KLF4 Kruppel like factor 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KLF4provided by HGNC
Official Full Name: Kruppel like factor 4provided by HGNC
Primary source: HGNC:HGNC:6348
See related: Ensembl:ENSG00000136826 MIM:602253
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EZF; GKLF
Summary: 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]
Expression: Broad expression in colon (RPKM 75.2), esophagus (RPKM 73.6) and 22 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 9q31.2

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	9	NC_000009.12 (107484852..107489720, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (110247133..110252047, complement)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

the downstream targets of KLF4-mCpG binding, guanine nucleotide exchange factors, serve as the effector of KLF4-induced mitochondrial fusion, cell cycle arrest, and cell protection.
Title: Krüppel-like factor 4 (KLF4) induces mitochondrial fusion and increases spare respiratory capacity of human glioblastoma cells.
Human and mouse WNT10A mutant palmoplantar and tongue epithelia also display specific differentiation defects that are mimicked by loss of the transcription factor KLF4.
Title: WNT10A mutation causes ectodermal dysplasia by impairing progenitor cell proliferation and KLF4-mediated differentiation.
The KLF4 might be a potential marker to predict prognosis in solid cancer patients.
Title: Krüppel-like factor 4 expression in solid tumor prognosis: A meta-analysis.
SOX5 overexpression increased Kruppel-like factor 4 (KLF4) gene expression, which was decreased by SOX5 silencing. KLF4 knockdown abrogated the suppressive effect of SOX5 overexpression on osteogenic differentiation of hMSCs.
Title: TNF-α-Induced SOX5 Upregulation Is Involved in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Through KLF4 Signal Pathway.
Results showed that SIRT1 interacts with and deacetylated KLF4. The deacetylation by SIRT1 promoted nuclear accumulation of KLF4 and enhanced the binding of KLF4 to the CLDN5 promoter in the nucleus.
Title: SIRT1 deacetylates KLF4 to activate Claudin-5 transcription in ovarian cancer cells.
miR-145 promotes hepatic stellate cell activation and liver fibrosis by targeting KLF4.
Title: MircoRNA-145 promotes activation of hepatic stellate cells via targeting krüppel-like factor 4.
These findings identify a novel regulatory loop between miR-34a and KLF4 during keratinocytes replicative senescence.
Title: Kruppel-like factor 4 regulates keratinocyte senescence.
Knockdown of KLF4 promoted the migration and invasion of nonsmallcell lung cancer (NSCLC) cells, whereas rescue of KLF4 expression reduced cell motion ability in miR25overexpressing NSCLC cells.
Title: miR-25 enhances cell migration and invasion in non-small-cell lung cancer cells via ERK signaling pathway by inhibiting KLF4.
the subcellular localization of Klf4 might be related to the resistance of A549 cells to cisplatin.
Title: Subcellular localization of Klf4 in non-small cell lung cancer and its clinical significance.
Authors observed that saRNAs induced overexpression of KLF4 could promote cell migration/invasion in NCM460 and HCT116 cell lines.
Title: Activation of KLF4 expression by small activating RNA promotes migration and invasion in colorectal epithelial cells.

