Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY6IJ11)

• DOT Name: Serine/arginine-rich splicing factor 10 (SRSF10)
• Synonyms: 40 kDa SR-repressor protein; SRrp40; FUS-interacting serine-arginine-rich protein 1; Splicing factor SRp38; Splicing factor, arginine/serine-rich 13A; TLS-associated protein with Ser-Arg repeats; TASR; TLS-associated protein with SR repeats; TLS-associated serine-arginine protein; TLS-associated SR protein
• Gene Name: SRSF10
• Related Disease:
  Cervical cancer
  Cervical carcinoma
  Colorectal carcinoma
  Neoplasm
  Polycystic ovarian syndrome
  Schizophrenia
  Dental caries
  Endometrial carcinoma
  Endometrium neoplasm
  Hyperglycemia
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: SRS10_HUMAN
• Pfam ID: PF00076
• Sequence:
  MSRYLRPPNTSLFVRNVADDTRSEDLRREFGRYGPIVDVYVPLDFYTRRPRGFAYVQFED
  VRDAEDALHNLDRKWICGRQIEIQFAQGDRKTPNQMKAKEGRNVYSSSRYDDYDRYRRSR
  SRSYERRRSRSRSFDYNYRRSYSPRNSRPTGRPRRSRSHSDNDRFKHRNRSFSRSKSNSR
  SRSKSQPKKEMKAKSRSRSASHTKTRGTSKTDSKTHYKSGSRYEKESRKKEPPRSKSQSR
  SQSRSRSKSRSRSWTSPKSSGH
• Function: Splicing factor that in its dephosphorylated form acts as a general repressor of pre-mRNA splicing. Seems to interfere with the U1 snRNP 5'-splice recognition of SNRNP70. Required for splicing repression in M-phase cells and after heat shock. Also acts as a splicing factor that specifically promotes exon skipping during alternative splicing. Interaction with YTHDC1, a RNA-binding protein that recognizes and binds N6-methyladenosine (m6A)-containing RNAs, prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing. May be involved in regulation of alternative splicing in neurons, with isoform 1 acting as a positive and isoform 3 as a negative regulator.
• Tissue Specificity: Widely expressed.
• KEGG Pathway: Spliceosome (hsa03040)
• 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

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cervical cancer	DISFSHPF	Strong	Biomarker	[1]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[2]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[4]
Dental caries	DISRBCMD	Limited	Genetic Variation	[5]
Endometrial carcinoma	DISXR5CY	Limited	Biomarker	[6]
Endometrium neoplasm	DIS6OS2L	Limited	Biomarker	[6]
Hyperglycemia	DIS0BZB5	Limited	Altered Expression	[7]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[13]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[14]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[15]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate decreases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[16]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[22]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[23]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Serine/arginine-rich splicing factor 10 (SRSF10).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic decreases the methylation of Serine/arginine-rich splicing factor 10 (SRSF10).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Serine/arginine-rich splicing factor 10 (SRSF10).	[17]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Serine/arginine-rich splicing factor 10 (SRSF10).	[18]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Serine/arginine-rich splicing factor 10 (SRSF10).	[21]

References

• [1] SRSF10-mediated IL1RAP alternative splicing regulates cervical cancer oncogenesis via mIL1RAP-NF-B-CD47 axis.Oncogene. 2018 May;37(18):2394-2409. doi: 10.1038/s41388-017-0119-6. Epub 2018 Feb 12.
• [2] BCLAF1 and its splicing regulator SRSF10 regulate the tumorigenic potential of colon cancer cells.Nat Commun. 2014 Aug 5;5:4581. doi: 10.1038/ncomms5581.
• [3] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [4] Decrease in olfactory and taste receptor expression in the dorsolateral prefrontal cortex in chronic schizophrenia.J Psychiatr Res. 2015 Jan;60:109-16. doi: 10.1016/j.jpsychires.2014.09.012. Epub 2014 Oct 2.
• [5] GLUT2 and TAS1R2 Polymorphisms and Susceptibility to Dental Caries.Caries Res. 2015;49(4):417-24. doi: 10.1159/000430958. Epub 2015 Jun 24.
• [6] NSSR1 is regulated by testosterone in the mouse uterus and extensively expressed in endometrial carcinoma.Tumour Biol. 2011 Apr;32(2):359-66. doi: 10.1007/s13277-010-0128-3. Epub 2010 Nov 12.
• [7] Inflammation and hyperglycemia mediate Deaf1 splicing in the pancreatic lymph nodes via distinct pathways during type 1 diabetes.Diabetes. 2015 Feb;64(2):604-17. doi: 10.2337/db14-0803. Epub 2014 Sep 3.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [10] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [11] 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.
• [12] Association of Arsenic Exposure with Whole Blood DNA Methylation: An Epigenome-Wide Study of Bangladeshi Adults. Environ Health Perspect. 2019 May;127(5):57011. doi: 10.1289/EHP3849. Epub 2019 May 28.
• [13] 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.
• [14] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [15] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [16] Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins. Physiol Genomics. 2004 Jan 15;16(2):204-11.
• [17] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [18] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [19] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] 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.
• [22] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [23] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.
• [24] 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.