Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM49E8O)

• DOT Name: Solute carrier family 13 member 2 (SLC13A2)
• Synonyms: Na(+)/dicarboxylate cotransporter 1; NaDC-1; Renal sodium/dicarboxylate cotransporter
• Gene Name: SLC13A2
• UniProt ID: S13A2_HUMAN
• Pfam ID: PF00939
• Sequence:
  MATCWQALWAYRSYLIVFFVPILLLPLPILVPSKEAYCAYAIILMALFWCTEALPLAVTA
  LFPLILFPMMGIVDASEVAVEYLKDSNLLFFGGLLVAIAVEHWNLHKRIALRVLLIVGVR
  PAPLILGFMLVTAFLSMWISNTATSAMMVPIAHAVLDQLHSSQASSNVEEGSNNPTFELQ
  EPSPQKEVTKLDNGQALPVTSASSEGRAHLSQKHLHLTQCMSLCVCYSASIGGIATLTGT
  APNLVLQGQINSLFPQNGNVVNFASWFSFAFPTMVILLLLAWLWLQILFLGFNFRKNFGI
  GEKMQEQQQAAYCVIQTEHRLLGPMTFAEKAISILFVILVLLWFTREPGFFLGWGNLAFP
  NAKGESMVSDGTVAIFIGIIMFIIPSKFPGLTQDPENPGKLKAPLGLLDWKTVNQKMPWN
  IVLLLGGGYALAKGSERSGLSEWLGNKLTPLQSVPAPAIAIILSLLVATFTECTSNVATT
  TIFLPILASMAQAICLHPLYVMLPCTLATSLAFMLPVATPPNAIVFSFGDLKVLDMARAG
  FLLNIIGVLIIALAINSWGIPLFSLHSFPSWAQSNTTAQCLPSLANTTTPSP
• Function: Low-affinity sodium-dicarboxylate cotransporter, that mediates the entry of citric acid cycle intermediates, such as succinate, citrate, fumarate and alpha-ketoglutarate (2-oxoglutarate) into the small intestine and renal proximal tubule. Transports the dicarboxylate into the cell with a probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate, rendering the process electrogenic. Citrate is transported in protonated form as a divalent anion, rather than the trivalent form which is normally found in blood. Has a critical role in renal dicarboxylate transport.
• Tissue Specificity: Expressed in kidney and intestine . In kidney expressed in the proximal tubule (at protein level) .
• Reactome Pathway: Sodium-coupled sulphate, di- and tri-carboxylate transporters (R-HSA-433137)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Citrate	DM37NYK	Preclinical	Solute carrier family 13 member 2 (SLC13A2) increases the uptake of Citrate.	[4]

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 Solute carrier family 13 member 2 (SLC13A2).	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Solute carrier family 13 member 2 (SLC13A2).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Solute carrier family 13 member 2 (SLC13A2).	[3]

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] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [3] 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.
• [4] Human sodium-coupled citrate transporter, the orthologue of Drosophila Indy, as a novel target for lithium action. Biochem J. 2003 Aug 15;374(Pt 1):21-6.