Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2TUHO8)

• DOT Name: Peroxisomal membrane protein PMP34 (SLC25A17)
• Synonyms: 34 kDa peroxisomal membrane protein; Solute carrier family 25 member 17
• Gene Name: SLC25A17
• UniProt ID: PM34_HUMAN
• Pfam ID: PF00153
• Sequence:
  MASVLSYESLVHAVAGAVGSVTAMTVFFPLDTARLRLQVDEKRKSKTTHMVLLEIIKEEG
  LLAPYRGWFPVISSLCCSNFVYFYTFNSLKALWVKGQHSTTGKDLVVGFVAGVVNVLLTT
  PLWVVNTRLKLQGAKFRNEDIVPTNYKGIIDAFHQIIRDEGISALWNGTFPSLLLVFNPA
  IQFMFYEGLKRQLLKKRMKLSSLDVFIIGAVAKAIATTVTYPLQTVQSILRFGRHRLNPE
  NRTLGSLRNILYLLHQRVRRFGIMGLYKGLEAKLLQTVLTAALMFLVYEKLTAATFTVMG
  LKRAHQH
• Function: Peroxisomal transporter for multiple cofactors like coenzyme A (CoA), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN) and nucleotide adenosine monophosphate (AMP), and to a lesser extent for nicotinamide adenine dinucleotide (NAD(+)), adenosine diphosphate (ADP) and adenosine 3',5'-diphosphate (PAP). May catalyze the transport of free CoA, FAD and NAD(+) from the cytosol into the peroxisomal matrix by a counter-exchange mechanism.
• Tissue Specificity: Ubiquitous. Expressed in liver.
• KEGG Pathway: Peroxisome (hsa04146)
• Reactome Pathway:
  Class I peroxisomal membrane protein import (R-HSA-9603798)
  Alpha-oxidation of phytanate (R-HSA-389599)

Molecular Interaction Atlas (MIA) of This DOT

7 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 Peroxisomal membrane protein PMP34 (SLC25A17).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Peroxisomal membrane protein PMP34 (SLC25A17).	[2]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Peroxisomal membrane protein PMP34 (SLC25A17).	[4]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Peroxisomal membrane protein PMP34 (SLC25A17).	[5]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Peroxisomal membrane protein PMP34 (SLC25A17).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Peroxisomal membrane protein PMP34 (SLC25A17).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Peroxisomal membrane protein PMP34 (SLC25A17).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Peroxisomal membrane protein PMP34 (SLC25A17).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Peroxisomal membrane protein PMP34 (SLC25A17).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] 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.
• [4] 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.
• [5] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.