Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSRL6QO)

• DOT Name: U5 small nuclear ribonucleoprotein 40 kDa protein (SNRNP40)
• Synonyms: U5 snRNP 40 kDa protein; U5-40K; 38 kDa-splicing factor; Prp8-binding protein; hPRP8BP; U5 snRNP-specific 40 kDa protein; WD repeat-containing protein 57
• Gene Name: SNRNP40
• Related Disease:
  Immune system disorder
  Immunodeficiency
• UniProt ID: SNR40_HUMAN
• PDB ID: 3JCR; 5MQF; 5O9Z; 5XJC; 5YZG; 5Z56; 5Z57; 5Z58; 6AH0; 6AHD; 6FF7; 6ICZ; 6ID0; 6ID1; 6QDV; 6QW6; 6QX9; 6ZYM; 7ABG; 7ABI; 7DVQ; 7W59; 7W5A; 7W5B; 8C6J; 8CH6
• Pfam ID: PF00400
• Sequence:
  MIEQQKRKGPELPLVPVKRQRHELLLGAGSGPGAGQQQATPGALLQAGPPRCSSLQAPIM
  LLSGHEGEVYCCKFHPNGSTLASAGFDRLILLWNVYGDCDNYATLKGHSGAVMELHYNTD
  GSMLFSASTDKTVAVWDSETGERVKRLKGHTSFVNSCYPARRGPQLVCTGSDDGTVKLWD
  IRKKAAIQTFQNTYQVLAVTFNDTSDQIISGGIDNDIKVWDLRQNKLTYTMRGHADSVTG
  LSLSSEGSYLLSNAMDNTVRVWDVRPFAPKERCVKIFQGNVHNFEKNLLRCSWSPDGSKI
  AAGSADRFVYVWDTTSRRILYKLPGHAGSINEVAFHPDEPIIISASSDKRLYMGEIQ
• Function: Required for pre-mRNA splicing as component of the activated spliceosome. Component of the U5 small nuclear ribonucleoprotein (snRNP) complex and the U4/U6-U5 tri-snRNP complex, building blocks of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable).
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway:
  mRNA Splicing - Minor Pathway (R-HSA-72165)
  mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Immune system disorder	DISAEGPH	Strong	Altered Expression	[1]
Immunodeficiency	DIS093I0	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of U5 small nuclear ribonucleoprotein 40 kDa protein (SNRNP40).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of U5 small nuclear ribonucleoprotein 40 kDa protein (SNRNP40).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of U5 small nuclear ribonucleoprotein 40 kDa protein (SNRNP40).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of U5 small nuclear ribonucleoprotein 40 kDa protein (SNRNP40).	[5]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of U5 small nuclear ribonucleoprotein 40 kDa protein (SNRNP40).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of U5 small nuclear ribonucleoprotein 40 kDa protein (SNRNP40).	[7]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of U5 small nuclear ribonucleoprotein 40 kDa protein (SNRNP40).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of U5 small nuclear ribonucleoprotein 40 kDa protein (SNRNP40).	[12]

3 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 increases the methylation of U5 small nuclear ribonucleoprotein 40 kDa protein (SNRNP40).	[9]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of U5 small nuclear ribonucleoprotein 40 kDa protein (SNRNP40).	[10]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of U5 small nuclear ribonucleoprotein 40 kDa protein (SNRNP40).	[11]

References

• [1] Syndromic immune disorder caused by a viable hypomorphic allele of spliceosome component Snrnp40.Nat Immunol. 2019 Oct;20(10):1322-1334. doi: 10.1038/s41590-019-0464-4. Epub 2019 Aug 19.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [5] 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.
• [6] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.