Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1MJ5BD)

• DOT Name: Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 (SLC6A16)
• Synonyms: Solute carrier family 6 member 16
• Gene Name: SLC6A16
• Related Disease: Vibrio cholerae infection
• UniProt ID: S6A16_HUMAN
• Pfam ID: PF00209
• Sequence:
  MKTEAQPSTSLLANTSWTGTVISDSVPGSQTWEDKGSLTRSATSWTSEAQVSAARVAEAQ
  ARTSQPKQISVLEALTASALNQKPTHEKVQMTEKKESEVLLARPFWSSKTEYILAQVGFS
  MKPSCLWRFAYLWLNSGGCSFAAIYIFMLFLVGVPLLFLEMAAGQSMRQGGMGVWKIIAP
  WIGGVGYSSFMVCFILGLYFNVVNSWIIFYMSQSFQFPVPWEKCPLTMNSSGFDPECERT
  TPSIYFWYQQALKASDRIEDGGSPVYSLVLPFFLCWCLVGAFMINGLKSTGKVIYVLVLL
  PCFIIVGFFIRTLLLEGAKFGLQQLVVAKISDVYNMSVWSLAGGQVLSNTGIGLGSVASL
  ASYMPQSNNCLSDAFLVSVINLLTLLVFTSFNFCVLGFWATVITHRCCERNAEILLKLIN
  LGKLPPDAKPPVNLLYNPTSIYNAWLSGLPQHIKSMVLREVTECNIETQFLKASEGPKFA
  FLSFVEAMSFLPPSVFWSFIFFLMLLAMGLSSAIGIMQGIITPLQDTFSFFRKHTKLLIV
  GVFLLMFVCGLFFTRPSGSYFIRLLSDYWIVFPIIVVVVFETMAVSWAYGARRFLADLTI
  LLGHPISPIFGWLWPHLCPVVLLIIFVTMMVHLCMKPITYMSWDSSTSKEVLRPYPPWAL
  LLMITLFAIVILPIPAYFVYCRIHRIPFRPKSGDGPMTASTSLPLSHQLTPSKEVQKEEI
  LQVDETKYPSTCNVTS
• Tissue Specificity: Highly expressed in peripheral tissues, particularly in testis, pancreas, and prostate.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Vibrio cholerae infection	DISW7E3U	Strong	Biomarker	[1]

1 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 Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 (SLC6A16).	[2]

7 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 Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 (SLC6A16).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 (SLC6A16).	[4]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 (SLC6A16).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the expression of Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 (SLC6A16).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 (SLC6A16).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 (SLC6A16).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Orphan sodium- and chloride-dependent neurotransmitter transporter NTT5 (SLC6A16).	[9]

References

• [1] Nontoxigenic Vibrio cholerae 01 serotype Inaba biotype El Tor associated with a cluster of cases of cholera in southern India.J Clin Microbiol. 1996 May;34(5):1114-7. doi: 10.1128/jcm.34.5.1114-1117.1996.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [6] Transcriptional profiling of genes induced in the livers of patients treated with carbamazepine. Clin Pharmacol Ther. 2006 Nov;80(5):440-456.
• [7] 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.
• [8] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [9] 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.