Details of Drug Off-Target (DOT)

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

• DOT Name: Ribosome biogenesis protein BOP1 (BOP1)
• Synonyms: Block of proliferation 1 protein
• Gene Name: BOP1
• Related Disease:
  Colorectal carcinoma
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Melanoma
  Neoplasm
• UniProt ID: BOP1_HUMAN
• PDB ID: 8FKP; 8FKQ; 8FKR; 8FKS; 8FKT; 8FKU; 8FKV; 8FKW; 8FKX; 8FKY
• Pfam ID: PF08145 ; PF00400
• Sequence:
  MAGSRGAGRTAAPSVRPEKRRSEPELEPEPEPEPPLLCTSPLSHSTGSDSGVSDSEESVF
  SGLEDSGSDSSEDDDEGDEEGEDGALDDEGHSGIKKTTEEQVQASTPCPRTEMASARIGD
  EYAEDSSDEEDIRNTVGNVPLEWYDDFPHVGYDLDGRRIYKPLRTRDELDQFLDKMDDPD
  YWRTVQDPMTGRDLRLTDEQVALVRRLQSGQFGDVGFNPYEPAVDFFSGDVMIHPVTNRP
  ADKRSFIPSLVEKEKVSRMVHAIKMGWIQPRRPRDPTPSFYDLWAQEDPNAVLGRHKMHV
  PAPKLALPGHAESYNPPPEYLLSEEERLAWEQQEPGERKLSFLPRKFPSLRAVPAYGRFI
  QERFERCLDLYLCPRQRKMRVNVDPEDLIPKLPRPRDLQPFPTCQALVYRGHSDLVRCLS
  VSPGGQWLVSGSDDGSLRLWEVATARCVRTVPVGGVVKSVAWNPSPAVCLVAAAVEDSVL
  LLNPALGDRLVAGSTDQLLSAFVPPEEPPLQPARWLEASEEERQVGLRLRICHGKPVTQV
  TWHGRGDYLAVVLATQGHTQVLIHQLSRRRSQSPFRRSHGQVQRVAFHPARPFLLVASQR
  SVRLYHLLRQELTKKLMPNCKWVSSLAVHPAGDNVICGSYDSKLVWFDLDLSTKPYRMLR
  HHKKALRAVAFHPRYPLFASGSDDGSVIVCHGMVYNDLLQNPLLVPVKVLKGHVLTRDLG
  VLDVIFHPTQPWVFSSGADGTVRLFT
• Function: Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome.
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Biomarker	[2]
Gastric neoplasm	DISOKN4Y	Strong	Biomarker	[2]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Strong	Biomarker	[2]
Melanoma	DIS1RRCY	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Disputed	Altered Expression	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Topotecan	DMP6G8T	Approved	Ribosome biogenesis protein BOP1 (BOP1) affects the response to substance of Topotecan.	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Ribosome biogenesis protein BOP1 (BOP1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the phosphorylation of Ribosome biogenesis protein BOP1 (BOP1).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Ribosome biogenesis protein BOP1 (BOP1).	[10]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Ribosome biogenesis protein BOP1 (BOP1).	[10]

8 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 Ribosome biogenesis protein BOP1 (BOP1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ribosome biogenesis protein BOP1 (BOP1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Ribosome biogenesis protein BOP1 (BOP1).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ribosome biogenesis protein BOP1 (BOP1).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Ribosome biogenesis protein BOP1 (BOP1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Ribosome biogenesis protein BOP1 (BOP1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ribosome biogenesis protein BOP1 (BOP1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribosome biogenesis protein BOP1 (BOP1).	[14]

References

• [1] New Wnt/-catenin target genes promote experimental metastasis and migration of colorectal cancer cells through different signals.Gut. 2016 Oct;65(10):1690-701. doi: 10.1136/gutjnl-2014-307900. Epub 2015 Jul 8.
• [2] A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.PLoS One. 2011 Feb 18;6(2):e16694. doi: 10.1371/journal.pone.0016694.
• [3] Loss of BOP1 confers resistance to BRAF kinase inhibitors in melanoma by activating MAP kinase pathway.Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4583-4591. doi: 10.1073/pnas.1821889116. Epub 2019 Feb 19.
• [4] Contribution of the BOP1 gene, located on 8q24, to colorectal tumorigenesis.Genes Chromosomes Cancer. 2006 Sep;45(9):874-81. doi: 10.1002/gcc.20351.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [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] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [13] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [14] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [15] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.