Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGGU7N1)

• DOT Name: RNA-binding motif protein, X-linked 2 (RBMX2)
• Gene Name: RBMX2
• Related Disease:
  Cervical cancer
  Human papillomavirus infection
• UniProt ID: RBMX2_HUMAN
• PDB ID: 5Z56; 5Z57; 5Z58; 6FF4; 6FF7; 7ABH; 7ABI; 7DVQ
• Pfam ID: PF00076
• Sequence:
  MNPLTKVKLINELNEREVQLGVADKVSWHSEYKDSAWIFLGGLPYELTEGDIICVFSQYG
  EIVNINLVRDKKTGKSKGFCFLCYEDQRSTILAVDNFNGIKIKGRTIRVDHVSNYRAPKD
  SEEIDDVTRQLQEKGCGARTPSPSLSESSEDEKPTKKHKKDKKEKKKKKKEKEKADREVQ
  AEQPSSSSPRRKTVKEKDDTGPKKHSSKNSERAQKSEPREGQKLPKSRTAYSGGAEDLER
  ELKKEKPKHEHKSSSRREAREEKTRIRDRGRSSDAHSSWYNGRSEGRSYRSRSRSRDKSH
  RHKRARRSRERESSNPSDRWRH
• Function: Involved in pre-mRNA splicing as component of the activated spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable).
• Reactome Pathway: 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
Cervical cancer	DISFSHPF	Strong	Biomarker	[1]
Human papillomavirus infection	DISX61LX	Strong	Biomarker	[1]

8 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 RNA-binding motif protein, X-linked 2 (RBMX2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RNA-binding motif protein, X-linked 2 (RBMX2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RNA-binding motif protein, X-linked 2 (RBMX2).	[4]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of RNA-binding motif protein, X-linked 2 (RBMX2).	[5]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of RNA-binding motif protein, X-linked 2 (RBMX2).	[6]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of RNA-binding motif protein, X-linked 2 (RBMX2).	[7]
Permethrin	DMZ0Q1G	Approved	Permethrin increases the expression of RNA-binding motif protein, X-linked 2 (RBMX2).	[8]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate increases the expression of RNA-binding motif protein, X-linked 2 (RBMX2).	[11]

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 decreases the methylation of RNA-binding motif protein, X-linked 2 (RBMX2).	[9]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of RNA-binding motif protein, X-linked 2 (RBMX2).	[10]

References

• [1] Enhanced specificity of the p53 family proteins-based adenoviral gene therapy in uterine cervical cancer cells with E2F1-responsive promoters.Cancer Biol Ther. 2006 Nov;5(11):1502-10. doi: 10.4161/cbt.5.11.3300. Epub 2006 Nov 19.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [6] 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.
• [7] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [8] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [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] 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.
• [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.