Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8RQW3W)

• DOT Name: UPF0690 protein C1orf52 (C1ORF52)
• Synonyms: BCL10-associated gene protein
• Gene Name: C1ORF52
• Related Disease:
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Carcinoma
  Castration-resistant prostate carcinoma
  Colitis
  Cystic fibrosis
  Cytomegalovirus infection
  Epilepsy syndrome
  Kidney cancer
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Renal carcinoma
  Sleep apnea syndrome
  Stroke
  Neuroblastoma
  Osteomyelitis
  Tuberculosis
  Young-onset Parkinson disease
• UniProt ID: CA052_HUMAN
• Pfam ID: PF15559
• Sequence:
  MAAEEKDPLSYFAAYGSSSSGSSDEEDNIEPEETSRRTPDPAKSAGGCRNKAEKRLPGPD
  ELFRSVTRPAFLYNPLNKQIDWERHVVKAPEEPPKEFKIWKSNYVPPPETYTTEKKPPPP
  ELDMAIKWSNIYEDNGDDAPQNAKKARLLPEGEETLESDDEKDEHTSKKRKVEPGEPAKK
  KK
• Tissue Specificity: Expressed in all tissues tested including heart, placenta, liver, skeletal muscle, kidney and pancreas. Weak expression in brain and lung.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Altered Expression	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Carcinoma	DISH9F1N	Strong	Genetic Variation	[3]
Castration-resistant prostate carcinoma	DISVGAE6	Strong	Biomarker	[3]
Colitis	DISAF7DD	Strong	Altered Expression	[4]
Cystic fibrosis	DIS2OK1Q	Strong	Genetic Variation	[5]
Cytomegalovirus infection	DISCEMGC	Strong	Biomarker	[6]
Epilepsy syndrome	DISLYXJ3	Strong	Biomarker	[7]
Kidney cancer	DISBIPKM	Strong	Biomarker	[8]
Neoplasm	DISZKGEW	Strong	Biomarker	[9]
Prostate cancer	DISF190Y	Strong	Altered Expression	[3]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[3]
Renal carcinoma	DISER9XT	Strong	Biomarker	[8]
Sleep apnea syndrome	DISER6KS	Strong	Genetic Variation	[7]
Stroke	DISX6UHX	Strong	Biomarker	[10]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[11]
Osteomyelitis	DIS0VUZL	Limited	Biomarker	[12]
Tuberculosis	DIS2YIMD	Limited	Biomarker	[13]
Young-onset Parkinson disease	DIS05LFS	Limited	Biomarker	[14]

3 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 UPF0690 protein C1orf52 (C1ORF52).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of UPF0690 protein C1orf52 (C1ORF52).	[20]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of UPF0690 protein C1orf52 (C1ORF52).	[22]

5 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 UPF0690 protein C1orf52 (C1ORF52).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of UPF0690 protein C1orf52 (C1ORF52).	[17]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of UPF0690 protein C1orf52 (C1ORF52).	[18]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of UPF0690 protein C1orf52 (C1ORF52).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of UPF0690 protein C1orf52 (C1ORF52).	[21]

References

• [1] BAG-1M co-activates BACE1 transcription through NF-B and accelerates A production and memory deficit in Alzheimer's disease mouse model.Biochim Biophys Acta Mol Basis Dis. 2017 Sep;1863(9):2398-2407. doi: 10.1016/j.bbadis.2017.05.014. Epub 2017 May 11.
• [2] BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses.Br J Cancer. 2017 Jun 6;116(12):1585-1594. doi: 10.1038/bjc.2017.130. Epub 2017 May 16.
• [3] Overexpression and gene amplification of BAG-1L in hormone-refractory prostate cancer.J Pathol. 2007 Aug;212(4):395-401. doi: 10.1002/path.2186.
• [4] The BAG-1 isoform BAG-1M regulates keratin-associated Hsp70 chaperoning of aPKC in intestinal cells during activation of inflammatory signaling.J Cell Sci. 2014 Aug 15;127(Pt 16):3568-77. doi: 10.1242/jcs.151084. Epub 2014 May 29.
• [5] Silencing of the Hsp70-specific nucleotide-exchange factor BAG3 corrects the F508del-CFTR variant by restoring autophagy.J Biol Chem. 2018 Aug 31;293(35):13682-13695. doi: 10.1074/jbc.RA118.002607. Epub 2018 Jul 9.
• [6] Evaluation of the AmpliSensor PCR and the SHARP signal detection system for the early prediction of symptomatic CMV infection in solid transplant recipients.J Clin Virol. 1999 Jun;13(1-2):81-94. doi: 10.1016/s1386-6532(99)00013-x.
• [7] Obstructive sleep apnea in refractory epilepsy: A pilot study investigating frequency, clinical features, and association with risk of sudden unexpected death in epilepsy.Epilepsia. 2018 Oct;59(10):1973-1981. doi: 10.1111/epi.14548. Epub 2018 Sep 24.
• [8] Inhibition of the JNK signalling pathway enhances proteasome inhibitor-induced apoptosis of kidney cancer cells by suppression of BAG3 expression.Br J Pharmacol. 2009 Nov;158(5):1405-12. doi: 10.1111/j.1476-5381.2009.00455.x. Epub 2009 Aug 13.
• [9] BAG2 promotes tumorigenesis through enhancing mutant p53 protein levels and function.Elife. 2015 Aug 13;4:e08401. doi: 10.7554/eLife.08401.
• [10] Using a modified version of the "STOP-BANG" questionnaire and nocturnal oxygen desaturation to predict obstructive sleep apnea after stroke or TIA.Sleep Med. 2019 Apr;56:177-183. doi: 10.1016/j.sleep.2018.12.021. Epub 2019 Jan 7.
• [11] BAG-1L Protects SH-SY5Y Neuroblastoma Cells Against Hypoxia/Re-oxygenation Through Up-Regulating HSP70 and Activating PI3K/AKT Signaling Pathway.Neurochem Res. 2017 Oct;42(10):2861-2868. doi: 10.1007/s11064-017-2304-y. Epub 2017 May 18.
• [12] Antibacterial Bioactive Glass, S53P4, for Chronic Bone Infections - A Multinational Study.Adv Exp Med Biol. 2017;971:81-92. doi: 10.1007/5584_2016_156.
• [13] Evaluation of the hyplex TBC PCR test for detection of Mycobacterium tuberculosis complex in clinical samples.BMC Microbiol. 2010 Mar 31;10:95. doi: 10.1186/1471-2180-10-95.
• [14] BAG5 inhibits parkin and enhances dopaminergic neuron degeneration.Neuron. 2004 Dec 16;44(6):931-45. doi: 10.1016/j.neuron.2004.11.026.
• [15] 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.
• [16] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [17] 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.
• [18] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [19] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [20] 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.
• [21] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.
• [22] 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.