Details of Drug Off-Target (DOT)

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

DOT Name E3 ubiquitin-protein ligase TRIM68 (TRIM68)
Synonyms EC 2.3.2.27; RING finger protein 137; RING-type E3 ubiquitin transferase TRIM68; SSA protein SS-56; SS-56; Tripartite motif-containing protein 68
Gene Name TRIM68
Related Disease
Colorectal carcinoma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Sjogren syndrome ( )
Systemic lupus erythematosus ( )
UniProt ID
TRI68_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
2.3.2.27
Pfam ID
PF13765 ; PF00622 ; PF00643 ; PF15227
Sequence
MDPTALVEAIVEEVACPICMTFLREPMSIDCGHSFCHSCLSGLWEIPGESQNWGYTCPLC
RAPVQPRNLRPNWQLANVVEKVRLLRLHPGMGLKGDLCERHGEKLKMFCKEDVLIMCEAC
SQSPEHEAHSVVPMEDVAWEYKWELHEALEHLKKEQEEAWKLEVGERKRTATWKIQVETR
KQSIVWEFEKYQRLLEKKQPPHRQLGAEVAAALASLQREAAETMQKLELNHSELIQQSQV
LWRMIAELKERSQRPVRWMLQDIQEVLNRSKSWSLQQPEPISLELKTDCRVLGLREILKT
YAADVRLDPDTAYSRLIVSEDRKRVHYGDTNQKLPDNPERFYRYNIVLGSQCISSGRHYW
EVEVGDRSEWGLGVCKQNVDRKEVVYLSPHYGFWVIRLRKGNEYRAGTDEYPILSLPVPP
RRVGIFVDYEAHDISFYNVTDCGSHIFTFPRYPFPGRLLPYFSPCYSIGTNNTAPLAICS
LDGED
Function Functions as a ubiquitin E3 ligase. Acts as a coactivator of androgen receptor (AR) depending on its ubiquitin ligase activity.
Tissue Specificity Widely expressed. Expressed at high levels in prostate cancer cell lines. Up-regulation could be restricted to androgen-dependent cells.
Reactome Pathway
Interferon gamma signaling (R-HSA-877300 )

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colorectal carcinoma DIS5PYL0 Strong Biomarker [1]
Prostate cancer DISF190Y Strong Altered Expression [2]
Prostate carcinoma DISMJPLE Strong Altered Expression [2]
Prostate neoplasm DISHDKGQ Strong Altered Expression [3]
Sjogren syndrome DISUBX7H Strong Biomarker [4]
Systemic lupus erythematosus DISI1SZ7 Strong Biomarker [4]
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⏷ Show the Full List of 6 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 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 TRIM68 (TRIM68). [5]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of E3 ubiquitin-protein ligase TRIM68 (TRIM68). [6]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of E3 ubiquitin-protein ligase TRIM68 (TRIM68). [7]
Decitabine DMQL8XJ Approved Decitabine affects the expression of E3 ubiquitin-protein ligase TRIM68 (TRIM68). [7]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of E3 ubiquitin-protein ligase TRIM68 (TRIM68). [9]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of E3 ubiquitin-protein ligase TRIM68 (TRIM68). [10]
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⏷ Show the Full List of 6 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of E3 ubiquitin-protein ligase TRIM68 (TRIM68). [8]
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References

1 Lentivirus-mediated RNA interference of tripartite motif 68 inhibits the proliferation of colorectal cancer cell lines SW1116 and HCT116 in vitro.Oncol Lett. 2017 Apr;13(4):2649-2655. doi: 10.3892/ol.2017.5787. Epub 2017 Feb 28.
2 Epigenetic deregulation of miR-29a and miR-1256 by isoflavone contributes to the inhibition of prostate cancer cell growth and invasion.Epigenetics. 2012 Aug;7(8):940-9. doi: 10.4161/epi.21236. Epub 2012 Jul 18.
3 TRIM68 regulates ligand-dependent transcription of androgen receptor in prostate cancer cells.Cancer Res. 2008 May 1;68(9):3486-94. doi: 10.1158/0008-5472.CAN-07-6059.
4 SS-56, a novel cellular target of autoantibody responses in Sjgren syndrome and systemic lupus erythematosus.J Clin Invest. 2001 Sep;108(6):861-9. doi: 10.1172/JCI13469.
5 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.
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 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 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.
9 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.
10 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.