ID KLF4_HUMAN Reviewed; 513 AA. AC O43474; B2R8S4; B3KT79; L0R3I6; L0R4N5; P78338; Q5T3J8; Q5T3J9; Q8N717; AC Q9UNP3; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 10-FEB-2009, sequence version 3. DT 27-MAR-2024, entry version 213. 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 {ECO:0000312|HGNC:HGNC:6348}; Synonyms=EZF, GKLF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=9422764; DOI=10.1074/jbc.273.2.1026; RA Yet S.-F., McA'Nulty M.M., Folta S.C., Yen H.-W., Yoshizumi M., RA Hsieh C.-M., Layne M.D., Chin M.T., Wang H., Perrella M.A., Jain M.K., RA Lee M.-E.; RT "Human EZF, a Kruppel-like zinc finger protein, is expressed in vascular RT endothelial cells and contains transcriptional activation and repression RT domains."; RL J. Biol. Chem. 273:1026-1031(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=10392904; RA Foster K.W., Ren S., Louro I.D., Lobo-Ruppert S.M., McKie-Bell P., RA Grizzle W., Hayes M.R., Broker T.R., Chow L.T., Ruppert J.M.; RT "Oncogene expression cloning by retroviral transduction of adenovirus E1A- RT immortalized rat kidney RK3E cells: transformation of a host with RT epithelial features by c-MYC and the zinc finger protein GKLF."; RL Cell Growth Differ. 10:423-434(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5), AND ALTERNATIVE SPLICING. RX PubMed=23134681; DOI=10.1096/fj.12-220319; RA Camacho-Vanegas O., Till J., Miranda-Lorenzo I., Ozturk B., Camacho S.C., RA Martignetti J.A.; RT "Shaking the family tree: Identification of novel and biologically active RT alternatively spliced isoforms across the KLF family of transcription RT factors."; RL FASEB J. 27:432-436(2013). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS SER-315 AND PHE-321. RC TISSUE=Placenta; RA Garrett-Sinha L.A., de Crombrugghe B.; RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Substantia nigra, and Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., RA Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Cervix, and Lung; 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 [10] RP INTERACTION WITH MUC1, AND FUNCTION. RX PubMed=17308127; DOI=10.1158/0008-5472.can-06-3063; RA Wei X., Xu H., Kufe D.; RT "Human mucin 1 oncoprotein represses transcription of the p53 tumor RT suppressor gene."; RL Cancer Res. 67:1853-1858(2007). RN [11] RP BIOTECHNOLOGY. RX PubMed=18035408; DOI=10.1016/j.cell.2007.11.019; RA Takahashi K., Tanabe K., Ohnuki M., Narita M., Ichisaka T., Tomoda K., RA Yamanaka S.; RT "Induction of pluripotent stem cells from adult human fibroblasts by RT defined factors."; RL Cell 131:861-872(2007). RN [12] RP 9AATAD MOTIF. RX PubMed=17467953; DOI=10.1016/j.ygeno.2007.02.003; RA Piskacek S., Gregor M., Nemethova M., Grabner M., Kovarik P., Piskacek M.; RT "Nine-amino-acid transactivation domain: establishment and prediction RT utilities."; RL Genomics 89:756-768(2007). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [14] RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-32, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Liver; RX PubMed=18655026; DOI=10.1002/pmic.200700887; RA Tan F., Lu L., Cai Y., Wang J., Xie Y., Wang L., Gong Y., Xu B.-E., Wu J., RA Luo Y., Qiang B., Yuan J., Sun X., Peng X.; RT "Proteomic analysis of ubiquitinated proteins in normal hepatocyte cell RT line Chang liver cells."; RL Proteomics 8:2885-2896(2008). RN [15] 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-254, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [17] RP INTERACTION WITH PBX1 AND MEIS2. RX PubMed=21746878; DOI=10.1128/mcb.01456-10; RA Bjerke G.A., Hyman-Walsh C., Wotton D.; RT "Cooperative transcriptional activation by Klf4, Meis2, and Pbx1."; RL Mol. Cell. Biol. 31:3723-3733(2011). RN [18] RP INTERACTION WITH GLIS1. RX PubMed=21654807; DOI=10.1038/nature10106; RA Maekawa M., Yamaguchi K., Nakamura T., Shibukawa R., Kodanaka I., RA Ichisaka T., Kawamura Y., Mochizuki H., Goshima N., Yamanaka S.; RT "Direct reprogramming of somatic cells is promoted by maternal RT transcription factor Glis1."; RL Nature 474:225-229(2011). