Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6E2S48)

• DOT Name: M-phase phosphoprotein 6 (MPHOSPH6)
• Gene Name: MPHOSPH6
• Related Disease:
  Alzheimer disease
  Glioma
  Neoplasm
  Neuroblastoma
  Parkinson disease
  Parkinsonian disorder
  Tauopathy
  Mycoplasma pneumoniae pneumonia
  Nervous system disease
  Coronary atherosclerosis
  Coronary heart disease
  Familial male-limited precocious puberty
  Mesothelioma
• UniProt ID: MPH6_HUMAN
• PDB ID: 6D6Q; 6D6R; 6H25
• Pfam ID: PF10175
• Sequence:
  MAAERKTRLSKNLLRMKFMQRGLDSETKKQLEEEEKKIISEEHWYLDLPELKEKESFIIE
  EQSFLLCEDLLYGRMSFRGFNPEVEKLMLQMNAKHKAEEVEDETVELDVSDEEMARRYET
  LVGTIGKKFARKRDHANYEEDENGDITPIKAKKMFLKPQD
• Function: RNA-binding protein that associates with the RNA exosome complex. Involved in the 3'-processing of the 7S pre-RNA to the mature 5.8S rRNA and play a role in recruiting the RNA exosome complex to pre-rRNA; this function may include C1D.
• KEGG Pathway: R. degradation (hsa03018)
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[4]
Parkinson disease	DISQVHKL	Strong	Biomarker	[5]
Parkinsonian disorder	DISHGY45	Strong	Genetic Variation	[6]
Tauopathy	DISY2IPA	Strong	Biomarker	[1]
Mycoplasma pneumoniae pneumonia	DIS1AW2Z	moderate	Genetic Variation	[7]
Nervous system disease	DISJ7GGT	Disputed	Altered Expression	[8]
Coronary atherosclerosis	DISKNDYU	Limited	Genetic Variation	[9]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[9]
Familial male-limited precocious puberty	DISNNKVB	Limited	Biomarker	[10]
Mesothelioma	DISKWK9M	Limited	Altered Expression	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of M-phase phosphoprotein 6 (MPHOSPH6).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of M-phase phosphoprotein 6 (MPHOSPH6).	[13]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of M-phase phosphoprotein 6 (MPHOSPH6).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of M-phase phosphoprotein 6 (MPHOSPH6).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of M-phase phosphoprotein 6 (MPHOSPH6).	[16]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of M-phase phosphoprotein 6 (MPHOSPH6).	[17]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of M-phase phosphoprotein 6 (MPHOSPH6).	[18]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of M-phase phosphoprotein 6 (MPHOSPH6).	[19]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of M-phase phosphoprotein 6 (MPHOSPH6).	[21]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of M-phase phosphoprotein 6 (MPHOSPH6).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of M-phase phosphoprotein 6 (MPHOSPH6).	[23]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of M-phase phosphoprotein 6 (MPHOSPH6).	[24]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of M-phase phosphoprotein 6 (MPHOSPH6).	[20]

References

• [1] Alpha-Synuclein contributes to GSK-3beta-catalyzed Tau phosphorylation in Parkinson's disease models.FASEB J. 2009 Sep;23(9):2820-30. doi: 10.1096/fj.08-120410. Epub 2009 Apr 15.
• [2] Diagnostic accuracy of MRI texture analysis for grading gliomas.J Neurooncol. 2018 Dec;140(3):583-589. doi: 10.1007/s11060-018-2984-4. Epub 2018 Aug 25.
• [3] Baseline clinical and imaging predictors of treatment response and overall survival of patients with metastatic melanoma undergoing immunotherapy.Eur J Radiol. 2019 Dec;121:108688. doi: 10.1016/j.ejrad.2019.108688. Epub 2019 Oct 22.
• [4] The long noncoding RNA HOTAIR promotes Parkinson's disease by upregulating LRRK2 expression.Oncotarget. 2017 Apr 11;8(15):24449-24456. doi: 10.18632/oncotarget.15511.
• [5] SH-SY5Y and LUHMES cells display differential sensitivity to MPP+, tunicamycin, and epoxomicin in 2D and 3D cell culture.Biotechnol Prog. 2020 Mar;36(2):e2942. doi: 10.1002/btpr.2942. Epub 2019 Dec 12.
• [6] Oxidants induce alternative splicing of alpha-synuclein: Implications for Parkinson's disease. Free Radic Biol Med. 2010 Feb 1;48(3):377-83. doi: 10.1016/j.freeradbiomed.2009.10.045. Epub 2009 Oct 23.
• [7] Role of E-selectin for diagnosing myocardial injury in paediatric patients with mycoplasma pneumoniae pneumonia.Ann Clin Biochem. 2017 Jan;54(1):49-54. doi: 10.1177/0004563216631570. Epub 2016 Sep 28.
• [8] A Redox Modulatory Mn(3) O(4) Nanozyme with Multi-Enzyme Activity Provides Efficient Cytoprotection to Human Cells in a Parkinson's Disease Model.Angew Chem Int Ed Engl. 2017 Nov 6;56(45):14267-14271. doi: 10.1002/anie.201708573. Epub 2017 Oct 4.
• [9] Association between TNIP1, MPHOSPH6 and ZNF208 genetic polymorphisms and the coronary artery disease risk in Chinese Han population.Oncotarget. 2017 Aug 24;8(44):77233-77240. doi: 10.18632/oncotarget.20432. eCollection 2017 Sep 29.
• [10] Gonadotropin independent precocious puberty.J Pediatr Endocrinol Metab. 1998 Jul-Aug;11(4):497-507. doi: 10.1515/jpem.1998.11.4.497.
• [11] MicroRNA signature of malignant mesothelioma with potential diagnostic and prognostic implications.Am J Respir Cell Mol Biol. 2010 Mar;42(3):312-9. doi: 10.1165/rcmb.2009-0060OC. Epub 2009 Jun 5.
• [12] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [13] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [14] 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.
• [15] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [16] 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.
• [17] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [18] 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.
• [19] Curcumin restores corticosteroid function in monocytes exposed to oxidants by maintaining HDAC2. Am J Respir Cell Mol Biol. 2008 Sep;39(3):312-23. doi: 10.1165/rcmb.2008-0012OC. Epub 2008 Apr 17.
• [20] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [21] 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.
• [22] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [23] 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.
• [24] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.