Details of Drug Off-Target (DOT)

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

• DOT Name: Serine/arginine-rich splicing factor 8 (SRSF8)
• Synonyms: Pre-mRNA-splicing factor SRP46; Splicing factor SRp46; Splicing factor, arginine/serine-rich 2B
• Gene Name: SRSF8
• Related Disease: Post-traumatic stress disorder
• UniProt ID: SRSF8_HUMAN
• PDB ID: 2DNM
• Pfam ID: PF00076
• Sequence:
  MSCGRPPPDVDGMITLKVDNLTYRTSPDSLRRVFEKYGRVGDVYIPREPHTKAPRGFAFV
  RFHDRRDAQDAEAAMDGAELDGRELRVQVARYGRRDLPRSRQGEPRGRSRGGGYGRRSRS
  YGRRSRSPRRRHRSRSRGPSCSRSRSRSRYRGSRYSRSPYSRSPYSRSRYSRSPYSRSRY
  RESRYGGSHYSSSGYSNSRYSRYHSSRSHSKSGSSTSSRSASTSKSSSARRSKSSSVSRS
  RSRSRSSSMTRSPPRVSKRKSKSRSRSKRPPKSPEEEGQMSS
• Function: Involved in pre-mRNA alternative splicing.
• Tissue Specificity: Strongly expressed in pancreas, spleen and prostate. Weakly expressed in lung, liver and thymus.
• KEGG Pathway:
  Spliceosome (hsa03040)
  Herpes simplex virus 1 infection (hsa05168)
• Reactome Pathway:
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[1]

12 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 Serine/arginine-rich splicing factor 8 (SRSF8).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Serine/arginine-rich splicing factor 8 (SRSF8).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Serine/arginine-rich splicing factor 8 (SRSF8).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine/arginine-rich splicing factor 8 (SRSF8).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Serine/arginine-rich splicing factor 8 (SRSF8).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Serine/arginine-rich splicing factor 8 (SRSF8).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Serine/arginine-rich splicing factor 8 (SRSF8).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Serine/arginine-rich splicing factor 8 (SRSF8).	[9]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Serine/arginine-rich splicing factor 8 (SRSF8).	[10]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Serine/arginine-rich splicing factor 8 (SRSF8).	[11]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Serine/arginine-rich splicing factor 8 (SRSF8).	[12]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Serine/arginine-rich splicing factor 8 (SRSF8).	[13]

References

• [1] The Effect of Employment Status in Postdisaster Recovery: A Longitudinal Comparative Study Among Employed and Unemployed Affected Residents.J Trauma Stress. 2018 Jun;31(3):460-466. doi: 10.1002/jts.22282.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [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] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] 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.
• [8] 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.
• [9] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [10] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [11] 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.
• [12] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [13] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.