KLF4 KLF transcription factor 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: KLF4provided by HGNC
Official Full Name: KLF transcription factor 4provided by HGNC
Primary source: HGNC:HGNC:6348
See related: Ensembl:ENSG00000136826 MIM:602253; AllianceGenome:HGNC:6348
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
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Genomic context

Location:: 9q31.2

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (107484852..107489769, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (119656625..119661541, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (110247133..110252050, 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 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?

KLF4 regulates trophoblast function and associates with unexplained recurrent spontaneous abortion.
Title: KLF4 regulates trophoblast function and associates with unexplained recurrent spontaneous abortion.
KLF4-induced upregulation of SOCS1 ameliorates myocardial ischemia/reperfusion injury by attenuating AC16 cardiomyocyte damage and enhancing M2 macrophage polarization.
Title: KLF4-induced upregulation of SOCS1 ameliorates myocardial ischemia/reperfusion injury by attenuating AC16 cardiomyocyte damage and enhancing M2 macrophage polarization.
KLF4 Induces Colorectal Cancer by Promoting EMT via STAT3 Activation.
Title: KLF4 Induces Colorectal Cancer by Promoting EMT via STAT3 Activation.
Unveiling the role of the KLF4/Lnc18q22.2/ULBP3 axis in the tumorigenesis and immune escape of hepatocellular carcinoma under hypoxic condition.
Title: Unveiling the role of the KLF4/Lnc18q22.2/ULBP3 axis in the tumorigenesis and immune escape of hepatocellular carcinoma under hypoxic condition.
A review of KLF4 and inflammatory disease: Current status and future perspective.
Title: A review of KLF4 and inflammatory disease: Current status and future perspective.
METTL3-mediated N[6]-methyladenosine modification of STAT5A promotes gastric cancer progression by regulating KLF4.
Title: METTL3-mediated N(6)-methyladenosine modification of STAT5A promotes gastric cancer progression by regulating KLF4.
KLF4 Inhibits the Activation of Human Hepatic Stellate Cell In Vitro.
Title: KLF4 Inhibits the Activation of Human Hepatic Stellate Cell In Vitro.
KLF4 Suppresses the Progression of Hepatocellular Carcinoma by Reducing Tumor ATP Synthesis through Targeting the Mir-206/RICTOR Axis.
Title: KLF4 Suppresses the Progression of Hepatocellular Carcinoma by Reducing Tumor ATP Synthesis through Targeting the Mir-206/RICTOR Axis.
EphA2 promotes the transcription of KLF4 to facilitate stemness in oral squamous cell carcinoma.
Title: EphA2 promotes the transcription of KLF4 to facilitate stemness in oral squamous cell carcinoma.
HEG1 Protects Against Atherosclerosis by Regulating Stable Flow-Induced KLF2/4 Expression in Endothelial Cells.
Title: HEG1 Protects Against Atherosclerosis by Regulating Stable Flow-Induced KLF2/4 Expression in Endothelial Cells.

Submit: New GeneRIF Correction See all GeneRIFs (489)

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

EBI GWAS Catalog

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

Gene Ontology Provided by GOA

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

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

Component	Evidence Code	Pubs
located_in chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in euchromatin	IEA Inferred from Electronic Annotation more info
located_in microtubule cytoskeleton	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
part_of transcription regulator 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; 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

B2R8S4, B3KT79, L0R3I6, L0R4N5, O43474, P78338, Q5T3J8, Q5T3J9, Q8N717, Q9UNP3

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]

cl41729
Location:7 → 430

KLF1_2_4_N; N-terminal domain of Kruppel-like factor (KLF) 1, KLF2, KLF4, and similar proteins

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 (4) 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

cd21582
Location:7 → 396

KLF4_N; N-terminal domain of Kruppel-like factor 4