Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1PS84E)

DOT Name Proto-oncogene FRAT1 (FRAT1)
Synonyms Frequently rearranged in advanced T-cell lymphomas 1; FRAT-1
Gene Name FRAT1
Related Disease
Adult glioblastoma ( )
Advanced cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma of esophagus ( )
Cervical cancer ( )
Cervical carcinoma ( )
Esophageal cancer ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Glioma ( )
Hepatocellular carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Neoplasm of esophagus ( )
Prostate adenocarcinoma ( )
Stomach cancer ( )
T-cell lymphoma ( )
Adenocarcinoma ( )
Anal intraepithelial neoplasia ( )
Matthew-Wood syndrome ( )
Ovarian neoplasm ( )
Pancreatic ductal carcinoma ( )
Non-small-cell lung cancer ( )
Epithelial ovarian cancer ( )
Neoplasm ( )
Ovarian cancer ( )
UniProt ID
FRAT1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
1GNG; 3ZRK; 3ZRL; 3ZRM; 4AFJ; 5OY4
Pfam ID
PF05350
Sequence
MPCRREEEEEAGEEAEGEEEEEDSFLLLQQSVALGSSGEVDRLVAQIGETLQLDAAQHSP
ASPCGPPGAPLRAPGPLAAAVPADKARSPAVPLLLPPALAETVGPAPPGVLRCALGDRGR
VRGRAAPYCVAELATGPSALSPLPPQADLDGPPGAGKQGIPQPLSGPCRRGWLRGAAASR
RLQQRRGSQPETRTGDDDPHRLLQQLVLSGNLIKEAVRRLHSRRLQLRAKLPQRPLLGPL
SAPVHEPPSPRSPRAACSDPGASGRAQLRTGDGVLVPGS
Function
Positively regulates the Wnt signaling pathway by stabilizing beta-catenin through the association with GSK-3. May play a role in tumor progression and collaborate with PIM1 and MYC in lymphomagenesis.
KEGG Pathway
Wnt sig.ling pathway (hsa04310 )
Alzheimer disease (hsa05010 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Pathways in cancer (hsa05200 )
Breast cancer (hsa05224 )
Hepatocellular carcinoma (hsa05225 )
Gastric cancer (hsa05226 )
Reactome Pathway
Disassembly of the destruction complex and recruitment of AXIN to the membrane (R-HSA-4641262 )
Beta-catenin phosphorylation cascade (R-HSA-196299 )

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Strong Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Breast cancer DIS7DPX1 Strong Altered Expression [3]
Breast carcinoma DIS2UE88 Strong Altered Expression [3]
Carcinoma of esophagus DISS6G4D Strong Altered Expression [3]
Cervical cancer DISFSHPF Strong Altered Expression [4]
Cervical carcinoma DIST4S00 Strong Altered Expression [4]
Esophageal cancer DISGB2VN Strong Altered Expression [3]
Gastric cancer DISXGOUK Strong Altered Expression [4]
Glioblastoma multiforme DISK8246 Strong Biomarker [1]
Glioma DIS5RPEH Strong Biomarker [2]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [5]
Lung cancer DISCM4YA Strong Biomarker [6]
Lung carcinoma DISTR26C Strong Biomarker [6]
Neoplasm of esophagus DISOLKAQ Strong Altered Expression [7]
Prostate adenocarcinoma DISBZYU8 Strong Biomarker [8]
Stomach cancer DISKIJSX Strong Altered Expression [4]
T-cell lymphoma DISSXRTQ Strong Altered Expression [9]
Adenocarcinoma DIS3IHTY moderate Altered Expression [10]
Anal intraepithelial neoplasia DISJ0JW3 moderate Altered Expression [11]
Matthew-Wood syndrome DISA7HR7 moderate Altered Expression [11]
Ovarian neoplasm DISEAFTY moderate Altered Expression [10]
Pancreatic ductal carcinoma DIS26F9Q moderate Altered Expression [11]
Non-small-cell lung cancer DIS5Y6R9 Disputed Altered Expression [12]
Epithelial ovarian cancer DIS56MH2 Limited Altered Expression [13]
Neoplasm DISZKGEW Limited Altered Expression [8]
Ovarian cancer DISZJHAP Limited Altered Expression [13]
------------------------------------------------------------------------------------
⏷ Show the Full List of 27 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
19 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 Proto-oncogene FRAT1 (FRAT1). [14]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Proto-oncogene FRAT1 (FRAT1). [15]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Proto-oncogene FRAT1 (FRAT1). [16]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Proto-oncogene FRAT1 (FRAT1). [15]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Proto-oncogene FRAT1 (FRAT1). [17]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Proto-oncogene FRAT1 (FRAT1). [18]
Carbamazepine DMZOLBI Approved Carbamazepine affects the expression of Proto-oncogene FRAT1 (FRAT1). [19]
Selenium DM25CGV Approved Selenium increases the expression of Proto-oncogene FRAT1 (FRAT1). [20]
Lindane DMB8CNL Approved Lindane increases the expression of Proto-oncogene FRAT1 (FRAT1). [21]
Urethane DM7NSI0 Phase 4 Urethane decreases the expression of Proto-oncogene FRAT1 (FRAT1). [22]
Dihydrotestosterone DM3S8XC Phase 4 Dihydrotestosterone increases the expression of Proto-oncogene FRAT1 (FRAT1). [23]
Tocopherol DMBIJZ6 Phase 2 Tocopherol increases the expression of Proto-oncogene FRAT1 (FRAT1). [20]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Proto-oncogene FRAT1 (FRAT1). [24]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Proto-oncogene FRAT1 (FRAT1). [25]
Calphostin C DM9X2D0 Terminated Calphostin C increases the expression of Proto-oncogene FRAT1 (FRAT1). [26]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Proto-oncogene FRAT1 (FRAT1). [27]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of Proto-oncogene FRAT1 (FRAT1). [28]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the expression of Proto-oncogene FRAT1 (FRAT1). [21]
Rapamycin Immunosuppressant Drug DM678IB Investigative Rapamycin Immunosuppressant Drug increases the expression of Proto-oncogene FRAT1 (FRAT1). [21]
------------------------------------------------------------------------------------
⏷ Show the Full List of 19 Drug(s)

