ID KLF4_MOUSE Reviewed; 483 AA. AC Q60793; P70421; Q3U2D6; Q3URS6; Q78K30; Q9R255; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 10-FEB-2009, sequence version 3. DT 27-MAR-2024, entry version 200. DE RecName: Full=Krueppel-like factor 4; DE AltName: Full=Epithelial zinc finger protein EZF; DE AltName: Full=Gut-enriched krueppel-like factor; GN Name=Klf4; Synonyms=Ezf, Gklf, Zie; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8702718; DOI=10.1074/jbc.271.33.20009; RA Shields J.M., Christy R.J., Yang V.W.; RT "Identification and characterization of a gene encoding a gut-enriched RT Kruppel-like factor expressed during growth arrest."; RL J. Biol. Chem. 271:20009-20017(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6 X DBA/2; TISSUE=Embryonic fibroblast; RX PubMed=8940147; DOI=10.1074/jbc.271.49.31384; RA Garrett-Sinha L.A., Eberspaecher H., Seldin M.F., de Crombrugghe B.; RT "A gene for a novel zinc-finger protein expressed in differentiated RT epithelial cells and transiently in certain mesenchymal cells."; RL J. Biol. Chem. 271:31384-31390(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION. RC STRAIN=129/SvJ; RX PubMed=10556311; DOI=10.1093/nar/27.23.4562; RA Mahatan C.S., Kaestner K.H., Geiman D.E., Yang V.W.; RT "Characterization of the structure and regulation of the murine gene RT encoding gut-enriched Kruppel-like factor (Kruppel-like factor 4)."; RL Nucleic Acids Res. 27:4562-4569(1999). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INDUCTION. RC STRAIN=C57BL/6J; RX PubMed=12441126; DOI=10.1006/excr.2002.5633; RA Chen Z.-Y., Shie J.-L., Tseng C.-C.; RT "STAT1 is required for IFN-gamma-mediated gut-enriched Kruppel-like factor RT expression."; RL Exp. Cell Res. 281:19-27(2002). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J, and NOD; RC TISSUE=Dendritic cell, Embryonic stem cell, and Mammary gland; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N; TISSUE=Mammary tumor; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE. RX PubMed=10431239; DOI=10.1038/11926; RA Segre J.A., Bauer C., Fuchs E.; RT "Klf4 is a transcription factor required for establishing the barrier RT function of the skin."; RL Nat. Genet. 22:356-360(1999). RN [10] RP FUNCTION. RX PubMed=15358627; DOI=10.1182/blood-2004-07-2681; RA Li Y., McClintick J., Zhong L., Edenberg H.J., Yoder M.C., Chan R.J.; RT "Murine embryonic stem cell differentiation is promoted by SOCS-3 and RT inhibited by the zinc finger transcription factor Klf4."; RL Blood 105:635-637(2005). RN [11] RP BIOTECHNOLOGY. RX PubMed=16904174; DOI=10.1016/j.cell.2006.07.024; RA Takahashi K., Yamanaka S.; RT "Induction of pluripotent stem cells from mouse embryonic and adult RT fibroblast cultures by defined factors."; RL Cell 126:663-676(2006). RN [12] RP FUNCTION. RX PubMed=16954384; DOI=10.1128/mcb.00468-06; RA Nakatake Y., Fukui N., Iwamatsu Y., Masui S., Takahashi K., Yagi R., RA Yagi K., Miyazaki J., Matoba R., Ko M.S., Niwa H.; RT "Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter RT in embryonic stem cells."; RL Mol. Cell. Biol. 26:7772-7782(2006). RN [13] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=17060454; DOI=10.1128/mcb.00846-06; RA Swamynathan S.K., Katz J.P., Kaestner K.H., Ashery-Padan R., Crawford M.A., RA Piatigorsky J.; RT "Conditional deletion of the mouse Klf4 gene results in corneal epithelial RT fragility, stromal edema, and loss of conjunctival goblet cells."; RL Mol. Cell. Biol. 27:182-194(2007). RN [14] RP FUNCTION, INTERACTION WITH POU5F1/OCT4 AND SOX2, AND BIOTECHNOLOGY. RX PubMed=19816951; DOI=10.1002/stem.231; RA Wei Z., Yang Y., Zhang P., Andrianakos R., Hasegawa K., Lyu J., Chen X., RA Bai G., Liu C., Pera M., Lu W.; RT "Klf4 interacts directly with Oct4 and Sox2 to promote reprogramming."; RL Stem Cells 27:2969-2978(2009). