Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKTKCT1)

DOT Name	E3 ubiquitin-protein ligase TRIM52 (TRIM52)
Synonyms	EC 2.3.2.27; RING finger protein 102; Tripartite motif-containing protein 52
Gene Name	TRIM52
Related Disease	Advanced cancer ( ) Colorectal carcinoma ( ) Epithelial ovarian cancer ( ) Hepatitis B virus infection ( ) Hepatocellular carcinoma ( ) Lung cancer ( ) Lung carcinoma ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Neoplasm ( )
UniProt ID	TRI52_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	2.3.2.27
Pfam ID	PF00643 ; PF15227
Sequence	MAGYATTPSPMQTLQEEAVCAICLDYFKDPVSISCGHNFCRGCVTQLWSKEDEEDQNEEE DEWEEEEDEEAVGAMDGWDGSIREVLYRGNADEELFQDQDDDELWLGDSGITNWDNVDYM WDEEEEEEEEDQDYYLGGLRPDLRIDVYREEEILEAYDEDEDEELYPDIHPPPSLPLPGQ FTCPQCRKSFTRRSFRPNLQLANMVQIIRQMCPTPYRGNRSNDQGMCFKHQEALKLFCEV DKEAICVVCRESRSHKQHSVLPLEEVVQEYQEIKLETTLVGILQIEQESIHSKAYNQ
Function	E3 ubiquitin-protein ligase. Positively regulates the NF-kappa-B signaling pathway ; (Microbial infection) Exhibits antiviral activity against Japanese encephalitis virus (JEV). Ubiquitinates the viral non-structural protein 2 (NS2A) and targets it for proteasome-mediated degradation.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[1]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[4]
Lung cancer	DISCM4YA	Strong	Biomarker	[5]
Lung carcinoma	DISTR26C	Strong	Biomarker	[5]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Altered Expression	[2]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

9 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 E3 ubiquitin-protein ligase TRIM52 (TRIM52).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of E3 ubiquitin-protein ligase TRIM52 (TRIM52).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of E3 ubiquitin-protein ligase TRIM52 (TRIM52).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of E3 ubiquitin-protein ligase TRIM52 (TRIM52).	[9]
Selenium	DM25CGV	Approved	Selenium decreases the expression of E3 ubiquitin-protein ligase TRIM52 (TRIM52).	[10]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of E3 ubiquitin-protein ligase TRIM52 (TRIM52).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of E3 ubiquitin-protein ligase TRIM52 (TRIM52).	[6]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of E3 ubiquitin-protein ligase TRIM52 (TRIM52).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of E3 ubiquitin-protein ligase TRIM52 (TRIM52).	[13]
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References

1	TRIM52 plays an oncogenic role in ovarian cancer associated with NF-kB pathway.Cell Death Dis. 2018 Sep 5;9(9):908. doi: 10.1038/s41419-018-0881-6.
2	TRIM52 promotes colorectal cancer cell proliferation through the STAT3 signaling.Cancer Cell Int. 2019 Mar 14;19:57. doi: 10.1186/s12935-019-0775-4. eCollection 2019.
3	Tripartite Motif Containing 52 (TRIM52) Promotes Cell Proliferation in Hepatitis B Virus-Associated Hepatocellular Carcinoma.Med Sci Monit. 2017 Nov 1;23:5202-5210. doi: 10.12659/msm.907242.
4	TRIM52 up-regulation in hepatocellular carcinoma cells promotes proliferation, migration and invasion through the ubiquitination of PPM1A.J Exp Clin Cancer Res. 2018 Jun 13;37(1):116. doi: 10.1186/s13046-018-0780-9.
5	TRIM52 regulates the proliferation and invasiveness of lung cancer cells via the Wnt/catenin pathway.Oncol Rep. 2019 Jun;41(6):3325-3334. doi: 10.3892/or.2019.7110. Epub 2019 Apr 11.
6	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.
7	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.
8	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.
9	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.
10	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.
11	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.
12	Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
13	A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.