KLF15_MOUSE
ID KLF15_MOUSE Reviewed; 415 AA.
AC Q9EPW2; Q3UQB0;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Krueppel-like factor 15;
DE AltName: Full=Cardiovascular Krueppel-like factor;
GN Name=Klf15; Synonyms=Cklf;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=12097321; DOI=10.1074/jbc.m201304200;
RA Gray S.J., Feinberg M.W., Hull S., Kuo C.T., Watanabe M., Sen-Banerjee S.,
RA DePina A., Haspel R., Jain M.K.;
RT "The Kruppel-like factor KLF15 regulates the insulin-sensitive glucose
RT transporter GLUT4.";
RL J. Biol. Chem. 277:34322-34328(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [4]
RP FUNCTION AS INHIBITOR OF CARDIAC HYPERTROPHY, FUNCTION AS REPRESSOR OF
RP GATA4 AND MEF2A, AND DISRUPTION PHENOTYPE.
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 AS INHIBITOR OF CARDIAC FIBROSIS AND CCN2 EXPRESSION, AND
RP DISRUPTION PHENOTYPE.
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.
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 FUNCTION IN PODOCYTE DIFFERENTIATION, AND INDUCTION.
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 FUNCTION IN KCNIP2 CIRCADIAN EXPRESSION, INDUCTION, AND BINDING TO THE
RP KCNIP2 PROMOTER.
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, AND TISSUE SPECIFICITY.
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).
CC -!- FUNCTION: Transcriptional regulator that binds to the GA element of the
CC CLCNKA promoter (By similarity). Binds to the KCNIP2 promoter and
CC regulates KCNIP2 circadian expression in the heart. Is a repressor of
CC CCN2 expression, involved in the control of cardiac fibrosis. Is also
CC involved in the control of cardiac hypertrophy acting through the
CC inhibition of MEF2A, GATA4 and MYOCD activity. Is a negative regulator
CC of TP53 acetylation. Inhibits NF-kappa-B activation through repression
CC of EP300-dependent RELA acetylation (By similarity). Involved in
CC podocyte differentiation. {ECO:0000250, ECO:0000269|PubMed:17438289,
CC ECO:0000269|PubMed:18586263, ECO:0000269|PubMed:20375365,
CC ECO:0000269|PubMed:20566642, ECO:0000269|PubMed:22367544,
CC ECO:0000269|PubMed:22493483, ECO:0000269|PubMed:23999430}.
CC -!- SUBUNIT: Interacts with MYOCD. Interacts with EP300 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Expressed in aortic smooth muscle cells.
CC {ECO:0000269|PubMed:23999430}.
CC -!- INDUCTION: In the heart, up-regulated by the CLOCK/ARNTL heterodimer.
CC In podocytes, up-regulated by retinoic acid.
CC {ECO:0000269|PubMed:22367544, 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:0000250|UniProtKB:Q9UIH9}.
CC -!- DISRUPTION PHENOTYPE: KLF15 null mice are viable, but in response to
CC pressure overload, they develop cardiac hypertrophy and fibrosis.
CC {ECO:0000269|PubMed:17438289, ECO:0000269|PubMed:18586263}.
CC -!- SIMILARITY: Belongs to the Sp1 C2H2-type zinc-finger protein family.
CC {ECO:0000305}.
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DR EMBL; AF317225; AAG38597.1; -; mRNA.
DR EMBL; AK009739; BAB26470.1; -; mRNA.
DR EMBL; AK142618; BAE25132.1; -; mRNA.
DR EMBL; BC013486; AAH13486.1; -; mRNA.
DR CCDS; CCDS20360.1; -.
DR RefSeq; NP_075673.1; NM_023184.3.
DR AlphaFoldDB; Q9EPW2; -.
DR SMR; Q9EPW2; -.
DR BioGRID; 211350; 18.
DR STRING; 10090.ENSMUSP00000032174; -.
