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Protein

Krueppel-like factor 4

Gene

KLF4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri430 – 454C2H2-type 1PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri460 – 484C2H2-type 2PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri490 – 512C2H2-type 3PROSITE-ProRule annotationAdd BLAST23

GO - Molecular functioni

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 sprouting angiogenesis Source: BHF-UCL
  • positive regulation of telomerase activity Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • 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 functionActivator, DNA-binding
Biological processTranscription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-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
SignaLinkiO43474
SIGNORiO43474

Names & Taxonomyi

Protein namesi
Recommended name:
Krueppel-like factor 4
Alternative name(s):
Epithelial zinc finger protein EZF
Gut-enriched krueppel-like factor
Gene namesi
Name:KLF4
Synonyms:EZF, GKLF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000136826.14
HGNCiHGNC:6348 KLF4
MIMi602253 gene
neXtProtiNX_O43474

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

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

DisGeNETi9314
OpenTargetsiENSG00000136826
PharmGKBiPA30138

Polymorphism and mutation databases

BioMutaiKLF4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000471671 – 513Krueppel-like factor 4Add BLAST513

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki32Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei254PhosphoserineCombined sources1

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO43474
PeptideAtlasiO43474
PRIDEiO43474

PTM databases

iPTMnetiO43474
PhosphoSitePlusiO43474

Expressioni

Gene expression databases

BgeeiENSG00000136826
CleanExiHS_KLF4
ExpressionAtlasiO43474 baseline and differential
GenevisibleiO43474 HS

Organism-specific databases

HPAiHPA002926

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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114726, 32 interactors
DIPiDIP-57667N
IntActiO43474, 15 interactors
MINTiO43474

Structurei

3D structure databases

ProteinModelPortaliO43474
SMRiO43474
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni416 – 513Interaction with ZNF296By similarityAdd BLAST98
Regioni473 – 504Interaction with target DNABy similarityAdd BLAST32

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi101 – 1099aaTAD9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi125 – 149Ser-richAdd BLAST25
Compositional biasi179 – 415Pro-richAdd BLAST237

Domaini

the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.1 Publication

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri430 – 454C2H2-type 1PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri460 – 484C2H2-type 2PROSITE-ProRule annotationAdd BLAST25
Zinc fingeri490 – 512C2H2-type 3PROSITE-ProRule annotationAdd BLAST23

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

GeneTreeiENSGT00760000118998
HOVERGENiHBG006220
InParanoidiO43474
KOiK17846
OMAiSTCSFSY
OrthoDBiEOG091G1BN0
PhylomeDBiO43474
TreeFamiTF350556

Family and domain databases

InterProiView protein in InterPro
IPR036236 Znf_C2H2_sf
IPR013087 Znf_C2H2_type
SMARTiView protein in SMART
SM00355 ZnF_C2H2, 3 hits
SUPFAMiSSF57667 SSF57667, 2 hits
PROSITEiView protein in PROSITE
PS00028 ZINC_FINGER_C2H2_1, 3 hits
PS50157 ZINC_FINGER_C2H2_2, 3 hits

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative 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.

« Hide

        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
Length:513
Mass (Da):54,671
Last modified:February 10, 2009 - v3
Checksum:i3B6113A3EF333935
GO
Isoform 2 (identifier: O43474-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     367-400: Missing.

Show »
Length:479
Mass (Da):51,076
Checksum:i039095BBF3E3F78D
GO
Isoform 3 (identifier: O43474-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.
     367-400: Missing.

Note: No experimental confirmation available.
Show »
Length:429
Mass (Da):45,639
Checksum:i99B86BE95A31F23D
GO
Isoform 4 (identifier: O43474-5) [UniParc]FASTAAdd to basket
Also known as: 1a

The sequence of this isoform differs from the canonical sequence as follows:
     43-118: RWREELSHMK...LSNSLTHPPE → SSCHPVPACQ...VDGNSPAQMN
     119-513: Missing.

Show »
Length:118
Mass (Da):12,329
Checksum:i9E900F0852665920
GO
Isoform 5 (identifier: O43474-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     43-63: RWREELSHMKRLPPVLPGRPY → VRNLTTVTGTAVDGNSPAQMN
     64-513: Missing.

Show »
Length:63
Mass (Da):6,489
Checksum:i2A7B5BE789162A89
GO

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 keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti60 – 61GR → AG in AAC03462 (PubMed:9422764).Curated2
Sequence conflicti77G → A in AAC03462 (PubMed:9422764).Curated1
Sequence conflicti251S → T in AAC03462 (PubMed:9422764).Curated1
Sequence conflicti304D → N in AAB48399 (Ref. 4) Curated1
Sequence conflicti329D → E in AAB48399 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059888315T → S1 PublicationCorresponds to variant dbSNP:rs1059913Ensembl.1
Natural variantiVAR_059889321L → F1 PublicationCorresponds to variant dbSNP:rs1059914Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0405691 – 50Missing in isoform 3. 1 PublicationAdd BLAST50
Alternative sequenceiVSP_04747043 – 118RWREE…THPPE → SSCHPVPACQRSPSQRGEDD RGPGKGPPPTLVITRAAAKP TQRVPISRHTCEPTQVRNLT TVTGTAVDGNSPAQMN in isoform 4. 1 PublicationAdd BLAST76
Alternative sequenceiVSP_04747143 – 63RWREE…PGRPY → VRNLTTVTGTAVDGNSPAQM N in isoform 5. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_04747264 – 513Missing in isoform 5. 1 PublicationAdd BLAST450
Alternative sequenceiVSP_047473119 – 513Missing in isoform 4. 1 PublicationAdd BLAST395
Alternative sequenceiVSP_036399367 – 400Missing in isoform 2 and isoform 3. 5 PublicationsAdd BLAST34

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.
CCDSiCCDS6770.2 [O43474-1]
RefSeqiNP_001300981.1, NM_001314052.1 [O43474-3]
NP_004226.3, NM_004235.5 [O43474-1]
UniGeneiHs.376206

Genome annotation databases

EnsembliENST00000374672; ENSP00000363804; ENSG00000136826 [O43474-1]
GeneIDi9314
KEGGihsa:9314
UCSCiuc004bdg.4 human [O43474-3]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiKLF4_HUMAN
AccessioniPrimary (citable) accession number: O43474
Secondary accession number(s): B2R8S4
, B3KT79, L0R3I6, L0R4N5, P78338, Q5T3J8, Q5T3J9, Q8N717, Q9UNP3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: February 10, 2009
Last modified: April 25, 2018
This is version 175 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health