Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCL6DU6)

DOT Name	Zinc transporter ZIP3 (SLC39A3)
Synonyms	Solute carrier family 39 member 3; Zrt- and Irt-like protein 3; ZIP-3
Gene Name	SLC39A3
UniProt ID	S39A3_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF02535
Sequence	MVKLLVAKILCMVGVFFFMLLGSLLPVKIIETDFEKAHRSKKILSLCNTFGGGVFLATCF NALLPAVREKLQKVLSLGHISTDYPLAETILLLGFFMTVFLEQLILTFRKEKPSFIDLET FNAGSDVGSDSEYESPFMGGARGHALYVEPHGHGPSLSVQGLSRASPVRLLSLAFALSAH SVFEGLALGLQEEGEKVVSLFVGVAVHETLVAVALGISMARSAMPLRDAAKLAVTVSAMI PLGIGLGLGIESAQGVPGSVASVLLQGLAGGTFLFITFLEILAKELEEKSDRLLKVLFLV LGYTVLAGMVFLKW
Function	Transporter for the divalent cation Zn(2+). Mediates the influx of Zn(2+) into cells from extracellular space. Controls Zn(2+) accumulation into dentate gyrus granule cells in the hippocampus. Mediates Zn(2+) reuptake from the secreted milk within the alveolar lumen.
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

Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Zinc transporter ZIP3 (SLC39A3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Zinc transporter ZIP3 (SLC39A3).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Zinc transporter ZIP3 (SLC39A3).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Zinc transporter ZIP3 (SLC39A3).	[7]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Zinc transporter ZIP3 (SLC39A3).	[2]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Zinc transporter ZIP3 (SLC39A3).	[3]
Marinol	DM70IK5	Approved	Marinol increases the expression of Zinc transporter ZIP3 (SLC39A3).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Zinc transporter ZIP3 (SLC39A3).	[6]
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References

1	Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
2	Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
3	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.
4	Genomic and proteomic analysis of the effects of cannabinoids on normal human astrocytes. Brain Res. 2008 Jan 29;1191:1-11.
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	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.
7	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.