Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVD7OU6)

• DOT Name: Protein FAM53B (FAM53B)
• Synonyms: Protein simplet
• Gene Name: FAM53B
• Related Disease:
  Cardiac failure
  Congestive heart failure
  Epithelial ovarian cancer
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Plasmodium falciparum malaria
  Rheumatoid arthritis
  Cocaine addiction
  Alopecia
  Androgenetic alopecia
  Baldness, male pattern
  Substance dependence
• UniProt ID: FA53B_HUMAN
• Pfam ID: PF15242
• Sequence:
  MVMVLSESLSTRGADSIACGTFSRELHTPKKMSQGPTLFSCGIMENDRWRDLDRKCPLQI
  DQPSTSIWECLPEKDSSLWHREAVTACAVTSLIKDLSISDHNGNPSAPPSKRQCRSLSFS
  DEMSSCRTSWRPLGSKVWTPVEKRRCYSGGSVQRYSNGFSTMQRSSSFSLPSRANVLSSP
  CDQAGLHHRFGGQPCQGVPGSAPCGQAGDTWSPDLHPVGGGRLDLQRSLSCSHEQFSFVE
  YCPPSANSTPASTPELARRSSGLSRSRSQPCVLNDKKVGVKRRRPEEVQEQRPSLDLAKM
  AQNCQTFSSLSCLSAGTEDCGPQSPFARHVSNTRAWTALLSASGPGGRTPAGTPVPEPLP
  PSFDDHLACQEDLSCEESDSCALDEDCGRRAEPAAAWRDRGAPGNSLCSLDGELDIEQIE
  KN
• Function: Acts as a regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) nuclear localization.
• Tissue Specificity: Detected in skeletal muscle, kidney, spleen, thyroid, testis, ovary, small intestine, colon and peripheral blood.

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Biomarker	[1]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[2]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[2]
Plasmodium falciparum malaria	DIS3Q9KF	Strong	Biomarker	[4]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[1]
Cocaine addiction	DISHTRXG	moderate	Genetic Variation	[5]
Alopecia	DIS37HU4	Limited	Genetic Variation	[6]
Androgenetic alopecia	DISSJR1P	Limited	Genetic Variation	[7]
Baldness, male pattern	DIS9C9RO	Limited	Genetic Variation	[7]
Substance dependence	DISDRAAR	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein FAM53B (FAM53B).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein FAM53B (FAM53B).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Protein FAM53B (FAM53B).	[10]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein FAM53B (FAM53B).	[11]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein FAM53B (FAM53B).	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Protein FAM53B (FAM53B).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Protein FAM53B (FAM53B).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein FAM53B (FAM53B).	[18]

6 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 Protein FAM53B (FAM53B).	[13]
Quercetin	DM3NC4M	Approved	Quercetin increases the phosphorylation of Protein FAM53B (FAM53B).	[14]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Protein FAM53B (FAM53B).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein FAM53B (FAM53B).	[17]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein FAM53B (FAM53B).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein FAM53B (FAM53B).	[16]

References

• [1] Reduction of SR Ca(2+) leak and arrhythmogenic cellular correlates by SMP-114, a novel CaMKII inhibitor with oral bioavailability.Basic Res Cardiol. 2017 Jul;112(4):45. doi: 10.1007/s00395-017-0637-y. Epub 2017 Jun 13.
• [2] Upregulation of circular RNA circFAM53B predicts adverse prognosis and accelerates the progression of ovarian cancer via the miR?46/VAMP2 and miR?47/MDM2 signaling pathways.Oncol Rep. 2019 Dec;42(6):2728-2737. doi: 10.3892/or.2019.7366. Epub 2019 Oct 10.
• [3] Stromal micropapillary pattern predominant lung adenocarcinoma--a report of two cases.Diagn Pathol. 2011 Sep 29;6:92. doi: 10.1186/1746-1596-6-92.
• [4] A fixed-dose 24-hour regimen of artesunate plus sulfamethoxypyrazine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan.Ann Clin Microbiol Antimicrob. 2006 Aug 26;5:18. doi: 10.1186/1476-0711-5-18.
• [5] Evaluation of previous substance dependence genome-wide significant findings in a Spanish sample.Drug Alcohol Depend. 2018 Jun 1;187:358-362. doi: 10.1016/j.drugalcdep.2018.03.013. Epub 2018 Apr 16.
• [6] Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
• [7] GWAS for male-pattern baldness identifies 71 susceptibility loci explaining 38% of the risk.Nat Commun. 2017 Nov 17;8(1):1584. doi: 10.1038/s41467-017-01490-8.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [10] 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.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] 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.
• [13] 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.
• [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] 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.
• [16] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [17] 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.
• [18] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.