Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWQBZ5Q)

• DOT Name: Sodium/glucose cotransporter 4 (SLC5A9)
• Synonyms: Na(+)/glucose cotransporter 4; hSGLT4; Solute carrier family 5 member 9
• Gene Name: SLC5A9
• UniProt ID: SC5A9_HUMAN
• Pfam ID: PF00474
• Sequence:
  MSKELAAMGPGASGDGVRTETAPHIALDSRVGLHAYDISVVVIYFVFVIAVGIWSSIRAS
  RGTIGGYFLAGRSMSWWPIGASLMSSNVGSGLFIGLAGTGAAGGLAVGGFEWNATWLLLA
  LGWVFVPVYIAAGVVTMPQYLKKRFGGQRIQVYMSVLSLILYIFTKISTDIFSGALFIQM
  ALGWNLYLSTGILLVVTAVYTIAGGLMAVIYTDALQTVIMVGGALVLMFLGFQDVGWYPG
  LEQRYRQAIPNVTVPNTTCHLPRPDAFHILRDPVSGDIPWPGLIFGLTVLATWCWCTDQV
  IVQRSLSAKSLSHAKGGSVLGGYLKILPMFFIVMPGMISRALFPDEVGCVDPDVCQRICG
  ARVGCSNIAYPKLVMALMPVGLRGLMIAVIMAALMSSLTSIFNSSSTLFTIDVWQRFRRK
  STEQELMVVGRVFVVFLVVISILWIPIIQSSNSGQLFDYIQAVTSYLAPPITALFLLAIF
  CKRVTEPGAFWGLVFGLGVGLLRMILEFSYPAPACGEVDRRPAVLKDFHYLYFAILLCGL
  TAIVIVIVSLCTTPIPEEQLTRLTWWTRNCPLSELEKEAHESTPEISERPAGECPAGGGA
  AENSSLGQEQPEAPSRSWGKLLWSWFCGLSGTPEQALSPAEKAALEQKLTSIEEEPLWRH
  VCNINAVLLLAINIFLWGYFA
• Function: Electrogenic Na(+)-coupled sugar symporter that may play a primary role in D-mannose and possibly D-fructose and D-glucose transport at the plasma membrane. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump. Exclusively recognizes sugar substrates having a pyranose ring with an axial hydroxyl group on carbon 2.
• Tissue Specificity: Expressed in the small intestine, kidney and liver.
• Reactome Pathway: Cellular hexose transport (R-HSA-189200)

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 Sodium/glucose cotransporter 4 (SLC5A9).	[1]

8 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 Sodium/glucose cotransporter 4 (SLC5A9).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Sodium/glucose cotransporter 4 (SLC5A9).	[3]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Sodium/glucose cotransporter 4 (SLC5A9).	[4]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Sodium/glucose cotransporter 4 (SLC5A9).	[5]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Sodium/glucose cotransporter 4 (SLC5A9).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Sodium/glucose cotransporter 4 (SLC5A9).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Sodium/glucose cotransporter 4 (SLC5A9).	[8]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Sodium/glucose cotransporter 4 (SLC5A9).	[9]

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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [6] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [7] 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.
• [8] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [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.