Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQC136Q)

• DOT Name: Protein SLC31A2 (SLC31A2)
• Synonyms: Copper transporter 2; hCTR2; Solute carrier family 31 member 2
• Gene Name: SLC31A2
• UniProt ID: COPT2_HUMAN
• Pfam ID: PF04145
• Sequence:
  MAMHFIFSDTAVLLFDFWSVHSPAGMALSVLVLLLLAVLYEGIKVGKAKLLNQVLVNLPT
  SISQQTIAETDGDSAGSDSFPVGRTHHRWYLCHFGQSLIHVIQVVIGYFIMLAVMSYNTW
  IFLGVVLGSAVGYYLAYPLLSTA
• Function: Does not function as a copper(1+) importer in vivo. However, in vitro functions as a low-affinity copper(1+) importer. Regulator of SLC31A1 which facilitates the cleavage of the SLC31A1 ecto-domain or which stabilizes the truncated form of SLC31A1 (Truncated CTR1 form), thereby drives the SLC31A1 truncated form-dependent endosomal copper export and modulates the copper and cisplatin accumulation via SLC31A1.
• Tissue Specificity: Ubiquitous with high expression in placenta and heart.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Coprexa	DMA0WEK	Phase 3	Protein SLC31A2 (SLC31A2) decreases the response to substance of Coprexa.	[16]

17 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 Protein SLC31A2 (SLC31A2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein SLC31A2 (SLC31A2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein SLC31A2 (SLC31A2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Protein SLC31A2 (SLC31A2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protein SLC31A2 (SLC31A2).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein SLC31A2 (SLC31A2).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein SLC31A2 (SLC31A2).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein SLC31A2 (SLC31A2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Protein SLC31A2 (SLC31A2).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein SLC31A2 (SLC31A2).	[8]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Protein SLC31A2 (SLC31A2).	[9]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Protein SLC31A2 (SLC31A2).	[10]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Protein SLC31A2 (SLC31A2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein SLC31A2 (SLC31A2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein SLC31A2 (SLC31A2).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Protein SLC31A2 (SLC31A2).	[14]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Protein SLC31A2 (SLC31A2).	[15]

References

• [1] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Regulation of copper transporter 2 expression by copper and cisplatin in human ovarian carcinoma cells. Mol Pharmacol. 2010 Jun;77(6):912-21. doi: 10.1124/mol.109.062836. Epub 2010 Mar 1.
• [5] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [6] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] Inflammation in methotrexate-induced pulmonary toxicity occurs via the p38 MAPK pathway. Toxicology. 2009 Feb 27;256(3):183-90. doi: 10.1016/j.tox.2008.11.016. Epub 2008 Nov 28.
• [10] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [11] 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.
• [12] 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.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [15] CD34+ derived macrophage and dendritic cells display differential responses to paraquat. Toxicol In Vitro. 2021 Sep;75:105198. doi: 10.1016/j.tiv.2021.105198. Epub 2021 Jun 9.
• [16] Copper transporter 2 regulates intracellular copper and sensitivity to cisplatin. Metallomics. 2014 Mar;6(3):654-61. doi: 10.1039/c3mt00331k. Epub 2014 Feb 13.