Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTTUL91)

• DOT Name: Solute carrier family 25 member 16 (SLC25A16)
• Synonyms: Graves disease autoantigen; GDA; Graves disease carrier protein; GDC; Graves' didease protein; hGP; Mitochondrial solute carrier protein homolog
• Gene Name: SLC25A16
• UniProt ID: GDC_HUMAN
• Pfam ID: PF00153
• Sequence:
  MAAATAAAALAAADPPPAMPQAAGAGGPTTRRDFYWLRSFLAGGIAGCCAKTTVAPLDRV
  KVLLQAHNHHYKHLGVFSALRAVPQKEGFLGLYKGNGAMMIRIFPYGAIQFMAFEHYKTL
  ITTKLGISGHVHRLMAGSMAGMTAVICTYPLDMVRVRLAFQVKGEHSYTGIIHAFKTIYA
  KEGGFFGFYRGLMPTILGMAPYAGVSFFTFGTLKSVGLSHAPTLLGRPSSDNPNVLVLKT
  HVNLLCGGVAGAIAQTISYPFDVTRRRMQLGTVLPEFEKCLTMRDTMKYVYGHHGIRKGL
  YRGLSLNYIRCIPSQAVAFTTYELMKQFFHLN
• Function: May be involved in the transport of coenzyme A in the mitochondrial matrix. Very little is known about the physiological function of this carrier.
• Reactome Pathway: Vitamin B5 (pantothenate) metabolism (R-HSA-199220)

Molecular Interaction Atlas (MIA) of This DOT

19 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 Solute carrier family 25 member 16 (SLC25A16).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Solute carrier family 25 member 16 (SLC25A16).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Solute carrier family 25 member 16 (SLC25A16).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Solute carrier family 25 member 16 (SLC25A16).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Solute carrier family 25 member 16 (SLC25A16).	[5]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Solute carrier family 25 member 16 (SLC25A16).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Solute carrier family 25 member 16 (SLC25A16).	[7]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Solute carrier family 25 member 16 (SLC25A16).	[8]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Solute carrier family 25 member 16 (SLC25A16).	[9]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Solute carrier family 25 member 16 (SLC25A16).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Solute carrier family 25 member 16 (SLC25A16).	[11]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Solute carrier family 25 member 16 (SLC25A16).	[12]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Solute carrier family 25 member 16 (SLC25A16).	[13]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Solute carrier family 25 member 16 (SLC25A16).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Solute carrier family 25 member 16 (SLC25A16).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Solute carrier family 25 member 16 (SLC25A16).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Solute carrier family 25 member 16 (SLC25A16).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Solute carrier family 25 member 16 (SLC25A16).	[17]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Solute carrier family 25 member 16 (SLC25A16).	[18]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] 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.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [7] 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.
• [8] 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.
• [9] Progestins regulate genes that can elicit both proliferative and antiproliferative effects in breast cancer cells. Oncol Rep. 2008 Jun;19(6):1627-34.
• [10] 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.
• [11] 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.
• [12] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [13] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [14] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [15] 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.
• [16] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.