Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8DGYZ5)

• DOT Name: Glutamate receptor-interacting protein 2 (GRIP2)
• Synonyms: GRIP-2
• Gene Name: GRIP2
• UniProt ID: GRIP2_HUMAN
• PDB ID: 1V62; 1X5R
• Pfam ID: PF00595 ; PF17820
• Sequence:
  MLCGLSRETPGEADDGPYSKGGKDAGGADVSLACRRQSIPEEFRGITVVELIKKEGSTLG
  LTISGGTDKDGKPRVSNLRPGGLAARSDLLNIGDYIRSVNGIHLTRLRHDEIITLLKNVG
  ERVVLEVEYELPPPAPENNPRIISKTVDVSLYKEGNSFGFVLRGGAHEDGHKSRPLVLTY
  VRPGGPADREGSLKVGDRLLSVDGIPLHGASHATALATLRQCSHEALFQVEYDVATPDTV
  ANASGPLMVEIVKTPGSALGISLTTTSLRNKSVITIDRIKPASVVDRSGALHPGDHILSI
  DGTSMEHCSLLEATKLLASISEKVRLEILPVPQSQRPLRPSEAVKVQRSEQLHRWDPCVP
  SCHSPRPGHCRMPTWATPAGQDQSRSLSSTPFSSPTLNHAFSCNNPSTLPRGSQPMSPRT
  TMGRRRQRRREHKSSLSLASSTVGPGGQIVHTETTEVVLCGDPLSGFGLQLQGGIFATET
  LSSPPLVCFIEPDSPAERCGLLQVGDRVLSINGIATEDGTMEEANQLLRDAALAHKVVLE
  VEFDVAESVIPSSGTFHVKLPKKRSVELGITISSASRKRGEPLIISDIKKGSVAHRTGTL
  EPGDKLLAIDNIRLDNCPMEDAVQILRQCEDLVKLKIRKDEDNSDELETTGAVSYTVELK
  RYGGPLGITISGTEEPFDPIVISGLTKRGLAERTGAIHVGDRILAINNVSLKGRPLSEAI
  HLLQVAGETVTLKIKKQLDRPLLPRKSGSLSETSDADEDPADALKGGLPAARFSPAVPSV
  DSAVESWDSSATEGGFGGPGSYTPQAAARGTTPQERRPGWLRGSPPPTEPRRTSYTPTPA
  DESFPEEEEEDDWEPPTSPAPGPAREEGFWRMFGEALEDLESCGQSELLRELEASIMTGT
  VQRVALEGRPGHRPWQRGREVRASPAEMEELLLPTPLEMHKVTLHKDPMRHDFGFSVSDG
  LLEKGVYVHTVRPDGPAHRGGLQPFDRVLQVNHVRTRDFDCCLAVPLLAEAGDVLELIIS
  RKPHTAHSSRAPRSPGPSSPRML
• Function: May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons.
• Reactome Pathway: Trafficking of GluR2-containing AMPA receptors (R-HSA-416993)

Molecular Interaction Atlas (MIA) of This DOT

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 Glutamate receptor-interacting protein 2 (GRIP2).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Glutamate receptor-interacting protein 2 (GRIP2).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Glutamate receptor-interacting protein 2 (GRIP2).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glutamate receptor-interacting protein 2 (GRIP2).	[2]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Glutamate receptor-interacting protein 2 (GRIP2).	[3]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Glutamate receptor-interacting protein 2 (GRIP2).	[4]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Glutamate receptor-interacting protein 2 (GRIP2).	[5]

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] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [4] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [5] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [6] 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.
• [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.