Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS5Z1QN)

DOT Name Kelch-like protein 29 (KLHL29)
Synonyms Kelch repeat and BTB domain-containing protein 9
Gene Name KLHL29
Related Disease
High blood pressure ( )
Major depressive disorder ( )
Mood disorder ( )
UniProt ID
KLH29_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF07707 ; PF00651 ; PF01344
Sequence
MSRHHSRFERDYRVGWDRREWSVNGTHGTTSICSVTSGAGGGTASSLSVRPGLLPLPVVP
SRLPTPATAPAPCTTGSSEAITSLVASSASAVTTKAPGISKGDSQSQGLATSIRWGQTPI
NQSTPWDTDEPPSKQMRESDNPGTGPWVTTVAAGNQPTLIAHSYGVAQPPTFSPAVNVQA
PVIGVTPSLPPHVGPQLPLMPGHYSLPQPPSQPLSSVVVNMPAQALYASPQPLAVSTLPG
VGQVARPGPTAVGNGHMAGPLLPPPPPAQPSATLPSGAPATNGPPTTDSAHGLQMLRTIG
VGKYEFTDPGHPREMLKELNQQRRAKAFTDLKIVVEGREFEVHQNVLASCSLYFKDLIQR
SVQDSGQGGREKLELVLSNLQADVLELLLEFVYTGSLVIDSANAKTLLEAASKFQFHTFC
KVCVSFLEKQLTASNCLGVLAMAEAMQCSELYHMAKAFALQIFPEVAAQEEILSISKDDF
IAYVSNDSLNTKAEELVYETVIKWIKKDPATRTQYAAELLAVVRLPFIHPSYLLNVVDNE
ELIKSSEACRDLVNEAKRYHMLPHARQEMQTPRTRPRLSAGVAEVIVLVGGRQMVGMTQR
SLVAVTCWNPQNNKWYPLASLPFYDREFFSVVSAGDNIYLSGGMESGVTLADVWCYMSLL
DNWNLVSRMTVPRCRHNSLVYDGKIYTLGGLGVAGNVDHVERYDTITNQWEAVAPLPKAV
HSAAATVCGGKIYVFGGVNEAGRAAGVLQSYVPQTNTWSFIESPMIDNKYAPAVTLNGFV
FILGGAYARATTIYDPEKGNIKAGPNMNHSRQFCSAVVLDGKIYATGGIVSSEGPALGNM
EAYEPTTNTWTLLPHMPCPVFRHGCVVIKKYIQSG

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
High blood pressure DISY2OHH Strong Genetic Variation [1]
Major depressive disorder DIS4CL3X Strong Genetic Variation [2]
Mood disorder DISLVMWO Strong Genetic Variation [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Kelch-like protein 29 (KLHL29). [3]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Kelch-like protein 29 (KLHL29). [9]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Kelch-like protein 29 (KLHL29). [14]
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13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Kelch-like protein 29 (KLHL29). [4]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Kelch-like protein 29 (KLHL29). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Kelch-like protein 29 (KLHL29). [6]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Kelch-like protein 29 (KLHL29). [7]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Kelch-like protein 29 (KLHL29). [8]
Triclosan DMZUR4N Approved Triclosan increases the expression of Kelch-like protein 29 (KLHL29). [10]
Phenobarbital DMXZOCG Approved Phenobarbital affects the expression of Kelch-like protein 29 (KLHL29). [11]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Kelch-like protein 29 (KLHL29). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Kelch-like protein 29 (KLHL29). [4]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Kelch-like protein 29 (KLHL29). [13]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of Kelch-like protein 29 (KLHL29). [15]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Kelch-like protein 29 (KLHL29). [16]
Sulforaphane DMQY3L0 Investigative Sulforaphane decreases the expression of Kelch-like protein 29 (KLHL29). [17]
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⏷ Show the Full List of 13 Drug(s)

References

1 Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.PLoS Genet. 2011 Feb 10;7(2):e1001300. doi: 10.1371/journal.pgen.1001300.
2 Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
3 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
4 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
5 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
6 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
7 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
8 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
9 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
10 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
11 Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
12 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
13 Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
14 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
15 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
16 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
17 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.