Details of Drug Off-Target (DOT)

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

• DOT Name: Microtubule-associated protein RP/EB family member 3 (MAPRE3)
• Synonyms: EB1 protein family member 3; EBF3; End-binding protein 3; EB3; RP3
• Gene Name: MAPRE3
• Related Disease:
  Congenital stationary night blindness 2A
  Familial adenomatous polyposis
  Myopia
  Night blindness
  Polycystic ovarian syndrome
  Retinitis pigmentosa
• UniProt ID: MARE3_HUMAN
• PDB ID: 1WYO; 3CO1; 3JAK; 3JAL; 3JAR; 3TQ7; 7SJ9
• Pfam ID: PF00307 ; PF03271
• Sequence:
  MAVNVYSTSVTSENLSRHDMLAWVNDSLHLNYTKIEQLCSGAAYCQFMDMLFPGCVHLRK
  VKFQAKLEHEYIHNFKVLQAAFKKMGVDKIIPVEKLVKGKFQDNFEFIQWFKKFFDANYD
  GKDYNPLLARQGQDVAPPPNPGDQIFNKSKKLIGTAVPQRTSPTGPKNMQTSGRLSNVAP
  PCILRKNPPSARNGGHETDAQILELNQQLVDLKLTVDGLEKERDFYFSKLRDIELICQEH
  ESENSPVISGIIGILYATEEGFAPPEDDEIEEHQQEDQDEY
• Function: Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth. May be involved in spindle function by stabilizing microtubules and anchoring them at centrosomes. Also acts as a regulator of minus-end microtubule organization: interacts with the complex formed by AKAP9 and PDE4DIP, leading to recruit CAMSAP2 to the Golgi apparatus, thereby tethering non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. Promotes elongation of CAMSAP2-decorated microtubule stretches on the minus-end of microtubules.
• Tissue Specificity: Predominantly expressed in brain and muscle.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital stationary night blindness 2A	DISA57KI	Strong	Genetic Variation	[1]
Familial adenomatous polyposis	DISW53RE	Strong	Biomarker	[2]
Myopia	DISK5S60	Strong	Genetic Variation	[3]
Night blindness	DIS335K9	Strong	Genetic Variation	[3]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[4]
Retinitis pigmentosa	DISCGPY8	Limited	Biomarker	[5]

13 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 Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[7]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[11]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[12]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[13]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[15]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[18]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[20]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[21]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Paclitaxel affects the localization of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[14]

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 affects the methylation of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Microtubule-associated protein RP/EB family member 3 (MAPRE3).	[19]

References

• [1] Localization of CSNBX (CSNB4) between the retinitis pigmentosa loci RP2 and RP3 on proximal Xp.Invest Ophthalmol Vis Sci. 1997 Dec;38(13):2750-5.
• [2] A Role for Postsynaptic Density 95 and Its Binding Partners in Models of Traumatic Brain Injury.J Neurotrauma. 2019 Jul 1;36(13):2129-2138. doi: 10.1089/neu.2018.6291. Epub 2019 Mar 28.
• [3] Phenotype-genotype correlations in X linked retinitis pigmentosa.J Med Genet. 1992 Sep;29(9):615-23. doi: 10.1136/jmg.29.9.615.
• [4] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [5] A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).Nat Genet. 1996 May;13(1):35-42. doi: 10.1038/ng0596-35.
• [6] 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.
• [7] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [8] 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.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] 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.
• [13] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [14] Olesoxime prevents microtubule-targeting drug neurotoxicity: selective preservation of EB comets in differentiated neuronal cells. Biochem Pharmacol. 2010 Sep 15;80(6):884-94. doi: 10.1016/j.bcp.2010.04.018. Epub 2010 Apr 22.
• [15] 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.
• [16] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [17] 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.
• [18] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [19] 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.
• [20] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [21] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.