Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTKJ9Y4)

DOT Name Progestin and adipoQ receptor family member 3 (PAQR3)
Synonyms Progestin and adipoQ receptor family member III; Raf kinase trapping to Golgi; RKTG
Gene Name PAQR3
Related Disease
Colorectal carcinoma ( )
Familial adenomatous polyposis ( )
Thyroid gland papillary carcinoma ( )
Benign prostatic hyperplasia ( )
Carcinoma of esophagus ( )
Esophageal cancer ( )
Esophageal squamous cell carcinoma ( )
Fatty liver disease ( )
Gastric cancer ( )
Glioma ( )
Hepatocellular carcinoma ( )
Lipid metabolism disorder ( )
Melanoma ( )
Neoplasm of esophagus ( )
Non-small-cell lung cancer ( )
Obesity ( )
Prostate adenocarcinoma ( )
Prostate cancer ( )
Renal fibrosis ( )
Skin cancer ( )
Stomach cancer ( )
Advanced cancer ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Diabetic kidney disease ( )
leukaemia ( )
Leukemia ( )
Osteosarcoma ( )
UniProt ID
PAQR3_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF03006
Sequence
MHQKLLKSAHYIELGSYQYWPVLVPRGIRLYTYEQIPGSLKDNPYITDGYRAYLPSRLCI
KSLFILSNETVNIWSHLLGFFLFFTLGIYDMTSVLPSASASREDFVICSICLFCFQVCML
CSVGYHLFSCHRSEKTCRRWMALDYAGISIGILGCYVSGVFYAFYCNNYWRQVYLITVLA
MILAVFFAQIHPNYLTQQWQRLRSIIFCSVSGYGVIPTLHWVWLNGGIGAPIVQDFAPRV
IVMYMIALLAFLFYISKVPERYFPGQLNYLGSSHQIWHILAVVMLYWWHQSTVYVMQYRH
SKPCPDYVSHL
Function Functions as a spatial regulator of RAF1 kinase by sequestrating it to the Golgi.
Tissue Specificity Widely expressed in a range of tissues.
Reactome Pathway
Negative regulation of MAPK pathway (R-HSA-5675221 )

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Colorectal carcinoma DIS5PYL0 Definitive Altered Expression [1]
Familial adenomatous polyposis DISW53RE Definitive Genetic Variation [1]
Thyroid gland papillary carcinoma DIS48YMM Definitive Altered Expression [2]
Benign prostatic hyperplasia DISI3CW2 Strong Posttranslational Modification [3]
Carcinoma of esophagus DISS6G4D Strong Biomarker [4]
Esophageal cancer DISGB2VN Strong Biomarker [4]
Esophageal squamous cell carcinoma DIS5N2GV Strong Biomarker [4]
Fatty liver disease DIS485QZ Strong Genetic Variation [5]
Gastric cancer DISXGOUK Strong Biomarker [6]
Glioma DIS5RPEH Strong Biomarker [7]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [8]
Lipid metabolism disorder DISEOA7S Strong Posttranslational Modification [9]
Melanoma DIS1RRCY Strong Biomarker [10]
Neoplasm of esophagus DISOLKAQ Strong Biomarker [4]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [11]
Obesity DIS47Y1K Strong Biomarker [5]
Prostate adenocarcinoma DISBZYU8 Strong Posttranslational Modification [3]
Prostate cancer DISF190Y Strong Posttranslational Modification [3]
Renal fibrosis DISMHI3I Strong Biomarker [12]
Skin cancer DISTM18U Strong Genetic Variation [13]
Stomach cancer DISKIJSX Strong Biomarker [6]
Advanced cancer DISAT1Z9 moderate Posttranslational Modification [3]
Bone osteosarcoma DIST1004 moderate Biomarker [14]
Breast cancer DIS7DPX1 moderate Posttranslational Modification [15]
Breast carcinoma DIS2UE88 moderate Posttranslational Modification [15]
Diabetic kidney disease DISJMWEY moderate Biomarker [12]
leukaemia DISS7D1V moderate Altered Expression [16]
Leukemia DISNAKFL moderate Altered Expression [16]
Osteosarcoma DISLQ7E2 moderate Biomarker [14]
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⏷ Show the Full List of 29 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
13 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [17]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [18]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [19]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [20]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate increases the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [21]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [22]
Estradiol DMUNTE3 Approved Estradiol increases the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [23]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [24]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [22]
Isotretinoin DM4QTBN Approved Isotretinoin decreases the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [25]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [26]
methyl p-hydroxybenzoate DMO58UW Investigative methyl p-hydroxybenzoate increases the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [29]
OXYQUINOLINE DMZVS9Y Investigative OXYQUINOLINE decreases the expression of Progestin and adipoQ receptor family member 3 (PAQR3). [24]
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⏷ Show the Full List of 13 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Progestin and adipoQ receptor family member 3 (PAQR3). [27]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Progestin and adipoQ receptor family member 3 (PAQR3). [28]
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References

