KLF4_HUMAN
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 03-AUG-2022, entry version 204.
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). {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.
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="http://atlasgeneticsoncology.org/Genes/KLF4ID44316ch9q31.html";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/klf4/";
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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; 148.
DR DIP; DIP-57667N; -.
DR IntAct; O43474; 115.
DR MINT; O43474; -.
DR STRING; 9606.ENSP00000363804; -.
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 PeptideAtlas; O43474; -.
DR PRIDE; O43474; -.
DR ProteomicsDB; 48962; -. [O43474-3]
DR ProteomicsDB; 48963; -. [O43474-1]
DR ProteomicsDB; 48964; -. [O43474-4]
DR Antibodypedia; 14888; 934 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 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; RDCHPSP; -.
DR OrthoDB; 1591573at2759; -.
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; 18 hits in 1091 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 199 other tissues.
DR ExpressionAtlas; O43474; baseline and differential.
DR Genevisible; O43474; HS.
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:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
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:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
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:0008270; F:zinc ion binding; NAS:UniProtKB.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:BHF-UCL.
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: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: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:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:1904798; P:positive regulation of core promoter binding; IEA:Ensembl.
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:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
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:0032526; P:response to retinoic acid; IEA:Ensembl.
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 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; Alternative splicing; 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
