Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT18J6E8)

• DOT Name: Small nuclear ribonucleoprotein E (SNRPE)
• Synonyms: snRNP-E; Sm protein E; Sm-E; SmE
• Gene Name: SNRPE
• Related Disease:
  Intellectual disability
  Isolated congenital microcephaly
  Neoplasm
  Fibrosarcoma
  Hypotrichosis 11
  Lupus nephritis
  Hypotrichosis simplex
• UniProt ID: RUXE_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:
  MAYRGQGQKVQKVMVQPINLIFRYLQNRSRIQVWLYEQVNMRIEGCIIGFDEYMNLVLDD
  AEEIHSKTKSRKQLGRIMLKGDNITLLQSVSN
• 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.
• Tissue Specificity: Widely expressed. In scalp skin, it is present in the hair follicle, the epidermis, and the dermis.
• 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

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability	DISMBNXP	Definitive	Genetic Variation	[1]
Isolated congenital microcephaly	DISUXHZ6	Definitive	Genetic Variation	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[2]
Fibrosarcoma	DISWX7MU	Strong	Altered Expression	[3]
Hypotrichosis 11	DISW3BLY	Strong	Autosomal dominant	[4]
Lupus nephritis	DISCVGPZ	Strong	Therapeutic	[5]
Hypotrichosis simplex	DIS8WHDJ	Supportive	Autosomal dominant	[4]

11 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 Small nuclear ribonucleoprotein E (SNRPE).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Small nuclear ribonucleoprotein E (SNRPE).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small nuclear ribonucleoprotein E (SNRPE).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Small nuclear ribonucleoprotein E (SNRPE).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Small nuclear ribonucleoprotein E (SNRPE).	[10]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Small nuclear ribonucleoprotein E (SNRPE).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Small nuclear ribonucleoprotein E (SNRPE).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small nuclear ribonucleoprotein E (SNRPE).	[13]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Small nuclear ribonucleoprotein E (SNRPE).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Small nuclear ribonucleoprotein E (SNRPE).	[15]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Small nuclear ribonucleoprotein E (SNRPE).	[16]

References

• [1] A missense mutation in SNRPE linked to non-syndromal microcephaly interferes with U snRNP assembly and pre-mRNA splicing.PLoS Genet. 2019 Oct 31;15(10):e1008460. doi: 10.1371/journal.pgen.1008460. eCollection 2019 Oct.
• [2] Genome-wide copy number analyses identified novel cancer genes in hepatocellular carcinoma.Hepatology. 2011 Oct;54(4):1227-36. doi: 10.1002/hep.24495. Epub 2011 Aug 24.
• [3] Inhibitory effects of a benz[f]indole-4,9-dione analog on cancer cell metastasis mediated by the down-regulation of matrix metalloproteinase expression in human HT1080 fibrosarcoma cells.Eur J Pharmacol. 2005 Dec 19;527(1-3):31-6. doi: 10.1016/j.ejphar.2005.10.009. Epub 2005 Nov 23.
• [4] Mutations in SNRPE, which encodes a core protein of the spliceosome, cause autosomal-dominant hypotrichosis simplex. Am J Hum Genet. 2013 Jan 10;92(1):81-7. doi: 10.1016/j.ajhg.2012.10.022. Epub 2012 Dec 13.
• [5] Intravenous injection of a D1 protein of the Smith proteins postpones murine lupus and induces type 1 regulatory T cells.J Immunol. 2004 Nov 1;173(9):5835-42. doi: 10.4049/jimmunol.173.9.5835.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [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] 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.
• [10] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [11] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] 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.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [16] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.