UniProtKB - O43474 (KLF4_HUMAN)
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Protein
Krueppel-like factor 4
Gene
KLF4
Organism
Homo sapiens (Human)
Status
Functioni
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.2 Publications
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 430 – 454 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 25 | |
Zinc fingeri | 460 – 484 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 25 | |
Zinc fingeri | 490 – 512 | C2H2-type 3PROSITE-ProRule annotationAdd BLAST | 23 |
GO - Molecular functioni
- beta-catenin binding Source: Ensembl
- core promoter binding Source: Ensembl
- DNA binding transcription factor activity Source: ProtInc
- histone deacetylase binding Source: Ensembl
- phosphatidylinositol 3-kinase regulator activity Source: Ensembl
- promoter-specific chromatin binding Source: UniProtKB
- proximal promoter sequence-specific DNA binding Source: BHF-UCL
- RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
- RNA polymerase II transcription factor binding Source: BHF-UCL
- transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: BHF-UCL
- transcriptional activator activity, RNA polymerase II transcription factor binding Source: BHF-UCL
- transcription cofactor binding Source: Ensembl
- transcription factor activity, sequence-specific DNA binding transcription factor recruiting Source: BHF-UCL
- transcription regulatory region DNA binding Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- canonical Wnt signaling pathway Source: Ensembl
- cellular response to cycloheximide Source: Ensembl
- cellular response to growth factor stimulus Source: BHF-UCL
- cellular response to hydrogen peroxide Source: Ensembl
- cellular response to laminar fluid shear stress Source: BHF-UCL
- cellular response to leukemia inhibitory factor Source: Ensembl
- cellular response to peptide Source: Ensembl
- cellular response to retinoic acid Source: Ensembl
- epidermal cell differentiation Source: Ensembl
- epidermis morphogenesis Source: Ensembl
- fat cell differentiation Source: BHF-UCL
- mesodermal cell fate determination Source: ProtInc
- negative regulation of angiogenesis Source: BHF-UCL
- negative regulation of cell migration involved in sprouting angiogenesis Source: BHF-UCL
- negative regulation of cell proliferation Source: ProtInc
- negative regulation of chemokine (C-X-C motif) ligand 2 production Source: BHF-UCL
- negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
- negative regulation of ERK1 and ERK2 cascade Source: Ensembl
- negative regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
- negative regulation of gene expression Source: BHF-UCL
- negative regulation of heterotypic cell-cell adhesion Source: BHF-UCL
- negative regulation of inflammatory response Source: BHF-UCL
- negative regulation of interleukin-8 biosynthetic process Source: BHF-UCL
- negative regulation of leukocyte adhesion to arterial endothelial cell Source: BHF-UCL
- negative regulation of muscle hyperplasia Source: Ensembl
- negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
- negative regulation of phosphatidylinositol 3-kinase signaling Source: Ensembl
- negative regulation of protein kinase B signaling Source: Ensembl
- negative regulation of response to cytokine stimulus Source: BHF-UCL
- negative regulation of smooth muscle cell proliferation Source: Ensembl
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: BHF-UCL
- positive regulation of cellular protein metabolic process Source: BHF-UCL
- positive regulation of core promoter binding Source: Ensembl
- positive regulation of gene expression Source: BHF-UCL
- positive regulation of hemoglobin biosynthetic process Source: BHF-UCL
- positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
- positive regulation of protein metabolic process Source: BHF-UCL
- positive regulation of telomerase activity Source: BHF-UCL
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- post-embryonic camera-type eye development Source: Ensembl
- post-embryonic hemopoiesis Source: BHF-UCL
- pri-miRNA transcription by RNA polymerase II Source: BHF-UCL
- regulation of axon regeneration Source: Ensembl
- regulation of cell differentiation Source: UniProtKB
- somatic stem cell population maintenance Source: Reactome
- stem cell population maintenance Source: UniProtKB
- transcription by RNA polymerase II Source: BHF-UCL
Keywordsi
Molecular function | Activator, DNA-binding |
Biological process | Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-HSA-381340. Transcriptional regulation of white adipocyte differentiation. R-HSA-422085. Synthesis, secretion, and deacylation of Ghrelin. R-HSA-452723. Transcriptional regulation of pluripotent stem cells. |
SignaLinki | O43474. |
SIGNORi | O43474. |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000136826.14. |
HGNCi | HGNC:6348. KLF4. |
MIMi | 602253. gene. |
neXtProti | NX_O43474. |
Pathology & Biotechi
Biotechnological usei
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.1 Publication
Organism-specific databases
DisGeNETi | 9314. |
OpenTargetsi | ENSG00000136826. |
PharmGKBi | PA30138. |
Polymorphism and mutation databases
BioMutai | KLF4. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000047167 | 1 – 513 | Krueppel-like factor 4Add BLAST | 513 |
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)1 Publication | ||
Modified residuei | 254 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
MaxQBi | O43474. |
PeptideAtlasi | O43474. |
PRIDEi | O43474. |
PTM databases
iPTMneti | O43474. |
PhosphoSitePlusi | O43474. |
Expressioni
Gene expression databases
Bgeei | ENSG00000136826. |
CleanExi | HS_KLF4. |
ExpressionAtlasi | O43474. baseline and differential. |
Genevisiblei | O43474. HS. |
Organism-specific databases
HPAi | HPA002926. |
Interactioni
Subunit structurei
Interacts with POU5F1/OCT4 and SOX2 (By similarity). Interacts with MUC1 (via the C-terminal domain) (PubMed:17308127). Interacts with MEIS2 isoform 4 and PBX1 isoform PBX1a (PubMed:21746878). Interacts with ZNF296 (By similarity).By similarity2 Publications
Binary interactionsi
GO - Molecular functioni
- beta-catenin binding Source: Ensembl
- histone deacetylase binding Source: Ensembl
- RNA polymerase II transcription factor binding Source: BHF-UCL
- transcription cofactor binding Source: Ensembl
Protein-protein interaction databases
BioGridi | 114726. 32 interactors. |
DIPi | DIP-57667N. |
IntActi | O43474. 15 interactors. |
MINTi | O43474. |
Structurei
3D structure databases
ProteinModelPortali | O43474. |
SMRi | O43474. |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 416 – 513 | Interaction with ZNF296By similarityAdd BLAST | 98 | |
Regioni | 473 – 504 | Interaction with target DNABy similarityAdd BLAST | 32 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 101 – 109 | 9aaTAD | 9 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 125 – 149 | Ser-richAdd BLAST | 25 | |
Compositional biasi | 179 – 415 | Pro-richAdd BLAST | 237 |
Domaini
the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.1 Publication
Sequence similaritiesi
Belongs to the krueppel C2H2-type zinc-finger protein family.Curated
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 430 – 454 | C2H2-type 1PROSITE-ProRule annotationAdd BLAST | 25 | |
Zinc fingeri | 460 – 484 | C2H2-type 2PROSITE-ProRule annotationAdd BLAST | 25 | |
Zinc fingeri | 490 – 512 | C2H2-type 3PROSITE-ProRule annotationAdd BLAST | 23 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
GeneTreei | ENSGT00760000118998. |
HOVERGENi | HBG006220. |
InParanoidi | O43474. |
KOi | K17846. |
OMAi | STCSFSY. |
OrthoDBi | EOG091G1BN0. |
PhylomeDBi | O43474. |
TreeFami | TF350556. |
Family and domain databases
InterProi | View protein in InterPro IPR036236. Znf_C2H2_sf. IPR013087. Znf_C2H2_type. |
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. |
s (5)i Sequence
Sequence statusi: Complete.
