Details of Drug Off-Target (DOT)

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

DOT Name Anterior gradient protein 3 (AGR3)
Synonyms AG-3; AG3; hAG-3; Anterior gradient 3 homolog; Breast cancer membrane protein 11; Protein disulfide isomerase family A, member 18
Gene Name AGR3
Related Disease
Breast cancer ( )
Adenocarcinoma ( )
Breast carcinoma ( )
Breast neoplasm ( )
Cholangiocarcinoma ( )
Dilated cardiomyopathy 1A ( )
Epithelial ovarian cancer ( )
Hepatocellular carcinoma ( )
Inflammatory bowel disease ( )
Intrahepatic cholangiocarcinoma ( )
Invasive ductal breast carcinoma ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Advanced cancer ( )
Colorectal carcinoma ( )
Methicillin-resistant staphylococci infection ( )
Cutaneous melanoma ( )
Papillary serous cystadenocarcinoma ( )
UniProt ID
AGR3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
3PH9
Pfam ID
PF13899
Sequence
MMLHSALGLCLLLVTVSSNLAIAIKKEKRPPQTLSRGWGDDITWVQTYEEGLFYAQKSKK
PLMVIHHLEDCQYSQALKKVFAQNEEIQEMAQNKFIMLNLMHETTDKNLSPDGQYVPRIM
FVDPSLTVRADIAGRYSNRLYTYEPRDLPLLIENMKKALRLIQSEL
Function Required for calcium-mediated regulation of ciliary beat frequency and mucociliary clearance in the airway. Might be involved in the regulation of intracellular calcium in tracheal epithelial cells.
Tissue Specificity
Expressed in the lung, in the ciliated cells of the airway epithelium . Expression increased with differentiation of airway epithelial cells . Not detected in the mucous cells . Expressed in ciliated cells in the oviduct . Also detected in stomach, colon, prostate and liver . Expressed in breast, ovary, prostate and liver cancer . Expression is associated with the level of differentiation of breast cancer (at protein level) .

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Breast cancer DIS7DPX1 Definitive Biomarker [1]
Adenocarcinoma DIS3IHTY Strong Posttranslational Modification [2]
Breast carcinoma DIS2UE88 Strong Biomarker [1]
Breast neoplasm DISNGJLM Strong Altered Expression [3]
Cholangiocarcinoma DIS71F6X Strong Biomarker [4]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Biomarker [1]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [5]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [4]
Inflammatory bowel disease DISGN23E Strong Biomarker [6]
Intrahepatic cholangiocarcinoma DIS6GOC8 Strong Altered Expression [4]
Invasive ductal breast carcinoma DIS43J58 Strong Biomarker [1]
Metastatic malignant neoplasm DIS86UK6 Strong Genetic Variation [7]
Neoplasm DISZKGEW Strong Altered Expression [3]
Ovarian cancer DISZJHAP Strong Altered Expression [5]
Ovarian neoplasm DISEAFTY Strong Altered Expression [5]
Advanced cancer DISAT1Z9 moderate Biomarker [8]
Colorectal carcinoma DIS5PYL0 moderate Altered Expression [8]
Methicillin-resistant staphylococci infection DIS6DRDZ moderate Biomarker [9]
Cutaneous melanoma DIS3MMH9 Limited Genetic Variation [10]
Papillary serous cystadenocarcinoma DISZV6Z3 Limited Biomarker [11]
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⏷ Show the Full List of 20 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
This DOT Affected the Drug Response of 2 Drug(s)
Drug Name Drug ID Highest Status Interaction REF
Temozolomide DMKECZD Approved Anterior gradient protein 3 (AGR3) affects the response to substance of Temozolomide. [16]
DTI-015 DMXZRW0 Approved Anterior gradient protein 3 (AGR3) affects the response to substance of DTI-015. [16]
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4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Anterior gradient protein 3 (AGR3). [12]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide affects the expression of Anterior gradient protein 3 (AGR3). [13]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Anterior gradient protein 3 (AGR3). [14]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Anterior gradient protein 3 (AGR3). [15]
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References

1 Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response.Cancer Res Treat. 2020 Jan;52(1):218-245. doi: 10.4143/crt.2019.217. Epub 2019 Jul 8.
2 Extracellular AGR3 regulates breast cancer cells migration via Src signaling.Oncol Lett. 2019 Nov;18(5):4449-4456. doi: 10.3892/ol.2019.10849. Epub 2019 Sep 10.
3 AGR3 in breast cancer: prognostic impact and suitable serum-based biomarker for early cancer detection.PLoS One. 2015 Apr 15;10(4):e0122106. doi: 10.1371/journal.pone.0122106. eCollection 2015.
4 Differential expression of anterior gradient protein 3 in intrahepatic cholangiocarcinoma and hepatocellular carcinoma.Exp Mol Pathol. 2014 Jun;96(3):375-81. doi: 10.1016/j.yexmp.2014.04.002. Epub 2014 Apr 18.
5 Anterior Gradient-3: a novel biomarker for ovarian cancer that mediates cisplatin resistance in xenograft models.J Immunol Methods. 2012 Apr 30;378(1-2):20-32. doi: 10.1016/j.jim.2012.01.013. Epub 2012 Feb 15.
6 Evaluation of AGR2 and AGR3 as candidate genes for inflammatory bowel disease. Genes Immun. 2006 Jan;7(1):11-8. doi: 10.1038/sj.gene.6364263.
7 Anterior gradient 2 and 3--two prototype androgen-responsive genes transcriptionally upregulated by androgens and by oestrogens in prostate cancer cells.FEBS J. 2013 Mar;280(5):1249-66. doi: 10.1111/febs.12118. Epub 2013 Feb 13.
8 AGR3 promotes the stemness of colorectal cancer via modulating Wnt/-catenin signalling.Cell Signal. 2020 Jan;65:109419. doi: 10.1016/j.cellsig.2019.109419. Epub 2019 Sep 14.
9 Detection of new methicillin-resistant Staphylococcus aureus clones containing the toxic shock syndrome toxin 1 gene responsible for hospital- and community-acquired infections in France.J Clin Microbiol. 2006 Mar;44(3):847-53. doi: 10.1128/JCM.44.3.847-853.2006.
10 Genome-wide association study in 176,678 Europeans reveals genetic loci for tanning response to sun exposure.Nat Commun. 2018 May 8;9(1):1684. doi: 10.1038/s41467-018-04086-y.
11 Combination of TP53 and AGR3 to distinguish ovarian high-grade serous carcinoma from low-grade serous carcinoma.Int J Oncol. 2018 Jun;52(6):2041-2050. doi: 10.3892/ijo.2018.4360. Epub 2018 Apr 4.
12 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
13 Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
14 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
15 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
16 Tumor necrosis factor-alpha-induced protein 3 as a putative regulator of nuclear factor-kappaB-mediated resistance to O6-alkylating agents in human glioblastomas. J Clin Oncol. 2006 Jan 10;24(2):274-87. doi: 10.1200/JCO.2005.02.9405. Epub 2005 Dec 19.