Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT80PQWX)

• DOT Name: Tetratricopeptide repeat protein 39A (TTC39A)
• Synonyms: TPR repeat protein 39A; Differentially expressed in MCF-7 with estradiol protein 6; DEME-6
• Gene Name: TTC39A
• Related Disease:
  Breast carcinoma
  Liver cancer
• UniProt ID: TT39A_HUMAN
• Pfam ID: PF10300
• Sequence:
  MGQKGHKDSLYPCGGTPESSLHEALDQCMTALDLFLTNQFSEALSYLKPRTKESMYHSLT
  YATILEMQAMMTFDPQDILLAGNMMKEAQMLCQRHRRKSSVTDSFSSLVNRPTLGQFTEE
  EIHAEVCYAECLLQRAALTFLQGSSHGGAVRPRALHDPSHACSCPPGPGRQHLFLLQDEN
  MVSFIKGGIKVRNSYQTYKELDSLVQSSQYCKGENHPHFEGGVKLGVGAFNLTLSMLPTR
  ILRLLEFVGFSGNKDYGLLQLEEGASGHSFRSVLCVMLLLCYHTFLTFVLGTGNVNIEEA
  EKLLKPYLNRYPKGAIFLFFAGRIEVIKGNIDAAIRRFEECCEAQQHWKQFHHMCYWELM
  WCFTYKGQWKMSYFYADLLSKENCWSKATYIYMKAAYLSMFGKEDHKPFGDDEVELFRAV
  PGLKLKIAGKSLPTEKFAIRKSRRYFSSNPISLPVPALEMMYIWNGYAVIGKQPKLTDGI
  LEIITKAEEMLEKGPENEYSVDDECLVKLLKGLCLKYLGRVQEAEENFRSISANEKKIKY
  DHYLIPNALLELALLLMEQDRNEEAIKLLESAKQNYKNYSMESRTHFRIQAATLQAKSSL
  ENSSRSMVSSVSL

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Liver cancer	DISDE4BI	Strong	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 increases the methylation of Tetratricopeptide repeat protein 39A (TTC39A).	[3]

12 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 Tetratricopeptide repeat protein 39A (TTC39A).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tetratricopeptide repeat protein 39A (TTC39A).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Tetratricopeptide repeat protein 39A (TTC39A).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tetratricopeptide repeat protein 39A (TTC39A).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tetratricopeptide repeat protein 39A (TTC39A).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Tetratricopeptide repeat protein 39A (TTC39A).	[8]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Tetratricopeptide repeat protein 39A (TTC39A).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Tetratricopeptide repeat protein 39A (TTC39A).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tetratricopeptide repeat protein 39A (TTC39A).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tetratricopeptide repeat protein 39A (TTC39A).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tetratricopeptide repeat protein 39A (TTC39A).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tetratricopeptide repeat protein 39A (TTC39A).	[14]

References

• [1] Differential screening and suppression subtractive hybridization identified genes differentially expressed in an estrogen receptor-positive breast carcinoma cell line.Nucleic Acids Res. 1998 Feb 15;26(4):1116-23. doi: 10.1093/nar/26.4.1116.
• [2] A comparison of transcriptomic and metabonomic technologies for identifying biomarkers predictive of two-year rodent cancer bioassays.Toxicol Sci. 2007 Mar;96(1):40-6. doi: 10.1093/toxsci/kfl171. Epub 2006 Nov 17.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [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] Epidermal growth factor receptor signalling in human breast cancer cells operates parallel to estrogen receptor alpha signalling and results in tamoxifen insensitive proliferation. BMC Cancer. 2014 Apr 23;14:283.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [11] 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.
• [12] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [13] BET bromodomain inhibition of MYC-amplified medulloblastoma. Clin Cancer Res. 2014 Feb 15;20(4):912-25.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.