Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2STDP4)

• DOT Name: Serine/arginine-rich splicing factor 9 (SRSF9)
• Synonyms: Pre-mRNA-splicing factor SRp30C; Splicing factor, arginine/serine-rich 9
• Gene Name: SRSF9
• Related Disease:
  Bladder cancer
  Cervical cancer
  Cervical carcinoma
  Frontotemporal dementia
  Glucocorticoid resistance
  HIV infectious disease
  Pick disease
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: SRSF9_HUMAN
• Pfam ID: PF00076
• Sequence:
  MSGWADERGGEGDGRIYVGNLPTDVREKDLEDLFYKYGRIREIELKNRHGLVPFAFVRFE
  DPRDAEDAIYGRNGYDYGQCRLRVEFPRTYGGRGGWPRGGRNGPPTRRSDFRVLVSGLPP
  SGSWQDLKDHMREAGDVCYADVQKDGVGMVEYLRKEDMEYALRKLDDTKFRSHEGETSYI
  RVYPERSTSYGYSRSRSGSRGRDSPYQSRGSPHYFSPFRPY
• Function: Plays a role in constitutive splicing and can modulate the selection of alternative splice sites. Represses the splicing of MAPT/Tau exon 10.
• Tissue Specificity: Expressed at high levels in the heart, kidney, pancreas and placenta, and at lower levels in the brain, liver, lung and skeletal muscle.
• KEGG Pathway:
  Spliceosome (hsa03040)
  Herpes simplex virus 1 infection (hsa05168)
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  mRNA 3'-end processing (R-HSA-72187)
  Processing of Capped Intron-Containing Pre-mRNA (R-HSA-72203)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  Transport of Mature mRNA derived from an Intron-Containing Transcript (R-HSA-159236)

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bladder cancer	DISUHNM0	Strong	Altered Expression	[1]
Cervical cancer	DISFSHPF	Strong	Biomarker	[2]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[2]
Frontotemporal dementia	DISKYHXL	Strong	Genetic Variation	[3]
Glucocorticoid resistance	DIS3HNXT	Strong	Altered Expression	[4]
HIV infectious disease	DISO97HC	Strong	Biomarker	[5]
Pick disease	DISP6X50	Strong	Genetic Variation	[3]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[1]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[1]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Serine/arginine-rich splicing factor 9 (SRSF9).	[6]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Serine/arginine-rich splicing factor 9 (SRSF9).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine/arginine-rich splicing factor 9 (SRSF9).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Serine/arginine-rich splicing factor 9 (SRSF9).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine/arginine-rich splicing factor 9 (SRSF9).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Serine/arginine-rich splicing factor 9 (SRSF9).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Serine/arginine-rich splicing factor 9 (SRSF9).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Serine/arginine-rich splicing factor 9 (SRSF9).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Serine/arginine-rich splicing factor 9 (SRSF9).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine/arginine-rich splicing factor 9 (SRSF9).	[14]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Serine/arginine-rich splicing factor 9 (SRSF9).	[16]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Serine/arginine-rich splicing factor 9 (SRSF9).	[12]

References

• [1] Tumor suppressive microRNA-1 mediated novel apoptosis pathways through direct inhibition of splicing factor serine/arginine-rich 9 (SRSF9/SRp30c) in bladder cancer.Biochem Biophys Res Commun. 2012 Jan 6;417(1):588-93. doi: 10.1016/j.bbrc.2011.12.011. Epub 2011 Dec 9.
• [2] microRNA-802 inhibits cell proliferation and induces apoptosis in human cervical cancer by targeting serine/arginine-rich splicing factor 9.J Cell Biochem. 2019 Jun;120(6):10370-10379. doi: 10.1002/jcb.28321. Epub 2018 Dec 19.
• [3] Tau exons 2 and 10, which are misregulated in neurodegenerative diseases, are partly regulated by silencers which bind a SRp30c.SRp55 complex that either recruits or antagonizes htra2beta1.J Biol Chem. 2005 Apr 8;280(14):14230-9. doi: 10.1074/jbc.M413846200. Epub 2005 Feb 3.
• [4] Bombesin attenuates pre-mRNA splicing of glucocorticoid receptor by regulating the expression of serine-arginine protein p30c (SRp30c) in prostate cancer cells.Biochim Biophys Acta. 2007 Jul;1773(7):1087-94. doi: 10.1016/j.bbamcr.2007.04.016. Epub 2007 May 3.
• [5] Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency.J Virol. 2004 Sep;78(17):9458-73. doi: 10.1128/JVI.78.17.9458-9473.2004.
• [6] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [11] 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.
• [12] Proteomic analysis of the cellular response to a potent sensitiser unveils the dynamics of haptenation in living cells. Toxicology. 2020 Dec 1;445:152603. doi: 10.1016/j.tox.2020.152603. Epub 2020 Sep 28.
• [13] Comparison of quantitation methods in proteomics to define relevant toxicological information on AhR activation of HepG2 cells by BaP. Toxicology. 2021 Jan 30;448:152652. doi: 10.1016/j.tox.2020.152652. Epub 2020 Dec 2.
• [14] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [16] Molecular targets of chloropicrin in human airway epithelial cells. Toxicol In Vitro. 2017 Aug;42:247-254.