Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG4PL7H)

• DOT Name: Centrin-3 (CETN3)
• Gene Name: CETN3
• Related Disease:
  Astrocytoma
  Meningioma
  Bladder cancer
  Squamous cell carcinoma
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: CETN3_HUMAN
• Pfam ID: PF13499
• Sequence:
  MSLALRSELVVDKTKRKKRRELSEEQKQEIKDAFELFDTDKDEAIDYHELKVAMRALGFD
  VKKADVLKILKDYDREATGKITFEDFNEVVTDWILERDPHEEILKAFKLFDDDDSGKISL
  RNLRRVARELGENMSDEELRAMIEEFDKDGDGEINQEEFIAIMTGDI
• Function: Plays a fundamental role in microtubule-organizing center structure and function.; As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Astrocytoma	DISL3V18	Strong	Altered Expression	[1]
Meningioma	DISPT4TG	Strong	Altered Expression	[1]
Bladder cancer	DISUHNM0	moderate	Biomarker	[2]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[3]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[2]
Urinary bladder neoplasm	DIS7HACE	moderate	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Centrin-3 (CETN3).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Centrin-3 (CETN3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Centrin-3 (CETN3).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Centrin-3 (CETN3).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Centrin-3 (CETN3).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Centrin-3 (CETN3).	[7]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Centrin-3 (CETN3).	[9]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Centrin-3 (CETN3).	[10]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Centrin-3 (CETN3).	[11]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Centrin-3 (CETN3).	[12]
Paraquat	DMR8O3X	Investigative	Paraquat decreases the expression of Centrin-3 (CETN3).	[13]

References

• [1] Differential expression of centrosome-associated proteins in human brain tumors: a possible role of hNinein isoform 6 in cell differentiation.Biofactors. 2012 Nov-Dec;38(6):470-7. doi: 10.1002/biof.1053. Epub 2012 Oct 10.
• [2] Companied P16 genetic and protein status together providing useful information on the clinical outcome of urinary bladder cancer.Medicine (Baltimore). 2018 Apr;97(15):e0353. doi: 10.1097/MD.0000000000010353.
• [3] Comparison of structural genetics of non-schistosoma-associated squamous cell carcinoma of the urinary bladder.Int J Clin Exp Pathol. 2015 Jul 1;8(7):8143-58. eCollection 2015.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [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] Rosiglitazone sensitizes MDA-MB-231 breast cancer cells to anti-tumour effects of tumour necrosis factor-alpha, CH11 and CYC202. Endocr Relat Cancer. 2007 Jun;14(2):305-15. doi: 10.1677/ERC-06-0003.
• [10] Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
• [11] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [12] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.
• [13] An in vitro strategy using multiple human induced pluripotent stem cell-derived models to assess the toxicity of chemicals: A case study on paraquat. Toxicol In Vitro. 2022 Jun;81:105333. doi: 10.1016/j.tiv.2022.105333. Epub 2022 Feb 16.