Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8O00YJ)

• DOT Name: GrpE protein homolog 1, mitochondrial (GRPEL1)
• Synonyms: HMGE; Mt-GrpE#1
• Gene Name: GRPEL1
• Related Disease:
  HIV infectious disease
  Goiter
• UniProt ID: GRPE1_HUMAN
• Pfam ID: PF01025
• Sequence:
  MAAQCVRLARRSLPALALSLRPSPRLLCTATKQKNSGQNLEEDMGQSEQKADPPATEKTL
  LEEKVKLEEQLKETVEKYKRALADTENLRQRSQKLVEEAKLYGIQAFCKDLLEVADVLEK
  ATQCVPKEEIKDDNPHLKNLYEGLVMTEVQIQKVFTKHGLLKLNPVGAKFDPYEHEALFH
  TPVEGKEPGTVALVSKVGYKLHGRTLRPALVGVVKEA
• Function: Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner. Seems to control the nucleotide-dependent binding of mitochondrial HSP70 to substrate proteins.
• Reactome Pathway: Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
HIV infectious disease	DISO97HC	Strong	Biomarker	[1]
Goiter	DISLCGI6	Limited	Genetic Variation	[2]

22 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 GrpE protein homolog 1, mitochondrial (GRPEL1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[11]
Marinol	DM70IK5	Approved	Marinol decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[12]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[14]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[7]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[7]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[7]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[7]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[7]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[18]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[19]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of GrpE protein homolog 1, mitochondrial (GRPEL1).	[20]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of GrpE protein homolog 1, mitochondrial (GRPEL1).	[15]

References

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• [2] Combined linkage analysis and exome sequencing identifies novel genes for familial goiter.J Hum Genet. 2013 Jun;58(6):366-77. doi: 10.1038/jhg.2013.20. Epub 2013 Mar 28.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [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] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [10] Nucleophosmin in the pathogenesis of arsenic-related bladder carcinogenesis revealed by quantitative proteomics. Toxicol Appl Pharmacol. 2010 Jan 15;242(2):126-35. doi: 10.1016/j.taap.2009.09.016. Epub 2009 Oct 7.
• [11] Protein expression profiling identifies molecular targets of quercetin as a major dietary flavonoid in human colon cancer cells. Proteomics. 2004 Jul;4(7):2160-74.
• [12] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [13] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [14] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [15] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [16] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [17] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [20] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.