Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLO1EOO)

• DOT Name: RNA 5'-monophosphate methyltransferase (BCDIN3D)
• Synonyms: EC 2.1.1.-; BCDIN3 domain-containing protein
• Gene Name: BCDIN3D
• Related Disease:
  Breast cancer
  Breast carcinoma
• UniProt ID: BN3D2_HUMAN
• PDB ID: 6L8U
• EC Number: 2.1.1.-
• Pfam ID: PF06859
• Sequence:
  MAVPTELDGGSVKETAAEEESRVLAPGAAPFGNFPHYSRFHPPEQRLRLLPPELLRQLFP
  ESPENGPILGLDVGCNSGDLSVALYKHFLSLPDGETCSDASREFRLLCCDIDPVLVKRAE
  KECPFPDALTFITLDFMNQRTRKVLLSSFLSQFGRSVFDIGFCMSITMWIHLNHGDHGLW
  EFLAHLSSLCHYLLVEPQPWKCYRAAARRLRKLGLHDFDHFHSLAIRGDMPNQIVQILTQ
  DHGMELICCFGNTSWDRSLLLFRAKQTIETHPIPESLIEKGKEKNRLSFQKQ
• Function: O-methyltransferase that specifically monomethylates 5'-monophosphate of cytoplasmic histidyl tRNA (tRNA(His)), acting as a capping enzyme by protecting tRNA(His) from cleavage by DICER1. Also able, with less efficiently, to methylate the 5' monophosphate of a subset of pre-miRNAs, acting as a negative regulator of miRNA processing. The 5' monophosphate of pre-miRNAs is recognized by DICER1 and is required for pre-miRNAs processing: methylation at this position reduces the processing of pre-miRNAs by DICER1. Was also reported to mediate dimethylation of pre-miR-145; however dimethylation cannot be reproduced by another group which observes a monomethylation of pre-miR-145.
• Reactome Pathway: MicroRNA (miRNA) biogenesis (R-HSA-203927)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of RNA 5'-monophosphate methyltransferase (BCDIN3D).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of RNA 5'-monophosphate methyltransferase (BCDIN3D).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RNA 5'-monophosphate methyltransferase (BCDIN3D).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of RNA 5'-monophosphate methyltransferase (BCDIN3D).	[5]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of RNA 5'-monophosphate methyltransferase (BCDIN3D).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of RNA 5'-monophosphate methyltransferase (BCDIN3D).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of RNA 5'-monophosphate methyltransferase (BCDIN3D).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of RNA 5'-monophosphate methyltransferase (BCDIN3D).	[2]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of RNA 5'-monophosphate methyltransferase (BCDIN3D).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of RNA 5'-monophosphate methyltransferase (BCDIN3D).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of RNA 5'-monophosphate methyltransferase (BCDIN3D).	[8]

References

• [1] RNA methyltransferase BCDIN3D is crucial for female fertility and miRNA and mRNA profiles in Drosophila ovaries.PLoS One. 2019 May 30;14(5):e0217603. doi: 10.1371/journal.pone.0217603. eCollection 2019.
• [2] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [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] 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.
• [6] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [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] 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.
• [9] 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.
• [10] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.