Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1NIRLK)

DOT Name Kelch repeat and BTB domain-containing protein 7 (KBTBD7)
Gene Name KBTBD7
Related Disease
Glioblastoma multiforme ( )
Myocardial infarction ( )
UniProt ID
KBTB7_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 ; PF20165 ; PF01344
Sequence
MQSREDVPRSRRLASPRGGRRPKRISKPSVSAFFTGPEELKDTAHSAALLAQLKSFYDAR
LLCDVTIEVVTPGSGPGTGRLFSCNRNVLAAACPYFKSMFTGGMYESQQASVTMHDVDAE
SFEVLVDYCYTGRVSLSEANVQRLYAASDMLQLEYVREACASFLARRLDLTNCTAILKFA
DAFDHHKLRSQAQSYIAHNFKQLSRMGSIREETLADLTLAQLLAVLRLDSLDIESERTVC
HVAVQWLEAAAKERGPSAAEVFKCVRWMHFTEEDQDYLEGLLTKPIVKKYCLDVIEGALQ
MRYGDLLYKSLVPVPNSSSSSSSSNSLVSAAENPPQRLGMCAKEMVIFFGHPRDPFLCYD
PYSGDIYTMPSPLTSFAHTKTVTSSAVCVSPDHDIYLAAQPRKDLWVYKPAQNSWQQLAD
RLLCREGMDVAYLNGYIYILGGRDPITGVKLKEVECYSVQRNQWALVAPVPHSFYSFELI
VVQNYLYAVNSKRMLCYDPSHNMWLNCASLKRSDFQEACVFNDEIYCICDIPVMKVYNPA
RGEWRRISNIPLDSETHNYQIVNHDQKLLLITSTTPQWKKNRVTVYEYDTREDQWINIGT
MLGLLQFDSGFICLCARVYPSCLEPGQSFITEEDDARSESSTEWDLDGFSELDSESGSSS
SFSDDEVWVQVAPQRNAQDQQGSL
Function
As part of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex functions as a substrate adapter for the RAC1 guanine exchange factor (GEF) TIAM1, mediating its 'Lys-48' ubiquitination and proteasomal degradation. By controlling this ubiquitination, regulates RAC1 signal transduction and downstream biological processes including the organization of the cytoskeleton, cell migration and cell proliferation. Ubiquitination of TIAM1 requires the membrane-associated protein GABARAP which may restrict locally the activity of the complex.
Reactome Pathway
Neddylation (R-HSA-8951664 )
Antigen processing (R-HSA-983168 )
Regulation of RAS by GAPs (R-HSA-5658442 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Glioblastoma multiforme DISK8246 Strong Biomarker [1]
Myocardial infarction DIS655KI Strong Biomarker [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [3]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [13]
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12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [5]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [6]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [8]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [9]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [7]
Hydroquinone DM6AVR4 Approved Hydroquinone decreases the expression of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [10]
Azathioprine DMMZSXQ Approved Azathioprine decreases the expression of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [11]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [8]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Kelch repeat and BTB domain-containing protein 7 (KBTBD7). [14]
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⏷ Show the Full List of 12 Drug(s)

References

1 Identifying the Ubiquitin Ligase complex that regulates the NF1 tumor suppressor and Ras.Cancer Discov. 2013 Aug;3(8):880-93. doi: 10.1158/2159-8290.CD-13-0146. Epub 2013 May 9.
2 MicroRNA-21 prevents excessive inflammation and cardiac dysfunction after myocardial infarction through targeting KBTBD7.Cell Death Dis. 2018 Jul 10;9(7):769. doi: 10.1038/s41419-018-0805-5.
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 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
7 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
8 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
9 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
10 Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
11 A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
12 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
13 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
14 Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.