Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT37JQ8Y)

DOT Name E3 ubiquitin-protein ligase TRIM36 (TRIM36)
Synonyms EC 2.3.2.27; RING finger protein 98; RING-type E3 ubiquitin transferase TRIM36; Tripartite motif-containing protein 36; Zinc-binding protein Rbcc728
Gene Name TRIM36
Related Disease
Anencephaly ( )
Gastric cancer ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Prostate neoplasm ( )
Stomach cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Anencephaly 1 ( )
UniProt ID
TRI36_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
7QS4
EC Number
2.3.2.27
Pfam ID
PF18568 ; PF00041 ; PF00643 ; PF13445
Sequence
MSESGEMSEFGYIMELIAKGKVTIKNIERELICPACKELFTHPLILPCQHSICHKCVKEL
LLTLDDSFNDVGSDNSNQSSPRLRLPSPSMDKIDRINRPGWKRNSLTPRTTVFPCPGCEH
DVDLGERGINGLFRNFTLETIVERYRQAARAATAIMCDLCKPPPQESTKSCMDCSASYCN
ECFKIHHPWGTIKAQHEYVGPTTNFRPKILMCPEHETERINMYCELCRRPVCHLCKLGGN
HANHRVTTMSSAYKTLKEKLSKDIDYLIGKESQVKSQISELNLLMKETECNGERAKEEAI
THFEKLFEVLEERKSSVLKAIDSSKKLRLDKFQTQMEEYQGLLENNGLVGYAQEVLKETD
QSCFVQTAKQLHLRIQKATESLKSFRPAAQTSFEDYVVNTSKQTELLGELSFFSSGIDVP
EINEEQSKVYNNALINWHHPEKDKADSYVLEYRKINRDDEMSWNEIEVCGTSKIIQDLEN
SSTYAFRVRAYKGSICSPCSRELILHTPPAPVFSFLFDEKCGYNNEHLLLNLKRDRVESR
AGFNLLLAAERIQVGYYTSLDYIIGDTGITKGKHFWAFRVEPYSYLVKVGVASSDKLQEW
LRSPRDAVSPRYEQDSGHDSGSEDACFDSSQPFTLVTIGMQKFFIPKSPTSSNEPENRVL
PMPTSIGIFLDCDKGKVDFYDMDQMKCLYERQVDCSHTLYPAFALMGSGGIQLEEPITAK
YLEYQEDM
Function
E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Involved in chromosome segregation and cell cycle regulation. May play a role in the acrosome reaction and fertilization.
Tissue Specificity Highly expressed in testis, prostate and brain . Weakly expressed in kidney, lung and heart . Expressed in fetal tissues .
Reactome Pathway
Antigen processing (R-HSA-983168 )

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Anencephaly DISIYW6T Strong Genetic Variation [1]
Gastric cancer DISXGOUK Strong Biomarker [2]
Neoplasm DISZKGEW Strong Biomarker [3]
Non-small-cell lung cancer DIS5Y6R9 Strong Posttranslational Modification [4]
Prostate neoplasm DISHDKGQ Strong Altered Expression [3]
Stomach cancer DISKIJSX Strong Biomarker [2]
Prostate cancer DISF190Y moderate Biomarker [5]
Prostate carcinoma DISMJPLE moderate Biomarker [5]
Anencephaly 1 DISJQL5R Limited Unknown [1]
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⏷ Show the Full List of 9 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
10 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin decreases the expression of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [6]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [7]
Selenium DM25CGV Approved Selenium decreases the expression of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [9]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [10]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [11]
Amiodarone DMUTEX3 Phase 2/3 Trial Amiodarone increases the expression of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [12]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [14]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [16]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [17]
GALLICACID DM6Y3A0 Investigative GALLICACID increases the expression of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [18]
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⏷ Show the Full List of 10 Drug(s)
4 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [8]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [13]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [15]
Coumarin DM0N8ZM Investigative Coumarin increases the phosphorylation of E3 ubiquitin-protein ligase TRIM36 (TRIM36). [15]
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References

1 A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family. Hum Mol Genet. 2017 Mar 15;26(6):1104-1114. doi: 10.1093/hmg/ddx020.
2 High expression of TRIM36 is associated with radiosensitivity in gastric cancer.Oncol Lett. 2019 May;17(5):4401-4408. doi: 10.3892/ol.2019.10122. Epub 2019 Mar 7.
3 Cloning and characterisation of the RBCC728/TRIM36 zinc-binding protein from the tumor suppressor gene region at chromosome 5q22.3.Gene. 2004 May 12;332:45-50. doi: 10.1016/j.gene.2004.02.045.
4 (TRIM36 hypermethylation is involved in polycyclic aromatic hydrocarbons-induced cell transformation).Environ Pollut. 2017 Jun;225:93-103. doi: 10.1016/j.envpol.2017.03.001. Epub 2017 Mar 27.
5 TRIM36, a novel androgen-responsive gene, enhances anti-androgen efficacy against prostate cancer by inhibiting MAPK/ERK signaling pathways.Cell Death Dis. 2018 Feb 5;9(2):155. doi: 10.1038/s41419-017-0197-y.
6 Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
7 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
8 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
9 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.
10 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
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 Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
13 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.
14 Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
15 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
16 From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
17 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
18 Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.