Submit: New GeneRIF Correction See all GeneRIFs (328)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
Genome-wide association study in Chinese men identifies two new prostate cancer risk loci at 9q31.2 and 19q13.4. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Novel breast cancer susceptibility locus at 9q31.2: results of a genome-wide association study. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
The Contribution of Common Genetic Variation to Nicotine and Cotinine Glucuronidation in Multiple Ethnic/Racial Populations. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Developmental Biology, organism-specific biosystem (from REACTOME)
Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
Mesodermal Commitment Pathway, organism-specific biosystem (from WikiPathways)
Mesodermal Commitment Pathway, organism-specific biosystemModel depicting mesodermal specification based on the literature and highly enriched gene expression profiles via comparison across dozens of independent induced and embryonic pluripotent stem cell l...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
Peptide hormone metabolism, organism-specific biosystem (from REACTOME)
Peptide hormone metabolism, organism-specific biosystemPeptide hormones are cleaved from larger precursors in the secretory system (endoplasmic reticulum, Golgi apparatus, secretory granules) of the cell. After secretion peptide hormones are modified and...
Preimplantation Embryo, organism-specific biosystem (from WikiPathways)
Preimplantation Embryo, organism-specific biosystemThe source of this pathway is RNA-Seq data from single-cell pre-implantation embryos (Supplemental Table 1): http://www.nature.com/nsmb/journal/v20/n9/full/nsmb.2660.html Analysis options for runnin...
Regulation of Wnt-mediated beta catenin signaling and target gene transcription, organism-specific biosystem (from Pathway Interaction Database)
Regulation of Wnt-mediated beta catenin signaling and target gene transcription, organism-specific biosystem
Regulation of Wnt-mediated beta catenin signaling and target gene transcription
SRF and miRs in Smooth Muscle Differentiation and Proliferation, organism-specific biosystem (from WikiPathways)
SRF and miRs in Smooth Muscle Differentiation and Proliferation, organism-specific biosystemSmooth muscle cells exhibit a unique plasticity, in that they are able to oscillate between proliferative and more quiescent, differentiated states. These two states are determined, in part, by a net...
Signaling pathways regulating pluripotency of stem cells, organism-specific biosystem (from KEGG)
Signaling pathways regulating pluripotency of stem cells, organism-specific biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
Signaling pathways regulating pluripotency of stem cells, conserved biosystem (from KEGG)
Signaling pathways regulating pluripotency of stem cells, conserved biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
Synthesis, secretion, and deacylation of Ghrelin, organism-specific biosystem (from REACTOME)
Synthesis, secretion, and deacylation of Ghrelin, organism-specific biosystemGhrelin is a peptide hormone of 28 amino acid residues which is acylated at the serine-3 of the mature peptide. Ghrelin is synthesized in several tissues: X/A-like cells of the gastric mucosa (the ma...
Transcriptional regulation of pluripotent stem cells, organism-specific biosystem (from REACTOME)
Transcriptional regulation of pluripotent stem cells, organism-specific biosystemPluripotent stem cells are undifferentiated cells posessing an abbreviated cell cycle (reviewed in Stein et al. 2012), a characteristic profile of gene expression (Rao et al. 2004, Kim et al. 2006, P...
Transcriptional regulation of white adipocyte differentiation, organism-specific biosystem (from REACTOME)
Transcriptional regulation of white adipocyte differentiation, organism-specific biosystemAdipogenesis is the process of cell differentiation by which preadipocytes become adipocytes. During this process the preadipocytes cease to proliferate, begin to accumulate lipid droplets and develo...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Klf4 (e-PCR), detects polymorphism
- UniSTS:256949

