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
109.20200228	current	GRCh38.p13 (GCF_000001405.39)	9	NC_000009.12 (107484852..107489769, 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 Functions

What's a GeneRIF?

Study demonstrated that ATXN3 significantly correlated with KLF4. High ATXN3/KLF4 expression was associated with a poor prognosis in breast cancer patients. KLF4 is deubiquitinated by ATXN3. This process is important in breast cancer metastasis.
Title: ATXN3 promotes breast cancer metastasis by deubiquitinating KLF4.
Our findings show that a KLF4 genomic variant (rs2236599) is associated with hydroxyurea treatment efficacy in sickle cell disease/beta-thalassemia compound heterozygous patients and two KLF10 genomic variants (rs980112, rs3191333) are associated with persistent HbF levels in nontransfusion dependent beta-thalassemia (NTDT) patients
Title: Genomic variants in members of the Krüppel-like factor gene family are associated with disease severity and hydroxyurea treatment efficacy in β-hemoglobinopathies patients.
Besides, our results also indicated that Kruppel-like factor 4 (KLF4) can negatively regulate GINS4 expression at the transcriptional level and the KLF/GINS4 pathway might play a vital role in the growth and prognosis of colorectal cancer (CRC).
Title: GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel-like factor 4, promotes the growth of colorectal cancer.
our results lead us to propose a model where elevated KLF4 levels sustains the oncogenic state of Head and neck squamous cell carcinoma by reactivating repressed chromatin domains at key downstream genes, often by targeting super-enhancers.
Title: Reactivation of super-enhancers by KLF4 in human Head and Neck Squamous Cell Carcinoma.
EC miR-92a can be transported to macrophages through extracellular vesicles to regulate KLF4 levels, thus leading to the atheroprone phenotypes of macrophage and, hence, atherosclerotic lesion formation
Title: Extracellular MicroRNA-92a Mediates Endothelial Cell-Macrophage Communication.
MiR-29 expression is suppressed by progestins in breast cancer cells.
Title: Progestin suppression of miR-29 potentiates dedifferentiation of breast cancer cells via KLF4.
A regulatory role of KLF4 in developmental angiogenesis through regulation of DLL4 transcription.
Title: Kruppel-like factor 4 regulates developmental angiogenesis through disruption of the RBP-J-NICD-MAML complex in intron 3 of Dll4.
miR-200c overexpression was shown to downregulate SRY (sex determining region Y)-box 2 (Sox2) and Kruppel-like factor 4 by directly targeting 3'-untranslated regions and upregulate the activity of Wnt signaling inhibited by Sox2.
Title: Enhancement of MicroRNA-200c on Osteogenic Differentiation and Bone Regeneration by Targeting Sox2-Mediated Wnt Signaling and Klf4.
The findings showed that regardless of the DNA Methylation status, KLF-4 gene expression may play a role in the development of Type 2 Diabetes and Diabetic Nephropathy.
Title: Kruppel-Like Transcription Factor-4 Gene Expression and DNA Methylation Status in Type 2 Diabetes and Diabetic Nephropathy Patients.
silence of KLF4 could reverse regulatory effects of LINC01210 on cellular behaviors of ovarian cancer.
Title: LINC01210 accelerates proliferation, invasion and migration in ovarian cancer through epigenetically downregulating KLF4.

Submit: New GeneRIF Correction See all GeneRIFs (373)

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)

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: 288 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
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 sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transcription regulatory region sequence-specific 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	IBA Inferred from Biological aspect of Ancestor 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
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 chromatin	ISA Inferred from Sequence Alignment more info
nuclear euchromatin	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
transcription factor complex	IEA Inferred from Electronic Annotation more info

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_001314052.2 → 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, AL359552, AL360218, BC030811

UniProtKB/Swiss-Prot

O43474

Related

ENST00000493306.1

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, ENST00000374672.5

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