Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMS4CVY)

• DOT Name: Choline transporter-like protein 5 (SLC44A5)
• Synonyms: Solute carrier family 44 member 5
• Gene Name: SLC44A5
• UniProt ID: CTL5_HUMAN
• Pfam ID: PF04515
• Sequence:
  MNDTEKPADTPSEEEDFGDPRTYDPDFKGPVANRSCTDVLCCMIFLLCIIGYIVLGLVAW
  VHGDPRRAAYPTDSQGHFCGQKGTPNENKTILFYFNLLRCTSPSVLLNLQCPTTQICVSK
  CPEKFLTYVEMQLLYTKDKSYWEDYRQFCKTTAKPVKSLTQLLLDDDCPTAIFPSKPFLQ
  RCFPDFSTKNGTLTIGSKMMFQDGNGGTRSVVELGIAANGINKLLDAKSLGLKVFEDYAR
  TWYWILIGLTIAMVLSWIFLILLRFIAGCLFWVFMIGVIGIIGYGIWHCYQQYTNLQERP
  SSVLTIYDIGIQTNISMYFELQQTWFTFMIILCIIEVIVILMLIFLRNRIRVAIILLKEG
  SKAIGYVPSTLVYPALTFILLSICICYWVVTAVFLATSGVPVYKVIAPGGHCIHENQTCD
  PEIFNTTEIAKACPGALCNFAFYGGKSLYHQYIPTFHVYNLFVFLWLINFVIALGQCALA
  GAFATYYWAMKKPDDIPRYPLFTAFGRAIRYHTGSLAFGSLIIALIQMFKIVLEYLDHRL
  KRTQNTLSKFLQCCLRCCFWCLENAIKFLNRNAYIMIAIYGRNFCRSAKDAFNLLMRNVL
  KVAVTDEVTYFVLFLGKLLVAGSIGVLAFLFFTQRLPVIAQGPASLNYYWVPLLTVIFGS
  YLIAHGFFSVYAMCVETIFICFCEDLERNDGSTEKPYFVTPNLHGILIKKQLVPQKQKE
• Function: Choline/H+ antiporter.
• KEGG Pathway: Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  Transport of bile salts and organic acids, metal ions and amine compounds (R-HSA-425366)
  Synthesis of PC (R-HSA-1483191)

Molecular Interaction Atlas (MIA) of This DOT

17 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 Choline transporter-like protein 5 (SLC44A5).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Choline transporter-like protein 5 (SLC44A5).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Choline transporter-like protein 5 (SLC44A5).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Choline transporter-like protein 5 (SLC44A5).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Choline transporter-like protein 5 (SLC44A5).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Choline transporter-like protein 5 (SLC44A5).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Choline transporter-like protein 5 (SLC44A5).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Choline transporter-like protein 5 (SLC44A5).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Choline transporter-like protein 5 (SLC44A5).	[9]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of Choline transporter-like protein 5 (SLC44A5).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Choline transporter-like protein 5 (SLC44A5).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Choline transporter-like protein 5 (SLC44A5).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Choline transporter-like protein 5 (SLC44A5).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Choline transporter-like protein 5 (SLC44A5).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Choline transporter-like protein 5 (SLC44A5).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Choline transporter-like protein 5 (SLC44A5).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Choline transporter-like protein 5 (SLC44A5).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Choline transporter-like protein 5 (SLC44A5).	[15]

References

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• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [5] Identification of novel biomarkers for doxorubicin-induced toxicity in human cardiomyocytes derived from pluripotent stem cells. Toxicology. 2015 Feb 3;328:102-11. doi: 10.1016/j.tox.2014.12.018. Epub 2014 Dec 18.
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• [8] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [13] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [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] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [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.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.