Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT09PIFE)

• DOT Name: Mitochondrial basic amino acids transporter (SLC25A29)
• Synonyms: Carnitine/acylcarnitine translocase-like; CACT-like; Mitochondrial carnitine/acylcarnitine carrier protein CACL; Mitochondrial ornithine transporter 3; Solute carrier family 25 member 29
• Gene Name: SLC25A29
• UniProt ID: S2529_HUMAN
• Pfam ID: PF00153
• Sequence:
  MALDFLAGCAGGVAGVLVGHPFDTVKVRLQVQSVEKPQYRGTLHCFKSIIKQESVLGLYK
  GLGSPLMGLTFINALVFGVQGNTLRALGHDSPLNQFLAGAAAGAIQCVICCPMELAKTRL
  QLQDAGPARTYKGSLDCLAQIYGHEGLRGVNRGMVSTLLRETPSFGVYFLTYDALTRALG
  CEPGDRLLVPKLLLAGGTSGIVSWLSTYPVDVVKSRLQADGLRGAPRYRGILDCVHQSYR
  AEGWRVFTRGLASTLLRAFPVNAATFATVTVVLTYARGEEAGPEGEAVPAAPAGPALAQP
  SSL
• Function: Mitochondrial transporter of arginine, lysine, homoarginine, methylarginine and, to a much lesser extent, ornithine and histidine. Does not transport carnitine nor acylcarnitines. Functions by both counter-exchange and uniport mechanisms. Plays a physiological role in the import of basic amino acids into mitochondria for mitochondrial protein synthesis and amino acid degradation.
• KEGG Pathway: Thermogenesis (hsa04714)
• Reactome Pathway: Amino acid transport across the plasma membrane (R-HSA-352230)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Mitochondrial basic amino acids transporter (SLC25A29).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mitochondrial basic amino acids transporter (SLC25A29).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mitochondrial basic amino acids transporter (SLC25A29).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial basic amino acids transporter (SLC25A29).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Mitochondrial basic amino acids transporter (SLC25A29).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mitochondrial basic amino acids transporter (SLC25A29).	[5]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Mitochondrial basic amino acids transporter (SLC25A29).	[6]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Mitochondrial basic amino acids transporter (SLC25A29).	[7]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Mitochondrial basic amino acids transporter (SLC25A29).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Mitochondrial basic amino acids transporter (SLC25A29).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Mitochondrial basic amino acids transporter (SLC25A29).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitochondrial basic amino acids transporter (SLC25A29).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Mitochondrial basic amino acids transporter (SLC25A29).	[13]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Mitochondrial basic amino acids transporter (SLC25A29).	[14]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Mitochondrial basic amino acids transporter (SLC25A29).	[15]

References

• [1] 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.
• [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] 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.
• [5] 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.
• [6] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [7] Endometrial receptivity is affected in women with high circulating progesterone levels at the end of the follicular phase: a functional genomics analysis. Hum Reprod. 2011 Jul;26(7):1813-25.
• [8] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [9] 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.
• [10] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [15] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.