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   27-MAR-2024, entry version 191.
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; Q9NX04: AIRIM; NbExp=3; IntAct=EBI-2796400, EBI-8643161;
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; 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}.
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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; 268.
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; 9606-ENSP00000296233; -.
DR   PeptideAtlas; Q9UIH9; -.
DR   Antibodypedia; 17142; 395 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   AGR; HGNC:14536; -.
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; NAAASWW; -.
DR   OrthoDB; 4209628at2759; -.
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; 13 hits in 1173 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 cell types or tissues.
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:1901653; P:cellular response to peptide; IEA:Ensembl.
DR   GO; GO:0010001; P:glial cell differentiation; IEA:Ensembl.
DR   GO; GO:0001678; P:intracellular glucose homeostasis; 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   CDD; cd21580; KLF15_N; 1.
DR   Gene3D; 3.30.160.60; Classic Zinc Finger; 3.
DR   InterPro; IPR036236; Znf_C2H2_sf.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   PANTHER; PTHR23235:SF120; KRUEPPEL-LIKE FACTOR 15; 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; Q9UIH9; HS.
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
//