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Q9UIH9 (KLF15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Krueppel-like factor 15
Alternative name(s):
Kidney-enriched krueppel-like factor
Gene names
Name:KLF15
Synonyms:KKLF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length416 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional regulator that binds to the GA element of the CLCNKA promoter. Binds to the KCNIP2 promoter and regulates KCNIP2 circadian expression in the heart By similarity. Is a repressor of CTGF expression, involved in the control of cardiac fibrosis. It is also involved in the control of cardiac hypertrophy acting through the inhibition of MEF2A and GATA4 By similarity. Involved in podocyte differentiation By similarity. Inhibits MYOCD activity. Is a negative regulator of TP53 acetylation. Inhibits NF-kappa-B activation through repression of EP300-dependent RELA acetylation. Ref.6 Ref.7 Ref.8 Ref.11

Subunit structure

Interacts with MYOCD and EP300. Ref.7 Ref.11

Subcellular location

Nucleus Ref.1 Ref.4.

Tissue specificity

Highly expressed in liver, skeletal muscle, and kidney. Expressed in cardiomyocytes. Expression is highly reduced in cardiac tissue of patients with non-ischemic cardiomyopathy and aortic aneurysm, and in glomerular disease. Not expressed in bone marrow or lymphoid tissues. Ref.1 Ref.4 Ref.8 Ref.9

Induction

In podocytes, up-regulated by retinoic acid. Ref.9

Involvement in disease

KLF15 deficiency results in loss of rhythmic QT variation and abnormal heart repolarization (Ref.10). It may play a role in susceptibility to ventricular arrhythmias (Ref.10), and development of pathological cardiac hypertrophy leading to heart failure (Ref.8).

Sequence similarities

Belongs to the Sp1 C2H2-type zinc-finger protein family.

Contains 3 C2H2-type zinc fingers.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 416416Krueppel-like factor 15
PRO_0000047187

Regions

Zinc finger321 – 34525C2H2-type 1
Zinc finger351 – 37525C2H2-type 2
Zinc finger381 – 40323C2H2-type 3

Secondary structure

...... 416
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UIH9 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 6335F85141BEB276

FASTA41643,992
        10         20         30         40         50         60 
MVDHLLPVDE NFSSPKCPVG YLGDRLVGRR AYHMLPSPVS EDDSDASSPC SCSSPDSQAL 

        70         80         90        100        110        120 
CSCYGGGLGT ESQDSILDFL LSQATLGSGG GSGSSIGASS GPVAWGPWRR AAAPVKGEHF 

       130        140        150        160        170        180 
CLPEFPLGDP DDVPRPFQPT LEEIEEFLEE NMEPGVKEVP EGNSKDLDAC SQLSAGPHKS 

       190        200        210        220        230        240 
HLHPGSSGRE RCSPPPGGAS AGGAQGPGGG PTPDGPIPVL LQIQPVPVKQ ESGTGPASPG 

       250        260        270        280        290        300 
QAPENVKVAQ LLVNIQGQTF ALVPQVVPSS NLNLPSKFVR IAPVPIAAKP VGSGPLGPGP 

       310        320        330        340        350        360 
AGLLMGQKFP KNPAAELIKM HKCTFPGCSK MYTKSSHLKA HLRRHTGEKP FACTWPGCGW 

