UniProtKB - Q60793 (KLF4_MOUSE)
Krueppel-like factor 4
Klf4
Functioni
Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence (PubMed:10431239, PubMed:10556311, PubMed:15358627, PubMed:16954384, PubMed:17060454, PubMed:19816951, PubMed:20071344, PubMed:29593216).
Binds to the promoter region of its own gene and can activate its own transcription (PubMed:10431239, PubMed:10556311, PubMed:15358627, PubMed:16954384, PubMed:17060454, PubMed:19816951, PubMed:20071344, PubMed:29593216).
Regulates the expression of key transcription factors during embryonic development (PubMed:10431239, PubMed:10556311, PubMed:15358627, PubMed:16954384, PubMed:17060454, PubMed:19816951, PubMed:20071344, PubMed:29593216).
Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation (PubMed:10431239, PubMed:10556311, PubMed:15358627, PubMed:16954384, PubMed:17060454, PubMed:19816951, PubMed:20071344, PubMed:29593216).
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 (By similarity).
By similarity8 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 400 – 424 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 25 | |
Zinc fingeri | 430 – 454 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 25 | |
Zinc fingeri | 460 – 482 | C2H2-type 3PROSITE-ProRule annotationAdd BLAST | 23 |
GO - Molecular functioni
- beta-catenin binding Source: BHF-UCL
- chromatin DNA binding Source: MGI
- cis-regulatory region sequence-specific DNA binding Source: MGI
- DNA binding Source: MGI
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: MGI
- DNA-binding transcription factor activity Source: MGI
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: CACAO
- double-stranded DNA binding Source: MGI
- histone deacetylase binding Source: MGI
- metal ion binding Source: UniProtKB-KW
- phosphatidylinositol 3-kinase regulator activity Source: MGI
- promoter-specific chromatin binding Source: UniProtKB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: BHF-UCL
- RNA polymerase II sequence-specific DNA-binding transcription factor recruiting activity Source: BHF-UCL
- RNA polymerase II-specific DNA-binding transcription factor binding Source: BHF-UCL
- sequence-specific DNA binding Source: MGI
- sequence-specific double-stranded DNA binding Source: MGI
- transcription cis-regulatory region binding Source: UniProtKB
- transcription coregulator binding Source: MGI
GO - Biological processi
- canonical Wnt signaling pathway Source: BHF-UCL
- cell differentiation Source: MGI
- cellular response to growth factor stimulus Source: MGI
- cellular response to laminar fluid shear stress Source: MGI
- cellular response to leukemia inhibitory factor Source: MGI
- defense response to tumor cell Source: MGI
- epidermal cell differentiation Source: MGI
- epidermis development Source: MGI
- epidermis morphogenesis Source: MGI
- establishment of skin barrier Source: MGI
- fat cell differentiation Source: BHF-UCL
- gene expression Source: MGI
- negative regulation of angiogenesis Source: MGI
- negative regulation of cell migration Source: CACAO
- negative regulation of cell migration involved in sprouting angiogenesis Source: MGI
- negative regulation of cell population proliferation Source: MGI
- negative regulation of chemokine (C-X-C motif) ligand 2 production Source: MGI
- negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
- negative regulation of DNA-binding transcription factor activity Source: MGI
- negative regulation of ERK1 and ERK2 cascade Source: MGI
- negative regulation of G1/S transition of mitotic cell cycle Source: MGI
- negative regulation of gene expression Source: MGI
- negative regulation of heterotypic cell-cell adhesion Source: MGI
- negative regulation of interleukin-8 production Source: MGI
- negative regulation of leukocyte adhesion to arterial endothelial cell Source: MGI
- negative regulation of muscle hyperplasia Source: MGI
- negative regulation of NF-kappaB transcription factor activity Source: MGI
- negative regulation of phosphatidylinositol 3-kinase signaling Source: MGI
- negative regulation of protein kinase B signaling Source: MGI
- negative regulation of response to cytokine stimulus Source: MGI
- negative regulation of smooth muscle cell proliferation Source: MGI
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: MGI
- positive regulation of cellular protein metabolic process Source: MGI
- positive regulation of core promoter binding Source: BHF-UCL
- positive regulation of gene expression Source: MGI
- positive regulation of hemoglobin biosynthetic process Source: MGI
- positive regulation of miRNA transcription Source: MGI
- positive regulation of nitric oxide biosynthetic process Source: MGI
- positive regulation of protein metabolic process Source: MGI
- positive regulation of sprouting angiogenesis Source: MGI
- positive regulation of telomerase activity Source: MGI
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: MGI
- post-embryonic camera-type eye development Source: MGI
- post-embryonic hemopoiesis Source: MGI
- regulation of axon regeneration Source: MGI
- regulation of blastocyst development Source: MGI
- regulation of cell differentiation Source: UniProtKB
- regulation of cell population proliferation Source: MGI
- regulation of transcription by RNA polymerase II Source: MGI
- response to organic substance Source: MGI
- response to retinoic acid Source: MGI
- stem cell population maintenance Source: UniProtKB
- transcription, DNA-templated Source: CACAO
Keywordsi
Molecular function | Activator, DNA-binding |
Biological process | Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Names & Taxonomyi
Protein namesi | Recommended name: Krueppel-like factor 4Alternative name(s): Epithelial zinc finger protein EZF Gut-enriched krueppel-like factor |
Gene namesi | Name:Klf4 Synonyms:Ezf, Gklf, Zie |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1342287, Klf4 |
VEuPathDBi | HostDB:ENSMUSG00000003032 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
Cytoskeleton
- microtubule cytoskeleton Source: Ensembl
Cytosol
- cytosol Source: Ensembl
Nucleus
- nucleoplasm Source: MGI
- nucleus Source: MGI
Other locations
- chromatin Source: MGI
- cytoplasm Source: MGI
- euchromatin Source: BHF-UCL
- transcription regulator complex Source: BHF-UCL
Keywords - Cellular componenti
NucleusPathology & Biotechi
Biotechnological usei
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 46 | E → A: No change in KLF4 polyglutamylation. 1 Publication | 1 | |
Mutagenesisi | 95 | E → A: No change in KLF4 polyglutamylation. 1 Publication | 1 | |
Mutagenesisi | 229 | K → R: Increased cell reprogramming and pluripotency. No change in promoter-binding of target genes. 1 Publication | 1 | |
Mutagenesisi | 326 | E → A: No change in KLF4 polyglutamylation. 1 Publication | 1 | |
Mutagenesisi | 381 | E → A: Loss of polyglutamylation, reduced cell reprogramming and pluripotency maintenance. Forms heterodimer with KLF5. No change in promoter-binding of target genes. Embryo lethality in mutant homozygous mice. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000047168 | 1 – 483 | Krueppel-like factor 4Add BLAST | 483 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 32 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Modified residuei | 251 | PhosphoserineBy similarity | 1 | |
Modified residuei | 381 | 5-glutamyl polyglutamate1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
MaxQBi | Q60793 |
PaxDbi | Q60793 |
PRIDEi | Q60793 |
ProteomicsDBi | 269224 |
PTM databases
iPTMneti | Q60793 |
PhosphoSitePlusi | Q60793 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000003032, Expressed in cornea and 315 other tissues |
ExpressionAtlasi | Q60793, baseline and differential |
Genevisiblei | Q60793, MM |
Interactioni
Subunit structurei
Interacts with MUC1 (via the C-terminal domain) (By similarity).
Interacts with POU5F1/OCT4 and SOX2 (PubMed:19816951).
Interacts with MEIS2 isoform MeisD and PBX1 isoform PBX1a (By similarity).
Interacts with ZNF296 (PubMed:24161396).
Interacts with GLIS1 (By similarity).
Interacts with BTRC; this interaction leads to KLF4 ubiquitination and subsequent degradation (PubMed:29593216).
