Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZXBQ45)

• DOT Name: Small nuclear ribonucleoprotein Sm D3 (SNRPD3)
• Synonyms: Sm-D3; snRNP core protein D3
• Gene Name: SNRPD3
• Related Disease:
  Carcinoma
  Undifferentiated carcinoma
  HIV infectious disease
  Non-small-cell lung cancer
  Lung cancer
  Lung carcinoma
• UniProt ID: SMD3_HUMAN
• PDB ID: 1D3B ; 3CW1 ; 3JCR ; 3PGW ; 3VRI ; 4PJO ; 4WZJ ; 5MQF ; 5O9Z ; 5XJC ; 5YZG ; 5Z56 ; 5Z57 ; 5Z58 ; 6AH0 ; 6AHD ; 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:
  MSIGVPIKVLHEAEGHIVTCETNTGEVYRGKLIEAEDNMNCQMSNITVTYRDGRVAQLEQ
  VYIRGSKIRFLILPDMLKNAPMLKSMKNKNQGSGAGRGKAAILKAQVAARGRGRGMGRGN
  IFQKRR
• 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 pre-mRNA 3'-end processing.
• KEGG Pathway:
  Spliceosome (hsa03040)
  Systemic lupus erythematosus (hsa05322)
• 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

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Definitive	Biomarker	[1]
Undifferentiated carcinoma	DISIAZST	Definitive	Biomarker	[1]
HIV infectious disease	DISO97HC	Strong	Biomarker	[2]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Limited	Posttranslational Modification	[4]
Lung carcinoma	DISTR26C	Limited	Posttranslational Modification	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Small nuclear ribonucleoprotein Sm D3 (SNRPD3).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Small nuclear ribonucleoprotein Sm D3 (SNRPD3).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small nuclear ribonucleoprotein Sm D3 (SNRPD3).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Small nuclear ribonucleoprotein Sm D3 (SNRPD3).	[8]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Small nuclear ribonucleoprotein Sm D3 (SNRPD3).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Small nuclear ribonucleoprotein Sm D3 (SNRPD3).	[10]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate increases the expression of Small nuclear ribonucleoprotein Sm D3 (SNRPD3).	[11]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Small nuclear ribonucleoprotein Sm D3 (SNRPD3).	[12]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Small nuclear ribonucleoprotein Sm D3 (SNRPD3).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Small nuclear ribonucleoprotein Sm D3 (SNRPD3).	[14]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Small nuclear ribonucleoprotein Sm D3 (SNRPD3).	[15]

References

• [1] Global gene expression profiling of chemically induced rat mammary gland carcinomas and adenomas.Toxicol Pathol. 2005;33(7):768-75. doi: 10.1080/01926230500437027.
• [2] Host cell gene expression during human immunodeficiency virus type 1 latency and reactivation and effects of targeting genes that are differentially expressed in viral latency.J Virol. 2004 Sep;78(17):9458-73. doi: 10.1128/JVI.78.17.9458-9473.2004.
• [3] A genome-wide siRNA screen for regulators of tumor suppressor p53 activity in human non-small cell lung cancer cells identifies components of the RNA splicing machinery as targets for anticancer treatment.Mol Oncol. 2017 May;11(5):534-551. doi: 10.1002/1878-0261.12052. Epub 2017 Apr 11.
• [4] Selective small-chemical inhibitors of protein arginine methyltransferase 5 with anti-lung cancer activity.PLoS One. 2017 Aug 14;12(8):e0181601. doi: 10.1371/journal.pone.0181601. eCollection 2017.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] 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.
• [8] Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull. 2013;36(6):944-51. doi: 10.1248/bpb.b12-01004.
• [9] Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
• [10] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [11] Application of the adverse outcome pathway concept for investigating developmental neurotoxicity potential of Chinese herbal medicines by using human neural progenitor cells in vitro. Cell Biol Toxicol. 2023 Feb;39(1):319-343. doi: 10.1007/s10565-022-09730-4. Epub 2022 Jun 15.
• [12] 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.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway. Sci Rep. 2019 Jan 24;9(1):675.