Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN1S03Q)

• DOT Name: Asc-type amino acid transporter 1 (SLC7A10)
• Synonyms: Asc-1; Solute carrier family 7 member 10
• Gene Name: SLC7A10
• UniProt ID: AAA1_HUMAN
• Pfam ID: PF13520
• Sequence:
  MAGHTQQPSGRGNPRPAPSPSPVPGTVPGASERVALKKEIGLLSACTIIIGNIIGSGIFI
  SPKGVLEHSGSVGLALFVWVLGGGVTALGSLCYAELGVAIPKSGGDYAYVTEIFGGLAGF
  LLLWSAVLIMYPTSLAVISMTFSNYVLQPVFPNCIPPTTASRVLSMACLMLLTWVNSSSV
  RWATRIQDMFTGGKLLALSLIIGVGLLQIFQGHFEELRPSNAFAFWMTPSVGHLALAFLQ
  GSFAFSGWNFLNYVTEEMVDARKNLPRAIFISIPLVTFVYTFTNIAYFTAMSPQELLSSN
  AVAVTFGEKLLGYFSWVMPVSVALSTFGGINGYLFTYSRLCFSGAREGHLPSLLAMIHVR
  HCTPIPALLVCCGATAVIMLVGDTYTLINYVSFINYLCYGVTILGLLLLRWRRPALHRPI
  KVNLLIPVAYLVFWAFLLVFSFISEPMVCGVGVIIILTGVPIFFLGVFWRSKPKCVHRLT
  ESMTHWGQELCFVVYPQDAPEEEENGPCPPSLLPATDKPSKPQ
• Function: Associates with SLC3A2/4F2hc to form a functional heterodimeric complex that translocates small neutral L- and D-amino acids across the plasma membrane. Preferentially mediates exchange transport, but can also operate via facilitated diffusion. Acts as a major transporter for glycine, L- and D-serine in the central nervous system. At the spinal cord and brainstem regulates glycine metabolism and glycinergic inhibitory neurotransmission by providing for glycine de novo synthesis from L-serine and glycine recycling from astrocytes to glycinergic motor neurons. At Schaffer collateral-CA1 synapses mediates D-serine and glycine release that modulates post-synaptic activation of NMDA receptors and excitatory glutamatergic transmission. May regulate D-serine release from mesenchymal progenitors located in developing subcutaneous adipose tissue, favoring white adipocyte over thermogenic beige adipocyte lineage commitment.
• Tissue Specificity: Expressed in brain, heart, kidney, liver, lung, pancreas, placenta, and skeletal muscle.
• Reactome Pathway:
  Amino acid transport across the plasma membrane (R-HSA-352230)
  Basigin interactions (R-HSA-210991)

Molecular Interaction Atlas (MIA) of This DOT

10 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 Asc-type amino acid transporter 1 (SLC7A10).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Asc-type amino acid transporter 1 (SLC7A10).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Asc-type amino acid transporter 1 (SLC7A10).	[3]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Asc-type amino acid transporter 1 (SLC7A10).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Asc-type amino acid transporter 1 (SLC7A10).	[3]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Asc-type amino acid transporter 1 (SLC7A10).	[5]
Zidovudine	DM4KI7O	Approved	Zidovudine decreases the expression of Asc-type amino acid transporter 1 (SLC7A10).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Asc-type amino acid transporter 1 (SLC7A10).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Asc-type amino acid transporter 1 (SLC7A10).	[8]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Asc-type amino acid transporter 1 (SLC7A10).	[9]

1 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 increases the methylation of Asc-type amino acid transporter 1 (SLC7A10).	[7]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [6] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [7] 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.
• [8] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [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.