KLF4_905 (e-PCR)
- UniSTS:277441

Homology

Homologs of the KLF4 gene: The KLF4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 213 organisms have orthologs with human gene KLF4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA-binding transcription activator activity, RNA polymerase II-specific	IMP Inferred from Mutant Phenotype more info	PubMed
DNA-binding transcription factor activity	NAS Non-traceable Author Statement more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
DNA-binding transcription factor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
RNA polymerase II proximal promoter sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
RNA polymerase II sequence-specific DNA-binding transcription factor recruiting activity	ISS Inferred from Sequence or Structural Similarity more info
RNA polymerase II transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
RNA polymerase II transcription factor binding	ISS Inferred from Sequence or Structural Similarity more info
beta-catenin binding	IEA Inferred from Electronic Annotation more info
histone deacetylase binding	IEA Inferred from Electronic Annotation more info
phosphatidylinositol 3-kinase regulator activity	IEA Inferred from Electronic Annotation more info
promoter-specific chromatin binding	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
proximal promoter sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
transcription cofactor binding	IEA Inferred from Electronic Annotation more info
transcription regulatory region DNA binding	ISS Inferred from Sequence or Structural Similarity more info
zinc ion binding	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
cellular response to cycloheximide	IEA Inferred from Electronic Annotation more info
cellular response to growth factor stimulus	IDA Inferred from Direct Assay more info	PubMed
cellular response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
cellular response to laminar fluid shear stress	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to leukemia inhibitory factor	IEA Inferred from Electronic Annotation more info
cellular response to peptide	IEA Inferred from Electronic Annotation more info
cellular response to retinoic acid	IEA Inferred from Electronic Annotation more info
epidermal cell differentiation	IEA Inferred from Electronic Annotation more info
epidermis morphogenesis	IEA Inferred from Electronic Annotation more info
fat cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
mesodermal cell fate determination	TAS Traceable Author Statement more info	PubMed
negative regulation of ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
negative regulation of G1/S transition of mitotic cell cycle	IDA Inferred from Direct Assay more info	PubMed
negative regulation of NF-kappaB transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of angiogenesis	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell migration involved in sprouting angiogenesis	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell proliferation	TAS Traceable Author Statement more info	PubMed
negative regulation of chemokine (C-X-C motif) ligand 2 production	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
negative regulation of heterotypic cell-cell adhesion	IDA Inferred from Direct Assay more info	PubMed
negative regulation of inflammatory response	TAS Traceable Author Statement more info	PubMed
negative regulation of interleukin-8 biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
negative regulation of leukocyte adhesion to arterial endothelial cell	IGI Inferred from Genetic Interaction more info	PubMed
negative regulation of muscle hyperplasia	IEA Inferred from Electronic Annotation more info
negative regulation of phosphatidylinositol 3-kinase signaling	IEA Inferred from Electronic Annotation more info
negative regulation of protein kinase B signaling	IEA Inferred from Electronic Annotation more info
negative regulation of response to cytokine stimulus	IDA Inferred from Direct Assay more info	PubMed
negative regulation of smooth muscle cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
negative regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cellular protein metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of core promoter binding	IEA Inferred from Electronic Annotation more info
positive regulation of gene expression	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of hemoglobin biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of nitric oxide biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of protein metabolic process	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of sprouting angiogenesis	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of telomerase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-templated	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription, DNA-templated	NAS Non-traceable Author Statement more info	PubMed
post-embryonic camera-type eye development	IEA Inferred from Electronic Annotation more info
post-embryonic hemopoiesis	IMP Inferred from Mutant Phenotype more info	PubMed
pri-miRNA transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
regulation of axon regeneration	IEA Inferred from Electronic Annotation more info
regulation of cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
regulation of phosphatidylinositol 3-kinase activity	IEA Inferred from Electronic Annotation more info
regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
somatic stem cell population maintenance	TAS Traceable Author Statement more info
stem cell population maintenance	ISS Inferred from Sequence or Structural Similarity more info
transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
nuclear chromatin	IDA Inferred from Direct Assay more info	PubMed
nuclear euchromatin	IEA Inferred from Electronic Annotation more info
nuclear transcription factor complex	IEA Inferred from Electronic Annotation more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: Krueppel-like factor 4

Names: Kruppel-like factor 4 (gut); endothelial Kruppel-like zinc finger protein; epithelial zinc finger protein EZF; gut Kruppel-like factor; gut-enriched krueppel-like factor

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001314052.1 → NP_001300981.1 Krueppel-like factor 4 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1, also known as GKLFa).

Source sequence(s)

AF105036, AL360218, BC030811

UniProtKB/Swiss-Prot

O43474

Conserved Domains (4) summary

COG5048
Location:425 → 508

COG5048; FOG: Zn-finger [General function prediction only]

sd00017
Location:432 → 454

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00096
Location:430 → 454

zf-C2H2; Zinc finger, C2H2 type

pfam13465
Location:476 → 501

zf-H2C2_2; Zinc-finger double domain
NM_004235.6 → NP_004226.3 Krueppel-like factor 4 isoform 2

See identical proteins and their annotated locations for NP_004226.3

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame segment in the 3' coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AF105036, AL360218, BU739190

Consensus CDS

CCDS6770.2

UniProtKB/Swiss-Prot

O43474

Related

ENSP00000363804.4, ENST00000374672.4

Conserved Domains (3) summary

COG5048
Location:391 → 474

COG5048; FOG: Zn-finger [General function prediction only]

sd00017
Location:398 → 420

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam13465
Location:442 → 467

zf-H2C2_2; Zinc-finger double domain