Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZSV6CZ)

• DOT Name: Serine/arginine-rich splicing factor 11 (SRSF11)
• Synonyms: Arginine-rich 54 kDa nuclear protein; p54; Splicing factor, arginine/serine-rich 11
• Gene Name: SRSF11
• Related Disease:
  Cognitive impairment
  Colon cancer
  Myelodysplastic syndrome
  Neoplasm
  Meningioma
  Rheumatoid arthritis
• UniProt ID: SRS11_HUMAN
• Pfam ID: PF00076
• Sequence:
  MSNTTVVPSTAGPGPSGGPGGGGGGGGGGGGTEVIQVTNVSPSASSEQMRTLFGFLGKID
  ELRLFPPDDSPLPVSSRVCFVKFHDPDSAVVAQHLTNTVFVDRALIVVPYAEGVIPDEAK
  ALSLLAPANAVAGLLPGGGLLPTPNPLTQIGAVPLAALGAPTLDPALAALGLPGANLNSQ
  SLAADQLLKLMSTVDPKLNHVAAGLVSPSLKSDTSSKEIEEAMKRVREAQSLISAAIEPD
  KKEEKRRHSRSRSRSRRRRTPSSSRHRRSRSRSRRRSHSKSRSRRRSKSPRRRRSHSRER
  GRRSRSTSKTRDKKKEDKEKKRSKTPPKSYSTARRSRSASRERRRRRSRSGTRSPKKPRS
  PKRKLSRSPSPRRHKKEKKKDKDKERSRDERERSTSKKKKSKDKEKDRERKSESDKDVKQ
  VTRDYDEEEQGYDSEKEKKEEKKPIETGSPKTKECSVEKGTGDSLRESKVNGDDHHEEDM
  DMSD
• Function: May function in pre-mRNA splicing.
• 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cognitive impairment	DISH2ERD	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[2]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[3]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[4]
Meningioma	DISPT4TG	moderate	Biomarker	[5]
Rheumatoid arthritis	DISTSB4J	Disputed	Altered Expression	[6]

16 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 11 (SRSF11).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[14]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[15]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[16]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[17]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[18]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[19]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[18]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[23]
cinnamaldehyde	DMZDUXG	Investigative	cinnamaldehyde increases the expression of Serine/arginine-rich splicing factor 11 (SRSF11).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Serine/arginine-rich splicing factor 11 (SRSF11).	[12]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Serine/arginine-rich splicing factor 11 (SRSF11).	[20]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Serine/arginine-rich splicing factor 11 (SRSF11).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Serine/arginine-rich splicing factor 11 (SRSF11).	[22]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Serine/arginine-rich splicing factor 11 (SRSF11).	[21]

References

• [1] SFRS11 Loss Leads to Aging-Associated Cognitive Decline by Modulating LRP8 and ApoE.Cell Rep. 2019 Jul 2;28(1):78-90.e6. doi: 10.1016/j.celrep.2019.06.002.
• [2] Structural Mechanism of the Oxygenase JMJD6 Recognition by the Extraterminal (ET) Domain of BRD4.Sci Rep. 2017 Nov 24;7(1):16272. doi: 10.1038/s41598-017-16588-8.
• [3] Discovering transcription and splicing networks in myelodysplastic syndromes.PLoS One. 2013 Nov 14;8(11):e79118. doi: 10.1371/journal.pone.0079118. eCollection 2013.
• [4] Machine learning for semi-automated classification of glioblastoma, brain metastasis and central nervous system lymphoma using magnetic resonance advanced imaging.Ann Transl Med. 2019 Jun;7(11):232. doi: 10.21037/atm.2018.08.05.
• [5] A comparison of the prevalence and risk factors of complications in intracranial tumor embolization between the Japanese Registry of NeuroEndovascular Therapy 2 (JR-NET2) and JR-NET3.Acta Neurochir (Wien). 2019 Aug;161(8):1675-1682. doi: 10.1007/s00701-019-03970-w. Epub 2019 Jun 7.
• [6] P54/nrb prompts rheumatoid arthritis progression mainly by transcriptionally activating NF-B signaling.Pharmazie. 2017 May 1;72(5):260-264. doi: 10.1691/ph.2017.6904.
• [7] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [8] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [9] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [10] 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.
• [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] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [13] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [14] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [15] 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.
• [16] 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.
• [17] Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray. Cancer Lett. 2004 Oct 8;214(1):19-33.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] 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.
• [20] 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.
• [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] Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int J Oncol. 2012 Jul;41(1):369-77.
• [23] 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.
• [24] Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde. Toxicol Appl Pharmacol. 2009 Sep 15;239(3):273-83.