Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLE0KQM)

• DOT Name: Arginine/serine-rich coiled-coil protein 2 (RSRC2)
• Gene Name: RSRC2
• Related Disease:
  Carcinoma of esophagus
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Neoplasm of esophagus
  Triple negative breast cancer
  Complex neurodevelopmental disorder
  Neoplasm
• UniProt ID: RSRC2_HUMAN
• Pfam ID: PF15477
• Sequence:
  MAASDTERDGLAPEKTSPDRDKKKEQSEVSVSPRASKHHYSRSRSRSRERKRKSDNEGRK
  HRSRSRSKEGRRHESKDKSSKKHKSEEHNDKEHSSDKGRERLNSSENGEDRHKRKERKSS
  RGRSHSRSRSRERRHRSRSRERKKSRSRSRERKKSRSRSRERKKSRSRSRERKRRIRSRS
  RSRSRHRHRTRSRSRTRSRSRDRKKRIEKPRRFSRSLSRTPSPPPFRGRNTAMDAQEALA
  RRLERAKKLQEQREKEMVEKQKQQEIAAAAATGGSVLNVAALLASGTQVTPQIAMAAQMA
  ALQAKALAETGIAVPSYYNPAAVNPMKFAEQEKKRKMLWQGKKEGDKSQSAEIWEKLNFG
  NKDQNVKFRKLMGIKSEDEAGCSSVDEESYKTLKQQEEVFRNLDAQYEMARSQTHTQRGM
  GLGFTSSMRGMDAV

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[1]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[1]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[1]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[2]
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal dominant	[3]
Neoplasm	DISZKGEW	Limited	Biomarker	[4]

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 Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[5]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[10]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[12]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[13]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[9]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[9]
Clodronate	DM9Y6X7	Approved	Clodronate affects the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[9]
Ibuprofen	DM8VCBE	Approved	Ibuprofen increases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[15]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[16]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Arginine/serine-rich coiled-coil protein 2 (RSRC2).	[17]

References

• [1] A novel gene, RSRC2, inhibits cell proliferation and affects survival in esophageal cancer patients.Int J Oncol. 2007 Feb;30(2):421-8.
• [2] TRA2A Promoted Paclitaxel Resistance and Tumor Progression in Triple-Negative Breast Cancers via Regulating Alternative Splicing.Mol Cancer Ther. 2017 Jul;16(7):1377-1388. doi: 10.1158/1535-7163.MCT-17-0026. Epub 2017 Apr 17.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] Discovery of non-ETS gene fusions in human prostate cancer using next-generation RNA sequencing.Genome Res. 2011 Jan;21(1):56-67. doi: 10.1101/gr.110684.110. Epub 2010 Oct 29.
• [5] 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.
• [6] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [7] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] 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.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] Identification of novel genes associated with the response to 5-FU treatment in gastric cancer cell lines using a cDNA microarray. Cancer Lett. 2004 Oct 8;214(1):19-33.
• [14] 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.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [17] In vitro effects of aldehydes present in tobacco smoke on gene expression in human lung alveolar epithelial cells. Toxicol In Vitro. 2013 Apr;27(3):1072-81.