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Kidney, and Lung; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [16] RP FUNCTION. RX PubMed=20071344; DOI=10.1074/jbc.m109.077958; RA Zhang P., Andrianakos R., Yang Y., Liu C., Lu W.; RT "Kruppel-like factor 4 (Klf4) prevents embryonic stem (ES) cell RT differentiation by regulating Nanog gene expression."; RL J. Biol. Chem. 285:9180-9189(2010). RN [17] RP INTERACTION WITH ZNF296, AND SUBCELLULAR LOCATION. RX PubMed=24161396; DOI=10.1016/j.bbrc.2013.10.073; RA Fujii Y., Kakegawa M., Koide H., Akagi T., Yokota T.; RT "Zfp296 is a novel Klf4-interacting protein and functions as a negative RT regulator."; RL Biochem. Biophys. Res. Commun. 441:411-417(2013). RN [18] RP FUNCTION, INTERACTION WITH BTRC, GLUTAMYLATION AT GLU-381, UBIQUITINATION, RP AND MUTAGENESIS OF GLU-46; GLU-95; LYS-229; GLU-326 AND GLU-381. RX PubMed=29593216; DOI=10.1038/s41467-018-03008-2; RA Ye B., Liu B., Hao L., Zhu X., Yang L., Wang S., Xia P., Du Y., Meng S., RA Huang G., Qin X., Wang Y., Yan X., Li C., Hao J., Zhu P., He L., Tian Y., RA Fan Z.; RT "Klf4 glutamylation is required for cell reprogramming and early embryonic RT development in mice."; RL Nat. Commun. 9:1261-1261(2018). RN [19] RP INTERACTION WITH IPO7, AND SUBCELLULAR LOCATION. RX PubMed=35922041; DOI=10.1093/stmcls/sxac055; RA Zhang Y., Zhang H., Xiao Z., Yuan G., Yang G.; RT "IPO7 Promotes Odontoblastic Differentiation and Inhibits Osteoblastic RT Differentiation Through Regulation of RUNX2 Expression and Translocation."; RL Stem Cells 40:1020-1030(2022). RN [20] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 395-483 IN COMPLEX WITH ZINC IONS RP AND DNA. RA Schuetz A., Zocher G., Carstanjen D., Heinemann U.; RT "Crystal structure in complex with DNA."; RL Submitted (APR-2010) to the PDB data bank. CC -!- FUNCTION: Transcription factor; can act both as activator and as CC repressor. Binds the 5'-CACCC-3' core sequence (PubMed:10431239, CC PubMed:10556311, PubMed:15358627, PubMed:16954384, PubMed:17060454, CC PubMed:19816951, PubMed:20071344, PubMed:29593216). Binds to the CC promoter region of its own gene and can activate its own transcription CC (PubMed:10431239, PubMed:10556311, PubMed:15358627, PubMed:16954384, CC PubMed:17060454, PubMed:19816951, PubMed:20071344, PubMed:29593216). CC Regulates the expression of key transcription factors during embryonic CC development (PubMed:10431239, PubMed:10556311, PubMed:15358627, CC PubMed:16954384, PubMed:17060454, PubMed:19816951, PubMed:20071344, CC PubMed:29593216). Plays an important role in maintaining embryonic stem CC cells, and in preventing their differentiation (PubMed:10431239, CC PubMed:10556311, PubMed:15358627, PubMed:16954384, PubMed:17060454, CC PubMed:19816951, PubMed:20071344, PubMed:29593216). Required for CC establishing the barrier function of the skin and for postnatal CC maturation and maintenance of the ocular surface. Involved in the CC differentiation of epithelial cells and may also function in skeletal CC and kidney development. Contributes to the down-regulation of p53/TP53 CC transcription (By similarity). {ECO:0000250, CC ECO:0000269|PubMed:10431239, ECO:0000269|PubMed:10556311, CC ECO:0000269|PubMed:15358627, ECO:0000269|PubMed:16954384, CC ECO:0000269|PubMed:17060454, ECO:0000269|PubMed:19816951, CC ECO:0000269|PubMed:20071344, ECO:0000269|PubMed:29593216}. CC -!