Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNF289O)

• DOT Name: GrpE protein homolog 2, mitochondrial (GRPEL2)
• Synonyms: Mt-GrpE#2
• Gene Name: GRPEL2
• UniProt ID: GRPE2_HUMAN
• Pfam ID: PF01025
• Sequence:
  MAVRSLWAGRLRVQRLLAWSAAWESKGWPLPFSTATQRTAGEDCRSEDPPDELGPPLAER
  ALRVKAVKLEKEVQDLTVRYQRAIADCENIRRRTQRCVEDAKIFGIQSFCKDLVEVADIL
  EKTTECISEESEPEDQKLTLEKVFRGLLLLEAKLKSVFAKHGLEKLTPIGDKYDPHEHEL
  ICHVPAGVGVQPGTVALVRQDGYKLHGRTIRLARVEVAVESQRRL
• 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. Stimulates ATPase activity of mt-HSP70. May also serve to modulate the interconversion of oligomeric (inactive) and monomeric (active) forms of mt-HSP70.
• Reactome Pathway: Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

16 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[8]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[11]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[13]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[15]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of GrpE protein homolog 2, mitochondrial (GRPEL2).	[16]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [8] 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.
• [9] 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.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [12] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [14] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.