This entry describes 5 produced by isoformsialternative splicing. AlignAdd to basket
Isoform 1 (identifier: O43474-3) [UniParc]FASTAAdd to basket
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MRQPPGESDM AVSDALLPSF STFASGPAGR EKTLRQAGAP NNRWREELSH
60 70 80 90 100
MKRLPPVLPG RPYDLAAATV ATDLESGGAG AACGGSNLAP LPRRETEEFN
110 120 130 140 150
DLLDLDFILS NSLTHPPESV AATVSSSASA SSSSSPSSSG PASAPSTCSF
160 170 180 190 200
TYPIRAGNDP GVAPGGTGGG LLYGRESAPP PTAPFNLADI NDVSPSGGFV
210 220 230 240 250
AELLRPELDP VYIPPQQPQP PGGGLMGKFV LKASLSAPGS EYGSPSVISV
260 270 280 290 300
SKGSPDGSHP VVVAPYNGGP PRTCPKIKQE AVSSCTHLGA GPPLSNGHRP
310 320 330 340 350
AAHDFPLGRQ LPSRTTPTLG LEEVLSSRDC HPALPLPPGF HPHPGPNYPS
360 370 380 390 400
FLPDQMQPQV PPLHYQGQSR GFVARAGEPC VCWPHFGTHG MMLTPPSSPL
410 420 430 440 450
ELMPPGSCMP EEPKPKRGRR SWPRKRTATH TCDYAGCGKT YTKSSHLKAH
460 470 480 490 500
LRTHTGEKPY HCDWDGCGWK FARSDELTRH YRKHTGHRPF QCQKCDRAFS
510
RSDHLALHMK RHF
Sequence cautioni
The sequence AAB48399 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAC03462 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAD42165 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH29923 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH30811 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence ABG25917 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence BAG36271 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence EAW59020 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW59021 differs from that shown. Reason: Erroneous gene model prediction.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 60 – 61 | GR → AG in AAC03462 (PubMed:9422764).Curated | 2 | |
Sequence conflicti | 77 | G → A in AAC03462 (PubMed:9422764).Curated | 1 | |
Sequence conflicti | 251 | S → T in AAC03462 (PubMed:9422764).Curated | 1 | |
Sequence conflicti | 304 | D → N in AAB48399 (Ref. 4) Curated | 1 | |
Sequence conflicti | 329 | D → E in AAB48399 (Ref. 4) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_059888 | 315 | T → S1 PublicationCorresponds to variant dbSNP:rs1059913Ensembl. | 1 | |
Natural variantiVAR_059889 | 321 | L → F1 PublicationCorresponds to variant dbSNP:rs1059914Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_040569 | 1 – 50 | Missing in isoform 3. 1 PublicationAdd BLAST | 50 | |
Alternative sequenceiVSP_047470 | 43 – 118 | RWREE…THPPE → SSCHPVPACQRSPSQRGEDD RGPGKGPPPTLVITRAAAKP TQRVPISRHTCEPTQVRNLT TVTGTAVDGNSPAQMN in isoform 4. 1 PublicationAdd BLAST | 76 | |
Alternative sequenceiVSP_047471 | 43 – 63 | RWREE…PGRPY → VRNLTTVTGTAVDGNSPAQM N in isoform 5. 1 PublicationAdd BLAST | 21 | |
Alternative sequenceiVSP_047472 | 64 – 513 | Missing in isoform 5. 1 PublicationAdd BLAST | 450 | |
Alternative sequenceiVSP_047473 | 119 – 513 | Missing in isoform 4. 1 PublicationAdd BLAST | 395 | |
Alternative sequenceiVSP_036399 | 367 – 400 | Missing in isoform 2 and isoform 3. 5 PublicationsAdd BLAST | 34 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF022184 mRNA. Translation: AAC03462.1. Different initiation. AF105036 mRNA. Translation: AAD42165.1. Different initiation. HF546201 mRNA. Translation: CCO02787.1. HF546202 mRNA. Translation: CCO02788.1. U70663 mRNA. Translation: AAB48399.1. Different initiation. AK095134 mRNA. Translation: BAG52991.1. AK313489 mRNA. Translation: BAG36271.1. Different initiation. DQ658241 Genomic DNA. Translation: ABG25917.1. Sequence problems. AL360218 Genomic DNA. No translation available. CH471105 Genomic DNA. Translation: EAW59020.1. Sequence problems. CH471105 Genomic DNA. Translation: EAW59021.1. Sequence problems. BC029923 mRNA. Translation: AAH29923.1. Different initiation. BC030811 mRNA. Translation: AAH30811.1. Different initiation. |
CCDSi | CCDS6770.2. [O43474-1] |
RefSeqi | NP_001300981.1. NM_001314052.1. [O43474-3] NP_004226.3. NM_004235.5. [O43474-1] |
UniGenei | Hs.376206. |
Genome annotation databases
Ensembli | ENST00000374672; ENSP00000363804; ENSG00000136826. [O43474-1] |
GeneIDi | 9314. |
KEGGi | hsa:9314. |
UCSCi | uc004bdg.4. human. [O43474-3] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | KLF4_HUMAN | |
Accessioni | O43474Primary (citable) accession number: O43474 Secondary accession number(s): B2R8S4 Q9UNP3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
Last sequence update: | February 10, 2009 | |
Last modified: | March 28, 2018 | |
This is version 174 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |