KLF15_HUMAN
ID KLF15_HUMAN Reviewed; 416 AA.
AC Q9UIH9;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Krueppel-like factor 15;
DE AltName: Full=Kidney-enriched krueppel-like factor;
GN Name=KLF15; Synonyms=KKLF;
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], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Kidney;
RX PubMed=10982849; DOI=10.1128/mcb.20.19.7319-7331.2000;
RA Uchida S., Tanaka Y., Ito H., Saitoh-Ohara F., Inazawa J., Yokoyama K.K.,
RA Sasaki S., Marumo F.;
RT "Transcriptional regulation of the CLC-K1 promoter by myc-associated zinc
RT finger protein and kidney-enriched Kruppel-like factor, a novel zinc finger
RT repressor.";
RL Mol. Cell. Biol. 20:7319-7331(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [3]
RP STRUCTURE BY NMR OF 346-380.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the second C2H2-type zinc finger domain from human
RT krueppel-like factor 15.";
RL Submitted (APR-2008) to the PDB data bank.
RN [4]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17438289; DOI=10.1073/pnas.0701981104;
RA Fisch S., Gray S., Heymans S., Haldar S.M., Wang B., Pfister O., Cui L.,
RA Kumar A., Lin Z., Sen-Banerjee S., Das H., Petersen C.A., Mende U.,
RA Burleigh B.A., Zhu Y., Pinto Y.M., Pinto Y., Liao R., Jain M.K.;
RT "Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:7074-7079(2007).
RN [5]
RP ERRATUM OF PUBMED:17438289.
RA Fisch S., Gray S., Heymans S., Haldar S.M., Wang B., Pfister O., Cui L.,
RA Kumar A., Lin Z., Sen-Banerjee S., Das H., Petersen C.A., Mende U.,
RA Burleigh B.A., Zhu Y., Pinto Y.M., Pinto Y., Liao R., Jain M.K.;
RL Proc. Natl. Acad. Sci. U.S.A. 104:13851-13851(2007).
RN [6]
RP FUNCTION.
RX PubMed=18586263; DOI=10.1016/j.yjmcc.2008.05.005;
RA Wang B., Haldar S.M., Lu Y., Ibrahim O.A., Fisch S., Gray S., Leask A.,
RA Jain M.K.;
RT "The Kruppel-like factor KLF15 inhibits connective tissue growth factor
RT (CTGF) expression in cardiac fibroblasts.";
RL J. Mol. Cell. Cardiol. 45:193-197(2008).
RN [7]
RP FUNCTION AS NEGATIVE REGULATOR OF MYOCD, AND INTERACTION WITH MYOCD.
RX PubMed=20566642; DOI=10.1074/jbc.m110.107292;
RA Leenders J.J., Wijnen W.J., Hiller M., van der Made I., Lentink V.,
RA van Leeuwen R.E., Herias V., Pokharel S., Heymans S., de Windt L.J.,
RA Hoeydal M.A., Pinto Y.M., Creemers E.E.;
RT "Regulation of cardiac gene expression by KLF15, a repressor of myocardin
RT activity.";
RL J. Biol. Chem. 285:27449-27456(2010).
RN [8]
RP FUNCTION AS NEGATIVE REGULATOR OF TP53 ACETYLATION, TISSUE SPECIFICITY, AND
RP INVOLVEMENT IN HEART FAILURE.
RX PubMed=20375365; DOI=10.1126/scitranslmed.3000502;
RA Haldar S.M., Lu Y., Jeyaraj D., Kawanami D., Cui Y., Eapen S.J., Hao C.,
RA Li Y., Doughman Y.Q., Watanabe M., Shimizu K., Kuivaniemi H., Sadoshima J.,
RA Margulies K.B., Cappola T.P., Jain M.K.;
RT "Klf15 deficiency is a molecular link between heart failure and aortic
RT aneurysm formation.";
RL Sci. Transl. Med. 2:26RA26-26RA26(2010).
RN [9]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=22493483; DOI=10.1074/jbc.m112.345983;
RA Mallipattu S.K., Liu R., Zheng F., Narla G., Ma'ayan A., Dikman S.,
RA Jain M.K., Saleem M., D'Agati V., Klotman P., Chuang P.Y., He J.C.;
RT "Kruppel-like factor 15 (KLF15) is a key regulator of podocyte
RT differentiation.";
RL J. Biol. Chem. 287:19122-19135(2012).
RN [10]
RP INVOLVEMENT IN SUSCEPTIBILITY TO VENTRICULAR ARRHYTHMIAS.
RX PubMed=22367544; DOI=10.1038/nature10852;
RA Jeyaraj D., Haldar S.M., Wan X., McCauley M.D., Ripperger J.A., Hu K.,
RA Lu Y., Eapen B.L., Sharma N., Ficker E., Cutler M.J., Gulick J., Sanbe A.,
RA Robbins J., Demolombe S., Kondratov R.V., Shea S.A., Albrecht U.,
RA Wehrens X.H., Rosenbaum D.S., Jain M.K.;
RT "Circadian rhythms govern cardiac repolarization and arrhythmogenesis.";
RL Nature 483:96-99(2012).
RN [11]
RP FUNCTION AS INHIBITOR OF VASCULAR INFLAMMATION, FUNCTION AS NF-KAPPA-B
RP REPRESSOR, AND INTERACTION WITH EP300.
RX PubMed=23999430; DOI=10.1172/jci68552;
RA Lu Y., Zhang L., Liao X., Sangwung P., Prosdocimo D.A., Zhou G.,
RA Votruba A.R., Brian L., Han Y.J., Gao H., Wang Y., Shimizu K.,
RA Weinert-Stein K., Khrestian M., Simon D.I., Freedman N.J., Jain M.K.;
RT "Kruppel-like factor 15 is critical for vascular inflammation.";
RL J. Clin. Invest. 123:4232-4241(2013).
RN [12]
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: Transcriptional regulator that binds to the GA element of the
CC CLCNKA promoter. Binds to the KCNIP2 promoter and regulates KCNIP2
CC circadian expression in the heart (By similarity). Is a repressor of
CC CCN2 expression, involved in the control of cardiac fibrosis. It is
CC also involved in the control of cardiac hypertrophy acting through the
CC inhibition of MEF2A and GATA4 (By similarity). Involved in podocyte
CC differentiation (By similarity). Inhibits MYOCD activity. Is a negative
CC regulator of TP53 acetylation. Inhibits NF-kappa-B activation through
CC repression of EP300-dependent RELA acetylation. {ECO:0000250,
CC ECO:0000269|PubMed:18586263, ECO:0000269|PubMed:20375365,
CC ECO:0000269|PubMed:20566642, ECO:0000269|PubMed:23999430}.
CC -!- SUBUNIT: Interacts with MYOCD and EP300. {ECO:0000269|PubMed:20566642,
CC ECO:0000269|PubMed:23999430}.
CC -!- INTERACTION:
CC Q9UIH9; P46379-2: BAG6; NbExp=3; IntAct=EBI-2796400, EBI-10988864;
CC Q9UIH9; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-2796400, EBI-11524452;
CC Q9UIH9; Q9H3H3-3: C11orf68; NbExp=3; IntAct=EBI-2796400, EBI-12002214;
CC Q9UIH9; Q9NX04: C1orf109; NbExp=3; IntAct=EBI-2796400, EBI-8643161;
CC Q9UIH9; Q2TAC2-2: CCDC57; NbExp=3; IntAct=EBI-2796400, EBI-10961624;
CC Q9UIH9; Q96A83-2: COL26A1; NbExp=3; IntAct=EBI-2796400, EBI-21553822;
CC Q9UIH9; O14645: DNALI1; NbExp=3; IntAct=EBI-2796400, EBI-395638;
CC Q9UIH9; Q01658: DR1; NbExp=3; IntAct=EBI-2796400, EBI-750300;
CC Q9UIH9; Q92997: DVL3; NbExp=5; IntAct=EBI-2796400, EBI-739789;
CC Q9UIH9; P01100: FOS; NbExp=3; IntAct=EBI-2796400, EBI-852851;
CC Q9UIH9; P62993: GRB2; NbExp=3; IntAct=EBI-2796400, EBI-401755;
CC Q9UIH9; P42261: GRIA1; NbExp=3; IntAct=EBI-2796400, EBI-6980805;
CC Q9UIH9; P28799: GRN; NbExp=3; IntAct=EBI-2796400, EBI-747754;
CC Q9UIH9; Q00403: GTF2B; NbExp=3; IntAct=EBI-2796400, EBI-389564;
CC Q9UIH9; Q9Y5Q9: GTF3C3; NbExp=3; IntAct=EBI-2796400, EBI-1054873;
CC Q9UIH9; P52597: HNRNPF; NbExp=3; IntAct=EBI-2796400, EBI-352986;
CC Q9UIH9; Q00613: HSF1; NbExp=3; IntAct=EBI-2796400, EBI-719620;
CC Q9UIH9; P04792: HSPB1; NbExp=3; IntAct=EBI-2796400, EBI-352682;
