Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT04411Q)

DOT Name Zinc transporter ZIP10 (SLC39A10)
Synonyms Solute carrier family 39 member 10; Zrt- and Irt-like protein 10; ZIP-10
Gene Name SLC39A10
UniProt ID
S39AA_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF02535
Sequence
MKVHMHTKFCLICLLTFIFHHCNHCHEEHDHGPEALHRQHRGMTELEPSKFSKQAAENEK
KYYIEKLFERYGENGRLSFFGLEKLLTNLGLGERKVVEINHEDLGHDHVSHLDILAVQEG
KHFHSHNHQHSHNHLNSENQTVTSVSTKRNHKCDPEKETVEVSVKSDDKHMHDHNHRLRH
HHRLHHHLDHNNTHHFHNDSITPSERGEPSNEPSTETNKTQEQSDVKLPKGKRKKKGRKS
NENSEVITPGFPPNHDQGEQYEHNRVHKPDRVHNPGHSHVHLPERNGHDPGRGHQDLDPD
NEGELRHTRKREAPHVKNNAIISLRKDLNEDDHHHECLNVTQLLKYYGHGANSPISTDLF
TYLCPALLYQIDSRLCIEHFDKLLVEDINKDKNLVPEDEANIGASAWICGIISITVISLL
SLLGVILVPIINQGCFKFLLTFLVALAVGTMSGDALLHLLPHSQGGHDHSHQHAHGHGHS
HGHESNKFLEEYDAVLKGLVALGGIYLLFIIEHCIRMFKHYKQQRGKQKWFMKQNTEEST
IGRKLSDHKLNNTPDSDWLQLKPLAGTDDSVVSEDRLNETELTDLEGQQESPPKNYLCIE
EEKIIDHSHSDGLHTIHEHDLHAAAHNHHGENKTVLRKHNHQWHHKHSHHSHGPCHSGSD
LKETGIANIAWMVIMGDGIHNFSDGLAIGAAFSAGLTGGISTSIAVFCHELPHELGDFAV
LLKAGMTVKQAIVYNLLSAMMAYIGMLIGTAVGQYANNITLWIFAVTAGMFLYVALVDML
PEMLHGDGDNEEHGFCPVGQFILQNLGLLFGFAIMLVIALYEDKIVFDIQF
Function
Zinc-influx transporter. When associated with SLC39A6, the heterodimer formed by SLC39A10 and SLC39A6 mediates cellular zinc uptake to trigger cells to undergo epithelial-to-mesenchymal transition (EMT). SLC39A10-SLC39A6 heterodimers play also an essentiel role in initiating mitosis by importing zinc into cells to initiate a pathway resulting in the onset of mitosis. Plays an important for both mature B-cell maintenance and humoral immune responses. When associated with SLC39A10, the heterodimer controls NCAM1 phosphorylation and integration into focal adhesion complexes during EMT.
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
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Zinc transporter ZIP10 (SLC39A10). [1]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of Zinc transporter ZIP10 (SLC39A10). [20]
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21 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Zinc transporter ZIP10 (SLC39A10). [2]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Zinc transporter ZIP10 (SLC39A10). [3]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Zinc transporter ZIP10 (SLC39A10). [4]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Zinc transporter ZIP10 (SLC39A10). [5]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Zinc transporter ZIP10 (SLC39A10). [6]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Zinc transporter ZIP10 (SLC39A10). [2]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Zinc transporter ZIP10 (SLC39A10). [7]
Quercetin DM3NC4M Approved Quercetin increases the expression of Zinc transporter ZIP10 (SLC39A10). [8]
Temozolomide DMKECZD Approved Temozolomide decreases the expression of Zinc transporter ZIP10 (SLC39A10). [9]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Zinc transporter ZIP10 (SLC39A10). [10]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Zinc transporter ZIP10 (SLC39A10). [11]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Zinc transporter ZIP10 (SLC39A10). [12]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Zinc transporter ZIP10 (SLC39A10). [13]
Zoledronate DMIXC7G Approved Zoledronate decreases the expression of Zinc transporter ZIP10 (SLC39A10). [14]
Zidovudine DM4KI7O Approved Zidovudine decreases the expression of Zinc transporter ZIP10 (SLC39A10). [15]
Acetic Acid, Glacial DM4SJ5Y Approved Acetic Acid, Glacial affects the expression of Zinc transporter ZIP10 (SLC39A10). [16]
Motexafin gadolinium DMEJKRF Approved Motexafin gadolinium affects the expression of Zinc transporter ZIP10 (SLC39A10). [16]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Zinc transporter ZIP10 (SLC39A10). [17]
GSK2110183 DMZHB37 Phase 2 GSK2110183 decreases the expression of Zinc transporter ZIP10 (SLC39A10). [18]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Zinc transporter ZIP10 (SLC39A10). [2]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Zinc transporter ZIP10 (SLC39A10). [19]
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⏷ Show the Full List of 21 Drug(s)

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 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
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 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
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 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
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 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.
10 Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
11 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
12 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.
13 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
14 Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
15 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.
16 Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
17 LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
18 Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
19 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
20 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.