DR iPTMnet; Q9EPW2; -.
DR PhosphoSitePlus; Q9EPW2; -.
DR PaxDb; Q9EPW2; -.
DR PRIDE; Q9EPW2; -.
DR ProteomicsDB; 264768; -.
DR Antibodypedia; 17142; 370 antibodies from 36 providers.
DR DNASU; 66277; -.
DR Ensembl; ENSMUST00000032174; ENSMUSP00000032174; ENSMUSG00000030087.
DR Ensembl; ENSMUST00000113530; ENSMUSP00000109158; ENSMUSG00000030087.
DR Ensembl; ENSMUST00000203039; ENSMUSP00000144962; ENSMUSG00000030087.
DR Ensembl; ENSMUST00000203607; ENSMUSP00000144808; ENSMUSG00000030087.
DR GeneID; 66277; -.
DR KEGG; mmu:66277; -.
DR UCSC; uc009cxj.1; mouse.
DR CTD; 28999; -.
DR MGI; MGI:1929988; Klf15.
DR VEuPathDB; HostDB:ENSMUSG00000030087; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000156977; -.
DR HOGENOM; CLU_035818_0_0_1; -.
DR InParanoid; Q9EPW2; -.
DR OMA; SGRAYHM; -.
DR OrthoDB; 891966at2759; -.
DR PhylomeDB; Q9EPW2; -.
DR TreeFam; TF350556; -.
DR BioGRID-ORCS; 66277; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Cklf; mouse.
DR PRO; PR:Q9EPW2; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9EPW2; protein.
DR Bgee; ENSMUSG00000030087; Expressed in left lobe of liver and 232 other tissues.
DR ExpressionAtlas; Q9EPW2; baseline and differential.
DR Genevisible; Q9EPW2; MM.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
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; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IMP:UniProtKB.
DR GO; GO:0001678; P:cellular glucose homeostasis; IDA:MGI.
DR GO; GO:1901653; P:cellular response to peptide; IEA:Ensembl.
DR GO; GO:0010001; P:glial cell differentiation; IDA:MGI.
DR GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; IMP:UniProtKB.
DR GO; GO:0072112; P:podocyte differentiation; IMP:UniProtKB.
DR GO; GO:0046326; P:positive regulation of glucose import; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:UniProtKB.
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; IMP:MGI.
DR GO; GO:0032868; P:response to insulin; IDA:MGI.
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 Activator; DNA-binding; Metal-binding; Nucleus; Reference proteome; Repeat;
KW Transcription; Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..415
FT /note="Krueppel-like factor 15"
FT /id="PRO_0000047188"
FT ZN_FING 320..344
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 350..374
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 380..402
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 172..216
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 75..83
FT /note="9aaTAD"
FT /evidence="ECO:0000250|UniProtKB:Q9UIH9"
SQ SEQUENCE 415 AA; 44253 MW; 127A7B80DB3E33CC CRC64;
MVDHLLPVDE TFSSPKCSVG YLGDRLASRQ PYHMLPSPIS EDDSDVSSPC SCASPDSQAF
CSCYSAGPGP EAQGSILDFL LSRATLGSGG GSGGIGDSSG PVTWGSWRRA SVPVKEEHFC
FPEFLSGDTD DVSRPFQPTL EEIEEFLEEN MEAEVKEAPE NGSRDLETCS QLSAGSHRSH
LHPESAGRER CTPPPGGTSG GGAQSAGEGP AHDGPVPVLL QIQPVAVKQE AGTGPASPGQ
APESVKVAQL LVNIQGQTFA LLPQVVPSSN LNLPSKFVRI APVPIAAKPI GSGSLGPGPA
GLLVGQKFPK NPAAELLKMH KCTFPGCSKM YTKSSHLKAH LRRHTGEKPF ACTWPGCGWR
FSRSDELSRH RRSHSGVKPY QCPVCEKKFA RSDHLSKHIK VHRFPRSSRA VRAIN