CC Q9UIH9; Q8WVZ9: KBTBD7; NbExp=3; IntAct=EBI-2796400, EBI-473695;
CC Q9UIH9; O60333-2: KIF1B; NbExp=3; IntAct=EBI-2796400, EBI-10975473;
CC Q9UIH9; O14901: KLF11; NbExp=3; IntAct=EBI-2796400, EBI-948266;
CC Q9UIH9; P31153: MAT2A; NbExp=3; IntAct=EBI-2796400, EBI-1050743;
CC Q9UIH9; Q13952-2: NFYC; NbExp=3; IntAct=EBI-2796400, EBI-11956831;
CC Q9UIH9; Q16656-4: NRF1; NbExp=3; IntAct=EBI-2796400, EBI-11742836;
CC Q9UIH9; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-2796400, EBI-473160;
CC Q9UIH9; D3DTS7: PMP22; NbExp=3; IntAct=EBI-2796400, EBI-25882629;
CC Q9UIH9; O15160: POLR1C; NbExp=3; IntAct=EBI-2796400, EBI-1055079;
CC Q9UIH9; O43741: PRKAB2; NbExp=9; IntAct=EBI-2796400, EBI-1053424;
CC Q9UIH9; O60260-5: PRKN; NbExp=3; IntAct=EBI-2796400, EBI-21251460;
CC Q9UIH9; P62491: RAB11A; NbExp=3; IntAct=EBI-2796400, EBI-745098;
CC Q9UIH9; Q9Y3C5: RNF11; NbExp=3; IntAct=EBI-2796400, EBI-396669;
CC Q9UIH9; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-2796400, EBI-748391;
CC Q9UIH9; Q9NUL5-4: SHFL; NbExp=3; IntAct=EBI-2796400, EBI-11955083;
CC Q9UIH9; P37840: SNCA; NbExp=3; IntAct=EBI-2796400, EBI-985879;
CC Q9UIH9; P12931: SRC; NbExp=3; IntAct=EBI-2796400, EBI-621482;
CC Q9UIH9; Q13148: TARDBP; NbExp=6; IntAct=EBI-2796400, EBI-372899;
CC Q9UIH9; O76024: WFS1; NbExp=3; IntAct=EBI-2796400, EBI-720609;
CC Q9UIH9; O43167: ZBTB24; NbExp=10; IntAct=EBI-2796400, EBI-744471;
CC Q9UIH9; Q9Y3S2: ZNF330; NbExp=5; IntAct=EBI-2796400, EBI-373456;
CC Q9UIH9; P36508: ZNF76; NbExp=3; IntAct=EBI-2796400, EBI-7254550;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10982849,
CC ECO:0000269|PubMed:17438289}.
CC -!- TISSUE SPECIFICITY: Highly expressed in liver, skeletal muscle, and
CC kidney. Expressed in cardiomyocytes. Expression is highly reduced in
CC cardiac tissue of patients with non-ischemic cardiomyopathy and aortic
CC aneurysm, and in glomerular disease. Not expressed in bone marrow or
CC lymphoid tissues. {ECO:0000269|PubMed:10982849,
CC ECO:0000269|PubMed:17438289, ECO:0000269|PubMed:20375365,
CC ECO:0000269|PubMed:22493483}.
CC -!- INDUCTION: In podocytes, up-regulated by retinoic acid.
CC {ECO:0000269|PubMed:22493483}.
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:31375868}.
CC -!- DISEASE: Note=KLF15 deficiency results in loss of rhythmic QT variation
CC and abnormal heart repolarization (PubMed:22367544). It may play a role
CC in susceptibility to ventricular arrhythmias (PubMed:22367544), and
CC development of pathological cardiac hypertrophy leading to heart
CC failure (PubMed:20375365). {ECO:0000269|PubMed:20375365,
CC ECO:0000269|PubMed:22367544}.
CC -!- SIMILARITY: Belongs to the Sp1 C2H2-type zinc-finger protein family.
CC {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; AB029254; BAA88561.1; -; mRNA.
DR EMBL; BC036733; AAH36733.1; -; mRNA.
DR CCDS; CCDS3036.1; -.
DR RefSeq; NP_054798.1; NM_014079.3.
DR RefSeq; XP_005247457.1; XM_005247400.3.
DR PDB; 2ENT; NMR; -; A=346-380.
DR PDBsum; 2ENT; -.
DR AlphaFoldDB; Q9UIH9; -.
DR SMR; Q9UIH9; -.
DR BioGRID; 118818; 267.
DR IntAct; Q9UIH9; 292.
DR MINT; Q9UIH9; -.
DR STRING; 9606.ENSP00000296233; -.
DR iPTMnet; Q9UIH9; -.
