Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2L4STK)

DOT Name E3 ubiquitin-protein ligase TRIM48 (TRIM48)
Synonyms EC 2.3.2.27; RING finger protein 101; Tripartite motif-containing protein 48
Gene Name TRIM48
Related Disease
Adult glioblastoma ( )
Glioblastoma multiforme ( )
UniProt ID
TRI48_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
PF00643 ; PF15227
Sequence
MSRRIIVGTLQRTQRNMNSGISQVFQRELTCPICMNYFIDPVTIDCGHSFCRPCFYLNWQ
DIPILTQCFECIKTIQQRNLKTNIRLKKMASLARKASLWLFLSSEEQMCGIHRETKKMFC
EVDRSLLCLLCSSSQEHRYHRHCPAEWAAEEHWEKLLKKMQSLWEKACENQRNLNVETTR
ISHWKAFGDILYRSESVLLHMPQPLNLALRAGPITGLRDRLNQF
Function
E3 ubiquitin-protein ligase which promotes K48-linked polyubiquitination of protein methyltransferase PRMT1, leading to PRMT1 degradation. This suppresses methylation of the PRMT1 substrate MAP3K5/ASK1, promoting its activation and increasing MAP3K5-dependent cell death induced by oxidative stress. TRIM48-mediated ubiquitination of PRMT1 also suppresses methylation of FOXO1 by PRMT1, leading to inhibition of FOXO1 transcriptional activity.
Reactome Pathway
Interferon gamma signaling (R-HSA-877300 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Definitive Altered Expression [1]
Glioblastoma multiforme DISK8246 Definitive Biomarker [1]
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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
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of E3 ubiquitin-protein ligase TRIM48 (TRIM48). [2]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of E3 ubiquitin-protein ligase TRIM48 (TRIM48). [3]
Testosterone DM7HUNW Approved Testosterone increases the expression of E3 ubiquitin-protein ligase TRIM48 (TRIM48). [3]
Malathion DMXZ84M Approved Malathion decreases the expression of E3 ubiquitin-protein ligase TRIM48 (TRIM48). [4]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of E3 ubiquitin-protein ligase TRIM48 (TRIM48). [5]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of E3 ubiquitin-protein ligase TRIM48 (TRIM48). [6]
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⏷ Show the Full List of 6 Drug(s)

References

1 Overexpression of Tripartite Motif-Containing 48 (TRIM48) Inhibits Growth of Human Glioblastoma Cells by Suppressing Extracellular Signal Regulated Kinase 1/2 (ERK1/2) Pathway.Med Sci Monit. 2019 Nov 8;25:8422-8429. doi: 10.12659/MSM.916024.
2 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
3 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
4 Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
5 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.
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.