Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9ZANTL)

• DOT Name: Zinc transporter 6 (SLC30A6)
• Synonyms: ZnT-6; Solute carrier family 30 member 6
• Gene Name: SLC30A6
• UniProt ID: ZNT6_HUMAN
• Pfam ID: PF01545
• Sequence:
  MGTIHLFRKPQRSFFGKLLREFRLVAADRRSWKILLFGVINLICTGFLLMWCSSTNSIAL
  TAYTYLTIFDLFSLMTCLISYWVTLRKPSPVYSFGFERLEVLAVFASTVLAQLGALFILK
  ESAERFLEQPEIHTGRLLVGTFVALCFNLFTMLSIRNKPFAYVSEAASTSWLQEHVADLS
  RSLCGIIPGLSSIFLPRMNPFVLIDLAGAFALCITYMLIEINNYFAVDTASAIAIALMTF
  GTMYPMSVYSGKVLLQTTPPHVIGQLDKLIREVSTLDGVLEVRNEHFWTLGFGSLAGSVH
  VRIRRDANEQMVLAHVTNRLYTLVSTLTVQIFKDDWIRPALLSGPVAANVLNFSDHHVIP
  MPLLKGTDDLNPVTSTPAKPSSPPPEFSFNTPGKNVNPVILLNTQTRPYGFGLNHGHTPY
  SSMLNQGLGVPGIGATQGLRTGFTNIPSRYGTNNRIGQPRP
• Function: Has probably no intrinsic transporter activity but together with SLC30A5 forms a functional zinc ion:proton antiporter heterodimer, mediating zinc entry into the lumen of organelles along the secretory pathway. As part of that zinc ion:proton antiporter, contributes to zinc ion homeostasis within the early secretory pathway and regulates the activation and folding of enzymes like alkaline phosphatases and enzymes involved in phosphatidylinositol glycan anchor biosynthesis.
• Tissue Specificity: Expressed in brain; especially in cerebellum, hippocampus, parahippocampal gyrus, superior and middle temporal gyrus. Also expressed in B-cells, colon, eye, and lung. Lower expression was present in bone, brain, cervix, ear, heart, kidney, muscle, nerve, pancreas, prostate, skin, stomach, and testis.

Molecular Interaction Atlas (MIA) of This DOT

7 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 6 (SLC30A6).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Zinc transporter 6 (SLC30A6).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Zinc transporter 6 (SLC30A6).	[3]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Zinc transporter 6 (SLC30A6).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Zinc transporter 6 (SLC30A6).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Zinc transporter 6 (SLC30A6).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Zinc transporter 6 (SLC30A6).	[8]

1 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 6 (SLC30A6).	[4]

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] 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] 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.
• [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] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.