DR PhosphoSitePlus; Q9UIH9; -.
DR BioMuta; KLF15; -.
DR DMDM; 20138787; -.
DR MassIVE; Q9UIH9; -.
DR PaxDb; Q9UIH9; -.
DR PeptideAtlas; Q9UIH9; -.
DR PRIDE; Q9UIH9; -.
DR ProteomicsDB; 84523; -.
DR Antibodypedia; 17142; 370 antibodies from 36 providers.
DR DNASU; 28999; -.
DR Ensembl; ENST00000296233.4; ENSP00000296233.3; ENSG00000163884.4.
DR GeneID; 28999; -.
DR KEGG; hsa:28999; -.
DR MANE-Select; ENST00000296233.4; ENSP00000296233.3; NM_014079.4; NP_054798.1.
DR UCSC; uc011bkk.2; human.
DR CTD; 28999; -.
DR DisGeNET; 28999; -.
DR GeneCards; KLF15; -.
DR HGNC; HGNC:14536; KLF15.
DR HPA; ENSG00000163884; Tissue enhanced (liver).
DR MIM; 606465; gene.
DR neXtProt; NX_Q9UIH9; -.
DR OpenTargets; ENSG00000163884; -.
DR PharmGKB; PA30134; -.
DR VEuPathDB; HostDB:ENSG00000163884; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000156977; -.
DR HOGENOM; CLU_035818_0_0_1; -.
DR InParanoid; Q9UIH9; -.
DR OMA; SGRAYHM; -.
DR PhylomeDB; Q9UIH9; -.
DR TreeFam; TF350556; -.
DR PathwayCommons; Q9UIH9; -.
DR Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression.
DR SignaLink; Q9UIH9; -.
DR SIGNOR; Q9UIH9; -.
DR BioGRID-ORCS; 28999; 12 hits in 1095 CRISPR screens.
DR ChiTaRS; KLF15; human.
DR EvolutionaryTrace; Q9UIH9; -.
DR GeneWiki; KLF15; -.
DR GenomeRNAi; 28999; -.
DR Pharos; Q9UIH9; Tbio.
DR PRO; PR:Q9UIH9; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9UIH9; protein.
DR Bgee; ENSG00000163884; Expressed in parotid gland and 175 other tissues.
DR Genevisible; Q9UIH9; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP:BHF-UCL.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA: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:0014898; P:cardiac muscle hypertrophy in response to stress; IEA:Ensembl.
DR GO; GO:0001678; P:cellular glucose homeostasis; IEA:Ensembl.
DR GO; GO:1901653; P:cellular response to peptide; IEA:Ensembl.
DR GO; GO:0010001; P:glial cell differentiation; IEA:Ensembl.
DR GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; IMP:UniProtKB.
DR GO; GO:0072112; P:podocyte differentiation; ISS:UniProtKB.
DR GO; GO:0046326; P:positive regulation of glucose import; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
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; Metal-binding; Nucleus;
KW Reference proteome; Repeat; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..416
FT /note="Krueppel-like factor 15"
FT /id="PRO_0000047187"
FT ZN_FING 321..345
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 351..375
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 381..403
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 156..219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 75..83
FT /note="9aaTAD"
FT /evidence="ECO:0000269|PubMed:31375868"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:2ENT"
FT STRAND 361..364
FT /evidence="ECO:0007829|PDB:2ENT"
FT HELIX 365..372
FT /evidence="ECO:0007829|PDB:2ENT"
SQ SEQUENCE 416 AA; 43992 MW; 6335F85141BEB276 CRC64;
MVDHLLPVDE NFSSPKCPVG YLGDRLVGRR AYHMLPSPVS EDDSDASSPC SCSSPDSQAL
CSCYGGGLGT ESQDSILDFL LSQATLGSGG GSGSSIGASS GPVAWGPWRR AAAPVKGEHF
CLPEFPLGDP DDVPRPFQPT LEEIEEFLEE NMEPGVKEVP EGNSKDLDAC SQLSAGPHKS
HLHPGSSGRE RCSPPPGGAS AGGAQGPGGG PTPDGPIPVL LQIQPVPVKQ ESGTGPASPG
QAPENVKVAQ LLVNIQGQTF ALVPQVVPSS NLNLPSKFVR IAPVPIAAKP VGSGPLGPGP
AGLLMGQKFP KNPAAELIKM HKCTFPGCSK MYTKSSHLKA HLRRHTGEKP FACTWPGCGW
RFSRSDELSR HRRSHSGVKP YQCPVCEKKF ARSDHLSKHI KVHRFPRSSR SVRSVN
