Human Gene KLF4 (uc004bdh.3)
  Description: Homo sapiens Kruppel-like factor 4 (gut) (KLF4), mRNA.
RefSeq Summary (NM_004235): 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].
Transcript (Including UTRs)
   Position: hg19 chr9:110,247,133-110,252,047 Size: 4,915 Total Exon Count: 4 Strand: -
Coding Region
   Position: hg19 chr9:110,248,032-110,251,309 Size: 3,278 Coding Exon Count: 3 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr9:110,247,133-110,252,047)mRNA (may differ from genome)Protein (504 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: KLF4_HUMAN
DESCRIPTION: RecName: Full=Krueppel-like factor 4; AltName: Full=Epithelial zinc finger protein EZF; AltName: Full=Gut-enriched krueppel-like factor;
FUNCTION: 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.
SUBUNIT: Interacts with POU5F1/OCT4 and SOX2 (By similarity). Interacts with MUC1 (via the C-terminal domain).
SUBCELLULAR LOCATION: Nucleus.
DOMAIN: the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
BIOTECHNOLOGY: POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein family.
SIMILARITY: Contains 3 C2H2-type zinc fingers.
SEQUENCE CAUTION: Sequence=AAB48399.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAC03462.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAD42165.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAH29923.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAH30811.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=ABG25917.1; Type=Erroneous gene model prediction; Sequence=BAG36271.1; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=EAW59020.1; Type=Erroneous gene model prediction; Sequence=EAW59021.1; Type=Erroneous gene model prediction;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/KLF4ID44316ch9q31.html";
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/klf4/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): KLF4
CDC HuGE Published Literature: KLF4
Positive Disease Associations: Electrocardiography , Myocardial Infarction
Related Studies:
  1. Electrocardiography
    Christopher Newton-Cheh et al. BMC medical genetics 2007, Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study., BMC medical genetics. [PubMed 17903306]
    In the community-based Framingham Heart Study none of the ECG and HRV results individually attained genomewide significance. However, the presence of bona fide QT-associated SNPs among the top 117 results for QT duration supports the importance of efforts to validate top results from the reported scans. Finding genetic variants associated with ECG and HRV quantitative traits may identify novel genes and pathways implicated in arrhythmogenesis and allow for improved recognition of individuals at high risk for arrhythmias in the general population.
  2. Myocardial Infarction
    , , . [PubMed 0]
  3. Myocardial Infarction
    , , . [PubMed 0]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: KLF4
Diseases sorted by gene-association score: venous hemangioma (15), secretory meningioma (14), skin squamous cell carcinoma (11), germ cell and embryonal cancer (8), pediatric lymphoma (5), wolfram syndrome 2 (5), esophageal cancer (4), colorectal cancer (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 267.73 RPKM in Skin - Not Sun Exposed (Suprapubic)
Total median expression: 1618.46 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -250.30621-0.403 Picture PostScript Text
3' UTR -229.99899-0.256 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007087 - Znf_C2H2
IPR015880 - Znf_C2H2-like
IPR013087 - Znf_C2H2/integrase_DNA-bd