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [21] RP GLYTAMYLATION. 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 [22] RP 9AATAD MOTIF. RX PubMed=31375868; DOI=10.1007/s00018-019-03251-w; RA Piskacek M., Havelka M., Jendruchova K., Knight A., Keegan L.P.; RT "The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with RT valines and intron reservoirs."; RL Cell. Mol. Life Sci. 77:1793-1810(2020). CC -!- FUNCTION: Transcription factor; can act both as activator and as CC repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter CC region of its own gene and can activate its own transcription. CC Regulates the expression of key transcription factors during embryonic CC development. Plays an important role in maintaining embryonic stem CC cells, and in preventing their differentiation. 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. {ECO:0000269|PubMed:17308127, CC ECO:0000269|PubMed:20071344}. CC -!- SUBUNIT: Interacts with POU5F1/OCT4 and SOX2 (By similarity). Interacts CC with MUC1 (via the C-terminal domain) (PubMed:17308127). Interacts with CC MEIS2 isoform 4 and PBX1 isoform PBX1a (PubMed:21746878). Interacts CC with ZNF296 (By similarity). Interacts with GLIS1 (PubMed:21654807). CC Interacts with BTRC; this interaction leads to KLF4 ubiquitination and CC subsequent degradation (By similarity). Interacts with IPO7; the CC interaction facilitates nuclear translocation of KLF4 in dental papilla CC cells (By similarity). {ECO:0000250|UniProtKB:Q60793, CC ECO:0000269|PubMed:17308127, ECO:0000269|PubMed:21654807, CC ECO:0000269|PubMed:21746878}. CC -!- INTERACTION: CC O43474; Q13363: CTBP1; NbExp=4; IntAct=EBI-7232405, EBI-908846; CC O43474; Q92997: DVL3; NbExp=3; IntAct=EBI-7232405, EBI-739789; CC O43474; P13807: GYS1; NbExp=5; IntAct=EBI-7232405, EBI-740553; CC O43474; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-7232405, EBI-14103818; CC O43474; O14964: HGS; NbExp=3; IntAct=EBI-7232405, EBI-740220; CC O43474; O75031: HSF2BP; NbExp=3; IntAct=EBI-7232405, EBI-7116203; CC O43474; O95983: MBD3; NbExp=3; IntAct=EBI-7232405, EBI-1783068; CC O43474; P55771: PAX9; NbExp=3; IntAct=EBI-7232405, EBI-12111000; CC O43474; Q08117-2: TLE5; NbExp=3; IntAct=EBI-7232405, EBI-11741437; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q60793}. Cytoplasm CC {ECO:0000250|UniProtKB:Q60793}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=O43474-3; Sequence=Displayed; CC Name=2; CC IsoId=O43474-1; Sequence=VSP_036399; CC Name=3; CC IsoId=O43474-4; Sequence=VSP_040569, VSP_036399; CC Name=4; Synonyms=1a; CC IsoId=O43474-5; Sequence=VSP_047470, VSP_047473; CC Name=5; CC IsoId=O43474-6; Sequence=VSP_047471, VSP_047472; CC -!- DOMAIN: the 9aaTAD motif is a transactivation domain present in a large CC number of yeast and animal transcription factors. CC {ECO:0000269|PubMed:17467953, ECO:0000269|PubMed:31375868}. 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:0000250|UniProtKB:Q60793}. CC -!- PTM: Polyglutamylated by TTLL1 and TTLL4 at Glu-411, which inhibits CC KLF4 binding with E3 ligase component BTRC, thereby impeding CC ubiquitination. Deglutamylated by CCP1 and CCP6; deglutamylation CC promotes KLF4 ubiquitination. KLF4 glutamylation state plays a critical CC role in the regulation of its function in cell reprogramming, CC pluripotency maintenance and embryogenesis. CC {ECO:0000250|UniProtKB:Q60793}. 