- SUBUNIT: Interacts with MUC1 (via the C-terminal domain) (By CC similarity). Interacts with POU5F1/OCT4 and SOX2 (PubMed:19816951). CC Interacts with MEIS2 isoform MeisD and PBX1 isoform PBX1a (By CC similarity). Interacts with ZNF296 (PubMed:24161396). Interacts with CC GLIS1 (By similarity). Interacts with BTRC; this interaction leads to CC KLF4 ubiquitination and subsequent degradation (PubMed:29593216). CC Interacts with IPO7; the interaction facilitates nuclear translocation CC of KLF4 in dental papilla cells (PubMed:35922041). CC {ECO:0000250|UniProtKB:O43474, ECO:0000269|PubMed:19816951, CC ECO:0000269|PubMed:24161396, ECO:0000269|PubMed:29593216, CC ECO:0000269|PubMed:35922041}. CC -!- INTERACTION: CC Q60793; Q63844: Mapk3; NbExp=3; IntAct=EBI-3043905, EBI-397682; CC Q60793; Q9Y297: BTRC; Xeno; NbExp=3; IntAct=EBI-3043905, EBI-307461; CC Q60793; Q9UKB1: FBXW11; Xeno; NbExp=4; IntAct=EBI-3043905, EBI-355189; CC Q60793; P27361: MAPK3; Xeno; NbExp=2; IntAct=EBI-3043905, EBI-73995; CC Q60793; O95793: STAU1; Xeno; NbExp=7; IntAct=EBI-3043905, EBI-358174; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10431239, CC ECO:0000269|PubMed:24161396, ECO:0000269|PubMed:35922041}. Cytoplasm CC {ECO:0000269|PubMed:35922041}. CC -!- TISSUE SPECIFICITY: Highest expression in the colon. Lower levels in CC testis, lung and small intestine. CC -!- INDUCTION: By interferon-gamma in Stat1-dependent manner. CC {ECO:0000269|PubMed:12441126}. CC -!- DOMAIN: the 9aaTAD motif is a transactivation domain present in a large CC number of yeast and animal transcription factors. CC {ECO:0000250|UniProtKB:O43474}. CC -!- PTM: Ubiquitinated. 'Lys-48'-linked ubiquitinated and targeted for CC proteasomal degradation by the SCF(BTRC) E3 ubiquitin-protein ligase CC complex, thereby negatively regulating cell pluripotency maintenance CC and embryogenesis. {ECO:0000269|PubMed:29593216}. CC -!- PTM: Polyglutamylated by TTLL1 and TTLL4 at Glu-381, which inhibits CC KLF4 binding with E3 ligase component BTRC, thereby impeding CC ubiquitination (PubMed:29593216). Deglutamylated by CCP1 and CCP6; CC deglutamylation promotes KLF4 ubiquitination (PubMed:29593216). KLF4 CC glutamylation state plays a critical role in the regulation of its CC function in cell reprogramming, pluripotency maintenance and CC embryogenesis (PubMed:29593216). {ECO:0000269|PubMed:29593216}. CC -!- DISRUPTION PHENOTYPE: Death shortly after birth due to loss of CC epidermal barrier function resulting from perturbation of late-stage CC epidermal differentiation structures including the cornified envelope. CC When selectively deleted in the surface ectoderm-derived structures of CC the eye, embryos develop normally and adults are viable and fertile but CC mutants display down-regulation of Krt12 and Aqp5 and multiple ocular CC defects including corneal epithelial fragility, stromal edema, CC defective lens and loss of conjunctival goblet cells. CC {ECO:0000269|PubMed:10431239, ECO:0000269|PubMed:17060454}. CC -!- BIOTECHNOLOGY: POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four CC Yamanaka factors. When combined, these factors are sufficient to CC reprogram differentiated cells to an embryonic-like state designated CC iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology CC and growth properties of ES cells and express ES cell marker genes. CC {ECO:0000269|PubMed:16904174, ECO:0000269|PubMed:19816951}. CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC52939.