Pfam Domains:
PF00096 - Zinc finger, C2H2 type

SCOP Domains:
57667 - C2H2 and C2HC zinc fingers

ModBase Predicted Comparative 3D Structure on O43474
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0000987 core promoter proximal region sequence-specific DNA binding
GO:0001010 transcription factor activity, sequence-specific DNA binding transcription factor recruiting
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001085 RNA polymerase II transcription factor binding
GO:0001190 transcriptional activator activity, RNA polymerase II transcription factor binding
GO:0001221 transcription cofactor binding
GO:0003676 nucleic acid binding
GO:0003677 DNA binding
GO:0003690 double-stranded DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0005515 protein binding
GO:0008013 beta-catenin binding
GO:0008134 transcription factor binding
GO:0008270 zinc ion binding
GO:0035014 phosphatidylinositol 3-kinase regulator activity
GO:0042826 histone deacetylase binding
GO:0043565 sequence-specific DNA binding
GO:0044212 transcription regulatory region DNA binding
GO:0046872 metal ion binding
GO:1990841 promoter-specific chromatin binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006366 transcription from RNA polymerase II promoter
GO:0007500 mesodermal cell fate determination
GO:0008285 negative regulation of cell proliferation
GO:0009913 epidermal cell differentiation
GO:0010033 response to organic substance
GO:0010628 positive regulation of gene expression
GO:0010629 negative regulation of gene expression
GO:0014067 negative regulation of phosphatidylinositol 3-kinase signaling
GO:0014740 negative regulation of muscle hyperplasia
GO:0016525 negative regulation of angiogenesis
GO:0019827 stem cell population maintenance
GO:0030154 cell differentiation
GO:0030336 negative regulation of cell migration
GO:0031077 post-embryonic camera-type eye development
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032270 positive regulation of cellular protein metabolic process
GO:0032526 response to retinoic acid
GO:0034115 negative regulation of heterotypic cell-cell adhesion
GO:0035019 somatic stem cell population maintenance
GO:0035166 post-embryonic hemopoiesis
GO:0042127 regulation of cell proliferation
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0043551 regulation of phosphatidylinositol 3-kinase activity
GO:0045415 negative regulation of interleukin-8 biosynthetic process
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045444 fat cell differentiation
GO:0045595 regulation of cell differentiation
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046985 positive regulation of hemoglobin biosynthetic process
GO:0048662 negative regulation of smooth muscle cell proliferation
GO:0048679 regulation of axon regeneration
GO:0048730 epidermis morphogenesis
GO:0050728 negative regulation of inflammatory response
GO:0051247 positive regulation of protein metabolic process
GO:0051898 negative regulation of protein kinase B signaling
GO:0051973 positive regulation of telomerase activity
GO:0060070 canonical Wnt signaling pathway
GO:0060761 negative regulation of response to cytokine stimulus
GO:0061614 pri-miRNA transcription from RNA polymerase II promoter
GO:0070301 cellular response to hydrogen peroxide
GO:0070373 negative regulation of ERK1 and ERK2 cascade
GO:0071300 cellular response to retinoic acid
GO:0071363 cellular response to growth factor stimulus
GO:0071407 cellular response to organic cyclic compound
GO:0071409 cellular response to cycloheximide
GO:0071499 cellular response to laminar fluid shear stress
GO:0090051 negative regulation of cell migration involved in sprouting angiogenesis
GO:1901653 cellular response to peptide
GO:1903672 positive regulation of sprouting angiogenesis
GO:1904798 positive regulation of core promoter binding
GO:1904998 negative regulation of leukocyte adhesion to arterial endothelial cell
GO:1990830 cellular response to leukemia inhibitory factor
GO:2000134 negative regulation of G1/S transition of mitotic cell cycle
GO:2000342 negative regulation of chemokine (C-X-C motif) ligand 2 production

Cellular Component:
GO:0000785 chromatin
GO:0000790 nuclear chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005719 nuclear euchromatin
GO:0005737 cytoplasm
GO:0044798 nuclear transcription factor complex


