Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPH8CZY)

• DOT Name: MAGUK p55 subfamily member 2 (MPP2)
• Synonyms: Discs large homolog 2; Protein MPP2
• Gene Name: MPP2
• Related Disease:
  Attention deficit hyperactivity disorder
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Lung cancer
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Schizophrenia
  Tuberous sclerosis
  Pituitary tumor
• UniProt ID: MPP2_HUMAN
• PDB ID: 2E7K
• Pfam ID: PF00625 ; PF02828 ; PF00595 ; PF07653
• Sequence:
  MPVAATNSETAMQQVLDNLGSLPSATGAAELDLIFLRGIMESPIVRSLAKVIMVLWFMQQ
  NVFVPMKYMLKYFGAHERLEETKLEAVRDNNLELVQEILRDLAHVAEQSSTAAELAHILQ
  EPHFQSLLETHDSVASKTYETPPPSPGLDPTFSNQPVPPDAVRMVGIRKTAGEHLGVTFR
  VEGGELVIARILHGGMVAQQGLLHVGDIIKEVNGQPVGSDPRALQELLRNASGSVILKIL
  PSYQEPHLPRQVFVKCHFDYDPARDSLIPCKEAGLRFNAGDLLQIVNQDDANWWQACHVE
  GGSAGLIPSQLLEEKRKAFVKRDLELTPNSGTLCGSLSGKKKKRMMYLTTKNAEFDRHEL
  LIYEEVARMPPFRRKTLVLIGAQGVGRRSLKNKLIMWDPDRYGTTVPYTSRRPKDSEREG
  QGYSFVSRGEMEADVRAGRYLEHGEYEGNLYGTRIDSIRGVVAAGKVCVLDVNPQAVKVL
  RTAEFVPYVVFIEAPDFETLRAMNRAALESGISTKQLTEADLRRTVEESSRIQRGYGHYF
  DLCLVNSNLERTFRELQTAMEKLRTEPQWVPVSWVY
• Function: Postsynaptic MAGUK scaffold protein that links CADM1 cell adhesion molecules to core components of the postsynaptic density. In CA1 pyramidal neurons, required for synaptic KCNN2-containing channel function and long-term potentiation expression. Seems to negatively regulate SRC function in epithelial cells.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[2]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[5]
Tuberous sclerosis	DISEMUGZ	moderate	Biomarker	[6]
Pituitary tumor	DISN67JD	Limited	Biomarker	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	MAGUK p55 subfamily member 2 (MPP2) decreases the response to substance of Cisplatin.	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of MAGUK p55 subfamily member 2 (MPP2).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of MAGUK p55 subfamily member 2 (MPP2).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of MAGUK p55 subfamily member 2 (MPP2).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of MAGUK p55 subfamily member 2 (MPP2).	[11]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of MAGUK p55 subfamily member 2 (MPP2).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of MAGUK p55 subfamily member 2 (MPP2).	[8]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of MAGUK p55 subfamily member 2 (MPP2).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of MAGUK p55 subfamily member 2 (MPP2).	[15]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of MAGUK p55 subfamily member 2 (MPP2).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of MAGUK p55 subfamily member 2 (MPP2).	[17]

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 decreases the methylation of MAGUK p55 subfamily member 2 (MPP2).	[14]

References

• [1] RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network ("Rhesactome") in the striatum.Sci Signal. 2016 Nov 15;9(454):ra111. doi: 10.1126/scisignal.aaf6670.
• [2] MicroRNA-23a depletion promotes apoptosis of ovarian cancer stem cell and inhibits cell migration by targeting DLG2.Cancer Biol Ther. 2019;20(6):897-911. doi: 10.1080/15384047.2019.1579960. Epub 2019 Mar 12.
• [3] siRNA suppression of hTERT using activatable cell-penetrating peptides in hepatoma cells.Biosci Rep. 2015 Mar 18;35(2):e00181. doi: 10.1042/BSR20140145.
• [4] Transgenic expression of the forkhead box M1 transcription factor induces formation of lung tumors.Oncogene. 2008 Jul 10;27(30):4137-49. doi: 10.1038/onc.2008.60. Epub 2008 Mar 17.
• [5] Novel putative nonprotein-coding RNA gene from 11q14 displays decreased expression in brains of patients with schizophrenia.J Neurosci Res. 2003 Oct 1;74(1):111-22. doi: 10.1002/jnr.10752.
• [6] Cells derived from tuberous sclerosis show a prolonged S phase of the cell cycle and increased apoptosis.Arch Dermatol Res. 2001 Sep;293(9):460-9. doi: 10.1007/s004030100259.
• [7] Identification of differentially coexpressed genes in gonadotrope tumors and normal pituitary using bioinformatics methods.Pathol Oncol Res. 2014 Apr;20(2):375-80. doi: 10.1007/s12253-013-9706-1. Epub 2013 Nov 7.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] 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.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [12] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [13] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [14] 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.
• [15] 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.
• [16] Bisphenol-A and estradiol exert novel gene regulation in human MCF-7 derived breast cancer cells. Mol Cell Endocrinol. 2004 Jun 30;221(1-2):47-55. doi: 10.1016/j.mce.2004.04.010.
• [17] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [18] A sensitized RNA interference screen identifies a novel role for the PI3K p110 isoform in medulloblastoma cell proliferation and chemoresistance. Mol Cancer Res. 2011 Jul;9(7):925-35. doi: 10.1158/1541-7786.MCR-10-0200. Epub 2011 Jun 7.