References

1 Knockdown of FRAT1 expression by RNA interference inhibits human glioblastoma cell growth, migration and invasion.PLoS One. 2013 Apr 17;8(4):e61206. doi: 10.1371/journal.pone.0061206. Print 2013.
2 Overexpression of FRAT1 is associated with malignant phenotype and poor prognosis in human gliomas.Dis Markers. 2015;2015:289750. doi: 10.1155/2015/289750. Epub 2015 Apr 2.
3 Molecular cloning and expression of proto-oncogene FRAT1 in human cancer.Int J Oncol. 2002 Apr;20(4):785-9.
4 FRAT1 and FRAT2, clustered in human chromosome 10q24.1 region, are up-regulated in gastric cancer.Int J Oncol. 2001 Aug;19(2):311-5. doi: 10.3892/ijo.19.2.311.
5 Knockdown of FRAT1 inhibits hypoxia-induced epithelial-to-mesenchymal transition via suppression of the Wnt/-catenin pathway in hepatocellular carcinoma cells.Oncol Rep. 2016 Nov;36(5):2999-3004. doi: 10.3892/or.2016.5130. Epub 2016 Sep 23.
6 Expression of Frat1 correlates with expression of -catenin and is associated with a poor clinical outcome in human SCC and AC.Tumour Biol. 2012 Oct;33(5):1437-44. doi: 10.1007/s13277-012-0394-3. Epub 2012 Apr 17.
7 FRAT1 overexpression leads to aberrant activation of beta-catenin/TCF pathway in esophageal squamous cell carcinoma.Int J Cancer. 2008 Aug 1;123(3):561-8. doi: 10.1002/ijc.23600.
8 Frequently rearranged in advanced Tcell lymphomas? demonstrates oncogenic properties in prostate cancer.Mol Med Rep. 2016 Oct;14(4):3551-8. doi: 10.3892/mmr.2016.5704. Epub 2016 Sep 5.
9 Epigenetic silencing of miR-490-3p promotes development of an aggressive colorectal cancer phenotype through activation of the Wnt/-catenin signaling pathway.Cancer Lett. 2016 Jun 28;376(1):178-87. doi: 10.1016/j.canlet.2016.03.024. Epub 2016 Mar 29.
10 Tissue microarray analysis of human FRAT1 expression and its correlation with the subcellular localisation of beta-catenin in ovarian tumours.Br J Cancer. 2006 Mar 13;94(5):686-91. doi: 10.1038/sj.bjc.6602988.
11 The clinical significance of FRAT1 and ABCG2 expression in pancreatic ductal adenocarcinoma.Tumour Biol. 2015 Dec;36(12):9961-8. doi: 10.1007/s13277-015-3752-0. Epub 2015 Jul 16.
12 LncRNA SNHG1 influences cell proliferation, migration, invasion, and apoptosis of non-small cell lung cancer cells via the miR-361-3p/FRAT1 axis.Thorac Cancer. 2020 Feb;11(2):295-304. doi: 10.1111/1759-7714.13256. Epub 2019 Dec 2.
13 Overexpression of Frat1 correlates with malignant phenotype and advanced stage in human non-small cell lung cancer.Virchows Arch. 2011 Sep;459(3):255-63. doi: 10.1007/s00428-011-1135-5. Epub 2011 Aug 5.
14 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.
15 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.
16 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
17 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.
18 A comprehensive analysis of Wnt/beta-catenin signaling pathway-related genes and crosstalk pathways in the treatment of As2O3 in renal cancer. Ren Fail. 2018 Nov;40(1):331-339.
19 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
20 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
21 Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
22 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
23 Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
24 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
25 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
26 Targeting the beta-catenin/TCF transcriptional complex in the treatment of multiple myeloma. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7516-21. doi: 10.1073/pnas.0610299104. Epub 2007 Apr 23.
27 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
28 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.