Details of Drug Off-Target (DOT)

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

• DOT Name: Inactive sodium-dependent neutral amino acid transporter B(0)AT3 (SLC6A18)
• Synonyms: Sodium- and chloride-dependent transporter XTRP2; Solute carrier family 6 member 18; System B(0) neutral amino acid transporter AT3
• Gene Name: SLC6A18
• UniProt ID: S6A18_HUMAN
• Pfam ID: PF00209
• Sequence:
  MAHAPEPDPAACDLGDERPKWDNKAQYLLSCTGFAVGLGNIWRFPYLCQTYGGGAFLIPY
  VIALVFEGIPIFHVELAIGQRLRKGSVGVWTAISPYLSGVGLGCVTLSFLISLYYNTIVA
  WVLWYLLNSFQHPLPWSSCPPDLNRTGFVEECQGSSAVSYFWYRQTLNITADINDSGSIQ
  WWLLICLAASWAVVYMCVIRGIETTGKVIYFTALFPYLVLTIFLIRGLTLPGATKGLIYL
  FTPNMHILQNPRVWLDAATQIFFSLSLAFGGHIAFASYNSPRNDCQKDAVVIALVNRMTS
  LYASIAVFSVLGFKATNDYEHCLDRNILSLINDFDFPEQSISRDDYPAVLMHLNATWPKR
  VAQLPLKACLLEDFLDKSASGPGLAFVVFTETDLHMPGAPVWAMLFFGMLFTLGLSTMFG
  TVEAVITPLLDVGVLPRWVPKEALTGLVCLVCFLSATCFTLQSGNYWLEIFDNFAASPNL
  LMLAFLEVVGVVYVYGMKRFCDDIAWMTGRRPSPYWRLTWRVVSPLLLTIFVAYIILLFW
  KPLRYKAWNPKYELFPSRQEKLYPGWARAACVLLSLLPVLWVPVAALAQLLTRRRRTWRD
  RDARPDTDMRPDTDTRPDTDMRPDTDMR
• Function: Does not show neutral amino acid transporter activity.
• Tissue Specificity: Abundantly expressed in kidney, but not in intestine.
• Reactome Pathway:
  Na+/Cl- dependent neurotransmitter transporters (R-HSA-442660)
  Defective SLC6A18 may confer susceptibility to iminoglycinuria and/or hyperglycinuria (R-HSA-5619079)
  Defective SLC6A18 may confer susceptibility to iminoglycinuria and/or hyperglycinuria (R-HSA-5659729)
  Amino acid transport across the plasma membrane (R-HSA-352230)

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
3-iodothyronamine	DM3L0F8	Investigative	Inactive sodium-dependent neutral amino acid transporter B(0)AT3 (SLC6A18) affects the uptake of 3-iodothyronamine.	[4]

3 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 Inactive sodium-dependent neutral amino acid transporter B(0)AT3 (SLC6A18).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Inactive sodium-dependent neutral amino acid transporter B(0)AT3 (SLC6A18).	[2]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Inactive sodium-dependent neutral amino acid transporter B(0)AT3 (SLC6A18).	[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] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [3] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [4] Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.