Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFDQT4E)

DOT Name E3 ubiquitin-protein ligase TRIM45 (TRIM45)
Synonyms EC 2.3.2.27; RING finger protein 99
Gene Name TRIM45
Related Disease
Adult glioblastoma ( )
Advanced cancer ( )
Glioblastoma multiforme ( )
Glioma ( )
Lung cancer ( )
Lung carcinoma ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
UniProt ID
TRI45_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2DS4
EC Number
2.3.2.27
Pfam ID
PF00630 ; PF00643 ; PF13445
Sequence
MSENRKPLLGFVSKLTSGTALGNSGKTHCPLCLGLFKAPRLLPCLHTVCTTCLEQLEPFS
VVDIRGGDSDTSSEGSIFQELKPRSLQSQIGILCPVCDAQVDLPMGGVKALTIDHLAVND
VMLESLRGEGQGLVCDLCNDREVEKRCQTCKANLCHFCCQAHRRQKKTTYHTMVDLKDLK
GYSRIGKPILCPVHPAEELRLFCEFCDRPVCQDCVVGEHREHPCDFTSNVIHKHGDSVWE
LLKGTQPHVEALEEALAQIHIINSALQKRVEAVAADVRTFSEGYIKAIEEHRDKLLKQLE
DIRAQKENSLQLQKAQLEQLLADMRTGVEFTEHLLTSGSDLEILITKRVVVERLRKLNKV
QYSTRPGVNDKIRFCPQEKAGQCRGYEIYGTINTKEVDPAKCVLQGEDLHRAREKQTASF
TLLCKDAAGEIMGRGGDNVQVAVVPKDKKDSPVRTMVQDNKDGTYYISYTPKEPGVYTVW
VCIKEQHVQGSPFTVMVRRKHRPHSGVFHCCTFCSSGGQKTARCACGGTMPGGYLGCGHG
HKGHPGHPHWSCCGKFNEKSECTWTGGQSAPRSLLRTVAL
Function
E3 ubiquitin-protein ligase that plays a role in the regulation of inflammatory response. Mechanistically, mediates the 'Lys-48'-linked polyubiquitination of TAB2, a regulatory protein of the kinase TAK1, leading to its degradation via the proteasomal pathway and inhibition of the TLR-mediated inflammatory immune response. May act as a transcriptional repressor in mitogen-activated protein kinase signaling pathway.
Tissue Specificity Expressed in skeletal muscle, brain, heart and pancreas.
Reactome Pathway
Interferon gamma signaling (R-HSA-877300 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Strong Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Glioblastoma multiforme DISK8246 Strong Biomarker [1]
Glioma DIS5RPEH Strong Biomarker [1]
Lung cancer DISCM4YA Strong Altered Expression [2]
Lung carcinoma DISTR26C Strong Altered Expression [2]
Neoplasm DISZKGEW Strong Biomarker [2]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [2]
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Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of E3 ubiquitin-protein ligase TRIM45 (TRIM45). [3]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of E3 ubiquitin-protein ligase TRIM45 (TRIM45). [4]
Tretinoin DM49DUI Approved Tretinoin increases the expression of E3 ubiquitin-protein ligase TRIM45 (TRIM45). [5]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of E3 ubiquitin-protein ligase TRIM45 (TRIM45). [6]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of E3 ubiquitin-protein ligase TRIM45 (TRIM45). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of E3 ubiquitin-protein ligase TRIM45 (TRIM45). [8]
GALLICACID DM6Y3A0 Investigative GALLICACID decreases the expression of E3 ubiquitin-protein ligase TRIM45 (TRIM45). [9]
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⏷ Show the Full List of 7 Drug(s)

References

1 TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination.Cell Death Dis. 2017 May 25;8(5):e2831. doi: 10.1038/cddis.2017.149.
2 TRIM45 Suppresses the Development of Non-small Cell Lung Cancer.Curr Mol Med. 2020;20(4):299-306. doi: 10.2174/1566524019666191017143833.
3 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
4 Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
5 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
6 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
7 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
8 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
9 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.