Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG2EXFP)

• DOT Name: Major facilitator superfamily domain-containing protein 10 (MFSD10)
• Synonyms: Tetracycline transporter-like protein
• Gene Name: MFSD10
• UniProt ID: MFS10_HUMAN
• PDB ID: 6S4M
• Pfam ID: PF07690
• Sequence:
  MGWGGGGGCTPRPPIHQQPPERRVVTVVFLGLLLDLLAFTLLLPLLPGLLESHGRAHDPL
  YGSWQGGVDWFATAIGMPVEKRYNSVLFGGLIGSAFSVLQFLCAPLTGATSDCLGRRPVM
  LLCLMGVATSYAVWATSRSFAAFLASRLIGGISKGNVSLSTAIVADLGSPLARSQGMAVI
  GVAFSLGFTLGPMLGASLPLEMAPWFALLFAASDLLFIFCFLPETLPLEKRAPSIALGFR
  DAADLLSPLALLRFSAVARGQDPPSGDRLSSLRRLGLVYFLYLFLFSGLEYTLSFLTHQR
  FQFSSLQQGKMFFLIGLTMATIQGAYARRIHPGGEVAAVKRALLLLVPAFLLIGWGRSLP
  VLGLGLLLYSFAAAVVVPCLSSVVAGYGSPGQKGTVMGTLRSLGALARAAGPLVAASVYW
  LAGAQACFTTWSGLFLLPFFLLQKLSYPAQTLKAE
• Function: Probable organic anion transporter which may serve as a transporter for some non-steroidal anti-inflammatory drugs (NSAIDs) as well as other organic anions across the luminal membranes of renal proximal tubules at the final excretion step into the urine.
• Tissue Specificity: Expressed in luminal membrane of renal tubules (at protein level) . Detected in all tissues tested with higher expression in heart, splee, kidney, leukocytes and prostate .

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 increases the methylation of Major facilitator superfamily domain-containing protein 10 (MFSD10).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Major facilitator superfamily domain-containing protein 10 (MFSD10).	[9]

10 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 Major facilitator superfamily domain-containing protein 10 (MFSD10).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Major facilitator superfamily domain-containing protein 10 (MFSD10).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Major facilitator superfamily domain-containing protein 10 (MFSD10).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Major facilitator superfamily domain-containing protein 10 (MFSD10).	[5]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Major facilitator superfamily domain-containing protein 10 (MFSD10).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Major facilitator superfamily domain-containing protein 10 (MFSD10).	[7]
Selenium	DM25CGV	Approved	Selenium increases the expression of Major facilitator superfamily domain-containing protein 10 (MFSD10).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Major facilitator superfamily domain-containing protein 10 (MFSD10).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Major facilitator superfamily domain-containing protein 10 (MFSD10).	[6]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Major facilitator superfamily domain-containing protein 10 (MFSD10).	[11]

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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [3] Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity. Blood. 2007 May 15;109(10):4450-60.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] 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.
• [6] Gene alterations of ovarian cancer cells expressing estrogen receptors by estrogen and bisphenol a using microarray analysis. Lab Anim Res. 2011 Jun;27(2):99-107. doi: 10.5625/lar.2011.27.2.99. Epub 2011 Jun 22.
• [7] 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.
• [8] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [9] 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.
• [10] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [11] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.