Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNOL0HA)

• DOT Name: MAGUK p55 subfamily member 3 (MPP3)
• Synonyms: Discs large homolog 3; Protein MPP3
• Gene Name: MPP3
• Related Disease:
  Carcinoma
  Colorectal carcinoma
  Leukopenia
  Neoplasm
• UniProt ID: MPP3_HUMAN
• Pfam ID: PF00625 ; PF02828 ; PF00595 ; PF07653
• Sequence:
  MPVLSEDSGLHETLALLTSQLRPDSNHKEEMGFLRDVFSEKSLSYLMKIHEKLRYYERQS
  PTPVLHSAVALAEDVMEELQAASVHSDERELLQLLSTPHLRAVLMVHDTVAQKNFDPVLP
  PLPDNIDEDFDEESVKIVRLVKNKEPLGATIRRDEHSGAVVVARIMRGGAADRSGLVHVG
  DELREVNGIAVLHKRPDEISQILAQSQGSITLKIIPATQEEDRLKESKVFMRALFHYNPR
  EDRAIPCQEAGLPFQRRQVLEVVSQDDPTWWQAKRVGDTNLRAGLIPSKGFQERRLSYRR
  AAGTLPSPQSLRKPPYDQPCDKETCDCEGYLKGHYVAGLRRSFRLGCRERLGGSQEGKMS
  SGAESPELLTYEEVARYQHQPGERPRLVVLIGSLGARLHELKQKVVAENPQHFGVAVPHT
  TRPRKSHEKEGVEYHFVSKQAFEADLHHNKFLEHGEYKENLYGTSLEAIQAVMAKNKVCL
  VDVEPEALKQLRTSEFKPYIIFVKPAIQEKRKTPPMSPACEDTAAPFDEQQQEMAASAAF
  IDRHYGHLVDAVLVKEDLQGAYSQLKVVLEKLSKDTHWVPVSWVR
• Function: Participates in cell spreading through the phosphoinositide-3-kinase (PI3K) pathway by connecting CADM1 to DLG1 and the regulatory subunit of phosphoinositide-3-kinase (PI3K). Stabilizes HTR2C at the plasma membrane and prevents its desensitization. May participates in the maintenance of adherens junctions.
• Tissue Specificity: Expressed in retina (at protein level) at the subapical region (SAR) adjacent to adherens junctions at the OLM, and at the OPL.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Definitive	Posttranslational Modification	[1]
Leukopenia	DISJMBMM	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]

1 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 MAGUK p55 subfamily member 3 (MPP3).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of MAGUK p55 subfamily member 3 (MPP3).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of MAGUK p55 subfamily member 3 (MPP3).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of MAGUK p55 subfamily member 3 (MPP3).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of MAGUK p55 subfamily member 3 (MPP3).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of MAGUK p55 subfamily member 3 (MPP3).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of MAGUK p55 subfamily member 3 (MPP3).	[9]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of MAGUK p55 subfamily member 3 (MPP3).	[10]
Paclitaxel	DMLB81S	Approved	Paclitaxel increases the expression of MAGUK p55 subfamily member 3 (MPP3).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of MAGUK p55 subfamily member 3 (MPP3).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of MAGUK p55 subfamily member 3 (MPP3).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of MAGUK p55 subfamily member 3 (MPP3).	[14]

References

• [1] MPP3 inactivation by promoter CpG islands hypermethylation in colorectal carcinogenesis.Cancer Biomark. 2012;11(2-3):99-106. doi: 10.3233/CBM-2012-0264.
• [2] TLR5 signaling in murine bone marrow induces hematopoietic progenitor cell proliferation and aids survival from radiation.Blood Adv. 2017 Sep 14;1(21):1796-1806. doi: 10.1182/bloodadvances.2017006981. eCollection 2017 Sep 26.
• [3] 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.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] 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.
• [11] Proteomic analysis of anti-cancer effects by paclitaxel treatment in cervical cancer cells. Gynecol Oncol. 2005 Jul;98(1):45-53. doi: 10.1016/j.ygyno.2005.04.010.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [14] 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.