       370        380        390        400        410 
RFSRSDELSR HRRSHSGVKP YQCPVCEKKF ARSDHLSKHI KVHRFPRSSR SVRSVN 

« Hide

References

« Hide 'large scale' references
[1]"Transcriptional regulation of the CLC-K1 promoter by myc-associated zinc finger protein and kidney-enriched Kruppel-like factor, a novel zinc finger repressor."
Uchida S., Tanaka Y., Ito H., Saitoh-Ohara F., Inazawa J., Yokoyama K.K., Sasaki S., Marumo F.
Mol. Cell. Biol. 20:7319-7331(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
Tissue: Kidney.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Skin.
[3]"Solution structure of the second C2H2-type zinc finger domain from human krueppel-like factor 15."
RIKEN structural genomics initiative (RSGI)
Submitted (APR-2008) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 346-380.
[4]"Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy."
Fisch S., Gray S., Heymans S., Haldar S.M., Wang B., Pfister O., Cui L., Kumar A., Lin Z., Sen-Banerjee S., Das H., Petersen C.A., Mende U., Burleigh B.A., Zhu Y., Pinto Y.M., Pinto Y., Liao R., Jain M.K.
Proc. Natl. Acad. Sci. U.S.A. 104:7074-7079(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]Erratum
Fisch S., Gray S., Heymans S., Haldar S.M., Wang B., Pfister O., Cui L., Kumar A., Lin Z., Sen-Banerjee S., Das H., Petersen C.A., Mende U., Burleigh B.A., Zhu Y., Pinto Y.M., Pinto Y., Liao R., Jain M.K.
Proc. Natl. Acad. Sci. U.S.A. 104:13851-13851(2007)
[6]"The Kruppel-like factor KLF15 inhibits connective tissue growth factor (CTGF) expression in cardiac fibroblasts."
Wang B., Haldar S.M., Lu Y., Ibrahim O.A., Fisch S., Gray S., Leask A., Jain M.K.
J. Mol. Cell. Cardiol. 45:193-197(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Regulation of cardiac gene expression by KLF15, a repressor of myocardin activity."
Leenders J.J., Wijnen W.J., Hiller M., van der Made I., Lentink V., van Leeuwen R.E., Herias V., Pokharel S., Heymans S., de Windt L.J., Hoeydal M.A., Pinto Y.M., Creemers E.E.
J. Biol. Chem. 285:27449-27456(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS NEGATIVE REGULATOR OF MYOCD, INTERACTION WITH MYOCD.
[8]"Klf15 deficiency is a molecular link between heart failure and aortic aneurysm formation."
Haldar S.M., Lu Y., Jeyaraj D., Kawanami D., Cui Y., Eapen S.J., Hao C., Li Y., Doughman Y.Q., Watanabe M., Shimizu K., Kuivaniemi H., Sadoshima J., Margulies K.B., Cappola T.P., Jain M.K.
Sci. Transl. Med. 2:26ra26-26ra26(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS NEGATIVE REGULATOR OF TP53 ACETYLATION, TISSUE SPECIFICITY, INVOLVEMENT IN HEART FAILURE.
[9]"Kruppel-like factor 15 (KLF15) is a key regulator of podocyte differentiation."
Mallipattu S.K., Liu R., Zheng F., Narla G., Ma'ayan A., Dikman S., Jain M.K., Saleem M., D'Agati V., Klotman P., Chuang P.Y., He J.C.
J. Biol. Chem. 287:19122-19135(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, TISSUE SPECIFICITY.
[10]"Circadian rhythms govern cardiac repolarization and arrhythmogenesis."
Jeyaraj D., Haldar S.M., Wan X., McCauley M.D., Ripperger J.A., Hu K., Lu Y., Eapen B.L., Sharma N., Ficker E., Cutler M.J., Gulick J., Sanbe A., Robbins J., Demolombe S., Kondratov R.V., Shea S.A., Albrecht U. expand/collapse author list , Wehrens X.H., Rosenbaum D.S., Jain M.K.
Nature 483:96-99(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO VENTRICULAR ARRHYTHMIAS.
[11]"Kruppel-like factor 15 is critical for vascular inflammation."
Lu Y., Zhang L., Liao X., Sangwung P., Prosdocimo D.A., Zhou G., Votruba A.R., Brian L., Han Y.J., Gao H., Wang Y., Shimizu K., Weinert-Stein K., Khrestian M., Simon D.I., Freedman N.J., Jain M.K.
J. Clin. Invest. 123:4232-4241(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS INHIBITOR OF VASCULAR INFLAMMATION, FUNCTION AS NF-KAPPA-B REPRESSOR, INTERACTION WITH EP300.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB029254 mRNA. Translation: BAA88561.1.
BC036733 mRNA. Translation: AAH36733.1.
RefSeqNP_054798.1. NM_014079.3.
XP_005247457.1. XM_005247400.1.
UniGeneHs.272215.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ENTNMR-A346-380[»]
ProteinModelPortalQ9UIH9.
SMRQ9UIH9. Positions 318-403.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118818. 4 interactions.
IntActQ9UIH9. 4 interactions.
MINTMINT-8417681.
STRING9606.ENSP00000296233.

PTM databases

PhosphoSiteQ9UIH9.

Polymorphism databases

DMDM20138787.

Proteomic databases

PaxDbQ9UIH9.
PRIDEQ9UIH9.

Protocols and materials databases

DNASU28999.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296233; ENSP00000296233; ENSG00000163884.
GeneID28999.
KEGGhsa:28999.
UCSCuc011bkk.1. human.

Organism-specific databases

CTD28999.
GeneCardsGC03M126061.
HGNCHGNC:14536. KLF15.
HPAHPA028866.
MIM606465. gene.
neXtProtNX_Q9UIH9.
PharmGKBPA30134.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5048.
HOGENOMHOG000294058.
HOVERGENHBG052266.
InParanoidQ9UIH9.
KOK09210.
OMASSGPMAW.
OrthoDBEOG7JMGF2.
PhylomeDBQ9UIH9.
TreeFamTF350556.

Enzyme and pathway databases

SignaLinkQ9UIH9.

Gene expression databases

BgeeQ9UIH9.
CleanExHS_KLF15.
GenevestigatorQ9UIH9.

Family and domain databases

Gene3D3.30.160.60. 3 hits.
InterProIPR007087. Znf_C2H2.
IPR015880. Znf_C2H2-like.
IPR013087. Znf_C2H2/integrase_DNA-bd.
[Graphical view]
SMARTSM00355. ZnF_C2H2. 3 hits.
[Graphical view]
PROSITEPS00028. ZINC_FINGER_C2H2_1. 3 hits.
PS50157. ZINC_FINGER_C2H2_2. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9UIH9.
GeneWikiKLF15.
GenomeRNAi28999.
NextBio51936.
PROQ9UIH9.
SOURCESearch...

Entry information

Entry nameKLF15_HUMAN
AccessionPrimary (citable) accession number: Q9UIH9
Entry history
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: May 1, 2000
Last modified: April 16, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM