Details of Drug Off-Target (DOT)

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

• DOT Name: Thymocyte nuclear protein 1 (THYN1)
• Synonyms: Thymocyte protein Thy28
• Gene Name: THYN1
• Related Disease:
  Prostate cancer
  Prostate neoplasm
  Nervous system inflammation
• UniProt ID: THYN1_HUMAN
• PDB ID: 3EOP; 5J3E
• Pfam ID: PF01878
• Sequence:
  MSRPRKRLAGTSGSDKGLSGKRTKTENSGEALAKVEDSNPQKTSATKNCLKNLSSHWLMK
  SEPESRLEKGVDVKFSIEDLKAQPKQTTCWDGVRNYQARNFLRAMKLGEEAFFYHSNCKE
  PGIAGLMKIVKEAYPDHTQFEKNNPHYDPSSKEDNPKWSMVDVQFVRMMKRFIPLAELKS
  YHQAHKATGGPLKNMVLFTRQRLSIQPLTQEEFDFVLSLEEKEPS
• Function: Specifically binds 5-hydroxymethylcytosine (5hmC), suggesting that it acts as a specific reader of 5hmC.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Prostate cancer	DISF190Y	Strong	Biomarker	[1]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[1]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[2]

16 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 Thymocyte nuclear protein 1 (THYN1).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Thymocyte nuclear protein 1 (THYN1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Thymocyte nuclear protein 1 (THYN1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Thymocyte nuclear protein 1 (THYN1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Thymocyte nuclear protein 1 (THYN1).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Thymocyte nuclear protein 1 (THYN1).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Thymocyte nuclear protein 1 (THYN1).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Thymocyte nuclear protein 1 (THYN1).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Thymocyte nuclear protein 1 (THYN1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Thymocyte nuclear protein 1 (THYN1).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Thymocyte nuclear protein 1 (THYN1).	[13]
Selenium	DM25CGV	Approved	Selenium increases the expression of Thymocyte nuclear protein 1 (THYN1).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Thymocyte nuclear protein 1 (THYN1).	[15]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Thymocyte nuclear protein 1 (THYN1).	[16]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Thymocyte nuclear protein 1 (THYN1).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Thymocyte nuclear protein 1 (THYN1).	[17]

References

• [1] Global analysis of differentially expressed genes in androgen-independent prostate cancer.Prostate Cancer Prostatic Dis. 2007;10(2):167-74. doi: 10.1038/sj.pcan.4500933. Epub 2007 Jan 2.
• [2] Thy28 protects against anti-CD3-mediated thymic cell death in vivo.Apoptosis. 2015 Apr;20(4):444-54. doi: 10.1007/s10495-014-1082-0.
• [3] 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.
• [4] 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.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] 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.
• [10] 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.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [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] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [14] 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.
• [15] 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.
• [16] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [17] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.