Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFW0IGK)

• DOT Name: Pre-mRNA-splicing factor RBM22 (RBM22)
• Synonyms: RNA-binding motif protein 22; Zinc finger CCCH domain-containing protein 16
• Gene Name: RBM22
• UniProt ID: RBM22_HUMAN
• PDB ID: 2YTC; 5MQF; 5XJC; 5YZG; 5Z56; 5Z57; 6FF4; 6FF7; 6ICZ; 6ID0; 6ID1; 6QDV; 6ZYM; 7A5P; 7AAV; 7ABG; 7ABI; 7QTT; 7W59; 7W5A; 7W5B; 8C6J; 8CH6
• Pfam ID: PF00076 ; PF21369
• Sequence:
  MATSLGSNTYNRQNWEDADFPILCQTCLGENPYIRMTKEKYGKECKICARPFTVFRWCPG
  VRMRFKKTEVCQTCSKLKNVCQTCLLDLEYGLPIQVRDAGLSFKDDMPKSDVNKEYYTQN
  MEREISNSDGTRPVGMLGKATSTSDMLLKLARTTPYYKRNRPHICSFWVKGECKRGEECP
  YRHEKPTDPDDPLADQNIKDRYYGINDPVADKLLKRASTMPRLDPPEDKTITTLYVGGLG
  DTITETDLRNHFYQFGEIRTITVVQRQQCAFIQFATRQAAEVAAEKSFNKLIVNGRRLNV
  KWGRSQAARGKEKEKDGTTDSGIKLEPVPGLPGALPPPPAAEEEASANYFNLPPSGPPAV
  VNIALPPPPGIAPPPPPGFGPHMFHPMGPPPPFMRAPGPIHYPSQDPQRMGAHAGKHSSP
• Function: Required for pre-mRNA splicing as component of the activated spliceosome. Involved in the first step of pre-mRNA splicing. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle. Involved in both translocations of the nuclear SLU7 to the cytoplasm and the cytosolic calcium-binding protein PDCD6 to the nucleus upon cellular stress responses.
• KEGG Pathway: Spliceosome (hsa03040)
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

12 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 Pre-mRNA-splicing factor RBM22 (RBM22).	[1]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Pre-mRNA-splicing factor RBM22 (RBM22).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Pre-mRNA-splicing factor RBM22 (RBM22).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pre-mRNA-splicing factor RBM22 (RBM22).	[4]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Pre-mRNA-splicing factor RBM22 (RBM22).	[5]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Pre-mRNA-splicing factor RBM22 (RBM22).	[6]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Pre-mRNA-splicing factor RBM22 (RBM22).	[7]
Scriptaid	DM9JZ21	Preclinical	Scriptaid decreases the expression of Pre-mRNA-splicing factor RBM22 (RBM22).	[6]
Oxamflatin	DM1TG3C	Terminated	Oxamflatin decreases the expression of Pre-mRNA-splicing factor RBM22 (RBM22).	[6]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Pre-mRNA-splicing factor RBM22 (RBM22).	[10]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of Pre-mRNA-splicing factor RBM22 (RBM22).	[11]
Octanedioic acid bis-hydroxyamide	DMJNQ9K	Investigative	Octanedioic acid bis-hydroxyamide decreases the expression of Pre-mRNA-splicing factor RBM22 (RBM22).	[6]

2 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 Pre-mRNA-splicing factor RBM22 (RBM22).	[8]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Pre-mRNA-splicing factor RBM22 (RBM22).	[9]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [6] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] 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.
• [10] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [11] Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.