1 PAQR3 plays a suppressive role in the tumorigenesis of colorectal cancers.Carcinogenesis. 2012 Nov;33(11):2228-35. doi: 10.1093/carcin/bgs245. Epub 2012 Jul 24.
2 Associations of the BRAF V600E Mutation and PAQR3 Protein Expression with Papillary Thyroid Carcinoma Clinicopathological Features.Pathol Oncol Res. 2020 Jul;26(3):1833-1841. doi: 10.1007/s12253-019-00779-x. Epub 2019 Nov 22.
3 Aberrant promoter methylation of the PAQR3 gene is associated with prostate cancer.Pathol Res Pract. 2018 Jan;214(1):126-129. doi: 10.1016/j.prp.2017.10.010. Epub 2017 Oct 10.
4 Suppressor PAQR3 associated with the clinical significance and prognosis in esophageal squamous cell carcinoma.Oncol Lett. 2018 Apr;15(4):5703-5711. doi: 10.3892/ol.2018.8004. Epub 2018 Feb 8.
5 PAQR3 has modulatory roles in obesity, energy metabolism, and leptin signaling.Endocrinology. 2013 Dec;154(12):4525-35. doi: 10.1210/en.2013-1633. Epub 2013 Sep 13.
6 Overexpression of miR-15b-5p promotes gastric cancer metastasis by regulating PAQR3.Oncol Rep. 2017 Jul;38(1):352-358. doi: 10.3892/or.2017.5673. Epub 2017 May 26.
7 PAQR3 inhibits the proliferation, migration and invasion in human glioma cells.Biomed Pharmacother. 2017 Aug;92:24-32. doi: 10.1016/j.biopha.2017.05.046. Epub 2017 May 18.
8 Identification of PAQR3 as a new candidate tumor suppressor in hepatocellular carcinoma.Oncol Rep. 2014 Dec;32(6):2687-95. doi: 10.3892/or.2014.3532. Epub 2014 Oct 6.
9 PAQR3 regulates phosphorylation of FoxO1 in insulin-resistant HepG2 cells via NF-B signaling pathway.Exp Cell Res. 2019 Aug 15;381(2):301-310. doi: 10.1016/j.yexcr.2019.04.031. Epub 2019 May 13.
10 RKTG sequesters B-Raf to the Golgi apparatus and inhibits the proliferation and tumorigenicity of human malignant melanoma cells.Carcinogenesis. 2008 Jun;29(6):1157-63. doi: 10.1093/carcin/bgn119. Epub 2008 May 29.
11 PAQR3 suppresses the growth of non-small cell lung cancer cells via modulation of EGFR-mediated autophagy.Autophagy. 2020 Jul;16(7):1236-1247. doi: 10.1080/15548627.2019.1659654. Epub 2019 Aug 30.
12 Progestin and AdipoQ Receptor 3 Upregulates Fibronectin and Intercellular Adhesion Molecule-1 in Glomerular Mesangial Cells via Activating NF-B Signaling Pathway Under High Glucose Conditions.Front Endocrinol (Lausanne). 2018 Jun 7;9:275. doi: 10.3389/fendo.2018.00275. eCollection 2018.
13 Functional cooperation of RKTG with p53 in tumorigenesis and epithelial-mesenchymal transition.Cancer Res. 2011 Apr 15;71(8):2959-68. doi: 10.1158/0008-5472.CAN-10-4077. Epub 2011 Mar 8.
14 The tumor suppressor role of PAQR3 in osteosarcoma.Tumour Biol. 2015 May;36(5):3319-24. doi: 10.1007/s13277-014-2964-z. Epub 2014 Dec 17.
15 The role of PAQR3 gene promoter hypermethylation in breast cancer and prognosis.Oncol Rep. 2016 Sep;36(3):1612-8. doi: 10.3892/or.2016.4951. Epub 2016 Jul 19.
16 RKTG overexpression inhibits proliferation and induces apoptosis of human leukemia cells via suppression of the ERK and PI3K/AKT signaling pathways.Oncol Lett. 2017 Jul;14(1):965-970. doi: 10.3892/ol.2017.6182. Epub 2017 May 17.
17 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.
18 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
19 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.
20 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
21 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
22 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
23 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.
24 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
25 Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
26 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
27 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.
28 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
29 Transcriptome dynamics of alternative splicing events revealed early phase of apoptosis induced by methylparaben in H1299 human lung carcinoma cells. Arch Toxicol. 2020 Jan;94(1):127-140. doi: 10.1007/s00204-019-02629-w. Epub 2019 Nov 20.