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:18035408}. CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB48399.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAC03462.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAD42165.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH29923.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAH30811.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=ABG25917.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=BAG36271.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=EAW59020.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=EAW59021.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44316/KLF4"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/klf4/"; 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; AF022184; AAC03462.1; ALT_INIT; mRNA. DR EMBL; AF105036; AAD42165.1; ALT_INIT; mRNA. DR EMBL; HF546201; CCO02787.1; -; mRNA. DR EMBL; HF546202; CCO02788.1; -; mRNA. DR EMBL; U70663; AAB48399.1; ALT_INIT; mRNA. DR EMBL; AK095134; BAG52991.1; -; mRNA. DR EMBL; AK313489; BAG36271.1; ALT_INIT; mRNA. DR EMBL; DQ658241; ABG25917.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL360218; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471105; EAW59020.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471105; EAW59021.1; ALT_SEQ; Genomic_DNA. DR EMBL; BC029923; AAH29923.1; ALT_INIT; mRNA. DR EMBL; BC030811; AAH30811.1; ALT_INIT; mRNA. DR CCDS; CCDS6770.2; -. [O43474-1] DR RefSeq; NP_001300981.1; NM_001314052.1. [O43474-3] DR RefSeq; NP_004226.3; NM_004235.5. [O43474-1] DR PDB; 6VTX; X-ray; 2.14 A; A=430-513. DR PDBsum; 6VTX; -. DR AlphaFoldDB; O43474; -. DR SMR; O43474; -. DR BioGRID; 114726; 155. DR DIP; DIP-57667N; -. DR IntAct; O43474; 116. DR MINT; O43474; -. DR STRING; 9606.ENSP00000363804; -. DR GlyCosmos; O43474; 1 site, 1 glycan. DR GlyGen; O43474; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O43474; -. DR PhosphoSitePlus; O43474; -. DR BioMuta; KLF4; -. DR EPD; O43474; -. DR jPOST; O43474; -. DR MassIVE; O43474; -. DR MaxQB; O43474; -. DR PaxDb; 9606-ENSP00000363804; -. DR PeptideAtlas; O43474; -. DR ProteomicsDB; 48962; -. [O43474-3] DR ProteomicsDB; 48963; -. [O43474-1] DR ProteomicsDB; 48964; -. [O43474-4] DR Pumba; O43474; -. DR Antibodypedia; 14888; 1083 antibodies from 45 providers. DR DNASU; 9314; -. DR Ensembl; ENST00000374672.5; ENSP00000363804.4; ENSG00000136826.15. [O43474-1] DR GeneID; 9314; -. DR KEGG; hsa:9314; -. DR MANE-Select; ENST00000374672.5; ENSP00000363804.4; NM_004235.6; NP_004226.3. [O43474-1] DR UCSC; uc004bdg.4; human. [O43474-3] DR AGR; HGNC:6348; -. DR CTD; 9314; -. DR DisGeNET; 9314; -. DR GeneCards; KLF4; -. DR HGNC; HGNC:6348; KLF4. DR HPA; ENSG00000136826; Tissue enhanced (skin). DR MIM; 602253; gene. DR neXtProt; NX_O43474; -. DR OpenTargets; ENSG00000136826; -. DR PharmGKB; PA30138; -. DR VEuPathDB; HostDB:ENSG00000136826; -. DR eggNOG; KOG1721; Eukaryota. DR GeneTree; ENSGT00940000156229; -. DR HOGENOM; CLU_002678_33_1_1; -. DR InParanoid; O43474; -. DR OMA; FPCHRIK; -. DR OrthoDB; 5484790at2759; -. DR PhylomeDB; O43474; -. DR TreeFam; TF350556; -. DR PathwayCommons; O43474; -. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR Reactome; R-HSA-422085; Synthesis, secretion, and deacylation of Ghrelin. DR Reactome; R-HSA-452723; Transcriptional regulation of pluripotent stem cells. DR Reactome; R-HSA-9617828; FOXO-mediated transcription of cell cycle genes. DR SignaLink; O43474; -. DR SIGNOR; O43474; -. DR BioGRID-ORCS; 9314; 21 hits in 1177 CRISPR screens. DR ChiTaRS; KLF4; human. DR GeneWiki; KLF4; -. DR GenomeRNAi; 9314; -. DR Pharos; O43474; Tbio. DR PRO; PR:O43474; -. DR Proteomes; UP000005640; Chromosome 9. DR RNAct; O43474; Protein. DR Bgee; ENSG00000136826; Expressed in upper leg skin and 201 other cell types or tissues. DR ExpressionAtlas; O43474; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0000791; C:euchromatin; IEA:Ensembl. DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl. DR GO; GO:0008013; F:beta-catenin binding; IEA:Ensembl. DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP:BHF-UCL. DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0042826; F:histone deacetylase binding; IEA:Ensembl. DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA: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; ISS:BHF-UCL. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB. DR GO; GO:0001221; F:transcription coregulator binding; IEA:Ensembl. DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0071409; P:cellular response to cycloheximide; IEA:Ensembl. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:BHF-UCL. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; IMP:BHF-UCL. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl. 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; IMP:ARUK-UCL. DR GO; GO:0009913; P:epidermal cell differentiation; IEA:Ensembl. DR GO; GO:0048730; P:epidermis morphogenesis; IEA:Ensembl. DR GO; GO:0061436; P:establishment of skin barrier; IEA:Ensembl. DR GO; GO:0045444; P:fat cell differentiation; ISS:BHF-UCL. DR GO; GO:0002067; P:glandular epithelial cell differentiation; IEA:Ensembl. DR GO; GO:0007500; P:mesodermal cell fate determination; TAS:ProtInc. DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:BHF-UCL. DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; IDA:BHF-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:2000342; P:negative regulation of chemokine (C-X-C motif) ligand 2 production; IDA:BHF-UCL. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IDA:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IGI:BHF-UCL. DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; IDA:BHF-UCL. DR GO; GO:0050728; P:negative regulation of inflammatory response; TAS:BHF-UCL. DR GO; GO:0032717; P:negative regulation of interleukin-8 production; IDA:BHF-UCL. DR GO; GO:1904998; P:negative regulation of leukocyte adhesion to arterial endothelial cell; IGI:BHF-UCL. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:BHF-UCL. DR GO; GO:0060761; P:negative regulation of response to cytokine stimulus; IDA:BHF-UCL. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IGI:BHF-UCL. DR GO; GO:0046985; P:positive regulation of hemoglobin biosynthetic process; IMP:BHF-UCL. DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:BHF-UCL. DR GO; GO:0051247; P:positive regulation of protein metabolic process; IMP:BHF-UCL. DR GO; GO:1903672; P:positive regulation of sprouting angiogenesis; IGI:BHF-UCL. DR GO; GO:0051973; P:positive regulation of telomerase activity; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB. DR GO; GO:0031077; P:post-embryonic camera-type eye development; IEA:Ensembl. DR GO; GO:0035166; P:post-embryonic hemopoiesis; IMP:BHF-UCL. DR GO; GO:0048679; P:regulation of axon regeneration; IEA:Ensembl. DR GO; GO:0120222; P:regulation of blastocyst development; IEA:Ensembl. DR GO; GO:0045595; P:regulation of cell differentiation; ISS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR GO; GO:0019827; P:stem cell population maintenance; ISS:UniProtKB. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR DisProt; DP01174; -. 