Details of Drug Off-Target (DOT)

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

• DOT Name: U2 small nuclear ribonucleoprotein A' (SNRPA1)
• Synonyms: U2 snRNP A'
• Gene Name: SNRPA1
• Related Disease:
  Advanced cancer
  Colorectal carcinoma
  Neoplasm
• UniProt ID: RU2A_HUMAN
• PDB ID: 1A9N; 5MQF; 5O9Z; 5XJC; 5YZG; 5Z56; 5Z57; 5Z58; 6AH0; 6AHD; 6FF7; 6ICZ; 6ID0; 6ID1; 6QDV; 6QX9; 6Y53; 6Y5Q; 7A5P; 7ABG; 7ABI; 7EVO; 7VPX; 7W59; 7W5A; 7W5B; 8C6J; 8CH6; 8HK1
• Pfam ID: PF14580
• Sequence:
  MVKLTAELIEQAAQYTNAVRDRELDLRGYKIPVIENLGATLDQFDAIDFSDNEIRKLDGF
  PLLRRLKTLLVNNNRICRIGEGLDQALPCLTELILTNNSLVELGDLDPLASLKSLTYLSI
  LRNPVTNKKHYRLYVIYKVPQVRVLDFQKVKLKERQEAEKMFKGKRGAQLAKDIARRSKT
  FNPGAGLPTDKKKGGPSPGDVEAIKNAIANASTLAEVERLKGLLQSGQIPGRERRSGPTD
  DGEEEMEEDTVTNGS
• Function: Involved in pre-mRNA splicing as component of the spliceosome. Associated with sn-RNP U2, where it contributes to the binding of stem loop IV of U2 snRNA.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway:
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	U2 small nuclear ribonucleoprotein A' (SNRPA1) affects the response to substance of Paclitaxel.	[13]
Topotecan	DMP6G8T	Approved	U2 small nuclear ribonucleoprotein A' (SNRPA1) affects the response to substance of Topotecan.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of U2 small nuclear ribonucleoprotein A' (SNRPA1).	[2]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of U2 small nuclear ribonucleoprotein A' (SNRPA1).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of U2 small nuclear ribonucleoprotein A' (SNRPA1).	[3]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of U2 small nuclear ribonucleoprotein A' (SNRPA1).	[4]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of U2 small nuclear ribonucleoprotein A' (SNRPA1).	[5]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of U2 small nuclear ribonucleoprotein A' (SNRPA1).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of U2 small nuclear ribonucleoprotein A' (SNRPA1).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of U2 small nuclear ribonucleoprotein A' (SNRPA1).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of U2 small nuclear ribonucleoprotein A' (SNRPA1).	[10]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of U2 small nuclear ribonucleoprotein A' (SNRPA1).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of U2 small nuclear ribonucleoprotein A' (SNRPA1).	[12]

References

• [1] An oncogenic gene, SNRPA1, regulates PIK3R1, VEGFC, MKI67, CDK1 and other genes in colorectal cancer.Biomed Pharmacother. 2019 Sep;117:109076. doi: 10.1016/j.biopha.2019.109076. Epub 2019 Jun 14.
• [2] 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.
• [3] 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.
• [4] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [5] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [6] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [7] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [8] 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.
• [9] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [10] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [11] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [13] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.