Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYRRYP5)

DOT Name	Splicing regulator SDE2 (SDE2)
Synonyms	Replication stress response regulator SDE2
Gene Name	SDE2
UniProt ID	SDE2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	6QDV; 7N99; 8C6J
Pfam ID	PF13297 ; PF13019
Sequence	MAEAAALVWIRGPGFGCKAVRCASGRCTVRDFIHRHCQDQNVPVENFFVKCNGALINTSD TVQHGAVYSLEPRLCGGKGGFGSMLRALGAQIEKTTNREACRDLSGRRLRDVNHEKAMAE WVKQQAEREAEKEQKRLERLQRKLVEPKHCFTSPDYQQQCHEMAERLEDSVLKGMQAASS KMVSAEISENRKRQWPTKSQTDRGASAGKRRCFWLGMEGLETAEGSNSESSDDDSEEAPS TSGMGFHAPKIGSNGVEMAAKFPSGSQRARVVNTDHGSPEQLQIPVTDSGRHILEDSCAE LGESKEHMESRMVTETEETQEKKAESKEPIEEEPTGAGLNKDKETEERTDGERVAEVAPE ERENVAVAKLQESQPGNAVIDKETIDLLAFTSVAELELLGLEKLKCELMALGLKCGGTLQ ERAARLFSVRGLAKEQIDPALFAKPLKGKKK
Function	Inhibits translesion DNA synthesis by preventing monoubiquitination of PCNA, this is necessary to counteract damage due to ultraviolet light-induced replication stress. SDE2 is cleaved following PCNA binding, and its complete degradation is necessary to allow S-phase progression following DNA damage ; Plays a role in pre-mRNA splicing by facilitating excision of relatively short introns featuring weak 3'-splice sites (ss) and high GC content. May recruit CACTIN to the spliceosome; Plays a role in ribosome biogenesis by enabling SNORD3- and SNORD118-dependent cleavage of the 47S rRNA precursor. Binds ncRNA (non-coding RNA) including the snoRNAs SNORD3 and SNORD118.
Tissue Specificity	Ubiquitously expressed; enriched in brain, lung and liver.
Reactome Pathway	mRNA Splicing - Major Pathway (R-HSA-72163 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

11 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Splicing regulator SDE2 (SDE2).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Splicing regulator SDE2 (SDE2).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Splicing regulator SDE2 (SDE2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Splicing regulator SDE2 (SDE2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Splicing regulator SDE2 (SDE2).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Splicing regulator SDE2 (SDE2).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Splicing regulator SDE2 (SDE2).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Splicing regulator SDE2 (SDE2).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Splicing regulator SDE2 (SDE2).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Splicing regulator SDE2 (SDE2).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Splicing regulator SDE2 (SDE2).	[11]
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⏷ Show the Full List of 11 Drug(s)

References

1	Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
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	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6	Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
7	Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
8	Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
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	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.
11	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.