Details of Drug Off-Target (DOT)

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

• DOT Name: Sodium/myo-inositol cotransporter 2 (SLC5A11)
• Synonyms: Na(+)/myo-inositol cotransporter 2; Sodium-dependent glucose cotransporter; Sodium/glucose cotransporter KST1; Sodium/myo-inositol transporter 2; SMIT2; Solute carrier family 5 member 11
• Gene Name: SLC5A11
• UniProt ID: SC5AB_HUMAN
• Pfam ID: PF00474
• Sequence:
  MESGTSSPQPPQLDPLDAFPQKGLEPGDIAVLVLYFLFVLAVGLWSTVKTKRDTVKGYFL
  AGGDMVWWPVGASLFASNVGSGHFIGLAGSGAATGISVSAYELNGLFSVLMLAWIFLPIY
  IAGQVTTMPEYLRKRFGGIRIPIILAVLYLFIYIFTKISVDMYAGAIFIQQSLHLDLYLA
  IVGLLAITAVYTVAGGLAAVIYTDALQTLIMLIGALTLMGYSFAAVGGMEGLKEKYFLAL
  ASNRSENSSCGLPREDAFHIFRDPLTSDLPWPGVLFGMSIPSLWYWCTDQVIVQRTLAAK
  NLSHAKGGALMAAYLKVLPLFIMVFPGMVSRILFPDQVACADPEICQKICSNPSGCSDIA
  YPKLVLELLPTGLRGLMMAVMVAALMSSLTSIFNSASTIFTMDLWNHLRPRASEKELMIV
  GRVFVLLLVLVSILWIPVVQASQGGQLFIYIQSISSYLQPPVAVVFIMGCFWKRTNEKGA
  FWGLISGLLLGLVRLVLDFIYVQPRCDQPDERPVLVKSIHYLYFSMILSTVTLITVSTVS
  WFTEPPSKEMVSHLTWFTRHDPVVQKEQAPPAAPLSLTLSQNGMPEASSSSSVQFEMVQE
  NTSKTHSCDMTPKQSKVVKAILWLCGIQEKGKEELPARAEAIIVSLEENPLVKTLLDVNL
  IFCVSCAIFIWGYFA
• Function: Involved in the sodium-dependent cotransport of myo-inositol (MI) with a Na(+):MI stoichiometry of 2:1. Exclusively responsible for apical MI transport and absorption in intestine. Can also transport D-chiro-inositol (DCI) but not L-fucose. Exhibits stereospecific cotransport of both D-glucose and D-xylose. May induce apoptosis through the TNF-alpha, PDCD1 pathway. May play a role in the regulation of MI concentration in serum, involving reabsorption in at least the proximal tubule of the kidney.
• Tissue Specificity: Highest expression in heart, skeletal muscle, kidney, liver and placenta. Weaker expression in brain, colon, spleen, lung and peripheral blood leukocytes.
• Reactome Pathway: Inositol transporters (R-HSA-429593)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Sodium/myo-inositol cotransporter 2 (SLC5A11).	[1]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Sodium/myo-inositol cotransporter 2 (SLC5A11).	[2]
Phenobarbital	DMXZOCG	Approved	Phenobarbital increases the expression of Sodium/myo-inositol cotransporter 2 (SLC5A11).	[3]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Sodium/myo-inositol cotransporter 2 (SLC5A11).	[4]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Sodium/myo-inositol cotransporter 2 (SLC5A11).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Sodium/myo-inositol cotransporter 2 (SLC5A11).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Sodium/myo-inositol cotransporter 2 (SLC5A11).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Sodium/myo-inositol cotransporter 2 (SLC5A11).	[8]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Sodium/myo-inositol cotransporter 2 (SLC5A11).	[9]

References

• [1] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [2] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [3] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [4] Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
• [5] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [6] 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.
• [7] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [8] Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals. Toxicology. 2013 Jan 7;303:17-24.
• [9] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.