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
110	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (107484852..107489769, complement)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (119656625..119661541, complement)
105.20220307	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
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?

Lef1 is transcriptionally activated by Klf4 and suppresses hyperoxia-induced alveolar epithelial cell injury.
Title: <i>Lef1</i> is transcriptionally activated by <i>Klf4</i> and suppresses hyperoxia-induced alveolar epithelial cell injury.
SAMHD1, positively regulated by KLF4, suppresses the proliferation of gastric cancer cells through MAPK p38 signaling pathway.
Title: SAMHD1, positively regulated by KLF4, suppresses the proliferation of gastric cancer cells through MAPK p38 signaling pathway.
KLF4 Mutation Shapes Pathologic Characteristics of Foveolar-Type Gastric Adenoma in Helicobacter pylori-Naive Patients.
Title: KLF4 Mutation Shapes Pathologic Characteristics of Foveolar-Type Gastric Adenoma in Helicobacter pylori-Naive Patients.
KLF4 is a therapeutically tractable brake on fibroblast activation that promotes resolution of pulmonary fibrosis.
Title: KLF4 is a therapeutically tractable brake on fibroblast activation that promotes resolution of pulmonary fibrosis.
Epithelial-mesenchymal reprogramming by KLF4-regulated Rictor expression contributes to metastasis of non-small cell lung cancer cells.
Title: Epithelial-mesenchymal reprogramming by KLF4-regulated Rictor expression contributes to metastasis of non-small cell lung cancer cells.
Long Noncoding RNA AF131217.1 Regulated Coronary Slow Flow-Induced Inflammation Affecting Coronary Slow Flow via KLF4.
Title: Long Noncoding RNA AF131217.1 Regulated Coronary Slow Flow-Induced Inflammation Affecting Coronary Slow Flow via KLF4.
Loss-of-function variants in KLF4 underlie autosomal dominant palmoplantar keratoderma.
Title: Loss-of-function variants in KLF4 underlie autosomal dominant palmoplantar keratoderma.
Silencing of FSTL1 Alleviated LPS-Induced Inflammatory Damage and Oxidative Damage in Human Bronchial Epithelial Cells via BMP4/KLF4 Axis.
Title: Silencing of FSTL1 Alleviated LPS-Induced Inflammatory Damage and Oxidative Damage in Human Bronchial Epithelial Cells via BMP4/KLF4 Axis.
Decreased Kruppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells.
Title: Decreased Krüppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells.
SIRT2-KLF4 Interactions are Critical for Myeloma Survival and Migration.
Title: SIRT2-KLF4 Interactions are Critical for Myeloma Survival and Migration.

Submit: New GeneRIF Correction See all GeneRIFs (456)

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

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: 429 organisms have orthologs with human gene KLF4
Orthologs

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	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	PubMed
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	PubMed
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 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 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 growth factor stimulus	IDA Inferred from Direct Assay more info	PubMed
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 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 NF-kappaB transcription factor activity	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 cell migration involved in sprouting angiogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
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 cysteine-type endopeptidase activity involved in apoptotic process	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 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 core promoter binding	IEA Inferred from Electronic Annotation more info
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
involved_in positive regulation of telomerase activity	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	PubMed
involved_in response to retinoic acid	IEA Inferred from Electronic Annotation 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

O43474, 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