Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5ZGKU5)

• DOT Name: Small nuclear ribonucleoprotein Sm D2 (SNRPD2)
• Synonyms: Sm-D2; snRNP core protein D2
• Gene Name: SNRPD2
• UniProt ID: SMD2_HUMAN
• PDB ID: 1B34 ; 3CW1 ; 3JCR ; 3PGW ; 4F7U ; 4PJO ; 4V98 ; 4WZJ ; 5MQF ; 5O9Z ; 5XJC ; 5XJL ; 5XJQ ; 5XJR ; 5XJS ; 5XJT ; 5XJU ; 5YZG ; 5Z56 ; 5Z57 ; 5Z58 ; 6AH0 ; 6AHD ; 6FF7 ; 6ICZ ; 6ID0 ; 6ID1 ; 6QDV ; 6QW6 ; 6QX9 ; 6Y53 ; 6Y5Q ; 7A5P ; 7ABG ; 7ABI ; 7B0Y ; 7DVQ ; 7EVO ; 7QTT ; 7VPX ; 7W59 ; 7W5A ; 7W5B ; 8C6J ; 8CH6 ; 8HK1
• Pfam ID: PF01423
• Sequence:
  MSLLNKPKSEMTPEELQKREEEEFNTGPLSVLTQSVKNNTQVLINCRNNKKLLGRVKAFD
  RHCNMVLENVKEMWTEVPKSGKGKKKSKPVNKDRYISKMFLRGDSVIVVLRNPLIAGK
• 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.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway:
  mRNA Splicing - Major Pathway (R-HSA-72163)
  mRNA Splicing - Minor Pathway (R-HSA-72165)
  SARS-CoV-2 modulates host translation machinery (R-HSA-9754678)
  snRNP Assembly (R-HSA-191859)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Small nuclear ribonucleoprotein Sm D2 (SNRPD2).	[1]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Small nuclear ribonucleoprotein Sm D2 (SNRPD2).	[6]

6 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 Small nuclear ribonucleoprotein Sm D2 (SNRPD2).	[2]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Small nuclear ribonucleoprotein Sm D2 (SNRPD2).	[3]
Benzatropine	DMF7EXL	Approved	Benzatropine increases the expression of Small nuclear ribonucleoprotein Sm D2 (SNRPD2).	[4]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Small nuclear ribonucleoprotein Sm D2 (SNRPD2).	[7]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Small nuclear ribonucleoprotein Sm D2 (SNRPD2).	[8]
AHPN	DM8G6O4	Investigative	AHPN decreases the expression of Small nuclear ribonucleoprotein Sm D2 (SNRPD2).	[9]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Small nuclear ribonucleoprotein Sm D2 (SNRPD2).	[5]

References

• [1] 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.
• [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] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [5] Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells. Chem Res Toxicol. 2015 Oct 19;28(10):1903-13. doi: 10.1021/acs.chemrestox.5b00105. Epub 2015 Sep 21.
• [6] 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.
• [7] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [8] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [9] 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.