Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTO19X5C)

• DOT Name: Glutamate receptor ionotropic, kainate 1 (GRIK1)
• Synonyms: GluK1; Excitatory amino acid receptor 3; EAA3; Glutamate receptor 5; GluR-5; GluR5
• Gene Name: GRIK1
• UniProt ID: GRIK1_HUMAN
• PDB ID: 2ZNS; 2ZNT; 2ZNU; 3FUZ; 3FV1; 3FV2; 3FVG; 3FVK; 3FVN; 3FVO; 4MF3
• Pfam ID: PF01094 ; PF00060 ; PF10613
• Sequence:
  MEHGTLLAQPGLWTRDTSWALLYFLCYILPQTAPQVLRIGGIFETVENEPVNVEELAFKF
  AVTSINRNRTLMPNTTLTYDIQRINLFDSFEASRRACDQLALGVAALFGPSHSSSVSAVQ
  SICNALEVPHIQTRWKHPSVDNKDLFYINLYPDYAAISRAILDLVLYYNWKTVTVVYEDS
  TGLIRLQELIKAPSRYNIKIKIRQLPSGNKDAKPLLKEMKKGKEFYVIFDCSHETAAEIL
  KQILFMGMMTEYYHYFFTTLDLFALDLELYRYSGVNMTGFRLLNIDNPHVSSIIEKWSME
  RLQAPPRPETGLLDGMMTTEAALMYDAVYMVAIASHRASQLTVSSLQCHRHKPWRLGPRF
  MNLIKEARWDGLTGHITFNKTNGLRKDFDLDIISLKEEGTEKAAGEVSKHLYKVWKKIGI
  WNSNSGLNMTDSNKDKSSNITDSLANRTLIVTTILEEPYVMYRKSDKPLYGNDRFEGYCL
  DLLKELSNILGFIYDVKLVPDGKYGAQNDKGEWNGMVKELIDHRADLAVAPLTITYVREK
  VIDFSKPFMTLGISILYRKPNGTNPGVFSFLNPLSPDIWMYVLLACLGVSCVLFVIARFT
  PYEWYNPHPCNPDSDVVENNFTLLNSFWFGVGALMQQGSELMPKALSTRIVGGIWWFFTL
  IIISSYTANLAAFLTVERMESPIDSADDLAKQTKIEYGAVRDGSTMTFFKKSKISTYEKM
  WAFMSSRQQTALVRNSDEGIQRVLTTDYALLMESTSIEYVTQRNCNLTQIGGLIDSKGYG
  VGTPIGSPYRDKITIAILQLQEEGKLHMMKEKWWRGNGCPEEDNKEASALGVENIGGIFI
  VLAAGLVLSVFVAIGEFIYKSRKNNDIEQAFCFFYGLQCKQTHPTNSTSGTTLSTDLECG
  KLIREERGIRKQSSVHTV
• Function: Ionotropic glutamate receptor. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. May be involved in the transmission of light information from the retina to the hypothalamus.
• Tissue Specificity: Most abundant in the cerebellum and the suprachiasmatic nuclei (SCN) of the hypothalamus.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Glutamatergic sy.pse (hsa04724)
• Reactome Pathway:
  Activation of Ca-permeable Kainate Receptor (R-HSA-451308)
  Activation of Na-permeable kainate receptors (R-HSA-451307)

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
Topiramate	DM82Z30	Approved	Glutamate receptor ionotropic, kainate 1 (GRIK1) affects the response to substance of Topiramate.	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glutamate receptor ionotropic, kainate 1 (GRIK1).	[1]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Glutamate receptor ionotropic, kainate 1 (GRIK1).	[2]
Marinol	DM70IK5	Approved	Marinol increases the expression of Glutamate receptor ionotropic, kainate 1 (GRIK1).	[3]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Glutamate receptor ionotropic, kainate 1 (GRIK1).	[4]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Glutamate receptor ionotropic, kainate 1 (GRIK1).	[7]

2 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 Glutamate receptor ionotropic, kainate 1 (GRIK1).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Glutamate receptor ionotropic, kainate 1 (GRIK1).	[6]

References

• [1] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [2] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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] 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.
• [7] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [8] A preliminary pharmacogenetic investigation of adverse events from topiramate in heavy drinkers. Exp Clin Psychopharmacol. 2009 Apr;17(2):122-9. doi: 10.1037/a0015700.