KLF4_MOUSE
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 03-AUG-2022, entry version 191.
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 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 {ECO:0000250|UniProtKB:O43474, ECO:0000269|PubMed:19816951,
CC ECO:0000269|PubMed:24161396, ECO:0000269|PubMed:29593216}.
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}.
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};
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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 iPTMnet; Q60793; -.
DR PhosphoSitePlus; Q60793; -.
DR MaxQB; Q60793; -.
DR PaxDb; Q60793; -.
DR PRIDE; Q60793; -.
DR ProteomicsDB; 269224; -.
DR Antibodypedia; 14888; 934 antibodies from 45 providers.
DR DNASU; 16600; -.
DR Ensembl; ENSMUST00000107619; ENSMUSP00000103245; ENSMUSG00000003032.
DR GeneID; 16600; -.
DR KEGG; mmu:16600; -.
DR UCSC; uc008sxk.2; mouse.
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; RDCHPSP; -.
DR OrthoDB; 1591573at2759; -.
DR PhylomeDB; Q60793; -.
DR TreeFam; TF350556; -.
DR BioGRID-ORCS; 16600; 2 hits in 75 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 244 other tissues.
DR ExpressionAtlas; Q60793; baseline and differential.
DR Genevisible; Q60793; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
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:MGI.
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:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO: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:0071363; P:cellular response to growth factor stimulus; ISO:MGI.
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:0002357; P:defense response to tumor cell; ISO:MGI.
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:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:MGI.
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:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; ISO:MGI.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; 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:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:1904798; P:positive regulation of core promoter binding; IMP:BHF-UCL.
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:0051973; P:positive regulation of telomerase activity; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
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 GO; GO:0006351; P:transcription, DNA-templated; IMP:CACAO.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00355; ZnF_C2H2; 3.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; DNA-binding; Isopeptide bond; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; 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