By similarity3 PublicationsBinary interactionsi
Q60793
GO - Molecular functioni
- beta-catenin binding Source: BHF-UCL
- histone deacetylase binding Source: MGI
- RNA polymerase II-specific DNA-binding transcription factor binding Source: BHF-UCL
- transcription coregulator binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 200966, 15 interactors |
DIPi | DIP-59920N |
ELMi | Q60793 |
IntActi | Q60793, 16 interactors |
MINTi | Q60793 |
STRINGi | 10090.ENSMUSP00000103245 |
Miscellaneous databases
RNActi | Q60793, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q60793 |
SMRi | Q60793 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q60793 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 22 – 42 | DisorderedSequence analysisAdd BLAST | 21 | |
Regioni | 294 – 395 | DisorderedSequence analysisAdd BLAST | 102 | |
Regioni | 386 – 483 | Interaction with ZNF2961 PublicationAdd BLAST | 98 | |
Regioni | 443 – 474 | Interaction with target DNAAdd BLAST | 32 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 99 – 107 | 9aaTADBy similarity | 9 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 312 – 327 | Polar residuesSequence analysisAdd BLAST | 16 | |
Compositional biasi | 339 – 355 | Pro residuesSequence analysisAdd BLAST | 17 |
Domaini
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 400 – 424 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 25 | |
Zinc fingeri | 430 – 454 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 25 | |
Zinc fingeri | 460 – 482 | C2H2-type 3PROSITE-ProRule annotationAdd BLAST | 23 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG1721, Eukaryota |
GeneTreei | ENSGT00940000156229 |
HOGENOMi | CLU_002678_33_1_1 |
InParanoidi | Q60793 |
OMAi | RDCHPSP |
OrthoDBi | 1591573at2759 |
PhylomeDBi | Q60793 |
TreeFami | TF350556 |
Family and domain databases
InterProi | View protein in InterPro IPR036236, Znf_C2H2_sf IPR013087, Znf_C2H2_type |
Pfami | View protein in Pfam PF00096, zf-C2H2, 3 hits |
SMARTi | View protein in SMART SM00355, ZnF_C2H2, 3 hits |
SUPFAMi | SSF57667, SSF57667, 2 hits |
PROSITEi | View protein in PROSITE PS00028, ZINC_FINGER_C2H2_1, 3 hits PS50157, ZINC_FINGER_C2H2_2, 3 hits |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MRQPPGESDM AVSDALLPSF STFASGPAGR EKTLRPAGAP TNRWREELSH
60 70 80 90 100
MKRLPPLPGR PYDLAATVAT DLESGGAGAA CSSNNPALLA RRETEEFNDL
110 120 130 140 150
LDLDFILSNS LTHQESVAAT VTTSASASSS SSPASSGPAS APSTCSFSYP
160 170 180 190 200
IRAGGDPGVA ASNTGGGLLY SRESAPPPTA PFNLADINDV SPSGGFVAEL
210 220 230 240 250
LRPELDPVYI PPQQPQPPGG GLMGKFVLKA SLTTPGSEYS SPSVISVSKG
260 270 280 290 300
SPDGSHPVVV APYSGGPPRM CPKIKQEAVP SCTVSRSLEA HLSAGPQLSN
310 320 330 340 350
GHRPNTHDFP LGRQLPTRTT PTLSPEELLN SRDCHPGLPL PPGFHPHPGP
360 370 380 390 400
NYPPFLPDQM QSQVPSLHYQ ELMPPGSCLP EEPKPKRGRR SWPRKRTATH
410 420 430 440 450
TCDYAGCGKT YTKSSHLKAH LRTHTGEKPY HCDWDGCGWK FARSDELTRH
460 470 480
YRKHTGHRPF QCQKCDRAFS RSDHLALHMK RHF
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketB7ZCH2 | B7ZCH2_MOUSE | Krueppel-like factor 4 | Klf4 | 160 | Annotation score: | ||
B7ZCH1 | B7ZCH1_MOUSE | Krueppel-like factor 4 | Klf4 | 82 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 162 | S → R in AAC52939 (PubMed:8940147).Curated | 1 | |
Sequence conflicti | 185 | A → G in AAC52939 (PubMed:8940147).Curated | 1 | |
Sequence conflicti | 302 | H → Q in BAE33205 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 350 | P → A in AAC52939 (PubMed:8940147).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U20344 mRNA Translation: AAC04892.1 U70662 mRNA Translation: AAC52939.1 Different initiation. AF117109 Genomic DNA Translation: AAD17223.1 AY071827 Genomic DNA Translation: AAL60058.1 AK141244 mRNA Translation: BAE24612.1 AK144942 mRNA Translation: BAE26147.1 AK155343 mRNA Translation: BAE33205.1 AL732494 Genomic DNA No translation available. CH466565 Genomic DNA Translation: EDL02262.1 BC010301 mRNA Translation: AAH10301.2 Different initiation. |
