Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZE5W6G)

• DOT Name: Small nuclear ribonucleoprotein F (SNRPF)
• Synonyms: snRNP-F; Sm protein F; Sm-F; SmF
• Gene Name: SNRPF
• Related Disease:
  Parkinson disease
  Primary myelofibrosis
  Pulmonary emphysema
  Rhabdomyosarcoma
• UniProt ID: RUXF_HUMAN
• PDB ID: 3CW1 ; 3JCR ; 3PGW ; 4F7U ; 4PJO ; 4V98 ; 4WZJ ; 5MQF ; 5O9Z ; 5XJC ; 5XJL ; 5XJQ ; 5XJR ; 5XJS ; 5XJT ; 5XJU ; 5YZG ; 5Z56 ; 5Z57 ; 5Z58 ; 6AH0 ; 6FF7 ; 6ICZ ; 6ID0 ; 6ID1 ; 6QDV ; 6QW6 ; 6QX9 ; 6V4X ; 6Y53 ; 6Y5Q ; 7A5P ; 7ABG ; 7ABI ; 7B0Y ; 7DVQ ; 7EVO ; 7QTT ; 7VPX ; 7W59 ; 7W5A ; 7W5B ; 8C6J ; 8CH6 ; 8HK1
• Pfam ID: PF01423
• Sequence:
  MSLPLNPKPFLNGLTGKPVMVKLKWGMEYKGYLVSVDGYMNMQLANTEEYIDGALSGHLG
  EVLIRCNNVLYIRGVEEEEEDGEMRE
• Function: Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. As part of the U7 snRNP it is involved in histone 3'-end processing.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway:
  snRNP Assembly (R-HSA-191859)
  mRNA Splicing - Major Pathway (R-HSA-72163)
  mRNA Splicing - Minor Pathway (R-HSA-72165)
  RNA Polymerase II Transcription Termination (R-HSA-73856)
  SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs (R-HSA-77588)
  SARS-CoV-2 modulates host translation machinery (R-HSA-9754678)
  SLBP independent Processing of Histone Pre-mRNAs (R-HSA-111367)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Strong	Altered Expression	[1]
Primary myelofibrosis	DIS6L0CN	Strong	Biomarker	[2]
Pulmonary emphysema	DIS5M7HZ	Strong	Genetic Variation	[3]
Rhabdomyosarcoma	DISNR7MS	Strong	Biomarker	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Irinotecan	DMP6SC2	Approved	Small nuclear ribonucleoprotein F (SNRPF) increases the response to substance of Irinotecan.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Small nuclear ribonucleoprotein F (SNRPF).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Small nuclear ribonucleoprotein F (SNRPF).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Small nuclear ribonucleoprotein F (SNRPF).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small nuclear ribonucleoprotein F (SNRPF).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Small nuclear ribonucleoprotein F (SNRPF).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Small nuclear ribonucleoprotein F (SNRPF).	[10]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Small nuclear ribonucleoprotein F (SNRPF).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Small nuclear ribonucleoprotein F (SNRPF).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Small nuclear ribonucleoprotein F (SNRPF).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small nuclear ribonucleoprotein F (SNRPF).	[15]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Small nuclear ribonucleoprotein F (SNRPF).	[16]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Small nuclear ribonucleoprotein F (SNRPF).	[17]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Small nuclear ribonucleoprotein F (SNRPF).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Small nuclear ribonucleoprotein F (SNRPF).	[12]

References

• [1] The metal transporter SMF-3/DMT-1 mediates aluminum-induced dopamine neuron degeneration. J Neurochem. 2013 Jan;124(1):147-57. doi: 10.1111/jnc.12072. Epub 2012 Nov 21.
• [2] Post-ET and Post-PV Myelofibrosis: Updates on a Distinct Prognosis from Primary Myelofibrosis.Curr Hematol Malig Rep. 2018 Jun;13(3):173-182. doi: 10.1007/s11899-018-0453-y.
• [3] Genome-wide study of percent emphysema on computed tomography in the general population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study.Am J Respir Crit Care Med. 2014 Feb 15;189(4):408-18. doi: 10.1164/rccm.201306-1061OC.
• [4] Cloning and identification of genes differentially expressed in metastatic and non-metastatic rat rhabdomyosarcoma cell lines.Clin Exp Metastasis. 1995 Sep;13(5):345-56. doi: 10.1007/BF00121911.
• [5] 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.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] 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.
• [9] 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.
• [10] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [11] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [12] 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.
• [13] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [14] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [17] ST1926, a novel and orally active retinoid-related molecule inducing apoptosis in myeloid leukemia cells: modulation of intracellular calcium homeostasis. Blood. 2004 Jan 1;103(1):194-207.
• [18] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.
• [19] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.