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; O43474; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Cytoplasm; DNA-binding; KW Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..513 FT /note="Krueppel-like factor 4" FT /id="PRO_0000047167" FT ZN_FING 430..454 FT /note="C2H2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 460..484 FT /note="C2H2-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 490..512 FT /note="C2H2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT REGION 22..45 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 416..513 FT /note="Interaction with ZNF296" FT /evidence="ECO:0000250|UniProtKB:Q60793" FT REGION 473..504 FT /note="Interaction with target DNA" FT /evidence="ECO:0000250" FT MOTIF 101..109 FT /note="9aaTAD" FT /evidence="ECO:0000269|PubMed:31375868" FT MOD_RES 254 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 411 FT /note="5-glutamyl polyglutamate" FT /evidence="ECO:0000250|UniProtKB:Q60793" FT CROSSLNK 32 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:18655026" FT VAR_SEQ 1..50 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_040569" FT VAR_SEQ 43..118 FT /note="RWREELSHMKRLPPVLPGRPYDLAAATVATDLESGGAGAACGGSNLAPLPRR FT ETEEFNDLLDLDFILSNSLTHPPE -> SSCHPVPACQRSPSQRGEDDRGPGKGPPPTL FT VITRAAAKPTQRVPISRHTCEPTQVRNLTTVTGTAVDGNSPAQMN (in isoform FT 4)" FT /evidence="ECO:0000303|PubMed:23134681" FT /id="VSP_047470" FT VAR_SEQ 43..63 FT /note="RWREELSHMKRLPPVLPGRPY -> VRNLTTVTGTAVDGNSPAQMN (in FT isoform 5)" FT /evidence="ECO:0000303|PubMed:23134681" FT /id="VSP_047471" FT VAR_SEQ 64..513 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:23134681" FT /id="VSP_047472" FT VAR_SEQ 119..513 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:23134681" FT /id="VSP_047473" FT VAR_SEQ 367..400 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:10392904, FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9422764, ECO:0000303|Ref.4" FT /id="VSP_036399" FT VARIANT 315 FT /note="T -> S (in dbSNP:rs1059913)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_059888" FT VARIANT 321 FT /note="L -> F (in dbSNP:rs1059914)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_059889" FT CONFLICT 60..61 FT /note="GR -> AG (in Ref. 1; AAC03462)" FT /evidence="ECO:0000305" FT CONFLICT 77 FT /note="G -> A (in Ref. 1; AAC03462)" FT /evidence="ECO:0000305" FT CONFLICT 251 FT /note="S -> T (in Ref. 1; AAC03462)" FT /evidence="ECO:0000305" FT CONFLICT 304 FT /note="D -> N (in Ref. 4; AAB48399)" FT /evidence="ECO:0000305" FT CONFLICT 329 FT /note="D -> E (in Ref. 4; AAB48399)" FT /evidence="ECO:0000305" FT STRAND 434..436 FT /evidence="ECO:0007829|PDB:6VTX" FT HELIX 444..455 FT /evidence="ECO:0007829|PDB:6VTX" FT STRAND 470..473 FT /evidence="ECO:0007829|PDB:6VTX" FT HELIX 474..485 FT /evidence="ECO:0007829|PDB:6VTX" FT STRAND 493..496 FT /evidence="ECO:0007829|PDB:6VTX" FT STRAND 498..501 FT /evidence="ECO:0007829|PDB:6VTX" FT HELIX 502..510 FT /evidence="ECO:0007829|PDB:6VTX" SQ SEQUENCE 513 AA; 54671 MW; 3B6113A3EF333935 CRC64; MRQPPGESDM AVSDALLPSF STFASGPAGR EKTLRQAGAP NNRWREELSH MKRLPPVLPG RPYDLAAATV ATDLESGGAG AACGGSNLAP LPRRETEEFN DLLDLDFILS NSLTHPPESV AATVSSSASA SSSSSPSSSG PASAPSTCSF TYPIRAGNDP GVAPGGTGGG LLYGRESAPP PTAPFNLADI NDVSPSGGFV AELLRPELDP VYIPPQQPQP PGGGLMGKFV LKASLSAPGS EYGSPSVISV SKGSPDGSHP VVVAPYNGGP PRTCPKIKQE AVSSCTHLGA GPPLSNGHRP AAHDFPLGRQ LPSRTTPTLG LEEVLSSRDC HPALPLPPGF HPHPGPNYPS FLPDQMQPQV PPLHYQGQSR GFVARAGEPC VCWPHFGTHG MMLTPPSSPL ELMPPGSCMP EEPKPKRGRR SWPRKRTATH TCDYAGCGKT YTKSSHLKAH LRTHTGEKPY HCDWDGCGWK FARSDELTRH YRKHTGHRPF QCQKCDRAFS RSDHLALHMK RHF //