CCDSi | CCDS18195.2 |
RefSeqi | NP_034767.2, NM_010637.3 |
Genome annotation databases
Ensembli | ENSMUST00000107619; ENSMUSP00000103245; ENSMUSG00000003032 |
GeneIDi | 16600 |
KEGGi | mmu:16600 |
UCSCi | uc008sxk.2, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U20344 mRNA Translation: AAC04892.1 U70662 mRNA Translation: AAC52939.1 Different initiation. AF117109 Genomic DNA Translation: AAD17223.1 AY071827 Genomic DNA Translation: AAL60058.1 AK141244 mRNA Translation: BAE24612.1 AK144942 mRNA Translation: BAE26147.1 AK155343 mRNA Translation: BAE33205.1 AL732494 Genomic DNA No translation available. CH466565 Genomic DNA Translation: EDL02262.1 BC010301 mRNA Translation: AAH10301.2 Different initiation. |
CCDSi | CCDS18195.2 |
RefSeqi | NP_034767.2, NM_010637.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2WBS | X-ray | 1.70 | A | 395-483 | [»] | |
2WBU | X-ray | 2.50 | A | 396-483 | [»] | |
4M9E | X-ray | 1.85 | A | 396-483 | [»] | |
5KE6 | X-ray | 1.99 | A | 396-483 | [»] | |
5KE7 | X-ray | 2.06 | A | 396-483 | [»] | |
5KE8 | X-ray | 2.45 | A | 396-483 | [»] | |
5KE9 | X-ray | 2.34 | A | 396-483 | [»] | |
5KEA | X-ray | 2.46 | A | 396-483 | [»] | |
5KEB | X-ray | 2.45 | A | 396-483 | [»] | |
AlphaFoldDBi | Q60793 | |||||
SMRi | Q60793 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 200966, 15 interactors |
DIPi | DIP-59920N |
ELMi | Q60793 |
IntActi | Q60793, 16 interactors |
MINTi | Q60793 |
STRINGi | 10090.ENSMUSP00000103245 |
PTM databases
iPTMneti | Q60793 |
PhosphoSitePlusi | Q60793 |
Proteomic databases
MaxQBi | Q60793 |
PaxDbi | Q60793 |
PRIDEi | Q60793 |
ProteomicsDBi | 269224 |
Protocols and materials databases
Antibodypediai | 14888, 926 antibodies from 45 providers |
DNASUi | 16600 |
Genome annotation databases
Ensembli | ENSMUST00000107619; ENSMUSP00000103245; ENSMUSG00000003032 |
GeneIDi | 16600 |
KEGGi | mmu:16600 |
UCSCi | uc008sxk.2, mouse |
Organism-specific databases
CTDi | 9314 |
MGIi | MGI:1342287, Klf4 |
VEuPathDBi | HostDB:ENSMUSG00000003032 |
Phylogenomic databases
eggNOGi | KOG1721, Eukaryota |
GeneTreei | ENSGT00940000156229 |
HOGENOMi | CLU_002678_33_1_1 |
InParanoidi | Q60793 |
OMAi | RDCHPSP |
OrthoDBi | 1591573at2759 |
PhylomeDBi | Q60793 |
TreeFami | TF350556 |
Miscellaneous databases
BioGRID-ORCSi | 16600, 2 hits in 75 CRISPR screens |
ChiTaRSi | Klf4, mouse |
EvolutionaryTracei | Q60793 |
PROi | PR:Q60793 |
RNActi | Q60793, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000003032, Expressed in cornea and 315 other tissues |
ExpressionAtlasi | Q60793, baseline and differential |
Genevisiblei | Q60793, MM |
Family and domain databases
InterProi | View protein in InterPro IPR036236, Znf_C2H2_sf IPR013087, Znf_C2H2_type |
Pfami | View protein in Pfam PF00096, zf-C2H2, 3 hits |
SMARTi | View protein in SMART SM00355, ZnF_C2H2, 3 hits |
SUPFAMi | SSF57667, SSF57667, 2 hits |
PROSITEi | View protein in PROSITE PS00028, ZINC_FINGER_C2H2_1, 3 hits PS50157, ZINC_FINGER_C2H2_2, 3 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | KLF4_MOUSE | |
Accessioni | Q60793Primary (citable) accession number: Q60793 Secondary accession number(s): P70421 Q9R255 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
Last sequence update: | February 10, 2009 | |
Last modified: | May 25, 2022 | |
This is version 190 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families