Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVN5C6W)

• DOT Name: Excitatory amino acid transporter 5 (SLC1A7)
• Synonyms: Retinal glutamate transporter; Solute carrier family 1 member 7
• Gene Name: SLC1A7
• UniProt ID: EAA5_HUMAN
• Pfam ID: PF00375
• Sequence:
  MVPHAILARGRDVCRRNGLLILSVLSVIVGCLLGFFLRTRRLSPQEISYFQFPGELLMRM
  LKMMILPLVVSSLMSGLASLDAKTSSRLGVLTVAYYLWTTFMAVIVGIFMVSIIHPGSAA
  QKETTEQSGKPIMSSADALLDLIRNMFPANLVEATFKQYRTKTTPVVKSPKVAPEEAPPR
  RILIYGVQEENGSHVQNFALDLTPPPEVVYKSEPGTSDGMNVLGIVFFSATMGIMLGRMG
  DSGAPLVSFCQCLNESVMKIVAVAVWYFPFGIVFLIAGKILEMDDPRAVGKKLGFYSVTV
  VCGLVLHGLFILPLLYFFITKKNPIVFIRGILQALLIALATSSSSATLPITFKCLLENNH
  IDRRIARFVLPVGATINMDGTALYEAVAAIFIAQVNNYELDFGQIITISITATAASIGAA
  GIPQAGLVTMVIVLTSVGLPTDDITLIIAVDWALDRFRTMINVLGDALAAGIMAHICRKD
  FARDTGTEKLLPCETKPVSLQEIVAAQQNGCVKSVAEASELTLGPTCPHHVPVQVEQDEE
  LPAASLNHCTIQISELETNV
• Function: Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate. Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion. Acts primarily as an inhibitory glutamate-gated chloride channel being a major inhibitory presynaptic receptor at mammalian rod bipolar cell axon terminals. Glutamate binding gates a large Cl(-) conductance that mediates inhibition, affecting visual processing in the retina.
• Tissue Specificity: Expressed primarily in retina. Detectable in liver, heart, muscle and brain.
• KEGG Pathway:
  Sy.ptic vesicle cycle (hsa04721)
  Glutamatergic sy.pse (hsa04724)
• Reactome Pathway:
  Transport of inorganic cations/anions and amino acids/oligopeptides (R-HSA-425393)
  Glutamate Neurotransmitter Release Cycle (R-HSA-210500)

Molecular Interaction Atlas (MIA) of This DOT

2 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 Excitatory amino acid transporter 5 (SLC1A7).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Excitatory amino acid transporter 5 (SLC1A7).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Excitatory amino acid transporter 5 (SLC1A7).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Excitatory amino acid transporter 5 (SLC1A7).	[2]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Excitatory amino acid transporter 5 (SLC1A7).	[3]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Excitatory amino acid transporter 5 (SLC1A7).	[4]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Excitatory amino acid transporter 5 (SLC1A7).	[2]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Excitatory amino acid transporter 5 (SLC1A7).	[2]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Excitatory amino acid transporter 5 (SLC1A7).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Excitatory amino acid transporter 5 (SLC1A7).	[7]

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] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [3] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [4] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [5] 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.
• [6] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [7] Involvement of the Endocrine-Disrupting Chemical Bisphenol A (BPA) in Human Placentation. J Clin Med. 2020 Feb 3;9(2):405. doi: 10.3390/jcm9020405.