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH10301.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U20344; AAC04892.1; -; mRNA. DR EMBL; U70662; AAC52939.1; ALT_INIT; mRNA. DR EMBL; AF117109; AAD17223.1; -; Genomic_DNA. DR EMBL; AY071827; AAL60058.1; -; Genomic_DNA. DR EMBL; AK141244; BAE24612.1; -; mRNA. DR EMBL; AK144942; BAE26147.1; -; mRNA. DR EMBL; AK155343; BAE33205.1; -; mRNA. DR EMBL; AL732494; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH466565; EDL02262.1; -; Genomic_DNA. DR EMBL; BC010301; AAH10301.2; ALT_INIT; mRNA. DR CCDS; CCDS18195.2; -. DR RefSeq; NP_034767.2; NM_010637.3. DR PDB; 2WBS; X-ray; 1.70 A; A=395-483. DR PDB; 2WBU; X-ray; 2.50 A; A=396-483. DR PDB; 4M9E; X-ray; 1.85 A; A=396-483. DR PDB; 5KE6; X-ray; 1.99 A; A=396-483. DR PDB; 5KE7; X-ray; 2.06 A; A=396-483. DR PDB; 5KE8; X-ray; 2.45 A; A=396-483. DR PDB; 5KE9; X-ray; 2.34 A; A=396-483. DR PDB; 5KEA; X-ray; 2.46 A; A=396-483. DR PDB; 5KEB; X-ray; 2.45 A; A=396-483. DR PDBsum; 2WBS; -. DR PDBsum; 2WBU; -. DR PDBsum; 4M9E; -. DR PDBsum; 5KE6; -. DR PDBsum; 5KE7; -. DR PDBsum; 5KE8; -. DR PDBsum; 5KE9; -. DR PDBsum; 5KEA; -. DR PDBsum; 5KEB; -. DR AlphaFoldDB; Q60793; -. DR SMR; Q60793; -. DR BioGRID; 200966; 15. DR DIP; DIP-59920N; -. DR ELM; Q60793; -. DR IntAct; Q60793; 16. DR MINT; Q60793; -. DR STRING; 10090.ENSMUSP00000103245; -. DR GlyGen; Q60793; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q60793; -. DR PhosphoSitePlus; Q60793; -. DR MaxQB; Q60793; -. DR PaxDb; 10090-ENSMUSP00000103245; -. DR ProteomicsDB; 269224; -. DR Pumba; Q60793; -. DR Antibodypedia; 14888; 1083 antibodies from 45 providers. DR DNASU; 16600; -. DR Ensembl; ENSMUST00000107619.3; ENSMUSP00000103245.3; ENSMUSG00000003032.9. DR GeneID; 16600; -. DR KEGG; mmu:16600; -. DR UCSC; uc008sxk.2; mouse. DR AGR; MGI:1342287; -. DR CTD; 9314; -. DR MGI; MGI:1342287; Klf4. DR VEuPathDB; HostDB:ENSMUSG00000003032; -. DR eggNOG; KOG1721; Eukaryota. DR GeneTree; ENSGT00940000156229; -. DR HOGENOM; CLU_002678_33_1_1; -. DR InParanoid; Q60793; -. DR OMA; FPCHRIK; -. DR OrthoDB; 5484790at2759; -. DR PhylomeDB; Q60793; -. DR TreeFam; TF350556; -. DR BioGRID-ORCS; 16600; 2 hits in 80 CRISPR screens. DR ChiTaRS; Klf4; mouse. DR EvolutionaryTrace; Q60793; -. DR PRO; PR:Q60793; -. DR Proteomes; UP000000589; Chromosome 4. DR RNAct; Q60793; Protein. DR Bgee; ENSMUSG00000003032; Expressed in epithelium of stomach and 247 other cell types or tissues. DR ExpressionAtlas; Q60793; baseline and differential. DR GO; GO:0000785; C:chromatin; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0000791; C:euchromatin; IDA:BHF-UCL. DR GO; GO:0015630; C:microtubule cytoskeleton; ISO:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005667; C:transcription regulator complex; IDA:BHF-UCL. DR GO; GO:0008013; F:beta-catenin binding; IPI:BHF-UCL. DR GO; GO:0031490; F:chromatin DNA binding; IDA:MGI. DR GO; GO:0003677; F:DNA binding; ISS:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:CACAO. DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI. DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0035014; F:phosphatidylinositol 3-kinase regulator activity; ISO:MGI. DR GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0001010; F:RNA polymerase II sequence-specific DNA-binding transcription factor recruiting activity; IDA:BHF-UCL. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0001221; F:transcription coregulator binding; ISO:MGI. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IMP:BHF-UCL. DR GO; GO:0071409; P:cellular response to cycloheximide; IEA:Ensembl. DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:MGI. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; ISO:MGI. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI. DR GO; GO:1901653; P:cellular response to peptide; IEA:Ensembl. DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl. DR GO; GO:0002357; P:defense response to tumor cell; ISO:MGI. DR GO; GO:0006351; P:DNA-templated transcription; IMP:CACAO. DR GO; GO:0009913; P:epidermal cell differentiation; IMP:MGI. DR GO; GO:0008544; P:epidermis development; IMP:MGI. DR GO; GO:0048730; P:epidermis morphogenesis; IMP:MGI. DR GO; GO:0061436; P:establishment of skin barrier; IMP:MGI. DR GO; GO:0045444; P:fat cell differentiation; IMP:BHF-UCL. DR GO; GO:0010467; P:gene expression; IMP:MGI. DR GO; GO:0002067; P:glandular epithelial cell differentiation; IMP:MGI. DR GO; GO:0016525; P:negative regulation of angiogenesis; ISO:MGI. DR GO; GO:0030336; P:negative regulation of cell migration; IMP:CACAO. DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; ISO:MGI. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:MGI. DR GO; GO:2000342; P:negative regulation of chemokine (C-X-C motif) ligand 2 production; ISO:MGI. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISS:UniProtKB. DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISO:MGI. DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; ISO:MGI. DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI. DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; ISO:MGI. DR GO; GO:0032717; P:negative regulation of interleukin-8 production; ISO:MGI. DR GO; GO:1904998; P:negative regulation of leukocyte adhesion to arterial endothelial cell; ISO:MGI. DR GO; GO:0014740; P:negative regulation of muscle hyperplasia; ISO:MGI. DR GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:MGI. DR GO; GO:0060761; P:negative regulation of response to cytokine stimulus; ISO:MGI. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:0046985; P:positive regulation of hemoglobin biosynthetic process; ISO:MGI. DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:MGI. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:MGI. DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISO:MGI. DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:CACAO. DR GO; GO:0031077; P:post-embryonic camera-type eye development; IMP:MGI. DR GO; GO:0035166; P:post-embryonic hemopoiesis; ISO:MGI. DR GO; GO:0048679; P:regulation of axon regeneration; IMP:MGI. DR GO; GO:0120222; P:regulation of blastocyst development; IMP:MGI. DR GO; GO:0045595; P:regulation of cell differentiation; IDA:UniProtKB. DR GO; GO:0042127; P:regulation of cell population proliferation; IGI:MGI. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:0010033; P:response to organic substance; IDA:MGI. DR GO; GO:0032526; P:response to retinoic acid; IDA:MGI. DR GO; GO:0035019; P:somatic stem cell population maintenance; IDA:MGI. DR GO; GO:0019827; P:stem cell population maintenance; IDA:UniProtKB. DR GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI. DR CDD; cd21582; KLF4_N; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 3. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR23235:SF117; KRUEPPEL-LIKE FACTOR 4; 1. DR PANTHER; PTHR23235; KRUEPPEL-LIKE TRANSCRIPTION FACTOR; 1. DR Pfam; PF00096; zf-C2H2; 3. DR SMART; SM00355; ZnF_C2H2; 3. DR SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 2. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3. DR Genevisible; Q60793; MM. PE 1: Evidence at protein level; KW 3D-structure; Activator; Cytoplasm; DNA-binding; Isopeptide bond; KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Transcription; Transcription regulation; Ubl conjugation; Zinc; KW Zinc-finger. FT CHAIN 1..483 FT /note="Krueppel-like factor 4" FT /id="PRO_0000047168" FT ZN_FING 400..424 FT /note="C2H2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 430..454 FT /note="C2H2-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 460..482 FT /note="C2H2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT REGION 22..42 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 294..395 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 386..483 FT /note="Interaction with ZNF296" FT /evidence="ECO:0000269|PubMed:24161396" FT REGION 443..474 FT /note="Interaction with target DNA" FT MOTIF 99..107 FT /note="9aaTAD" FT /evidence="ECO:0000250|UniProtKB:O43474" FT COMPBIAS 312..327 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 339..355 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 251 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O43474" FT MOD_RES 381 FT /note="5-glutamyl polyglutamate" FT /evidence="ECO:0000269|PubMed:29593216" FT CROSSLNK 32 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:O43474" FT MUTAGEN 46 FT /note="E->A: No change in KLF4 polyglutamylation." FT /evidence="ECO:0000269|PubMed:29593216" FT MUTAGEN 95 FT /note="E->A: No change in KLF4 polyglutamylation." FT /evidence="ECO:0000269|PubMed:29593216" FT MUTAGEN 229 FT /note="K->R: Increased cell reprogramming and pluripotency. FT No change in promoter-binding of target genes." FT /evidence="ECO:0000269|PubMed:29593216" FT MUTAGEN 326 FT /note="E->A: No change in KLF4 polyglutamylation." FT /evidence="ECO:0000269|PubMed:29593216" FT MUTAGEN 381 FT /note="E->A: Loss of polyglutamylation, reduced cell FT reprogramming and pluripotency maintenance. Forms FT heterodimer with KLF5. No change in promoter-binding of FT target genes. Embryo lethality in mutant homozygous mice." FT /evidence="ECO:0000269|PubMed:29593216" FT CONFLICT 162 FT /note="S -> R (in Ref. 2; AAC52939)" FT /evidence="ECO:0000305" FT CONFLICT 185 FT /note="A -> G (in Ref. 2; AAC52939)" FT /evidence="ECO:0000305" FT CONFLICT 302 FT /note="H -> Q (in Ref. 5; BAE33205)" FT /evidence="ECO:0000305" FT CONFLICT 350 FT /note="P -> A (in Ref. 2; AAC52939)" FT /evidence="ECO:0000305" FT TURN 405..407 FT /evidence="ECO:0007829|PDB:2WBS" FT STRAND 410..413 FT /evidence="ECO:0007829|PDB:2WBS" FT HELIX 414..421 FT /evidence="ECO:0007829|PDB:2WBS" FT TURN 435..437 FT /evidence="ECO:0007829|PDB:2WBS" FT STRAND 440..443 FT /evidence="ECO:0007829|PDB:2WBS" FT HELIX 444..455 FT /evidence="ECO:0007829|PDB:2WBS" FT STRAND 463..466 FT /evidence="ECO:0007829|PDB:2WBS" FT STRAND 468..471 FT /evidence="ECO:0007829|PDB:2WBS" FT HELIX 472..478 FT /evidence="ECO:0007829|PDB:2WBS" FT HELIX 479..482 FT /evidence="ECO:0007829|PDB:2WBS" SQ SEQUENCE 483 AA; 51880 MW; 5D1B0BF7948C49B3 CRC64; MRQPPGESDM AVSDALLPSF STFASGPAGR EKTLRPAGAP TNRWREELSH MKRLPPLPGR PYDLAATVAT DLESGGAGAA CSSNNPALLA RRETEEFNDL LDLDFILSNS LTHQESVAAT VTTSASASSS SSPASSGPAS APSTCSFSYP IRAGGDPGVA ASNTGGGLLY SRESAPPPTA PFNLADINDV SPSGGFVAEL LRPELDPVYI PPQQPQPPGG GLMGKFVLKA SLTTPGSEYS SPSVISVSKG SPDGSHPVVV APYSGGPPRM CPKIKQEAVP SCTVSRSLEA HLSAGPQLSN GHRPNTHDFP LGRQLPTRTT PTLSPEELLN SRDCHPGLPL PPGFHPHPGP NYPPFLPDQM QSQVPSLHYQ ELMPPGSCLP EEPKPKRGRR SWPRKRTATH TCDYAGCGKT YTKSSHLKAH LRTHTGEKPY HCDWDGCGWK FARSDELTRH YRKHTGHRPF QCQKCDRAFS RSDHLALHMK RHF //