Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8EB4TF)

• DOT Name: Solute carrier family 41 member 2 (SLC41A2)
• Gene Name: SLC41A2
• UniProt ID: S41A2_HUMAN
• Pfam ID: PF01769
• Sequence:
  MTNSKGRSITDKTSGGPSSGGGFVDWTLRLNTIQSDKFLNLLLSMVPVIYQKNQEDRHKK
  ANGIWQDGLSTAVQTFSNRSEQHMEYHSFSEQSFHANNGHASSSCSQKYDDYANYNYCDG
  RETSETTAMLQDEDISSDGDEDAIVEVTPKLPKESSGIMALQILVPFLLAGFGTVSAGMV
  LDIVQHWEVFRKVTEVFILVPALLGLKGNLEMTLASRLSTAVNIGKMDSPIEKWNLIIGN
  LALKQVQATVVGFLAAVAAIILGWIPEGKYYLDHSILLCSSSVATAFIASLLQGIIMVGV
  IVGSKKTGINPDNVATPIAASFGDLITLAILAWISQGLYSCLETYYYISPLVGVFFLALT
  PIWIIIAAKHPATRTVLHSGWEPVITAMVISSIGGLILDTTVSDPNLVGIVVYTPVINGI
  GGNLVAIQASRISTYLHLHSIPGELPDEPKGCYYPFRTFFGPGVNNKSAQVLLLLVIPGH
  LIFLYTIHLMKSGHTSLTIIFIVVYLFGAVLQVFTLLWIADWMVHHFWRKGKDPDSFSIP
  YLTALGDLLGTALLALSFHFLWLIGDRDGDVGD
• Function: Acts as a plasma-membrane magnesium transporter. Can also mediate the transport of other divalent metal cations in an order of Ba(2+) > Ni(2+) > Co(2+) > Fe(2+) > Mn(2+).
• Reactome Pathway: Metal ion SLC transporters (R-HSA-425410)

Molecular Interaction Atlas (MIA) 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 Solute carrier family 41 member 2 (SLC41A2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Solute carrier family 41 member 2 (SLC41A2).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Solute carrier family 41 member 2 (SLC41A2).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Solute carrier family 41 member 2 (SLC41A2).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Solute carrier family 41 member 2 (SLC41A2).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Solute carrier family 41 member 2 (SLC41A2).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Solute carrier family 41 member 2 (SLC41A2).	[6]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Solute carrier family 41 member 2 (SLC41A2).	[7]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Solute carrier family 41 member 2 (SLC41A2).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Solute carrier family 41 member 2 (SLC41A2).	[8]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Solute carrier family 41 member 2 (SLC41A2).	[9]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Solute carrier family 41 member 2 (SLC41A2).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Solute carrier family 41 member 2 (SLC41A2).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Solute carrier family 41 member 2 (SLC41A2).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Solute carrier family 41 member 2 (SLC41A2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Solute carrier family 41 member 2 (SLC41A2).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Solute carrier family 41 member 2 (SLC41A2).	[16]

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] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [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] 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.
• [7] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [8] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [9] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [12] 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.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] 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.
• [15] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.