Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRDVST4)

DOT Name Kelch-like protein 5 (KLHL5)
Gene Name KLHL5
Related Disease
Advanced cancer ( )
Carcinoma ( )
Cocaine addiction ( )
Neoplasm ( )
UniProt ID
KLHL5_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF07707 ; PF00651 ; PF01344
Sequence
MNVIYFPLHIFVVYSRAYTSLVLVGCTNLCAVLFARCLDDHLVSLRMSGSRKEFDVKQIL
KIRWRWFGHQASSPNSTVDSQQGEFWNRGQTGANGGRKFLDPCSLQLPLASIGYRRSSQL
DFQNSPSWPMASTSEVPAFEFTAEDCGGAHWLDRPEVDDGTSEEENESDSSSCRTSNSSQ
TLSSCHTMEPCTSDEFFQALNHAEQTFKKMENYLRHKQLCDVILVAGDRRIPAHRLVLSS
VSDYFAAMFTNDVREARQEEIKMEGVEPNSLWSLIQYAYTGRLELKEDNIECLLSTACLL
QLSQVVEACCKFLMKQLHPSNCLGIRSFADAQGCTDLHKVAHNYTMEHFMEVIRNQEFVL
LPASEIAKLLASDDMNIPNEETILNALLTWVRHDLEQRRKDLSKLLAYIRLPLLAPQFLA
DMENNVLFRDDIECQKLIMEAMKYHLLPERRPMLQSPRTKPRKSTVGTLFAVGGMDSTKG
ATSIEKYDLRTNMWTPVANMNGRRLQFGVAVLDDKLYVVGGRDGLKTLNTVECYNPKTKT
WSVMPPMSTHRHGLGVAVLEGPMYAVGGHDGWSYLNTVERWDPQARQWNFVATMSTPRST
VGVAVLSGKLYAVGGRDGSSCLKSVECFDPHTNKWTLCAQMSKRRGGVGVTTWNGLLYAI
GGHDAPASNLTSRLSDCVERYDPKTDMWTAVASMSISRDAVGVCLLGDKLYAVGGYDGQA
YLNTVEAYDPQTNEWTQVAPLCLGRAGACVVTVKL
Tissue Specificity Expressed in adrenal gland, ovary and thyroid gland and less abundantly in lymph node, prostate, spinal chord, testis and trachea.
Reactome Pathway
Antigen processing (R-HSA-983168 )
Neddylation (R-HSA-8951664 )

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Altered Expression [1]
Carcinoma DISH9F1N Strong Altered Expression [1]
Cocaine addiction DISHTRXG Strong Biomarker [2]
Neoplasm DISZKGEW Strong Biomarker [1]
------------------------------------------------------------------------------------
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 1 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Cocaine DMSOX7I Approved Kelch-like protein 5 (KLHL5) affects the response to substance of Cocaine. [2]
------------------------------------------------------------------------------------
17 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Kelch-like protein 5 (KLHL5). [3]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Kelch-like protein 5 (KLHL5). [4]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Kelch-like protein 5 (KLHL5). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Kelch-like protein 5 (KLHL5). [6]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Kelch-like protein 5 (KLHL5). [7]
Quercetin DM3NC4M Approved Quercetin increases the expression of Kelch-like protein 5 (KLHL5). [8]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Kelch-like protein 5 (KLHL5). [9]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Kelch-like protein 5 (KLHL5). [10]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Kelch-like protein 5 (KLHL5). [11]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of Kelch-like protein 5 (KLHL5). [12]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Kelch-like protein 5 (KLHL5). [13]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Kelch-like protein 5 (KLHL5). [14]
Troglitazone DM3VFPD Approved Troglitazone increases the expression of Kelch-like protein 5 (KLHL5). [15]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Kelch-like protein 5 (KLHL5). [16]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Kelch-like protein 5 (KLHL5). [12]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Kelch-like protein 5 (KLHL5). [8]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide increases the expression of Kelch-like protein 5 (KLHL5). [17]
------------------------------------------------------------------------------------
⏷ Show the Full List of 17 Drug(s)

References

1 KLHL5 knockdown increases cellular sensitivity to anticancer drugs.Oncotarget. 2018 Dec 21;9(100):37429-37438. doi: 10.18632/oncotarget.26462. eCollection 2018 Dec 21.
2 Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.
3 The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
4 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
5 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
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 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
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 Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
10 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
11 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
12 Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
13 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.
14 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.
15 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
16 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
17 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
18 Substance dependence low-density whole genome association study in two distinct American populations. Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.