Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBCQ8AQ)

• DOT Name: Cingulin (CGN)
• Gene Name: CGN
• Related Disease:
  Lung carcinoma
  Ulcerative colitis
• UniProt ID: CING_HUMAN
• Pfam ID: PF01576
• Sequence:
  MEQAPNMAEPRGPVDHGVQIRFITEPVSGAEMGTLRRGGRRPAKDARASTYGVAVRVQGI
  AGQPFVVLNSGEKGGDSFGVQIKGANDQGASGALSSDLELPENPYSQVKGFPAPSQSSTS
  DEEPGAYWNGKLLRSHSQASLAGPGPVDPSNRSNSMLELAPKVASPGSTIDTAPLSSVDS
  LINKFDSQLGGQARGRTGRRTRMLPPEQRKRSKSLDSRLPRDTFEERERQSTNHWTSSTK
  YDNHVGTSKQPAQSQNLSPLSGFSRSRQTQDWVLQSFEEPRRSAQDPTMLQFKSTPDLLR
  DQQEAAPPGSVDHMKATIYGILREGSSESETSVRRKVSLVLEKMQPLVMVSSGSTKAVAG
  QGELTRKVEELQRKLDEEVKKRQKLEPSQVGLERQLEEKTEECSRLQELLERRKGEAQQS
  NKELQNMKRLLDQGEDLRHGLETQVMELQNKLKHVQGPEPAKEVLLKDLLETRELLEEVL
  EGKQRVEEQLRLRERELTALKGALKEEVASRDQEVEHVRQQYQRDTEQLRRSMQDATQDH
  AVLEAERQKMSALVRGLQRELEETSEETGHWQSMFQKNKEDLRATKQELLQLRMEKEEME
  EELGEKIEVLQRELEQARASAGDTRQVEVLKKELLRTQEELKELQAERQSQEVAGRHRDR
  ELEKQLAVLRVEADRGRELEEQNLQLQKTLQQLRQDCEEASKAKMVAEAEATVLGQRRAA
  VETTLRETQEENDEFRRRILGLEQQLKETRGLVDGGEAVEARLRDKLQRLEAEKQQLEEA
  LNASQEEEGSLAAAKRALEARLEEAQRGLARLGQEQQTLNRALEEEGKQREVLRRGKAEL
  EEQKRLLDRTVDRLNKELEKIGEDSKQALQQLQAQLEDYKEKARREVADAQRQAKDWASE
  AEKTSGGLSRLQDEIQRLRQALQASQAERDTARLDKELLAQRLQGLEQEAENKKRSQDDR
  ARQLKGLEEKVSRLETELDEEKNTVELLTDRVNRGRDQVDQLRTELMQERSARQDLECDK
  ISLERQNKDLKTRLASSEGFQKPSASLSQLESQNQLLQERLQAEEREKTVLQSTNRKLER
  KVKELSIQIEDERQHVNDQKDQLSLRVKALKRQVDEAEEEIERLDGLRKKAQREVEEQHE
  VNEQLQARIKSLEKDSWRKASRSAAESALKNEGLSSDEEFDSVYDPSSIASLLTESNLQT
  SSC
• Function: Probably plays a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier.
• Tissue Specificity: Localized on the cytoplasmic face of tight junctions of polarized epithelia and some endothelia. Expressed in pancreas, kidney, liver and lung, but not in skeletal muscle, placenta, brain or heart.
• KEGG Pathway: Tight junction (hsa04530)
• Reactome Pathway: TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) (R-HSA-2173791)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung carcinoma	DISTR26C	Strong	Altered Expression	[1]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[2]

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 Cingulin (CGN).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cingulin (CGN).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cingulin (CGN).	[16]

18 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 Cingulin (CGN).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cingulin (CGN).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cingulin (CGN).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cingulin (CGN).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cingulin (CGN).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cingulin (CGN).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cingulin (CGN).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Cingulin (CGN).	[10]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Cingulin (CGN).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Cingulin (CGN).	[12]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Cingulin (CGN).	[13]
NVP-AUY922	DMTYXQF	Phase 2	NVP-AUY922 decreases the expression of Cingulin (CGN).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cingulin (CGN).	[17]
SB-431542	DM0YOXQ	Preclinical	SB-431542 increases the expression of Cingulin (CGN).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cingulin (CGN).	[19]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cingulin (CGN).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Cingulin (CGN).	[21]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Cingulin (CGN).	[22]

References

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• [2] miR-24 Is Elevated in Ulcerative Colitis Patients and Regulates Intestinal Epithelial Barrier Function.Am J Pathol. 2019 Sep;189(9):1763-1774. doi: 10.1016/j.ajpath.2019.05.018. Epub 2019 Jun 18.
• [3] 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.
• [4] 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.
• [5] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [6] 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.
• [7] 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.
• [8] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [11] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [12] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [13] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [14] Impact of Heat Shock Protein 90 Inhibition on the Proteomic Profile of Lung Adenocarcinoma as Measured by Two-Dimensional Electrophoresis Coupled with Mass Spectrometry. Cells. 2019 Jul 31;8(8):806. doi: 10.3390/cells8080806.
• [15] 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.
• [16] 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.
• [17] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [18] Activin/nodal signaling switches the terminal fate of human embryonic stem cell-derived trophoblasts. J Biol Chem. 2015 Apr 3;290(14):8834-48.
• [19] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [20] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [21] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [22] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.