Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZO53O0)

• DOT Name: Coordinator of PRMT5 and differentiation stimulator (COPRS)
• Synonyms: Cooperator of PRMT5; Protein TTP1
• Gene Name: COPRS
• Related Disease:
  Malignant peripheral nerve sheath tumor
  Familial isolated deficiency of vitamin E
• UniProt ID: COPRS_HUMAN
• Pfam ID: PF15340
• Sequence:
  MDLQAAGAQAQGAAEPSRGPPLPSARGAPPSPEAGFATADHSSQERETEKAMDRLARGTQ
  SIPNDSPARGEGTHSEEEGFAMDEEDSDGELNTWELSEGTNCPPKEQPGDLFNEDWDSEL
  KADQGNPYDADDIQESISQELKPWVCCAPQGDMIYDPSWHHPPPLIPYYSKMVFETGQFD
  DAED
• Function: Histone-binding protein required for histone H4 methyltransferase activity of PRMT5. Specifically required for histone H4 'Arg-3' methylation mediated by PRMT5, but not histone H3 'Arg-8' methylation, suggesting that it modulates the substrate specificity of PRMT5. Specifically interacts with the N-terminus of histone H4 but not with histone H3, suggesting that it acts by promoting the association between histone H4 and PRMT5. Involved in CCNE1 promoter repression. Plays a role in muscle cell differentiation by modulating the recruitment of PRMT5 to the promoter of genes involved in the coordination between cell cycle exit and muscle differentiation.
• Reactome Pathway: RMTs methylate histone arginines (R-HSA-3214858)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Biomarker	[1]
Familial isolated deficiency of vitamin E	DIS53306	Limited	Genetic Variation	[2]

7 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 Coordinator of PRMT5 and differentiation stimulator (COPRS).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Coordinator of PRMT5 and differentiation stimulator (COPRS).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Coordinator of PRMT5 and differentiation stimulator (COPRS).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Coordinator of PRMT5 and differentiation stimulator (COPRS).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Coordinator of PRMT5 and differentiation stimulator (COPRS).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Coordinator of PRMT5 and differentiation stimulator (COPRS).	[8]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Coordinator of PRMT5 and differentiation stimulator (COPRS).	[8]

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 Coordinator of PRMT5 and differentiation stimulator (COPRS).	[9]

References

• [1] Identification of genes potentially involved in the increased risk of malignancy in NF1-microdeleted patients.Mol Med. 2011 Jan-Feb;17(1-2):79-87. doi: 10.2119/molmed.2010.00079. Epub 2010 Sep 10.
• [2] Molecular determinants of heritable vitamin E deficiency.Biochemistry. 2004 Apr 13;43(14):4143-9. doi: 10.1021/bi0363073.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] 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.
• [7] 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.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] 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.