Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKP5JKH)

• DOT Name: Corepressor interacting with RBPJ 1 (CIR1)
• Synonyms: CBF1-interacting corepressor; Recepin
• Gene Name: CIR1
• Related Disease:
  Acute myelogenous leukaemia
  Friedreich's ataxia
  Liver cirrhosis
  Lung cancer
  Lung carcinoma
  Neuroblastoma
  Type-1/2 diabetes
  Graft-versus-host disease
• UniProt ID: CIR1_HUMAN
• PDB ID: 6ZYM
• Pfam ID: PF10197
• Sequence:
  MGKSFANFMCKKDFHPASKSNIKKVWMAEQKISYDKKKQEELMQQYLKEQESYDNRLLMG
  DERVKNGLNFMYEAPPGAKKENKEKEETEGETEYKFEWQKGAPREKYAKDDMNIRDQPFG
  IQVRNVRCIKCHKWGHVNTDRECPLFGLSGINASSVPTDGSGPSMHPSELIAEMRNSGFA
  LKRNVLGRNLTANDPSQEYVASEGEEDPEVEFLKSLTTKQKQKLLRKLDRLEKKKKKKDR
  KKKKFQKSRSKHKKHKSSSSSSSSSSSSSSTETSESSSESESNNKEKKIQRKKRKKNKCS
  GHNNSDSEEKDKSKKRKLHEELSSSHHNREKAKEKPRFLKHESSREDSKWSHSDSDKKSR
  THKHSPEKRGSERKEGSSRSHGREERSRRSRSRSPGSYKQRETRKRAQRNPGEEQSRRND
  SRSHGTDLYRGEKMYREHPGGTHTKVTQRE
• Function: May modulate splice site selection during alternative splicing of pre-mRNAs. Regulates transcription and acts as corepressor for RBPJ. Recruits RBPJ to the Sin3-histone deacetylase complex (HDAC). Required for RBPJ-mediated repression of transcription.
• Tissue Specificity: Highly expressed in heart, brain, placenta, liver, skeletal muscle and pancreas.
• KEGG Pathway:
  Notch sig.ling pathway (hsa04330)
  Epstein-Barr virus infection (hsa05169)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[1]
Friedreich's ataxia	DIS5DV35	Strong	Biomarker	[2]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[3]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[4]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[4]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[5]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[6]
Graft-versus-host disease	DIS0QADF	Limited	Genetic Variation	[7]

7 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 Corepressor interacting with RBPJ 1 (CIR1).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Corepressor interacting with RBPJ 1 (CIR1).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Corepressor interacting with RBPJ 1 (CIR1).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Corepressor interacting with RBPJ 1 (CIR1).	[11]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Corepressor interacting with RBPJ 1 (CIR1).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Corepressor interacting with RBPJ 1 (CIR1).	[13]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Corepressor interacting with RBPJ 1 (CIR1).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Corepressor interacting with RBPJ 1 (CIR1).	[14]

References

• [1] Correlation Between Isocitrate Dehydrogenase Gene Aberrations and Prognosis of Patients with Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis.Clin Cancer Res. 2017 Aug 1;23(15):4511-4522. doi: 10.1158/1078-0432.CCR-16-2628. Epub 2017 Feb 28.
• [2] Glucose intolerance in first-degree relatives of patients with Friedreich's ataxia is associated with insulin resistance: evidence for a closely linked inherited trait.Metabolism. 1991 Aug;40(8):788-93. doi: 10.1016/0026-0495(91)90004-g.
• [3] Intestinal microbiota in patients with chronic hepatitis C with and without cirrhosis compared with healthy controls.Liver Int. 2018 Jan;38(1):50-58. doi: 10.1111/liv.13485. Epub 2017 Jun 20.
• [4] Polymorphisms in cancer-related pathway genes and lung cancer.Eur Respir J. 2016 Oct;48(4):1184-1191. doi: 10.1183/13993003.02040-2015. Epub 2016 Sep 1.
• [5] Coexpression with potassium channel subunits used to clone the Y2 receptor for neuropeptide Y.Mol Pharmacol. 1996 Mar;49(3):387-90.
• [6] Family and genetic studies of indices of insulin sensitivity and insulin secretion in Pima Indians.Diabetes Metab Res Rev. 2001 Jul-Aug;17(4):296-303. doi: 10.1002/dmrr.213.
• [7] Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation.J Clin Oncol. 2019 Feb 10;37(5):375-385. doi: 10.1200/JCO.2018.79.2184. Epub 2018 Nov 7.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [10] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.