Details of Drug Off-Target (DOT)

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

• DOT Name: Probable RNA-binding protein 23 (RBM23)
• Synonyms: CAPER beta; CAPERbeta; RNA-binding motif protein 23; RNA-binding region-containing protein 4; Splicing factor SF2
• Gene Name: RBM23
• Related Disease:
  Hepatocellular carcinoma
  Non-small-cell lung cancer
  Schizophrenia
  Systemic lupus erythematosus
• UniProt ID: RBM23_HUMAN
• PDB ID: 2CQ4; 2DNZ
• Pfam ID: PF15519 ; PF00076
• Sequence:
  MASDDFDIVIEAMLEAPYKKEEDEQQRKEVKKDYPSNTTSSTSNSGNETSGSSTIGETSK
  KKRSRSHNKSRDRKRSRSRDRDRYRRRNSRSRSPGRQCRHRSRSWDRRHGSESRSRDHRR
  EDRVHYRSPPLATGYRYGHSKSPHFREKSPVREPVDNLSPEERDARTVFCMQLAARIRPR
  DLEDFFSAVGKVRDVRIISDRNSRRSKGIAYVEFCEIQSVPLAIGLTGQRLLGVPIIVQA
  SQAEKNRLAAMANNLQKGNGGPMRLYVGSLHFNITEDMLRGIFEPFGKIDNIVLMKDSDT
  GRSKGYGFITFSDSECARRALEQLNGFELAGRPMRVGHVTERLDGGTDITFPDGDQELDL
  GSAGGRFQLMAKLAEGAGIQLPSTAAAAAAAAAQAAALQLNGAVPLGALNPAALTALSPA
  LNLASQCFQLSSLFTPQTM
• Function: RNA-binding protein that acts both as a transcription coactivator and pre-mRNA splicing factor. Regulates steroid hormone receptor-mediated transcription, independently of the pre-mRNA splicing factor activity.
• Tissue Specificity: Highly expressed in placenta, liver, skeletal muscle, heart and kidney . Expressed at lower levels in the colon, thymus, spleen, small intestine and lung .

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]
Systemic lupus erythematosus	DISI1SZ7	Strong	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Probable RNA-binding protein 23 (RBM23).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Probable RNA-binding protein 23 (RBM23).	[6]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Probable RNA-binding protein 23 (RBM23).	[7]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Probable RNA-binding protein 23 (RBM23).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Probable RNA-binding protein 23 (RBM23).	[9]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Probable RNA-binding protein 23 (RBM23).	[10]

References

• [1] Glucose regulates heat shock factor 1 transcription activity via mTOR pathway in HCC cell lines.Cell Biol Int. 2015 Nov;39(11):1217-24. doi: 10.1002/cbin.10493. Epub 2015 Jul 6.
• [2] HnRNP A1/A2 and SF2/ASF regulate alternative splicing of interferon regulatory factor-3 and affect immunomodulatory functions in human non-small cell lung cancer cells.PLoS One. 2013 Apr 29;8(4):e62729. doi: 10.1371/journal.pone.0062729. Print 2013.
• [3] Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.Am J Hum Genet. 2019 Aug 1;105(2):334-350. doi: 10.1016/j.ajhg.2019.06.012.
• [4] Splicing factor SF2/ASF rescues IL-2 production in T cells from systemic lupus erythematosus patients by activating IL-2 transcription.Proc Natl Acad Sci U S A. 2013 Jan 29;110(5):1845-50. doi: 10.1073/pnas.1214207110. Epub 2013 Jan 14.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [7] 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.
• [8] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [9] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [10] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.