General Information of Drug Off-Target (DOT) (ID: OTEFU9Y2)

DOT Name Zinc finger protein RFP (TRIM27)
Synonyms EC 2.3.2.27; RING finger protein 76; Ret finger protein; Tripartite motif-containing protein 27
Gene Name TRIM27
UniProt ID
TRI27_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
MASGSVAECLQQETTCPVCLQYFAEPMMLDCGHNICCACLARCWGTAETNVSCPQCRETF
PQRHMRPNRHLANVTQLVKQLRTERPSGPGGEMGVCEKHREPLKLYCEEDQMPICVVCDR
SREHRGHSVLPLEEAVEGFKEQIQNQLDHLKRVKDLKKRRRAQGEQARAELLSLTQMERE
KIVWEFEQLYHSLKEHEYRLLARLEELDLAIYNSINGAITQFSCNISHLSSLIAQLEEKQ
QQPTRELLQDIGDTLSRAERIRIPEPWITPPDLQEKIHIFAQKCLFLTESLKQFTEKMQS
DMEKIQELREAQLYSVDVTLDPDTAYPSLILSDNLRQVRYSYLQQDLPDNPERFNLFPCV
LGSPCFIAGRHYWEVEVGDKAKWTIGVCEDSVCRKGGVTSAPQNGFWAVSLWYGKEYWAL
TSPMTALPLRTPLQRVGIFLDYDAGEVSFYNVTERCHTFTFSHATFCGPVRPYFSLSYSG
GKSAAPLIICPMSGIDGFSGHVGNHGHSMETSP
Function
E3 ubiquitin-protein ligase that mediates ubiquitination of various substrates and thereby plays a role in diffent processes including proliferation, innate immunity, apoptosis, immune response or autophagy. Ubiquitinates PIK3C2B and inhibits its activity by mediating the formation of 'Lys-48'-linked polyubiquitin chains; the function inhibits CD4 T-cell activation. Acts as a regulator of retrograde transport: together with MAGEL2, mediates the formation of 'Lys-63'-linked polyubiquitin chains at 'Lys-220' of WASHC1, leading to promote endosomal F-actin assembly. Has a transcriptional repressor activity by cooperating with EPC1. Induces apoptosis by activating Jun N-terminal kinase and p38 kinase and also increases caspase-3-like activity independently of mitochondrial events. May function in male germ cell development. Has DNA-binding activity and preferentially bound to double-stranded DNA. Forms a complex with and ubiquitinates the ubiquitin-specific protease USP7, which in turn deubiquitinates RIPK1 resulting in the positive regulation of TNF-alpha-induced apoptosis. In addition, acts with USP7 or PTPN11 as an inhibitor of the antiviral signaling pathway by promoting kinase TBK1 ubiquitination and degradation. Acts as a negative regulator of NOD2 signaling by mediating ubiquitination of NOD2, promoting its degradation by the proteasome. Alternatively, facilitates mitophagy via stabilization of active TBK1. Negatively regulates autophagy flux under basal conditions by directly polyubiquitinating ULK1. During starvation-induced autophagy, catalyzes non-degradative ubiquitination of the kinase STK38L promoting its activation and phosphorylation of ULK1 leading to its ubiquitination and degradation to restrain the amplitude and duration of autophagy ; (Microbial infection) Positively regulates hepatitis C virus replication by suppressing type I IFN response during infection.
Tissue Specificity Expressed in testis namely within the seminiferous tubules.
Reactome Pathway
Regulation of PTEN stability and activity (R-HSA-8948751 )
Suppression of apoptosis (R-HSA-9635465 )
SUMOylation of ubiquitinylation proteins (R-HSA-3232142 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
12 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Zinc finger protein RFP (TRIM27). [1]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Zinc finger protein RFP (TRIM27). [2]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Zinc finger protein RFP (TRIM27). [3]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Zinc finger protein RFP (TRIM27). [4]
Ivermectin DMDBX5F Approved Ivermectin decreases the expression of Zinc finger protein RFP (TRIM27). [5]
Temozolomide DMKECZD Approved Temozolomide increases the expression of Zinc finger protein RFP (TRIM27). [6]
Marinol DM70IK5 Approved Marinol decreases the expression of Zinc finger protein RFP (TRIM27). [7]
Selenium DM25CGV Approved Selenium decreases the expression of Zinc finger protein RFP (TRIM27). [8]
Tocopherol DMBIJZ6 Phase 2 Tocopherol decreases the expression of Zinc finger protein RFP (TRIM27). [8]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Zinc finger protein RFP (TRIM27). [10]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Zinc finger protein RFP (TRIM27). [12]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Zinc finger protein RFP (TRIM27). [13]
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⏷ Show the Full List of 12 Drug(s)
3 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 increases the methylation of Zinc finger protein RFP (TRIM27). [9]
TAK-243 DM4GKV2 Phase 1 TAK-243 increases the sumoylation of Zinc finger protein RFP (TRIM27). [11]
Octanal DMTN0OK Investigative Octanal increases the methylation of Zinc finger protein RFP (TRIM27). [14]
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References

1 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
2 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.
3 Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
4 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.
5 Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
6 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.
7 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
8 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.
9 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.
10 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
11 Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
12 Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
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.
14 DNA Methylome Analysis of Saturated Aliphatic Aldehydes in Pulmonary Toxicity. Sci Rep. 2018 Jul 12;8(1):10497. doi: 10.1038/s41598-018-28813-z.