Details of Drug Off-Target (DOT)

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

• DOT Name: Bystin (BYSL)
• Gene Name: BYSL
• Related Disease:
  B-cell lymphoma
  Breast cancer
  Breast carcinoma
• UniProt ID: BYST_HUMAN
• PDB ID: 6G18; 6G4S; 6G4W; 7WTT; 7WTU; 7WTV; 7WTW; 7WTX; 7WTZ; 7WU0
• Pfam ID: PF05291
• Sequence:
  MPKFKAARGVGGQEKHAPLADQILAGNAVRAGVREKRRGRGTGEAEEEYVGPRLSRRILQ
  QARQQQEELEAEHGTGDKPAAPRERTTRLGPRMPQDGSDDEDEEWPTLEKAATMTAAGHH
  AEVVVDPEDERAIEMFMNKNPPARRTLADIIMEKLTEKQTEVETVMSEVSGFPMPQLDPR
  VLEVYRGVREVLSKYRSGKLPKAFKIIPALSNWEQILYVTEPEAWTAAAMYQATRIFASN
  LKERMAQRFYNLVLLPRVRDDVAEYKRLNFHLYMALKKALFKPGAWFKGILIPLCESGTC
  TLREAIIVGSIITKCSIPVLHSSAAMLKIAEMEYSGANSIFLRLLLDKKYALPYRVLDAL
  VFHFLGFRTEKRELPVLWHQCLLTLVQRYKADLATDQKEALLELLRLQPHPQLSPEIRRE
  LQSAVPRDVEDVPITVE
• Function: Required for processing of 20S pre-rRNA precursor and biogenesis of 40S ribosomal subunits. May be required for trophinin-dependent regulation of cell adhesion during implantation of human embryos.
• Tissue Specificity: Found in the placenta from the sixth week of pregnancy. Was localized in the cytoplasm of the syncytiotrophoblast in the chorionic villi and in endometrial decidual cells at the uteroplacental interface. After week 10, the level decreased and then disappeared from placental villi.
• Reactome Pathway: Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Bystin (BYSL).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Bystin (BYSL).	[4]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Bystin (BYSL).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Bystin (BYSL).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Bystin (BYSL).	[8]
Selenium	DM25CGV	Approved	Selenium increases the expression of Bystin (BYSL).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Bystin (BYSL).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Bystin (BYSL).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Bystin (BYSL).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Bystin (BYSL).	[12]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Bystin (BYSL).	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Bystin (BYSL).	[7]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Bystin (BYSL).	[14]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Bystin (BYSL).	[15]

References

• [1] Identification of CCND3 and BYSL as candidate targets for the 6p21 amplification in diffuse large B-cell lymphoma.Clin Cancer Res. 2005 Dec 1;11(23):8265-72. doi: 10.1158/1078-0432.CCR-05-1028.
• [2] Amplified in Breast Cancer Regulates Transcription and Translation in Breast Cancer Cells.Neoplasia. 2016 Feb;18(2):100-10. doi: 10.1016/j.neo.2016.01.001.
• [3] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [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] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [13] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [14] 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.
• [15] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.