-  Descriptions from all associated GenBank mRNAs
  AK026253 - Homo sapiens cDNA: FLJ22600 fis, clone HSI04447, highly similar to AF105036 Homo sapiens zinc finger transcription factor GKLF mRNA.
AK095894 - Homo sapiens cDNA FLJ38575 fis, clone HCHON2007046.
AF105036 - Homo sapiens zinc finger transcription factor GKLF mRNA, complete cds.
BC029923 - Homo sapiens Kruppel-like factor 4 (gut), mRNA (cDNA clone MGC:34918 IMAGE:5111134), complete cds.
BC030811 - Homo sapiens Kruppel-like factor 4 (gut), mRNA (cDNA clone MGC:22411 IMAGE:4703002), complete cds.
AK095134 - Homo sapiens cDNA FLJ37815 fis, clone BRSSN2003012, highly similar to Krueppel-like factor 4 (Epithelial zinc-finger protein EZF).
LF335591 - JP 2014500723-A/143094: Polycomb-Associated Non-Coding RNAs.
LF335592 - JP 2014500723-A/143095: Polycomb-Associated Non-Coding RNAs.
HF546201 - Homo sapiens mRNA for Kruppel-like factor 4 (gut), splice variant 1a (KLF4 gene).
HF546202 - Homo sapiens mRNA for Kruppel-like factor 4 (gut), splice variant 2 (KLF4 gene).
HF546213 - Homo sapiens mRNA for Kruppel-like factor 4 (gut), splice variant 1b (KLF4 gene).
AF022184 - Homo sapiens Kruppel-like zinc finger protein (EZF) mRNA, complete cds.
U70663 - Human zinc finger transcription factor hEZF (EZF) mRNA, complete cds.
HM026463 - Homo sapiens Kruppel-like factor 4 short isoform (KLF4) mRNA, complete cds, alternatively spliced.
HW243461 - JP 2013512690-A/12: RNA PREPARATIONS COMPRISING PURIFIED MODIFIED RNA FOR REPROGRAMMING CELLS.
LF715483 - JP 2016171804-A/12: RNA PREPARATIONS COMPRISING PURIFIED MODIFIED RNA FOR REPROGRAMMING CELLS.
AK313489 - Homo sapiens cDNA, FLJ94042, highly similar to Homo sapiens Kruppel-like factor 4 (gut) (KLF4), mRNA.
DQ891793 - Synthetic construct clone IMAGE:100004423; FLH179976.01X; RZPDo839E07132D Kruppel-like factor 4 (gut) (KLF4) gene, encodes complete protein.
KJ901962 - Synthetic construct Homo sapiens clone ccsbBroadEn_11356 KLF4 gene, encodes complete protein.
DQ894975 - Synthetic construct Homo sapiens clone IMAGE:100009435; FLH179972.01L; RZPDo839E07131D Kruppel-like factor 4 (gut) (KLF4) gene, encodes complete protein.
AB385001 - Synthetic construct DNA, clone: pF1KB4940, Homo sapiens KLF4 gene for krueppel-like factor 4, complete cds, without stop codon, in Flexi system.
CU688792 - Synthetic construct Homo sapiens gateway clone IMAGE:100019550 5' read KLF4 mRNA.
LF211949 - JP 2014500723-A/19452: Polycomb-Associated Non-Coding RNAs.
CU689020 - Synthetic construct Homo sapiens gateway clone IMAGE:100022258 5' read KLF4 mRNA.
JD458073 - Sequence 439097 from Patent EP1572962.
JD374182 - Sequence 355206 from Patent EP1572962.
JD422217 - Sequence 403241 from Patent EP1572962.
JD436266 - Sequence 417290 from Patent EP1572962.
JD142033 - Sequence 123057 from Patent EP1572962.
MA571168 - JP 2018138019-A/143094: Polycomb-Associated Non-Coding RNAs.
MA571169 - JP 2018138019-A/143095: Polycomb-Associated Non-Coding RNAs.
MA447526 - JP 2018138019-A/19452: Polycomb-Associated Non-Coding RNAs.
LY605666 - KR 1020180081836-A/12: RNA PREPARATIONS COMPRISING PURIFIED MODIFIED RNA FOR REPROGRAMMING CELLS.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O43474 (Reactome details) participates in the following event(s):

R-HSA-480204 POU5F1 (OCT4), SOX2, NANOG, KLF4, PBX1, SMAD2 bind the NANOG promoter
R-HSA-452723 Transcriptional regulation of pluripotent stem cells
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: B2R8S4, B3KT79, BC030811, EZF, GKLF, KLF4_HUMAN, NM_004235, NP_004226, O43474, P78338, Q5T3J8, Q5T3J9, Q8N717, Q9UNP3
UCSC ID: uc004bdh.3
RefSeq Accession: NM_004235
Protein: O43474 (aka KLF4_HUMAN)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: BC030811.1
exon count: 4CDS single in 3' UTR: no RNA size: 2468
ORF size: 1515CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3030.50frame shift in genome: no % Coverage: 98.78
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: yes # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.