Details of Drug Off-Target (DOT)

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

• DOT Name: Zinc transporter ZIP1 (SLC39A1)
• Synonyms: Solute carrier family 39 member 1; Zinc-iron-regulated transporter-like; Zrt- and Irt-like protein 1; ZIP-1; hZIP1
• Gene Name: SLC39A1
• UniProt ID: S39A1_HUMAN
• Pfam ID: PF02535
• Sequence:
  MGPWGEPELLVWRPEAVASEPPVPVGLEVKLGALVLLLVLTLLCSLVPICVLRRPGANHE
  GSASRQKALSLVSCFAGGVFLATCLLDLLPDYLAAIDEALAALHVTLQFPLQEFILAMGF
  FLVLVMEQITLAYKEQSGPSPLEETRALLGTVNGGPQHWHDGPGVPQASGAPATPSALRA
  CVLVFSLALHSVFEGLAVGLQRDRARAMELCLALLLHKGILAVSLSLRLLQSHLRAQVVA
  GCGILFSCMTPLGIGLGAALAESAGPLHQLAQSVLEGMAAGTFLYITFLEILPQELASSE
  QRILKVILLLAGFALLTGLLFIQI
• Function: Transporter for the divalent cation Zn(2+). Mediates the influx of Zn(2+) into cells from extracellular space. Functions as the major importer of zinc from circulating blood plasma into prostate cells.
• Tissue Specificity: Ubiquitous . Expressed in most adult and fetal tissues including the epidermis.
• KEGG Pathway:
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
• Reactome Pathway: Zinc influx into cells by the SLC39 gene family (R-HSA-442380)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Zinc transporter ZIP1 (SLC39A1).	[1]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Zinc transporter ZIP1 (SLC39A1).	[2]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Zinc transporter ZIP1 (SLC39A1).	[3]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Zinc transporter ZIP1 (SLC39A1).	[4]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Zinc transporter ZIP1 (SLC39A1).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Zinc transporter ZIP1 (SLC39A1).	[5]

References

• [1] 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.
• [2] 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.
• [3] Dietary catechins and procyanidins modulate zinc homeostasis in human HepG2 cells. J Nutr Biochem. 2011 Feb;22(2):153-63.
• [4] 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.
• [5] 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.
• [6] Intracellular zinc stores protect the intestinal epithelium from Ochratoxin A toxicity. Toxicol In Vitro. 2009 Dec;23(8):1516-21.