Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD13PJN)

• DOT Name: RNA-binding motif, single-stranded-interacting protein 1 (RBMS1)
• Synonyms: Single-stranded DNA-binding protein MSSP-1; Suppressor of CDC2 with RNA-binding motif 2
• Gene Name: RBMS1
• Related Disease:
  Bruton-type agammaglobulinemia
  Obesity
  Non-insulin dependent diabetes
• UniProt ID: RBMS1_HUMAN
• PDB ID: 1X5O; 6M75; 7C36
• Pfam ID: PF00076
• Sequence:
  MGKVWKQQMYPQYATYYYPQYLQAKQSLVPAHPMAPPSPSTTSSNNNSSSSSNSGWDQLS
  KTNLYIRGLPPHTTDQDLVKLCQPYGKIVSTKAILDKTTNKCKGYGFVDFDSPAAAQKAV
  SALKASGVQAQMAKQQEQDPTNLYISNLPLSMDEQELENMLKPFGQVISTRILRDSSGTS
  RGVGFARMESTEKCEAVIGHFNGKFIKTPPGVSAPTEPLLCKFADGGQKKRQNPNKYIPN
  GRPWHREGEVRLAGMTLTYDPTTAAIQNGFYPSPYSIATNRMITQTSITPYIASPVSAYQ
  VQSPSWMQPQPYILQHPGAVLTPSMEHTMSLQPASMISPLAQQMSHLSLGSTGTYMPATS
  AMQGAYLPQYAHMQTTAVPVEEASGQQQVAVETSNDHSPYTFQPNK
• Function: Single-stranded DNA binding protein that interacts with the region upstream of the MYC gene. Binds specifically to the DNA sequence motif 5'-[AT]CT[AT][AT]T-3'. Probably has a role in DNA replication.
• Tissue Specificity: Highest amounts are found in placenta, lung and heart.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bruton-type agammaglobulinemia	DISQ5ZYP	Strong	Biomarker	[1]
Obesity	DIS47Y1K	Strong	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[3]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	RNA-binding motif, single-stranded-interacting protein 1 (RBMS1) affects the response to substance of Methotrexate.	[19]
Irinotecan	DMP6SC2	Approved	RNA-binding motif, single-stranded-interacting protein 1 (RBMS1) decreases the response to substance of Irinotecan.	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[4]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[11]
Selenium	DM25CGV	Approved	Selenium decreases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[12]
Menadione	DMSJDTY	Approved	Menadione affects the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[13]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[15]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[8]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of RNA-binding motif, single-stranded-interacting protein 1 (RBMS1).	[8]

References

• [1] Cellular origins of serum complement receptor type 2 in normal individuals and in hypogammaglobulinaemia.Clin Exp Immunol. 1991 Apr;84(1):16-22. doi: 10.1111/j.1365-2249.1991.tb08117.x.
• [2] Modulation of genetic associations with serum urate levels by body-mass-index in humans.PLoS One. 2015 Mar 26;10(3):e0119752. doi: 10.1371/journal.pone.0119752. eCollection 2015.
• [3] Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes.Nat Commun. 2018 Jan 22;9(1):321. doi: 10.1038/s41467-017-02380-9.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [7] 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.
• [8] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [9] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [10] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [11] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [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] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [14] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [15] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [16] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [17] 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.
• [18] Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation. Oncol Lett. 2021 Feb;21(2):101. doi: 10.3892/ol.2020.12362. Epub 2020 Dec 8.
• [19] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.
• [20] Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 2006 Jun;97(6):510-22. doi: 10.1111/j.1349-7006.2006.00204.x.