Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT11T33C)

• DOT Name: Choline transporter-like protein 2 (SLC44A2)
• Synonyms: Solute carrier family 44 member 2
• Gene Name: SLC44A2
• UniProt ID: CTL2_HUMAN
• Pfam ID: PF04515
• Sequence:
  MGDERPHYYGKHGTPQKYDPTFKGPIYNRGCTDIICCVFLLLAIVGYVAVGIIAWTHGDP
  RKVIYPTDSRGEFCGQKGTKNENKPYLFYFNIVKCASPLVLLEFQCPTPQICVEKCPDRY
  LTYLNARSSRDFEYYKQFCVPGFKNNKGVAEVLQDGDCPAVLIPSKPLARRCFPAIHAYK
  GVLMVGNETTYEDGHGSRKNITDLVEGAKKANGVLEARQLAMRIFEDYTVSWYWIIIGLV
  IAMAMSLLFIILLRFLAGIMVWVMIIMVILVLGYGIFHCYMEYSRLRGEAGSDVSLVDLG
  FQTDFRVYLHLRQTWLAFMIILSILEVIIILLLIFLRKRILIAIALIKEASRAVGYVMCS
  LLYPLVTFFLLCLCIAYWASTAVFLSTSNEAVYKIFDDSPCPFTAKTCNPETFPSSNESR
  QCPNARCQFAFYGGESGYHRALLGLQIFNAFMFFWLANFVLALGQVTLAGAFASYYWALR
  KPDDLPAFPLFSAFGRALRYHTGSLAFGALILAIVQIIRVILEYLDQRLKAAENKFAKCL
  MTCLKCCFWCLEKFIKFLNRNAYIMIAIYGTNFCTSARNAFFLLMRNIIRVAVLDKVTDF
  LFLLGKLLIVGSVGILAFFFFTHRIRIVQDTAPPLNYYWVPILTVIVGSYLIAHGFFSVY
  GMCVDTLFLCFLEDLERNDGSAERPYFMSSTLKKLLNKTNKKAAES
• Function: [Isoform 1]: Choline/H+ antiporter, mainly in mitochodria. Also acts as a low-affinity ethanolamine/H+ antiporter, regulating the supply of extracellular ethanolamine (Etn) for the CDP-Etn pathway, redistribute intracellular Etn and balance the CDP-Cho and CDP-Etn arms of the Kennedy pathway ; [Isoform 3]: Does not exhibit choline transporter activity.
• Tissue Specificity: Present in supporting cells of the inner ear (at protein level).; [Isoform 3]: Expressed in inner ear vestibular tissue.
• KEGG Pathway: Choline metabolism in cancer (hsa05231)
• Reactome Pathway:
  Transport of bile salts and organic acids, metal ions and amine compounds (R-HSA-425366)
  Neutrophil degranulation (R-HSA-6798695)
  Synthesis of PC (R-HSA-1483191)

Molecular Interaction Atlas (MIA) of This DOT

11 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 2 (SLC44A2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Choline transporter-like protein 2 (SLC44A2).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Choline transporter-like protein 2 (SLC44A2).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Choline transporter-like protein 2 (SLC44A2).	[4]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Choline transporter-like protein 2 (SLC44A2).	[6]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Choline transporter-like protein 2 (SLC44A2).	[7]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Choline transporter-like protein 2 (SLC44A2).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Choline transporter-like protein 2 (SLC44A2).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Choline transporter-like protein 2 (SLC44A2).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Choline transporter-like protein 2 (SLC44A2).	[12]
Resorcinol	DMM37C0	Investigative	Resorcinol decreases the expression of Choline transporter-like protein 2 (SLC44A2).	[13]

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 Choline transporter-like protein 2 (SLC44A2).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Choline transporter-like protein 2 (SLC44A2).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Evidence for a role of claudin 2 as a proximal tubular stress responsive paracellular water channel. Toxicol Appl Pharmacol. 2014 Sep 1;279(2):163-72.
• [3] 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.
• [4] Extremely low copper concentrations affect gene expression profiles of human prostate epithelial cell lines. Chem Biol Interact. 2010 Oct 6;188(1):214-9.
• [5] 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.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [13] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.