Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9J5J1C)

• DOT Name: Probable dimethyladenosine transferase (DIMT1)
• Synonyms: EC 2.1.1.183; DIM1 dimethyladenosine transferase 1 homolog; DIM1 dimethyladenosine transferase 1-like; Probable 18S rRNA (adenine(1779)-N(6)/adenine(1780)-N(6))-dimethyltransferase; Probable 18S rRNA dimethylase; Probable S-adenosylmethionine-6-N',N'-adenosyl(rRNA) dimethyltransferase
• Gene Name: DIMT1
• Related Disease:
  Stomach cancer
  Acute myelogenous leukaemia
  Plasma cell myeloma
• UniProt ID: DIM1_HUMAN
• PDB ID: 1ZQ9; 6W6C; 6W6F; 7MQA; 7WTS
• EC Number: 2.1.1.183
• Pfam ID: PF00398
• Sequence:
  MPKVKSGAIGRRRGRQEQRRELKSAGGLMFNTGIGQHILKNPLIINSIIDKAALRPTDVV
  LEVGPGTGNMTVKLLEKAKKVVACELDPRLVAELHKRVQGTPVASKLQVLVGDVLKTDLP
  FFDTCVANLPYQISSPFVFKLLLHRPFFRCAILMFQREFALRLVAKPGDKLYCRLSINTQ
  LLARVDHLMKVGKNNFRPPPKVESSVVRIEPKNPPPPINFQEWDGLVRITFVRKNKTLSA
  AFKSSAVQQLLEKNYRIHCSVHNIIIPEDFSIADKIQQILTSTGFSDKRARSMDIDDFIR
  LLHGFNAEGIHFS
• Function: Specifically dimethylates two adjacent adenosines in the loop of a conserved hairpin near the 3'-end of 18S rRNA in the 40S particle. Involved in the pre-rRNA processing steps leading to small-subunit rRNA production independently of its RNA-modifying catalytic activity. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.
• Reactome Pathway: rRNA modification in the nucleus and cytosol (R-HSA-6790901)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Stomach cancer	DISKIJSX	Strong	Biomarker	[1]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[2]
Plasma cell myeloma	DIS0DFZ0	moderate	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Probable dimethyladenosine transferase (DIMT1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Probable dimethyladenosine transferase (DIMT1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Probable dimethyladenosine transferase (DIMT1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Probable dimethyladenosine transferase (DIMT1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Probable dimethyladenosine transferase (DIMT1).	[8]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Probable dimethyladenosine transferase (DIMT1).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Probable dimethyladenosine transferase (DIMT1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Probable dimethyladenosine transferase (DIMT1).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Probable dimethyladenosine transferase (DIMT1).	[12]

References

• [1] DIMT1 overexpression correlates with progression and prognosis in gastric carcinoma.Hum Pathol. 2017 Dec;70:35-42. doi: 10.1016/j.humpath.2017.02.034. Epub 2017 Jun 7.
• [2] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [3] Hypoxia-inducible microRNA-210 regulates the DIMT1-IRF4 oncogenic axis in multiple myeloma.Cancer Sci. 2017 Apr;108(4):641-652. doi: 10.1111/cas.13183. Epub 2017 Apr 20.
• [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] 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.
• [7] 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.
• [8] 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.
• [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] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [12] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.