Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTEY876E)

• DOT Name: Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3)
• Synonyms: Solute carrier family 30 member 3; Zinc transporter 3; ZnT-3
• Gene Name: SLC30A3
• UniProt ID: ZNT3_HUMAN
• Pfam ID: PF01545
• Sequence:
  MEPSPAAGGLETTRLVSPRDRGGAGGSLRLKSLFTEPSEPLPEESKPVEMPFHHCHRDPL
  PPPGLTPERLHARRQLYAACAVCFVFMAGEVVGGYLAHSLAIMTDAAHLLADVGSMMGSL
  FSLWLSTRPATRTMTFGWHRSETLGALASVVSLWMVTGILLYLAFVRLLHSDYHIEGGAM
  LLTASIAVCANLLMAFVLHQAGPPHSHGSRGAEYAPLEEGPEEPLPLGNTSVRAAFVHVL
  GDLLQSFGVLAASILIYFKPQYKAADPISTFLFSICALGSTAPTLRDVLRILMEGTPRNV
  GFEPVRDTLLSVPGVRATHELHLWALTLTYHVASAHLAIDSTADPEAVLAEASSRLYSRF
  GFSSCTLQVEQYQPEMAQCLRCQEPPQA
• Function: Probable proton-coupled zinc ion antiporter mediating the import of zinc from cytoplasm into synaptic vesicles and participating to cellular zinc ion homeostasis in the brain.
• Reactome Pathway: Zinc efflux and compartmentalization by the SLC30 family (R-HSA-435368)

Molecular Interaction Atlas (MIA) of This DOT

10 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 Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3).	[1]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3).	[2]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3).	[4]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3).	[5]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3).	[6]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3).	[10]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3).	[11]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3).	[12]

2 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 Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Probable proton-coupled zinc antiporter SLC30A3 (SLC30A3).	[8]

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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] 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.
• [4] 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.
• [5] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [6] Gene expression profile induced by BCNU in human glioma cell lines with differential MGMT expression. J Neurooncol. 2005 Jul;73(3):189-98.
• [7] 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.
• [8] 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.
• [9] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [10] 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.
• [11] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
• [12] Zinc and metallothionein levels and expression of zinc transporters in androgen-independent subline of LNCaP cells. J Androl. 2004 Jan-Feb;25(1):154-61. doi: 10.1002/j.1939-4640.2004.tb02771.x.