Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFOOYB9)

• DOT Name: Probable small intestine urate exporter (SLC17A4)
• Synonyms: Solute carrier family 17 member 4
• Gene Name: SLC17A4
• UniProt ID: S17A4_HUMAN
• Pfam ID: PF07690
• Sequence:
  MSTGPDVKATVGDISSDGNLNVAQEECSRKGFCSVRHGLALILQLCNFSIYTQQMNLSIA
  IPAMVNNTAPPSQPNASTERPSTDSQGYWNETLKEFKAMAPAYDWSPEIQGIILSSLNYG
  SFLAPIPSGYVAGIFGAKYVVGAGLFISSFLTLFIPLAANAGVALLIVLRIVQGIAQVMV
  LTGQYSIWVKWAPPLERSQLTTIAGSGSMLGSFIVLLAGGLLCQTIGWPYVFYIFGGIGC
  ACCPLWFPLIYDDPVNHPFISAGEKRYIVCSLAQQDCSPGWSLPIRAMIKSLPLWAILVS
  YFCEYWLFYTIMAYTPTYISSVLQANLRDSGILSALPFVVGCICIILGGLLADFLLSRKI
  LRLITIRKLFTAIGVLFPSVILVSLPWVRSSHSMTMTFLVLSSAISSFCESGALVNFLDI
  APRYTGFLKGLLQVFAHIAGAISPTAAGFFISQDSEFGWRNVFLLSAAVNISGLVFYLIF
  GRADVQDWAKEQTFTHL
• Function: Acts as a membrane potential-dependent organic anion transporter, the transport requires a low concentration of chloride ions. Mediates chloride-dependent transport of urate. Mediates sodium-independent high affinity transport of thyroid hormones including L-thyroxine (T4) and 3,3',5-triiodo-L-thyronine (T3). Can actively transport inorganic phosphate into cells via Na(+) cotransport.
• Tissue Specificity: Abundantly expressed in pancreas, liver, colon and small intestine, less in kidney. Not detected in the adrenal glands, brain, placenta, heart, testis, skeletal muscle, and lungs.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Probable small intestine urate exporter (SLC17A4).	[1]

6 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 Probable small intestine urate exporter (SLC17A4).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Probable small intestine urate exporter (SLC17A4).	[3]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Probable small intestine urate exporter (SLC17A4).	[2]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Probable small intestine urate exporter (SLC17A4).	[4]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Probable small intestine urate exporter (SLC17A4).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Probable small intestine urate exporter (SLC17A4).	[6]

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] 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.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [5] Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
• [6] 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.