based On ExperimentTAS:BHF-UCL
Negative regulation of interleukin-8 productionManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of leukocyte adhesion to arterial endothelial cellManual Assertion Based On ExperimentIGI:BHF-UCL
Negative regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of response to cytokine stimulusManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of cellular protein metabolic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of core promoter bindingIEA:Ensembl
Positive regulation of gene expressionManual Assertion Based On ExperimentIGI:BHF-UCL
Positive regulation of hemoglobin biosynthetic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of nitric oxide biosynthetic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of pri-miRNA transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of protein metabolic processManual Assertion Based On ExperimentIGI:BHF-UCL
Positive regulation of sprouting angiogenesisManual Assertion Based On ExperimentIGI:BHF-UCL
Positive regulation of telomerase activityManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:BHF-UCL
Post-embryonic camera-type eye developmentIEA:Ensembl
Post-embryonic hemopoiesisManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of axon regenerationIEA:Ensembl
Regulation of blastocyst developmentIEA:Ensembl
Regulation of cell differentiationISS:UniProtKB
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Response to retinoic acidIEA:Ensembl
Stem cell population maintenanceISS:UniProtKB
Transcription, DNA-templatedIEA:Ensembl

Nucleus

Ubiquitinated. 'Lys-48'-linked ubiquitinated and targeted for proteasomal degradation by the SCF(BTRC) E3 ubiquitin-protein ligase complex, thereby negatively regulating cell pluripotency maintenance and embryogenesis.
Polyglutamylated by TTLL1 and TTLL4 at Glu-411, which inhibits KLF4 binding with E3 ligase component BTRC, thereby impeding ubiquitination. Deglutamylated by CCP1 and CCP6; deglutamylation promotes KLF4 ubiquitination. KLF4 glutamylation state plays a critical role in the regulation of its function in cell reprogramming, pluripotency maintenance and embryogenesis.