Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9ZAY6U)

• DOT Name: Sodium-coupled neutral amino acid transporter 7 (SLC38A7)
• Synonyms: Solute carrier family 38 member 7
• Gene Name: SLC38A7
• UniProt ID: S38A7_HUMAN
• Pfam ID: PF01490
• Sequence:
  MAQVSINNDYSEWDLSTDAGERARLLQSPCVDTAPKSEWEASPGGLDRGTTSTLGAIFIV
  VNACLGAGLLNFPAAFSTAGGVAAGIALQMGMLVFIISGLVILAYCSQASNERTYQEVVW
  AVCGKLTGVLCEVAIAVYTFGTCIAFLIIIGDQQDKIIAVMAKEPEGASGPWYTDRKFTI
  SLTAFLFILPLSIPREIGFQKYASFLSVVGTWYVTAIVIIKYIWPDKEMTPGNILTRPAS
  WMAVFNAMPTICFGFQCHVSSVPVFNSMQQPEVKTWGGVVTAAMVIALAVYMGTGICGFL
  TFGAAVDPDVLLSYPSEDMAVAVARAFIILSVLTSYPILHFCGRAVVEGLWLRYQGVPVE
  EDVGRERRRRVLQTLVWFLLTLLLALFIPDIGKVISVIGGLAACFIFVFPGLCLIQAKLS
  EMEEVKPASWWVLVSYGVLLVTLGAFIFGQTTANAIFVDLLA
• Function: Symporter that selectively cotransports sodium ions and amino acids, such as L-glutamine and L-asparagine from the lysosome into the cytoplasm and may participates in mTORC1 activation. The transport activity requires an acidic lysosomal lumen.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Sodium-coupled neutral amino acid transporter 7 (SLC38A7) affects the response to substance of Acetaminophen.	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Sodium-coupled neutral amino acid transporter 7 (SLC38A7).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Sodium-coupled neutral amino acid transporter 7 (SLC38A7).	[2]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sodium-coupled neutral amino acid transporter 7 (SLC38A7).	[3]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Sodium-coupled neutral amino acid transporter 7 (SLC38A7).	[5]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Sodium-coupled neutral amino acid transporter 7 (SLC38A7).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Sodium-coupled neutral amino acid transporter 7 (SLC38A7).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Sodium-coupled neutral amino acid transporter 7 (SLC38A7).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Sodium-coupled neutral amino acid transporter 7 (SLC38A7).	[7]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [4] 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.
• [5] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [6] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [7] 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.
• [8] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
• [9] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.