Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT71LCT2)

• DOT Name: Zinc transporter ZIP11 (SLC39A11)
• Synonyms: Solute carrier family 39 member 11; Zrt- and Irt-like protein 11; ZIP-11
• Gene Name: SLC39A11
• UniProt ID: S39AB_HUMAN
• Pfam ID: PF02535
• Sequence:
  MLQGHSSVFQALLGTFFTWGMTAAGAALVFVFSSGQRRILDGSLGFAAGVMLAASYWSLL
  APAVEMATSSGGFGAFAFFPVAVGFTLGAAFVYLADLLMPHLGAAEDPQTTLALNFGSTL
  MKKKSDPEGPALLFPESELSIRIGRAGLLSDKSENGEAYQRKKAAATGLPEGPAVPVPSR
  GNLAQPGGSSWRRIALLILAITIHNVPEGLAVGVGFGAIEKTASATFESARNLAIGIGIQ
  NFPEGLAVSLPLRGAGFSTWRAFWYGQLSGMVEPLAGVFGAFAVVLAEPILPYALAFAAG
  AMVYVVMDDIIPEAQISGNGKLASWASILGFVVMMSLDVGLG
• Function: Zinc importer that regulates cytosolic zinc concentrations either via zinc influx from the extracellular compartment or efflux from intracellular organelles such as Golgi apparatus. May transport copper ions as well. The transport mechanism remains to be elucidated.
• KEGG Pathway:
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Zinc transporter ZIP11 (SLC39A11) increases the Metabolic disorder ADR of Chlorothiazide.	[17]
NAPQI	DM8F5LR	Investigative	Zinc transporter ZIP11 (SLC39A11) affects the response to substance of NAPQI.	[18]

13 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 Zinc transporter ZIP11 (SLC39A11).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Zinc transporter ZIP11 (SLC39A11).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Zinc transporter ZIP11 (SLC39A11).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Zinc transporter ZIP11 (SLC39A11).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Zinc transporter ZIP11 (SLC39A11).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Zinc transporter ZIP11 (SLC39A11).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Zinc transporter ZIP11 (SLC39A11).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Zinc transporter ZIP11 (SLC39A11).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Zinc transporter ZIP11 (SLC39A11).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Zinc transporter ZIP11 (SLC39A11).	[11]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Zinc transporter ZIP11 (SLC39A11).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Zinc transporter ZIP11 (SLC39A11).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Zinc transporter ZIP11 (SLC39A11).	[16]

3 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 Zinc transporter ZIP11 (SLC39A11).	[7]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Zinc transporter ZIP11 (SLC39A11).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Zinc transporter ZIP11 (SLC39A11).	[14]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] 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.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] 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.
• [8] 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.
• [9] Cellular zinc homeostasis is a regulator in monocyte differentiation of HL-60 cells by 1 alpha,25-dihydroxyvitamin D3. J Leukoc Biol. 2010 May;87(5):833-44. doi: 10.1189/jlb.0409241. Epub 2010 Jan 20.
• [10] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [11] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [12] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [13] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.
• [18] Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 2011 Mar;120(1):33-41. doi: 10.1093/toxsci/kfq375. Epub 2010 Dec 22.